COMPREHENSIVE EXAMTHE MANAGEMENT OF

ALZHEIMERrsquoS DISEASE (AD)PRESENTER CAROLINE HUMBLES RN BSN

COMMITTEE DR JOAN NELSON (CHAIRPERSON) DR KRISTA

ESTES amp DR ERNESTINE KOTTHOFF-BURRELL

DATE OCTOBER 9TH 2014

bull SITUATION 87 yo Caucasian male at Assisted Living Memory Unit DX with Alzheimerrsquos disease (AD) 5 yrs ago Wife wants to discuss (1) Hospice care and (2) keeping JT on Simvastatin

bull BACKGROUND PMH MI 8 ya hyperlipidemia constipation insomnia PSH CABG 8 ya amp hernia repair MEDS ASA 325mg QD Citalopram 40mg QD Clonazepam 05mg QD Melatonin 3mg HS MVI 1tab QD Simvastatin 10mg HS Prune Juice amp Ensure daily Meds crushed

bull ASSESSMENT

o VS 12380 68 16 92 RA 120lbs 5rsquo6rdquo BMI 194

o Labs (1013) Chol 151 HDL 42 LDL 98 Trig 90

o ROS 5lbs loss in a month no change in appetite feeder bladder amp bowel incontinence weak amp stiff

o PE AampOx1 MMSE 13 whistling to self Poor skin turgor Unable to follow directions aphasia Abdomen flat BS x 4 WC bound 2 assist for transfers Left hand contracture HEENT Lymphatic CV amp Resp exam negative

EPIDEMIOLOGY

bull Most common form of Dementia (60-70 cases)

bull Sixth leading cause of death in the US - Diagnosis to Death varies

bull 23 of Americans with AD are women

bull 5 million Americans ge 65 years old with AD amp continues to uarr (14 million by 2050)

bull Number with AD doubles for every 5-year interval beyond age 65

bull About frac12 million Americans lt 65 years old have some kind of dementia

bull Direct cost to American Society (2014) ~ $214 billion ($12 trillion in 2050)

bull Annual cost per individual $18500 - $gt36000

PATHOPHYSIOLOGYbull Familial vs Sporadic ADbull Loss of Neurotransmitter

stimulation Mutation for encoding APP APOE alteration amp Ca influx

bull Most embraced theory Beta Amyloid plaques amp neurofibrillary tangles

o Beta-Secretase + Gamma-secretase = Beta-Amyloid rarr toxic insoluble APP rarrplaques

o Modified tau rarrmicrotubles fall apart rarrtangles

o uarr damage rarr brain shrinks

httpwwwnianihgovsitesdefaultfilesprogress_report_pg34highjpg

RISK FACTORS amp CLINICAL MANIFESTATION

RISK FACTORSbull Age family history and hereditybull HTN lipoproteins cerebrovascular

disease Type 2 diabetes Obesity brain trauma

bull Lifestyle and activity

PROTECTIVE FACTORSbull Liefelong activity APOE2

antioxidant substances estrogen replacement low caloric diet nonsteroidal anti-inflammatory agents and statins

CLINICAL MANIFESTATIONSVery Early Signs and Symptomsbull Memory amp thinking problems poor

judgment no functional impairmentMild AD (1-3 years)bull Confusion anxiety personality or

mood changes task completionModerate AD (2-8 years)bull Language reasoning sensory

processing amp conscious thoughts affected

Severe AD (6-12 years)bull Unable to recognize family or

communicate dependent for cares

TREATMENT GUIDELINESDeveloper European Federation of

Neurological Societies (EFNS)American Academy of Family Phsysicians (AAFP) amp American College of Physicians (ACP)

American Geriatrics Society(AGS)

Year 2010 2008 2013

Goal Revise 2007 EFNS recommendation on diagnosis and management of AD in pts with AD

Present available evidence on current pharmacologic treatment of Dementia (AD amp VaD)

Guide on the Dx amp Tx of dementiafrom Geriatrics at your fingertips amp Geriatrics review syllabus A core curriculum in geriatric medicine

Re

com

me

nd

atio

ns

Achetylcholinesterase Inhibior (AChEI) for mild to mod ADMemantine + AChEI for mod to severe AD Regular FU to assess cognition ADL behavior DC therapy if rapid worsening or loss of effectiveness

AChEI for mild to mod ADMemantine for mod to severe AD DC therapy with loss of effectiveness

AChEI for mild to mod ADMemantine + donepezil (Aricept) for mod to severe ADTrial Tx period at least 3 monthsMonitor MMSE Clinical Dementia Rating and Functional Assessment Staging scale DC therapy if develops severe impairment

Strengths Grading of evidence clear txoption conflict of interest disclosed

Grading of evidence clear tx option conflit of interest disclosed

Easy read treatment includes nonpharmacologic approaches amp treatment for agitation

Weaknesses European guideline no algorithm Outdated no algorithm No grading of evidence algorithm

SEARCHING THE LITERATURE

PICO Question

bull In patients with moderate Alzheimerrsquos disease does taking a statin slow the progression of dementia compared to not taking a statin

Literature Search Methods

bull Search Engines PubMed CINAHL Cochrane Library Ovid Medline

bull Search Terms Dementia Statins Alzheimerrsquos disease treatment progression older adults

bull Limits 2004-2014 (10 years) Humans English Full text RCT Systematic Reviews

bull Evidence Guide Center for Evidence Based Medicine (CEBM)

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

Randomized Controlled Trial of Atorvastatin in Mild to Moderate Alzheimer Disease LEADe by Feldman et al in 2010

Inclusion 50-90 yo mild to mod AD ondonepezil 10mg daily for ge 3 m prior to screen LDL-C 95-195 mgdL caregiver present le 4 on modified Hachinski Ischemic Scale not requiring tx for dyslipidemia with any lipid-lowering agent cranial CT or MRI within 12 m consistent with AD medically stable no other AchEIs

RCT with double blind randomized withdrawal phase evaluating the efficacy and safety of atorvastatin in patients with mild to moderate ADDuration 72wks trial then 8-wk atorvastatin withdrawal phaseLocation Multicenter in 10 countries Total n = 640 MMSE 13-25 96 white On donepezil 10mgday ge3-m priorIntervention Atorvastatin 80mgday n=297 Age 740 plusmn 80 47 maleControl Matching placebo n= 317 Age 732 plusmn 87 49 male

Outcome measure change in cognition (ADAS-Cog) and global function (ADCS-CGIC) at 72 wks

By 3-m mean LDL-C had darr -724 mgdL (-502) in atorvastatin group amp -10 mgdL (-02) in placebo group and changes remained constant through 18-mTotal Chol amp Trig had larger darr in atorvastatin vs placebo groupDifference in Alzheimerrsquos Disease Assessment Scale ndash Cognitive Subscale (ADAS-cog) scores between groups showed a primary analysis that was not significant (p=026) and in the Alzheimerrsquos Disease Cooperative Study ndash Clinical Glocal Impression of Change (ADCS-CGIC) scores it was also not significant (p=073)

Conclusion Adding atorvastation on a background of donepezil use was not associated with any significant clinical benefits on either cognition or global functioning over 72 wks

bull Inclusions amp Exclusion criteria stated

bull Any serious adverse effects or deaths stated

bull FU at 3-month intervals through month 18

bull Population in currentstudy restricted to those who did not have an indication for statin treatment

bull Pts with significant concurrent cardiac cerebrovascular or PVD were excluded but could atorvastatin have benefited those pts with AD

bull Power analysis for sample size stated

bull P-value cut-off value listed

Level IIA (Single RCT)

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

A Randomized Double-blindPlacebo-controlled Trial of Simvastatin to Treat Alzheimer Disease by Sano et al in 2011

Inclusion gt 50 yo not on lipid lowering drugs mild to mod AD LDL gt80 mgdL or Trig lt500mgdL ge 3m of cholinesterase inhibitors and memantine use allowed medically stable

RCT double blind determining if the lipid-lowering agent simvastatin slows the progression of symptoms of AD in individuals with mild to moderate AD and normal lipid levelsDuration 18 monthsLocation Multicenter in USATotal n = 406 MMSE 12-26Intervention Simvastatin 20mgday x 6-wk then 40mgday n=204 Age 740 plusmn 96 588 femaleControl Matching placebo n= 202 Age 751 plusmn90 599 female

Outcome measure Rate of change in cognitive portion of the Alzheimerrsquos Disease Assessment Scale-Cognitive subscale (ADAS-Cog) score

Rate of change in ADAS-Cog score did not differ between groups (p=025 95 CI -00462 to 01680)No significant differences between groups in the secondary outcomes (MMSE Dependent Scale ADCS-ADL and NPI or the additional cognitive measures) or the CGICTotal Chol and LDL levels were significantly darr by the tx compared to placebo (plt0001) the darr was 23 in total Chol amp 37 in LDL HDL levels were also uarr wiith tx by 2 (p=002)Use of antidementia drugs alone or in combination did not change primary results

Conclusion Simvastatin had no effect on the progression of symptoms in individuals with mild to moderate AD despite significant lowering of cholesterol

bull Inclusions amp Exclusion criteria stated

bull Funding by NationalInstitute of Aging disclosed

bull FU at 3- 6- 12- and 18-m after baseline

bull Any serious adverse effects or deaths stated

bull P-value cut-off value not listed so assumption 005

bull This study did not address the utility of statin in pts who do not otherwise require lipid lowering at predementia stages MCI or presymptomatic AD

bull Power analysis for sample size stated

Level IIA (Single RCT)

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

Atorvastatin for the Treatment of Mild to Moderate Alzheimerrsquos Disease Preliminary Results by Sparks et al in 2005

Inclusion ge 51 yo mild to mod AD 9th

grade education le 4 on modified Hachinski Ischemic Scale and le 20 on GDS stable dose of cholinesterase inhibitors for ge 3 m allowed accompanied by caregiver good general health speak english cholesterol gt90mgdL

Double-blind placebo-controlled randomized trial to determine if tx w atorvastatin calcium affects cognitive andor behavioral decline in pts with mild to mod ADDuration 1yearLocation single site in USATotal n = 63 MMSE 12-28Intervention Atorvastatin 80mgday n=32 Age 7815 plusmn 13 375 femaleControl Matching placebo n= 31 Age 789 plusmn 12 355 female

Outcome measure change in Alzheimerrsquos Disease Assessment Scale-cognitive subscale (ADAS-Cog) amp the Clinical Global Impression of Change Scale (CGIS) scores

Both groups showed deterioration on the ADAS-cog at 3-m Placebo group continued to deteriorate app 1 pointquarter Difference in ADAS-cog scores between groups was significant at 6-m (P=0003) amp 12-m (P=0055)A trend for a difference on the CGIC between groups was achieved at both 9 (P=0058) and 12-m (P=007)MMSE score in atorvastatin group showed limited improvement after 3-m visit amp the difference between groups was not significant (Pgt10) Atorvastatin Tx had significant darr in total Chol LDL VLDL compared to placebo group (Plt01)

Conclusion Atorvastatin tx may be of some clinical benefit amp could be established as an effective therapy for AD if the current findings are substantiated by a much larger multicenter trial (Promising results)

bull Inclusions amp Exclusion criteria stated

bull FU at 3- 6- 9- and 12-month

bull Pilot studybull Very small sample

groups ndash started with 98 participants 71 were eligible 67 randomized amp 63 completed 3-m visit amp were considered eligible

bull No power analysisbull Study is 9 years oldbull Results may or may not

be applicable to other types of statins

Level IIA (Single RCT)

SUMMARY OF LITERATURE amp TREATMENT GUIDELINES

bull Primary goal improve QOL and maximize functional performance by enhancing cognition and addressing mood and behavior

bull AChEI for mild to moderate AD

bull Memantidine + AChEI (Aricept) for moderate to severe AD

bull AVOID anticholinergic medications amp LIMIT prn psychotropic medication use

bull Consider referral to hospice if FAST (Functional Assessment Staging Scale) =7

bull Statins show NO CLEAR BENEFITS in slowing the progression of dementia

bull RCTs with larger populations and longer time frame needed

bull One study was gt5 years due to limited meta-analysis or systematic reviews to support PICO

HEALTH PROMOTION MODEL Katharine Kolcabarsquos Comfort Theory

bull Born and educated in Cleveland Ohio

bull In 1987 RN to MSN degree with a specialty in gerontology Maintained head nurse position on a dementia unit while in graduate school and began theorizing about comfort

bull While pursuing her doctorate in nursing she used her course work to further develop her theory over a 10 year period

bull Extensive publications compiled in her book Comfort Theory and Practice

bull Comfort means to strengthen greatly

bull It exists in three forms Relief Ease amp Transcendence

bull Four contexts in which comfort is experienced Physical Psychospiritual Sociocultural amp Environmental

CRITIQUE

STRENGTHS Applicable to other disciplines amp settings Adaptable to each patient situation or scenario Nurse works closely with the patient Patients can engage in HSB once comfort is achieved Provides direction for quality improvement Comfort rounds with pts amp work environment

WEAKNESS Enhanced comfort does not always produce the expected outcome like health seeking behaviors Places nurses at center of concept

APPLICATION TO PRACTICE Nurses play a critical role in helping patients achieve comfort and engage in health-seeking behaviors Nurses can impact patientrsquos quality care Nurses can work with patients to come up with interventions to impact their comfort and evaluate those interventions Nurses can impact institutional integrity

APPLICATION to CASE

Health Care NeedsFeeding Assistance uarr assistance with ADLs weight loss difficulty swallowingComfort InterventionsReview med list with family educate staff on ptrsquos uarr needs feeding assistance aspiration precautions address hospice eligibility include pt in activities toileting scheduleIntervening VariablesAdvanced age terminal illness

support system (wifePOA) assisted livingEnhanced ComfortJT is being strengthened through having comfort needs addressedHealth Seeking BehaviorsWeight gain acceptancewife is more trusting and calmer peaceful deathInstitutional IntegrityApplication of CT to other cases staff investment in implementing theory

JTrsquos PLAN OF CAREDIFFERENTIALS VaD Dementia with Lewy Bodies Frontotemporal dementiaEVALUATION Comprehensive physical and neurologic exam Assess functional status and evaluate mental status Labs CBC TSH B12 Folate metabolic screenPLANbull STOP Simvastatin 10mg PO bedtime amp Change Citalopram to 20mg PO QDbull No hospice referral ndash Needs to have lt 6m To livebull FAST ge 7A amp ASPNA or upper UTI or septicemia or multiple PU (stage 34) or

recurrent fever on ABX or weight loss gt10 in past 6 m Alb lt25bull Review Advance directive with POAbull Involve and encourage JT to participates in cares and activitiesbull One can of Ensure with every mealbull Aspiration precautionsbull Record weekly weightbull FU in 3-4 weeks or earlier if status change

REFERENCES

Alzheimerrsquos Association (2014) Alzheimerrsquos facts and figures Retrieved from httpwwwalzorgalzheimers_disease_facts_and_figuresasp

Alzheimerrsquos Association (2014) Medications for memory loss Retrieved from

httpwwwalzorgalzheimers_disease_standard_prescriptionsasp

Alzheimerrsquos Foundation of America (2014) About Alzheimerrsquos Retrieved from httpwwwalzfdnorgAboutAlzheimerscosthtml

American Geriatrics Society (2013) A guide to dementia diagnosis and treatment Retrieved from

httpwwwamericangeriatricsorgfilesdocumentsdementia_pocket_cardpdf

Buttaro T M Trybulski J Bailey P P amp Sandberg-Cook J (2013) Primary care A collaborative practice (4th ed) St Louis MO Elsevier

Centers for Medicare amp Medicaid Services (2013) Superseded local coverage determination (LCD) Hospice determining terminal status (L32015)

Retrieved from httpwwwcmsgovmedicare-coverage-databasedetailslcd-

detailsaspxLCDId=32015ampContrId=236ampver=14ampContrVer=2ampCntrctrSelected=2362ampCntrctr=236ampname=CGS+Administrators2c+LL

C+(150042c+HHH+MAC)amps=11ampDocType=Activeampbc=AggAAAIAAAAAAA3d3damp

bull SITUATION 87 yo Caucasian male at Assisted Living Memory Unit DX with Alzheimerrsquos disease (AD) 5 yrs ago Wife wants to discuss (1) Hospice care and (2) keeping JT on Simvastatin

bull BACKGROUND PMH MI 8 ya hyperlipidemia constipation insomnia PSH CABG 8 ya amp hernia repair MEDS ASA 325mg QD Citalopram 40mg QD Clonazepam 05mg QD Melatonin 3mg HS MVI 1tab QD Simvastatin 10mg HS Prune Juice amp Ensure daily Meds crushed

bull ASSESSMENT

o VS 12380 68 16 92 RA 120lbs 5rsquo6rdquo BMI 194

o Labs (1013) Chol 151 HDL 42 LDL 98 Trig 90

o ROS 5lbs loss in a month no change in appetite feeder bladder amp bowel incontinence weak amp stiff

o PE AampOx1 MMSE 13 whistling to self Poor skin turgor Unable to follow directions aphasia Abdomen flat BS x 4 WC bound 2 assist for transfers Left hand contracture HEENT Lymphatic CV amp Resp exam negative

EPIDEMIOLOGY

bull Most common form of Dementia (60-70 cases)

bull Sixth leading cause of death in the US - Diagnosis to Death varies

bull 23 of Americans with AD are women

bull 5 million Americans ge 65 years old with AD amp continues to uarr (14 million by 2050)

bull Number with AD doubles for every 5-year interval beyond age 65

bull About frac12 million Americans lt 65 years old have some kind of dementia

bull Direct cost to American Society (2014) ~ $214 billion ($12 trillion in 2050)

bull Annual cost per individual $18500 - $gt36000

PATHOPHYSIOLOGYbull Familial vs Sporadic ADbull Loss of Neurotransmitter

stimulation Mutation for encoding APP APOE alteration amp Ca influx

bull Most embraced theory Beta Amyloid plaques amp neurofibrillary tangles

o Beta-Secretase + Gamma-secretase = Beta-Amyloid rarr toxic insoluble APP rarrplaques

o Modified tau rarrmicrotubles fall apart rarrtangles

o uarr damage rarr brain shrinks

httpwwwnianihgovsitesdefaultfilesprogress_report_pg34highjpg

RISK FACTORS amp CLINICAL MANIFESTATION

RISK FACTORSbull Age family history and hereditybull HTN lipoproteins cerebrovascular

disease Type 2 diabetes Obesity brain trauma

bull Lifestyle and activity

PROTECTIVE FACTORSbull Liefelong activity APOE2

antioxidant substances estrogen replacement low caloric diet nonsteroidal anti-inflammatory agents and statins

CLINICAL MANIFESTATIONSVery Early Signs and Symptomsbull Memory amp thinking problems poor

judgment no functional impairmentMild AD (1-3 years)bull Confusion anxiety personality or

mood changes task completionModerate AD (2-8 years)bull Language reasoning sensory

processing amp conscious thoughts affected

Severe AD (6-12 years)bull Unable to recognize family or

communicate dependent for cares

TREATMENT GUIDELINESDeveloper European Federation of

Neurological Societies (EFNS)American Academy of Family Phsysicians (AAFP) amp American College of Physicians (ACP)

American Geriatrics Society(AGS)

Year 2010 2008 2013

Goal Revise 2007 EFNS recommendation on diagnosis and management of AD in pts with AD

Present available evidence on current pharmacologic treatment of Dementia (AD amp VaD)

Guide on the Dx amp Tx of dementiafrom Geriatrics at your fingertips amp Geriatrics review syllabus A core curriculum in geriatric medicine

Re

com

me

nd

atio

ns

Achetylcholinesterase Inhibior (AChEI) for mild to mod ADMemantine + AChEI for mod to severe AD Regular FU to assess cognition ADL behavior DC therapy if rapid worsening or loss of effectiveness

AChEI for mild to mod ADMemantine for mod to severe AD DC therapy with loss of effectiveness

AChEI for mild to mod ADMemantine + donepezil (Aricept) for mod to severe ADTrial Tx period at least 3 monthsMonitor MMSE Clinical Dementia Rating and Functional Assessment Staging scale DC therapy if develops severe impairment

Strengths Grading of evidence clear txoption conflict of interest disclosed

Grading of evidence clear tx option conflit of interest disclosed

Easy read treatment includes nonpharmacologic approaches amp treatment for agitation

Weaknesses European guideline no algorithm Outdated no algorithm No grading of evidence algorithm

SEARCHING THE LITERATURE

PICO Question

bull In patients with moderate Alzheimerrsquos disease does taking a statin slow the progression of dementia compared to not taking a statin

Literature Search Methods

bull Search Engines PubMed CINAHL Cochrane Library Ovid Medline

bull Search Terms Dementia Statins Alzheimerrsquos disease treatment progression older adults

bull Limits 2004-2014 (10 years) Humans English Full text RCT Systematic Reviews

bull Evidence Guide Center for Evidence Based Medicine (CEBM)

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

Randomized Controlled Trial of Atorvastatin in Mild to Moderate Alzheimer Disease LEADe by Feldman et al in 2010

Inclusion 50-90 yo mild to mod AD ondonepezil 10mg daily for ge 3 m prior to screen LDL-C 95-195 mgdL caregiver present le 4 on modified Hachinski Ischemic Scale not requiring tx for dyslipidemia with any lipid-lowering agent cranial CT or MRI within 12 m consistent with AD medically stable no other AchEIs

RCT with double blind randomized withdrawal phase evaluating the efficacy and safety of atorvastatin in patients with mild to moderate ADDuration 72wks trial then 8-wk atorvastatin withdrawal phaseLocation Multicenter in 10 countries Total n = 640 MMSE 13-25 96 white On donepezil 10mgday ge3-m priorIntervention Atorvastatin 80mgday n=297 Age 740 plusmn 80 47 maleControl Matching placebo n= 317 Age 732 plusmn 87 49 male

Outcome measure change in cognition (ADAS-Cog) and global function (ADCS-CGIC) at 72 wks

By 3-m mean LDL-C had darr -724 mgdL (-502) in atorvastatin group amp -10 mgdL (-02) in placebo group and changes remained constant through 18-mTotal Chol amp Trig had larger darr in atorvastatin vs placebo groupDifference in Alzheimerrsquos Disease Assessment Scale ndash Cognitive Subscale (ADAS-cog) scores between groups showed a primary analysis that was not significant (p=026) and in the Alzheimerrsquos Disease Cooperative Study ndash Clinical Glocal Impression of Change (ADCS-CGIC) scores it was also not significant (p=073)

Conclusion Adding atorvastation on a background of donepezil use was not associated with any significant clinical benefits on either cognition or global functioning over 72 wks

bull Inclusions amp Exclusion criteria stated

bull Any serious adverse effects or deaths stated

bull FU at 3-month intervals through month 18

bull Population in currentstudy restricted to those who did not have an indication for statin treatment

bull Pts with significant concurrent cardiac cerebrovascular or PVD were excluded but could atorvastatin have benefited those pts with AD

bull Power analysis for sample size stated

bull P-value cut-off value listed

Level IIA (Single RCT)

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

A Randomized Double-blindPlacebo-controlled Trial of Simvastatin to Treat Alzheimer Disease by Sano et al in 2011

Inclusion gt 50 yo not on lipid lowering drugs mild to mod AD LDL gt80 mgdL or Trig lt500mgdL ge 3m of cholinesterase inhibitors and memantine use allowed medically stable

RCT double blind determining if the lipid-lowering agent simvastatin slows the progression of symptoms of AD in individuals with mild to moderate AD and normal lipid levelsDuration 18 monthsLocation Multicenter in USATotal n = 406 MMSE 12-26Intervention Simvastatin 20mgday x 6-wk then 40mgday n=204 Age 740 plusmn 96 588 femaleControl Matching placebo n= 202 Age 751 plusmn90 599 female

Outcome measure Rate of change in cognitive portion of the Alzheimerrsquos Disease Assessment Scale-Cognitive subscale (ADAS-Cog) score

Rate of change in ADAS-Cog score did not differ between groups (p=025 95 CI -00462 to 01680)No significant differences between groups in the secondary outcomes (MMSE Dependent Scale ADCS-ADL and NPI or the additional cognitive measures) or the CGICTotal Chol and LDL levels were significantly darr by the tx compared to placebo (plt0001) the darr was 23 in total Chol amp 37 in LDL HDL levels were also uarr wiith tx by 2 (p=002)Use of antidementia drugs alone or in combination did not change primary results

Conclusion Simvastatin had no effect on the progression of symptoms in individuals with mild to moderate AD despite significant lowering of cholesterol

bull Inclusions amp Exclusion criteria stated

bull Funding by NationalInstitute of Aging disclosed

bull FU at 3- 6- 12- and 18-m after baseline

bull Any serious adverse effects or deaths stated

bull P-value cut-off value not listed so assumption 005

bull This study did not address the utility of statin in pts who do not otherwise require lipid lowering at predementia stages MCI or presymptomatic AD

bull Power analysis for sample size stated

Level IIA (Single RCT)

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

Atorvastatin for the Treatment of Mild to Moderate Alzheimerrsquos Disease Preliminary Results by Sparks et al in 2005

Inclusion ge 51 yo mild to mod AD 9th

grade education le 4 on modified Hachinski Ischemic Scale and le 20 on GDS stable dose of cholinesterase inhibitors for ge 3 m allowed accompanied by caregiver good general health speak english cholesterol gt90mgdL

Double-blind placebo-controlled randomized trial to determine if tx w atorvastatin calcium affects cognitive andor behavioral decline in pts with mild to mod ADDuration 1yearLocation single site in USATotal n = 63 MMSE 12-28Intervention Atorvastatin 80mgday n=32 Age 7815 plusmn 13 375 femaleControl Matching placebo n= 31 Age 789 plusmn 12 355 female

Outcome measure change in Alzheimerrsquos Disease Assessment Scale-cognitive subscale (ADAS-Cog) amp the Clinical Global Impression of Change Scale (CGIS) scores

Both groups showed deterioration on the ADAS-cog at 3-m Placebo group continued to deteriorate app 1 pointquarter Difference in ADAS-cog scores between groups was significant at 6-m (P=0003) amp 12-m (P=0055)A trend for a difference on the CGIC between groups was achieved at both 9 (P=0058) and 12-m (P=007)MMSE score in atorvastatin group showed limited improvement after 3-m visit amp the difference between groups was not significant (Pgt10) Atorvastatin Tx had significant darr in total Chol LDL VLDL compared to placebo group (Plt01)

Conclusion Atorvastatin tx may be of some clinical benefit amp could be established as an effective therapy for AD if the current findings are substantiated by a much larger multicenter trial (Promising results)

bull Inclusions amp Exclusion criteria stated

bull FU at 3- 6- 9- and 12-month

bull Pilot studybull Very small sample

groups ndash started with 98 participants 71 were eligible 67 randomized amp 63 completed 3-m visit amp were considered eligible

bull No power analysisbull Study is 9 years oldbull Results may or may not

be applicable to other types of statins

Level IIA (Single RCT)

SUMMARY OF LITERATURE amp TREATMENT GUIDELINES

bull Primary goal improve QOL and maximize functional performance by enhancing cognition and addressing mood and behavior

bull AChEI for mild to moderate AD

bull Memantidine + AChEI (Aricept) for moderate to severe AD

bull AVOID anticholinergic medications amp LIMIT prn psychotropic medication use

bull Consider referral to hospice if FAST (Functional Assessment Staging Scale) =7

bull Statins show NO CLEAR BENEFITS in slowing the progression of dementia

bull RCTs with larger populations and longer time frame needed

bull One study was gt5 years due to limited meta-analysis or systematic reviews to support PICO

HEALTH PROMOTION MODEL Katharine Kolcabarsquos Comfort Theory

bull Born and educated in Cleveland Ohio

bull In 1987 RN to MSN degree with a specialty in gerontology Maintained head nurse position on a dementia unit while in graduate school and began theorizing about comfort

bull While pursuing her doctorate in nursing she used her course work to further develop her theory over a 10 year period

bull Extensive publications compiled in her book Comfort Theory and Practice

bull Comfort means to strengthen greatly

bull It exists in three forms Relief Ease amp Transcendence

bull Four contexts in which comfort is experienced Physical Psychospiritual Sociocultural amp Environmental

CRITIQUE

STRENGTHS Applicable to other disciplines amp settings Adaptable to each patient situation or scenario Nurse works closely with the patient Patients can engage in HSB once comfort is achieved Provides direction for quality improvement Comfort rounds with pts amp work environment

WEAKNESS Enhanced comfort does not always produce the expected outcome like health seeking behaviors Places nurses at center of concept

APPLICATION TO PRACTICE Nurses play a critical role in helping patients achieve comfort and engage in health-seeking behaviors Nurses can impact patientrsquos quality care Nurses can work with patients to come up with interventions to impact their comfort and evaluate those interventions Nurses can impact institutional integrity

APPLICATION to CASE

Health Care NeedsFeeding Assistance uarr assistance with ADLs weight loss difficulty swallowingComfort InterventionsReview med list with family educate staff on ptrsquos uarr needs feeding assistance aspiration precautions address hospice eligibility include pt in activities toileting scheduleIntervening VariablesAdvanced age terminal illness

support system (wifePOA) assisted livingEnhanced ComfortJT is being strengthened through having comfort needs addressedHealth Seeking BehaviorsWeight gain acceptancewife is more trusting and calmer peaceful deathInstitutional IntegrityApplication of CT to other cases staff investment in implementing theory

JTrsquos PLAN OF CAREDIFFERENTIALS VaD Dementia with Lewy Bodies Frontotemporal dementiaEVALUATION Comprehensive physical and neurologic exam Assess functional status and evaluate mental status Labs CBC TSH B12 Folate metabolic screenPLANbull STOP Simvastatin 10mg PO bedtime amp Change Citalopram to 20mg PO QDbull No hospice referral ndash Needs to have lt 6m To livebull FAST ge 7A amp ASPNA or upper UTI or septicemia or multiple PU (stage 34) or

recurrent fever on ABX or weight loss gt10 in past 6 m Alb lt25bull Review Advance directive with POAbull Involve and encourage JT to participates in cares and activitiesbull One can of Ensure with every mealbull Aspiration precautionsbull Record weekly weightbull FU in 3-4 weeks or earlier if status change

REFERENCES

Alzheimerrsquos Association (2014) Alzheimerrsquos facts and figures Retrieved from httpwwwalzorgalzheimers_disease_facts_and_figuresasp

Alzheimerrsquos Association (2014) Medications for memory loss Retrieved from

httpwwwalzorgalzheimers_disease_standard_prescriptionsasp

Alzheimerrsquos Foundation of America (2014) About Alzheimerrsquos Retrieved from httpwwwalzfdnorgAboutAlzheimerscosthtml

American Geriatrics Society (2013) A guide to dementia diagnosis and treatment Retrieved from

httpwwwamericangeriatricsorgfilesdocumentsdementia_pocket_cardpdf

Buttaro T M Trybulski J Bailey P P amp Sandberg-Cook J (2013) Primary care A collaborative practice (4th ed) St Louis MO Elsevier

Centers for Medicare amp Medicaid Services (2013) Superseded local coverage determination (LCD) Hospice determining terminal status (L32015)

Retrieved from httpwwwcmsgovmedicare-coverage-databasedetailslcd-

detailsaspxLCDId=32015ampContrId=236ampver=14ampContrVer=2ampCntrctrSelected=2362ampCntrctr=236ampname=CGS+Administrators2c+LL

C+(150042c+HHH+MAC)amps=11ampDocType=Activeampbc=AggAAAIAAAAAAA3d3damp

EPIDEMIOLOGY

bull Most common form of Dementia (60-70 cases)

bull Sixth leading cause of death in the US - Diagnosis to Death varies

bull 23 of Americans with AD are women

bull 5 million Americans ge 65 years old with AD amp continues to uarr (14 million by 2050)

bull Number with AD doubles for every 5-year interval beyond age 65

bull About frac12 million Americans lt 65 years old have some kind of dementia

bull Direct cost to American Society (2014) ~ $214 billion ($12 trillion in 2050)

bull Annual cost per individual $18500 - $gt36000

PATHOPHYSIOLOGYbull Familial vs Sporadic ADbull Loss of Neurotransmitter

stimulation Mutation for encoding APP APOE alteration amp Ca influx

bull Most embraced theory Beta Amyloid plaques amp neurofibrillary tangles

o Beta-Secretase + Gamma-secretase = Beta-Amyloid rarr toxic insoluble APP rarrplaques

o Modified tau rarrmicrotubles fall apart rarrtangles

o uarr damage rarr brain shrinks

httpwwwnianihgovsitesdefaultfilesprogress_report_pg34highjpg

RISK FACTORS amp CLINICAL MANIFESTATION

RISK FACTORSbull Age family history and hereditybull HTN lipoproteins cerebrovascular

disease Type 2 diabetes Obesity brain trauma

bull Lifestyle and activity

PROTECTIVE FACTORSbull Liefelong activity APOE2

antioxidant substances estrogen replacement low caloric diet nonsteroidal anti-inflammatory agents and statins

CLINICAL MANIFESTATIONSVery Early Signs and Symptomsbull Memory amp thinking problems poor

judgment no functional impairmentMild AD (1-3 years)bull Confusion anxiety personality or

mood changes task completionModerate AD (2-8 years)bull Language reasoning sensory

processing amp conscious thoughts affected

Severe AD (6-12 years)bull Unable to recognize family or

communicate dependent for cares

TREATMENT GUIDELINESDeveloper European Federation of

Neurological Societies (EFNS)American Academy of Family Phsysicians (AAFP) amp American College of Physicians (ACP)

American Geriatrics Society(AGS)

Year 2010 2008 2013

Goal Revise 2007 EFNS recommendation on diagnosis and management of AD in pts with AD

Present available evidence on current pharmacologic treatment of Dementia (AD amp VaD)

Guide on the Dx amp Tx of dementiafrom Geriatrics at your fingertips amp Geriatrics review syllabus A core curriculum in geriatric medicine

Re

com

me

nd

atio

ns

Achetylcholinesterase Inhibior (AChEI) for mild to mod ADMemantine + AChEI for mod to severe AD Regular FU to assess cognition ADL behavior DC therapy if rapid worsening or loss of effectiveness

AChEI for mild to mod ADMemantine for mod to severe AD DC therapy with loss of effectiveness

AChEI for mild to mod ADMemantine + donepezil (Aricept) for mod to severe ADTrial Tx period at least 3 monthsMonitor MMSE Clinical Dementia Rating and Functional Assessment Staging scale DC therapy if develops severe impairment

Strengths Grading of evidence clear txoption conflict of interest disclosed

Grading of evidence clear tx option conflit of interest disclosed

Easy read treatment includes nonpharmacologic approaches amp treatment for agitation

Weaknesses European guideline no algorithm Outdated no algorithm No grading of evidence algorithm

SEARCHING THE LITERATURE

PICO Question

bull In patients with moderate Alzheimerrsquos disease does taking a statin slow the progression of dementia compared to not taking a statin

Literature Search Methods

bull Search Engines PubMed CINAHL Cochrane Library Ovid Medline

bull Search Terms Dementia Statins Alzheimerrsquos disease treatment progression older adults

bull Limits 2004-2014 (10 years) Humans English Full text RCT Systematic Reviews

bull Evidence Guide Center for Evidence Based Medicine (CEBM)

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

Randomized Controlled Trial of Atorvastatin in Mild to Moderate Alzheimer Disease LEADe by Feldman et al in 2010

Inclusion 50-90 yo mild to mod AD ondonepezil 10mg daily for ge 3 m prior to screen LDL-C 95-195 mgdL caregiver present le 4 on modified Hachinski Ischemic Scale not requiring tx for dyslipidemia with any lipid-lowering agent cranial CT or MRI within 12 m consistent with AD medically stable no other AchEIs

RCT with double blind randomized withdrawal phase evaluating the efficacy and safety of atorvastatin in patients with mild to moderate ADDuration 72wks trial then 8-wk atorvastatin withdrawal phaseLocation Multicenter in 10 countries Total n = 640 MMSE 13-25 96 white On donepezil 10mgday ge3-m priorIntervention Atorvastatin 80mgday n=297 Age 740 plusmn 80 47 maleControl Matching placebo n= 317 Age 732 plusmn 87 49 male

Outcome measure change in cognition (ADAS-Cog) and global function (ADCS-CGIC) at 72 wks

By 3-m mean LDL-C had darr -724 mgdL (-502) in atorvastatin group amp -10 mgdL (-02) in placebo group and changes remained constant through 18-mTotal Chol amp Trig had larger darr in atorvastatin vs placebo groupDifference in Alzheimerrsquos Disease Assessment Scale ndash Cognitive Subscale (ADAS-cog) scores between groups showed a primary analysis that was not significant (p=026) and in the Alzheimerrsquos Disease Cooperative Study ndash Clinical Glocal Impression of Change (ADCS-CGIC) scores it was also not significant (p=073)

Conclusion Adding atorvastation on a background of donepezil use was not associated with any significant clinical benefits on either cognition or global functioning over 72 wks

bull Inclusions amp Exclusion criteria stated

bull Any serious adverse effects or deaths stated

bull FU at 3-month intervals through month 18

bull Population in currentstudy restricted to those who did not have an indication for statin treatment

bull Pts with significant concurrent cardiac cerebrovascular or PVD were excluded but could atorvastatin have benefited those pts with AD

bull Power analysis for sample size stated

bull P-value cut-off value listed

Level IIA (Single RCT)

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

A Randomized Double-blindPlacebo-controlled Trial of Simvastatin to Treat Alzheimer Disease by Sano et al in 2011

Inclusion gt 50 yo not on lipid lowering drugs mild to mod AD LDL gt80 mgdL or Trig lt500mgdL ge 3m of cholinesterase inhibitors and memantine use allowed medically stable

RCT double blind determining if the lipid-lowering agent simvastatin slows the progression of symptoms of AD in individuals with mild to moderate AD and normal lipid levelsDuration 18 monthsLocation Multicenter in USATotal n = 406 MMSE 12-26Intervention Simvastatin 20mgday x 6-wk then 40mgday n=204 Age 740 plusmn 96 588 femaleControl Matching placebo n= 202 Age 751 plusmn90 599 female

Outcome measure Rate of change in cognitive portion of the Alzheimerrsquos Disease Assessment Scale-Cognitive subscale (ADAS-Cog) score

Rate of change in ADAS-Cog score did not differ between groups (p=025 95 CI -00462 to 01680)No significant differences between groups in the secondary outcomes (MMSE Dependent Scale ADCS-ADL and NPI or the additional cognitive measures) or the CGICTotal Chol and LDL levels were significantly darr by the tx compared to placebo (plt0001) the darr was 23 in total Chol amp 37 in LDL HDL levels were also uarr wiith tx by 2 (p=002)Use of antidementia drugs alone or in combination did not change primary results

Conclusion Simvastatin had no effect on the progression of symptoms in individuals with mild to moderate AD despite significant lowering of cholesterol

bull Inclusions amp Exclusion criteria stated

bull Funding by NationalInstitute of Aging disclosed

bull FU at 3- 6- 12- and 18-m after baseline

bull Any serious adverse effects or deaths stated

bull P-value cut-off value not listed so assumption 005

bull This study did not address the utility of statin in pts who do not otherwise require lipid lowering at predementia stages MCI or presymptomatic AD

bull Power analysis for sample size stated

Level IIA (Single RCT)

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

Atorvastatin for the Treatment of Mild to Moderate Alzheimerrsquos Disease Preliminary Results by Sparks et al in 2005

Inclusion ge 51 yo mild to mod AD 9th

grade education le 4 on modified Hachinski Ischemic Scale and le 20 on GDS stable dose of cholinesterase inhibitors for ge 3 m allowed accompanied by caregiver good general health speak english cholesterol gt90mgdL

Double-blind placebo-controlled randomized trial to determine if tx w atorvastatin calcium affects cognitive andor behavioral decline in pts with mild to mod ADDuration 1yearLocation single site in USATotal n = 63 MMSE 12-28Intervention Atorvastatin 80mgday n=32 Age 7815 plusmn 13 375 femaleControl Matching placebo n= 31 Age 789 plusmn 12 355 female

Outcome measure change in Alzheimerrsquos Disease Assessment Scale-cognitive subscale (ADAS-Cog) amp the Clinical Global Impression of Change Scale (CGIS) scores

Both groups showed deterioration on the ADAS-cog at 3-m Placebo group continued to deteriorate app 1 pointquarter Difference in ADAS-cog scores between groups was significant at 6-m (P=0003) amp 12-m (P=0055)A trend for a difference on the CGIC between groups was achieved at both 9 (P=0058) and 12-m (P=007)MMSE score in atorvastatin group showed limited improvement after 3-m visit amp the difference between groups was not significant (Pgt10) Atorvastatin Tx had significant darr in total Chol LDL VLDL compared to placebo group (Plt01)

Conclusion Atorvastatin tx may be of some clinical benefit amp could be established as an effective therapy for AD if the current findings are substantiated by a much larger multicenter trial (Promising results)

bull Inclusions amp Exclusion criteria stated

bull FU at 3- 6- 9- and 12-month

bull Pilot studybull Very small sample

groups ndash started with 98 participants 71 were eligible 67 randomized amp 63 completed 3-m visit amp were considered eligible

bull No power analysisbull Study is 9 years oldbull Results may or may not

be applicable to other types of statins

Level IIA (Single RCT)

SUMMARY OF LITERATURE amp TREATMENT GUIDELINES

bull Primary goal improve QOL and maximize functional performance by enhancing cognition and addressing mood and behavior

bull AChEI for mild to moderate AD

bull Memantidine + AChEI (Aricept) for moderate to severe AD

bull AVOID anticholinergic medications amp LIMIT prn psychotropic medication use

bull Consider referral to hospice if FAST (Functional Assessment Staging Scale) =7

bull Statins show NO CLEAR BENEFITS in slowing the progression of dementia

bull RCTs with larger populations and longer time frame needed

bull One study was gt5 years due to limited meta-analysis or systematic reviews to support PICO

HEALTH PROMOTION MODEL Katharine Kolcabarsquos Comfort Theory

bull Born and educated in Cleveland Ohio

bull In 1987 RN to MSN degree with a specialty in gerontology Maintained head nurse position on a dementia unit while in graduate school and began theorizing about comfort

bull While pursuing her doctorate in nursing she used her course work to further develop her theory over a 10 year period

bull Extensive publications compiled in her book Comfort Theory and Practice

bull Comfort means to strengthen greatly

bull It exists in three forms Relief Ease amp Transcendence

bull Four contexts in which comfort is experienced Physical Psychospiritual Sociocultural amp Environmental

CRITIQUE

STRENGTHS Applicable to other disciplines amp settings Adaptable to each patient situation or scenario Nurse works closely with the patient Patients can engage in HSB once comfort is achieved Provides direction for quality improvement Comfort rounds with pts amp work environment

WEAKNESS Enhanced comfort does not always produce the expected outcome like health seeking behaviors Places nurses at center of concept

APPLICATION TO PRACTICE Nurses play a critical role in helping patients achieve comfort and engage in health-seeking behaviors Nurses can impact patientrsquos quality care Nurses can work with patients to come up with interventions to impact their comfort and evaluate those interventions Nurses can impact institutional integrity

APPLICATION to CASE

Health Care NeedsFeeding Assistance uarr assistance with ADLs weight loss difficulty swallowingComfort InterventionsReview med list with family educate staff on ptrsquos uarr needs feeding assistance aspiration precautions address hospice eligibility include pt in activities toileting scheduleIntervening VariablesAdvanced age terminal illness

support system (wifePOA) assisted livingEnhanced ComfortJT is being strengthened through having comfort needs addressedHealth Seeking BehaviorsWeight gain acceptancewife is more trusting and calmer peaceful deathInstitutional IntegrityApplication of CT to other cases staff investment in implementing theory

JTrsquos PLAN OF CAREDIFFERENTIALS VaD Dementia with Lewy Bodies Frontotemporal dementiaEVALUATION Comprehensive physical and neurologic exam Assess functional status and evaluate mental status Labs CBC TSH B12 Folate metabolic screenPLANbull STOP Simvastatin 10mg PO bedtime amp Change Citalopram to 20mg PO QDbull No hospice referral ndash Needs to have lt 6m To livebull FAST ge 7A amp ASPNA or upper UTI or septicemia or multiple PU (stage 34) or

recurrent fever on ABX or weight loss gt10 in past 6 m Alb lt25bull Review Advance directive with POAbull Involve and encourage JT to participates in cares and activitiesbull One can of Ensure with every mealbull Aspiration precautionsbull Record weekly weightbull FU in 3-4 weeks or earlier if status change

REFERENCES

Alzheimerrsquos Association (2014) Alzheimerrsquos facts and figures Retrieved from httpwwwalzorgalzheimers_disease_facts_and_figuresasp

Alzheimerrsquos Association (2014) Medications for memory loss Retrieved from

httpwwwalzorgalzheimers_disease_standard_prescriptionsasp

Alzheimerrsquos Foundation of America (2014) About Alzheimerrsquos Retrieved from httpwwwalzfdnorgAboutAlzheimerscosthtml

American Geriatrics Society (2013) A guide to dementia diagnosis and treatment Retrieved from

httpwwwamericangeriatricsorgfilesdocumentsdementia_pocket_cardpdf

Buttaro T M Trybulski J Bailey P P amp Sandberg-Cook J (2013) Primary care A collaborative practice (4th ed) St Louis MO Elsevier

Centers for Medicare amp Medicaid Services (2013) Superseded local coverage determination (LCD) Hospice determining terminal status (L32015)

Retrieved from httpwwwcmsgovmedicare-coverage-databasedetailslcd-

detailsaspxLCDId=32015ampContrId=236ampver=14ampContrVer=2ampCntrctrSelected=2362ampCntrctr=236ampname=CGS+Administrators2c+LL

C+(150042c+HHH+MAC)amps=11ampDocType=Activeampbc=AggAAAIAAAAAAA3d3damp

PATHOPHYSIOLOGYbull Familial vs Sporadic ADbull Loss of Neurotransmitter

stimulation Mutation for encoding APP APOE alteration amp Ca influx

bull Most embraced theory Beta Amyloid plaques amp neurofibrillary tangles

o Beta-Secretase + Gamma-secretase = Beta-Amyloid rarr toxic insoluble APP rarrplaques

o Modified tau rarrmicrotubles fall apart rarrtangles

o uarr damage rarr brain shrinks

httpwwwnianihgovsitesdefaultfilesprogress_report_pg34highjpg

RISK FACTORS amp CLINICAL MANIFESTATION

RISK FACTORSbull Age family history and hereditybull HTN lipoproteins cerebrovascular

disease Type 2 diabetes Obesity brain trauma

bull Lifestyle and activity

PROTECTIVE FACTORSbull Liefelong activity APOE2

antioxidant substances estrogen replacement low caloric diet nonsteroidal anti-inflammatory agents and statins

CLINICAL MANIFESTATIONSVery Early Signs and Symptomsbull Memory amp thinking problems poor

judgment no functional impairmentMild AD (1-3 years)bull Confusion anxiety personality or

mood changes task completionModerate AD (2-8 years)bull Language reasoning sensory

processing amp conscious thoughts affected

Severe AD (6-12 years)bull Unable to recognize family or

communicate dependent for cares

TREATMENT GUIDELINESDeveloper European Federation of

Neurological Societies (EFNS)American Academy of Family Phsysicians (AAFP) amp American College of Physicians (ACP)

American Geriatrics Society(AGS)

Year 2010 2008 2013

Goal Revise 2007 EFNS recommendation on diagnosis and management of AD in pts with AD

Present available evidence on current pharmacologic treatment of Dementia (AD amp VaD)

Guide on the Dx amp Tx of dementiafrom Geriatrics at your fingertips amp Geriatrics review syllabus A core curriculum in geriatric medicine

Re

com

me

nd

atio

ns

Achetylcholinesterase Inhibior (AChEI) for mild to mod ADMemantine + AChEI for mod to severe AD Regular FU to assess cognition ADL behavior DC therapy if rapid worsening or loss of effectiveness

AChEI for mild to mod ADMemantine for mod to severe AD DC therapy with loss of effectiveness

AChEI for mild to mod ADMemantine + donepezil (Aricept) for mod to severe ADTrial Tx period at least 3 monthsMonitor MMSE Clinical Dementia Rating and Functional Assessment Staging scale DC therapy if develops severe impairment

Strengths Grading of evidence clear txoption conflict of interest disclosed

Grading of evidence clear tx option conflit of interest disclosed

Easy read treatment includes nonpharmacologic approaches amp treatment for agitation

Weaknesses European guideline no algorithm Outdated no algorithm No grading of evidence algorithm

SEARCHING THE LITERATURE

PICO Question

bull In patients with moderate Alzheimerrsquos disease does taking a statin slow the progression of dementia compared to not taking a statin

Literature Search Methods

bull Search Engines PubMed CINAHL Cochrane Library Ovid Medline

bull Search Terms Dementia Statins Alzheimerrsquos disease treatment progression older adults

bull Limits 2004-2014 (10 years) Humans English Full text RCT Systematic Reviews

bull Evidence Guide Center for Evidence Based Medicine (CEBM)

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

Randomized Controlled Trial of Atorvastatin in Mild to Moderate Alzheimer Disease LEADe by Feldman et al in 2010

Inclusion 50-90 yo mild to mod AD ondonepezil 10mg daily for ge 3 m prior to screen LDL-C 95-195 mgdL caregiver present le 4 on modified Hachinski Ischemic Scale not requiring tx for dyslipidemia with any lipid-lowering agent cranial CT or MRI within 12 m consistent with AD medically stable no other AchEIs

RCT with double blind randomized withdrawal phase evaluating the efficacy and safety of atorvastatin in patients with mild to moderate ADDuration 72wks trial then 8-wk atorvastatin withdrawal phaseLocation Multicenter in 10 countries Total n = 640 MMSE 13-25 96 white On donepezil 10mgday ge3-m priorIntervention Atorvastatin 80mgday n=297 Age 740 plusmn 80 47 maleControl Matching placebo n= 317 Age 732 plusmn 87 49 male

Outcome measure change in cognition (ADAS-Cog) and global function (ADCS-CGIC) at 72 wks

By 3-m mean LDL-C had darr -724 mgdL (-502) in atorvastatin group amp -10 mgdL (-02) in placebo group and changes remained constant through 18-mTotal Chol amp Trig had larger darr in atorvastatin vs placebo groupDifference in Alzheimerrsquos Disease Assessment Scale ndash Cognitive Subscale (ADAS-cog) scores between groups showed a primary analysis that was not significant (p=026) and in the Alzheimerrsquos Disease Cooperative Study ndash Clinical Glocal Impression of Change (ADCS-CGIC) scores it was also not significant (p=073)

Conclusion Adding atorvastation on a background of donepezil use was not associated with any significant clinical benefits on either cognition or global functioning over 72 wks

bull Inclusions amp Exclusion criteria stated

bull Any serious adverse effects or deaths stated

bull FU at 3-month intervals through month 18

bull Population in currentstudy restricted to those who did not have an indication for statin treatment

bull Pts with significant concurrent cardiac cerebrovascular or PVD were excluded but could atorvastatin have benefited those pts with AD

bull Power analysis for sample size stated

bull P-value cut-off value listed

Level IIA (Single RCT)

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

A Randomized Double-blindPlacebo-controlled Trial of Simvastatin to Treat Alzheimer Disease by Sano et al in 2011

Inclusion gt 50 yo not on lipid lowering drugs mild to mod AD LDL gt80 mgdL or Trig lt500mgdL ge 3m of cholinesterase inhibitors and memantine use allowed medically stable

RCT double blind determining if the lipid-lowering agent simvastatin slows the progression of symptoms of AD in individuals with mild to moderate AD and normal lipid levelsDuration 18 monthsLocation Multicenter in USATotal n = 406 MMSE 12-26Intervention Simvastatin 20mgday x 6-wk then 40mgday n=204 Age 740 plusmn 96 588 femaleControl Matching placebo n= 202 Age 751 plusmn90 599 female

Outcome measure Rate of change in cognitive portion of the Alzheimerrsquos Disease Assessment Scale-Cognitive subscale (ADAS-Cog) score

Rate of change in ADAS-Cog score did not differ between groups (p=025 95 CI -00462 to 01680)No significant differences between groups in the secondary outcomes (MMSE Dependent Scale ADCS-ADL and NPI or the additional cognitive measures) or the CGICTotal Chol and LDL levels were significantly darr by the tx compared to placebo (plt0001) the darr was 23 in total Chol amp 37 in LDL HDL levels were also uarr wiith tx by 2 (p=002)Use of antidementia drugs alone or in combination did not change primary results

Conclusion Simvastatin had no effect on the progression of symptoms in individuals with mild to moderate AD despite significant lowering of cholesterol

bull Inclusions amp Exclusion criteria stated

bull Funding by NationalInstitute of Aging disclosed

bull FU at 3- 6- 12- and 18-m after baseline

bull Any serious adverse effects or deaths stated

bull P-value cut-off value not listed so assumption 005

bull This study did not address the utility of statin in pts who do not otherwise require lipid lowering at predementia stages MCI or presymptomatic AD

bull Power analysis for sample size stated

Level IIA (Single RCT)

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

Atorvastatin for the Treatment of Mild to Moderate Alzheimerrsquos Disease Preliminary Results by Sparks et al in 2005

Inclusion ge 51 yo mild to mod AD 9th

grade education le 4 on modified Hachinski Ischemic Scale and le 20 on GDS stable dose of cholinesterase inhibitors for ge 3 m allowed accompanied by caregiver good general health speak english cholesterol gt90mgdL

Double-blind placebo-controlled randomized trial to determine if tx w atorvastatin calcium affects cognitive andor behavioral decline in pts with mild to mod ADDuration 1yearLocation single site in USATotal n = 63 MMSE 12-28Intervention Atorvastatin 80mgday n=32 Age 7815 plusmn 13 375 femaleControl Matching placebo n= 31 Age 789 plusmn 12 355 female

Outcome measure change in Alzheimerrsquos Disease Assessment Scale-cognitive subscale (ADAS-Cog) amp the Clinical Global Impression of Change Scale (CGIS) scores

Both groups showed deterioration on the ADAS-cog at 3-m Placebo group continued to deteriorate app 1 pointquarter Difference in ADAS-cog scores between groups was significant at 6-m (P=0003) amp 12-m (P=0055)A trend for a difference on the CGIC between groups was achieved at both 9 (P=0058) and 12-m (P=007)MMSE score in atorvastatin group showed limited improvement after 3-m visit amp the difference between groups was not significant (Pgt10) Atorvastatin Tx had significant darr in total Chol LDL VLDL compared to placebo group (Plt01)

Conclusion Atorvastatin tx may be of some clinical benefit amp could be established as an effective therapy for AD if the current findings are substantiated by a much larger multicenter trial (Promising results)

bull Inclusions amp Exclusion criteria stated

bull FU at 3- 6- 9- and 12-month

bull Pilot studybull Very small sample

groups ndash started with 98 participants 71 were eligible 67 randomized amp 63 completed 3-m visit amp were considered eligible

bull No power analysisbull Study is 9 years oldbull Results may or may not

be applicable to other types of statins

Level IIA (Single RCT)

SUMMARY OF LITERATURE amp TREATMENT GUIDELINES

bull Primary goal improve QOL and maximize functional performance by enhancing cognition and addressing mood and behavior

bull AChEI for mild to moderate AD

bull Memantidine + AChEI (Aricept) for moderate to severe AD

bull AVOID anticholinergic medications amp LIMIT prn psychotropic medication use

bull Consider referral to hospice if FAST (Functional Assessment Staging Scale) =7

bull Statins show NO CLEAR BENEFITS in slowing the progression of dementia

bull RCTs with larger populations and longer time frame needed

bull One study was gt5 years due to limited meta-analysis or systematic reviews to support PICO

HEALTH PROMOTION MODEL Katharine Kolcabarsquos Comfort Theory

bull Born and educated in Cleveland Ohio

bull In 1987 RN to MSN degree with a specialty in gerontology Maintained head nurse position on a dementia unit while in graduate school and began theorizing about comfort

bull While pursuing her doctorate in nursing she used her course work to further develop her theory over a 10 year period

bull Extensive publications compiled in her book Comfort Theory and Practice

bull Comfort means to strengthen greatly

bull It exists in three forms Relief Ease amp Transcendence

bull Four contexts in which comfort is experienced Physical Psychospiritual Sociocultural amp Environmental

CRITIQUE

STRENGTHS Applicable to other disciplines amp settings Adaptable to each patient situation or scenario Nurse works closely with the patient Patients can engage in HSB once comfort is achieved Provides direction for quality improvement Comfort rounds with pts amp work environment

WEAKNESS Enhanced comfort does not always produce the expected outcome like health seeking behaviors Places nurses at center of concept

APPLICATION TO PRACTICE Nurses play a critical role in helping patients achieve comfort and engage in health-seeking behaviors Nurses can impact patientrsquos quality care Nurses can work with patients to come up with interventions to impact their comfort and evaluate those interventions Nurses can impact institutional integrity

APPLICATION to CASE

Health Care NeedsFeeding Assistance uarr assistance with ADLs weight loss difficulty swallowingComfort InterventionsReview med list with family educate staff on ptrsquos uarr needs feeding assistance aspiration precautions address hospice eligibility include pt in activities toileting scheduleIntervening VariablesAdvanced age terminal illness

support system (wifePOA) assisted livingEnhanced ComfortJT is being strengthened through having comfort needs addressedHealth Seeking BehaviorsWeight gain acceptancewife is more trusting and calmer peaceful deathInstitutional IntegrityApplication of CT to other cases staff investment in implementing theory

JTrsquos PLAN OF CAREDIFFERENTIALS VaD Dementia with Lewy Bodies Frontotemporal dementiaEVALUATION Comprehensive physical and neurologic exam Assess functional status and evaluate mental status Labs CBC TSH B12 Folate metabolic screenPLANbull STOP Simvastatin 10mg PO bedtime amp Change Citalopram to 20mg PO QDbull No hospice referral ndash Needs to have lt 6m To livebull FAST ge 7A amp ASPNA or upper UTI or septicemia or multiple PU (stage 34) or

recurrent fever on ABX or weight loss gt10 in past 6 m Alb lt25bull Review Advance directive with POAbull Involve and encourage JT to participates in cares and activitiesbull One can of Ensure with every mealbull Aspiration precautionsbull Record weekly weightbull FU in 3-4 weeks or earlier if status change

REFERENCES

Alzheimerrsquos Association (2014) Alzheimerrsquos facts and figures Retrieved from httpwwwalzorgalzheimers_disease_facts_and_figuresasp

Alzheimerrsquos Association (2014) Medications for memory loss Retrieved from

httpwwwalzorgalzheimers_disease_standard_prescriptionsasp

Alzheimerrsquos Foundation of America (2014) About Alzheimerrsquos Retrieved from httpwwwalzfdnorgAboutAlzheimerscosthtml

American Geriatrics Society (2013) A guide to dementia diagnosis and treatment Retrieved from

httpwwwamericangeriatricsorgfilesdocumentsdementia_pocket_cardpdf

Buttaro T M Trybulski J Bailey P P amp Sandberg-Cook J (2013) Primary care A collaborative practice (4th ed) St Louis MO Elsevier

Centers for Medicare amp Medicaid Services (2013) Superseded local coverage determination (LCD) Hospice determining terminal status (L32015)

Retrieved from httpwwwcmsgovmedicare-coverage-databasedetailslcd-

detailsaspxLCDId=32015ampContrId=236ampver=14ampContrVer=2ampCntrctrSelected=2362ampCntrctr=236ampname=CGS+Administrators2c+LL

C+(150042c+HHH+MAC)amps=11ampDocType=Activeampbc=AggAAAIAAAAAAA3d3damp

RISK FACTORS amp CLINICAL MANIFESTATION

RISK FACTORSbull Age family history and hereditybull HTN lipoproteins cerebrovascular

disease Type 2 diabetes Obesity brain trauma

bull Lifestyle and activity

PROTECTIVE FACTORSbull Liefelong activity APOE2

antioxidant substances estrogen replacement low caloric diet nonsteroidal anti-inflammatory agents and statins

CLINICAL MANIFESTATIONSVery Early Signs and Symptomsbull Memory amp thinking problems poor

judgment no functional impairmentMild AD (1-3 years)bull Confusion anxiety personality or

mood changes task completionModerate AD (2-8 years)bull Language reasoning sensory

processing amp conscious thoughts affected

Severe AD (6-12 years)bull Unable to recognize family or

communicate dependent for cares

TREATMENT GUIDELINESDeveloper European Federation of

Neurological Societies (EFNS)American Academy of Family Phsysicians (AAFP) amp American College of Physicians (ACP)

American Geriatrics Society(AGS)

Year 2010 2008 2013

Goal Revise 2007 EFNS recommendation on diagnosis and management of AD in pts with AD

Present available evidence on current pharmacologic treatment of Dementia (AD amp VaD)

Guide on the Dx amp Tx of dementiafrom Geriatrics at your fingertips amp Geriatrics review syllabus A core curriculum in geriatric medicine

Re

com

me

nd

atio

ns

Achetylcholinesterase Inhibior (AChEI) for mild to mod ADMemantine + AChEI for mod to severe AD Regular FU to assess cognition ADL behavior DC therapy if rapid worsening or loss of effectiveness

AChEI for mild to mod ADMemantine for mod to severe AD DC therapy with loss of effectiveness

AChEI for mild to mod ADMemantine + donepezil (Aricept) for mod to severe ADTrial Tx period at least 3 monthsMonitor MMSE Clinical Dementia Rating and Functional Assessment Staging scale DC therapy if develops severe impairment

Strengths Grading of evidence clear txoption conflict of interest disclosed

Grading of evidence clear tx option conflit of interest disclosed

Easy read treatment includes nonpharmacologic approaches amp treatment for agitation

Weaknesses European guideline no algorithm Outdated no algorithm No grading of evidence algorithm

SEARCHING THE LITERATURE

PICO Question

bull In patients with moderate Alzheimerrsquos disease does taking a statin slow the progression of dementia compared to not taking a statin

Literature Search Methods

bull Search Engines PubMed CINAHL Cochrane Library Ovid Medline

bull Search Terms Dementia Statins Alzheimerrsquos disease treatment progression older adults

bull Limits 2004-2014 (10 years) Humans English Full text RCT Systematic Reviews

bull Evidence Guide Center for Evidence Based Medicine (CEBM)

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

Randomized Controlled Trial of Atorvastatin in Mild to Moderate Alzheimer Disease LEADe by Feldman et al in 2010

Inclusion 50-90 yo mild to mod AD ondonepezil 10mg daily for ge 3 m prior to screen LDL-C 95-195 mgdL caregiver present le 4 on modified Hachinski Ischemic Scale not requiring tx for dyslipidemia with any lipid-lowering agent cranial CT or MRI within 12 m consistent with AD medically stable no other AchEIs

RCT with double blind randomized withdrawal phase evaluating the efficacy and safety of atorvastatin in patients with mild to moderate ADDuration 72wks trial then 8-wk atorvastatin withdrawal phaseLocation Multicenter in 10 countries Total n = 640 MMSE 13-25 96 white On donepezil 10mgday ge3-m priorIntervention Atorvastatin 80mgday n=297 Age 740 plusmn 80 47 maleControl Matching placebo n= 317 Age 732 plusmn 87 49 male

Outcome measure change in cognition (ADAS-Cog) and global function (ADCS-CGIC) at 72 wks

By 3-m mean LDL-C had darr -724 mgdL (-502) in atorvastatin group amp -10 mgdL (-02) in placebo group and changes remained constant through 18-mTotal Chol amp Trig had larger darr in atorvastatin vs placebo groupDifference in Alzheimerrsquos Disease Assessment Scale ndash Cognitive Subscale (ADAS-cog) scores between groups showed a primary analysis that was not significant (p=026) and in the Alzheimerrsquos Disease Cooperative Study ndash Clinical Glocal Impression of Change (ADCS-CGIC) scores it was also not significant (p=073)

Conclusion Adding atorvastation on a background of donepezil use was not associated with any significant clinical benefits on either cognition or global functioning over 72 wks

bull Inclusions amp Exclusion criteria stated

bull Any serious adverse effects or deaths stated

bull FU at 3-month intervals through month 18

bull Population in currentstudy restricted to those who did not have an indication for statin treatment

bull Pts with significant concurrent cardiac cerebrovascular or PVD were excluded but could atorvastatin have benefited those pts with AD

bull Power analysis for sample size stated

bull P-value cut-off value listed

Level IIA (Single RCT)

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

A Randomized Double-blindPlacebo-controlled Trial of Simvastatin to Treat Alzheimer Disease by Sano et al in 2011

Inclusion gt 50 yo not on lipid lowering drugs mild to mod AD LDL gt80 mgdL or Trig lt500mgdL ge 3m of cholinesterase inhibitors and memantine use allowed medically stable

RCT double blind determining if the lipid-lowering agent simvastatin slows the progression of symptoms of AD in individuals with mild to moderate AD and normal lipid levelsDuration 18 monthsLocation Multicenter in USATotal n = 406 MMSE 12-26Intervention Simvastatin 20mgday x 6-wk then 40mgday n=204 Age 740 plusmn 96 588 femaleControl Matching placebo n= 202 Age 751 plusmn90 599 female

Outcome measure Rate of change in cognitive portion of the Alzheimerrsquos Disease Assessment Scale-Cognitive subscale (ADAS-Cog) score

Rate of change in ADAS-Cog score did not differ between groups (p=025 95 CI -00462 to 01680)No significant differences between groups in the secondary outcomes (MMSE Dependent Scale ADCS-ADL and NPI or the additional cognitive measures) or the CGICTotal Chol and LDL levels were significantly darr by the tx compared to placebo (plt0001) the darr was 23 in total Chol amp 37 in LDL HDL levels were also uarr wiith tx by 2 (p=002)Use of antidementia drugs alone or in combination did not change primary results

Conclusion Simvastatin had no effect on the progression of symptoms in individuals with mild to moderate AD despite significant lowering of cholesterol

bull Inclusions amp Exclusion criteria stated

bull Funding by NationalInstitute of Aging disclosed

bull FU at 3- 6- 12- and 18-m after baseline

bull Any serious adverse effects or deaths stated

bull P-value cut-off value not listed so assumption 005

bull This study did not address the utility of statin in pts who do not otherwise require lipid lowering at predementia stages MCI or presymptomatic AD

bull Power analysis for sample size stated

Level IIA (Single RCT)

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

Atorvastatin for the Treatment of Mild to Moderate Alzheimerrsquos Disease Preliminary Results by Sparks et al in 2005

Inclusion ge 51 yo mild to mod AD 9th

grade education le 4 on modified Hachinski Ischemic Scale and le 20 on GDS stable dose of cholinesterase inhibitors for ge 3 m allowed accompanied by caregiver good general health speak english cholesterol gt90mgdL

Double-blind placebo-controlled randomized trial to determine if tx w atorvastatin calcium affects cognitive andor behavioral decline in pts with mild to mod ADDuration 1yearLocation single site in USATotal n = 63 MMSE 12-28Intervention Atorvastatin 80mgday n=32 Age 7815 plusmn 13 375 femaleControl Matching placebo n= 31 Age 789 plusmn 12 355 female

Outcome measure change in Alzheimerrsquos Disease Assessment Scale-cognitive subscale (ADAS-Cog) amp the Clinical Global Impression of Change Scale (CGIS) scores

Both groups showed deterioration on the ADAS-cog at 3-m Placebo group continued to deteriorate app 1 pointquarter Difference in ADAS-cog scores between groups was significant at 6-m (P=0003) amp 12-m (P=0055)A trend for a difference on the CGIC between groups was achieved at both 9 (P=0058) and 12-m (P=007)MMSE score in atorvastatin group showed limited improvement after 3-m visit amp the difference between groups was not significant (Pgt10) Atorvastatin Tx had significant darr in total Chol LDL VLDL compared to placebo group (Plt01)

Conclusion Atorvastatin tx may be of some clinical benefit amp could be established as an effective therapy for AD if the current findings are substantiated by a much larger multicenter trial (Promising results)

bull Inclusions amp Exclusion criteria stated

bull FU at 3- 6- 9- and 12-month

bull Pilot studybull Very small sample

groups ndash started with 98 participants 71 were eligible 67 randomized amp 63 completed 3-m visit amp were considered eligible

bull No power analysisbull Study is 9 years oldbull Results may or may not

be applicable to other types of statins

Level IIA (Single RCT)

SUMMARY OF LITERATURE amp TREATMENT GUIDELINES

bull Primary goal improve QOL and maximize functional performance by enhancing cognition and addressing mood and behavior

bull AChEI for mild to moderate AD

bull Memantidine + AChEI (Aricept) for moderate to severe AD

bull AVOID anticholinergic medications amp LIMIT prn psychotropic medication use

bull Consider referral to hospice if FAST (Functional Assessment Staging Scale) =7

bull Statins show NO CLEAR BENEFITS in slowing the progression of dementia

bull RCTs with larger populations and longer time frame needed

bull One study was gt5 years due to limited meta-analysis or systematic reviews to support PICO

HEALTH PROMOTION MODEL Katharine Kolcabarsquos Comfort Theory

bull Born and educated in Cleveland Ohio

bull In 1987 RN to MSN degree with a specialty in gerontology Maintained head nurse position on a dementia unit while in graduate school and began theorizing about comfort

bull While pursuing her doctorate in nursing she used her course work to further develop her theory over a 10 year period

bull Extensive publications compiled in her book Comfort Theory and Practice

bull Comfort means to strengthen greatly

bull It exists in three forms Relief Ease amp Transcendence

bull Four contexts in which comfort is experienced Physical Psychospiritual Sociocultural amp Environmental

CRITIQUE

STRENGTHS Applicable to other disciplines amp settings Adaptable to each patient situation or scenario Nurse works closely with the patient Patients can engage in HSB once comfort is achieved Provides direction for quality improvement Comfort rounds with pts amp work environment

WEAKNESS Enhanced comfort does not always produce the expected outcome like health seeking behaviors Places nurses at center of concept

APPLICATION TO PRACTICE Nurses play a critical role in helping patients achieve comfort and engage in health-seeking behaviors Nurses can impact patientrsquos quality care Nurses can work with patients to come up with interventions to impact their comfort and evaluate those interventions Nurses can impact institutional integrity

APPLICATION to CASE

Health Care NeedsFeeding Assistance uarr assistance with ADLs weight loss difficulty swallowingComfort InterventionsReview med list with family educate staff on ptrsquos uarr needs feeding assistance aspiration precautions address hospice eligibility include pt in activities toileting scheduleIntervening VariablesAdvanced age terminal illness

support system (wifePOA) assisted livingEnhanced ComfortJT is being strengthened through having comfort needs addressedHealth Seeking BehaviorsWeight gain acceptancewife is more trusting and calmer peaceful deathInstitutional IntegrityApplication of CT to other cases staff investment in implementing theory

JTrsquos PLAN OF CAREDIFFERENTIALS VaD Dementia with Lewy Bodies Frontotemporal dementiaEVALUATION Comprehensive physical and neurologic exam Assess functional status and evaluate mental status Labs CBC TSH B12 Folate metabolic screenPLANbull STOP Simvastatin 10mg PO bedtime amp Change Citalopram to 20mg PO QDbull No hospice referral ndash Needs to have lt 6m To livebull FAST ge 7A amp ASPNA or upper UTI or septicemia or multiple PU (stage 34) or

recurrent fever on ABX or weight loss gt10 in past 6 m Alb lt25bull Review Advance directive with POAbull Involve and encourage JT to participates in cares and activitiesbull One can of Ensure with every mealbull Aspiration precautionsbull Record weekly weightbull FU in 3-4 weeks or earlier if status change

REFERENCES

Alzheimerrsquos Association (2014) Alzheimerrsquos facts and figures Retrieved from httpwwwalzorgalzheimers_disease_facts_and_figuresasp

Alzheimerrsquos Association (2014) Medications for memory loss Retrieved from

httpwwwalzorgalzheimers_disease_standard_prescriptionsasp

Alzheimerrsquos Foundation of America (2014) About Alzheimerrsquos Retrieved from httpwwwalzfdnorgAboutAlzheimerscosthtml

American Geriatrics Society (2013) A guide to dementia diagnosis and treatment Retrieved from

httpwwwamericangeriatricsorgfilesdocumentsdementia_pocket_cardpdf

Buttaro T M Trybulski J Bailey P P amp Sandberg-Cook J (2013) Primary care A collaborative practice (4th ed) St Louis MO Elsevier

Centers for Medicare amp Medicaid Services (2013) Superseded local coverage determination (LCD) Hospice determining terminal status (L32015)

Retrieved from httpwwwcmsgovmedicare-coverage-databasedetailslcd-

detailsaspxLCDId=32015ampContrId=236ampver=14ampContrVer=2ampCntrctrSelected=2362ampCntrctr=236ampname=CGS+Administrators2c+LL

C+(150042c+HHH+MAC)amps=11ampDocType=Activeampbc=AggAAAIAAAAAAA3d3damp

TREATMENT GUIDELINESDeveloper European Federation of

Neurological Societies (EFNS)American Academy of Family Phsysicians (AAFP) amp American College of Physicians (ACP)

American Geriatrics Society(AGS)

Year 2010 2008 2013

Goal Revise 2007 EFNS recommendation on diagnosis and management of AD in pts with AD

Present available evidence on current pharmacologic treatment of Dementia (AD amp VaD)

Guide on the Dx amp Tx of dementiafrom Geriatrics at your fingertips amp Geriatrics review syllabus A core curriculum in geriatric medicine

Re

com

me

nd

atio

ns

Achetylcholinesterase Inhibior (AChEI) for mild to mod ADMemantine + AChEI for mod to severe AD Regular FU to assess cognition ADL behavior DC therapy if rapid worsening or loss of effectiveness

AChEI for mild to mod ADMemantine for mod to severe AD DC therapy with loss of effectiveness

AChEI for mild to mod ADMemantine + donepezil (Aricept) for mod to severe ADTrial Tx period at least 3 monthsMonitor MMSE Clinical Dementia Rating and Functional Assessment Staging scale DC therapy if develops severe impairment

Strengths Grading of evidence clear txoption conflict of interest disclosed

Grading of evidence clear tx option conflit of interest disclosed

Easy read treatment includes nonpharmacologic approaches amp treatment for agitation

Weaknesses European guideline no algorithm Outdated no algorithm No grading of evidence algorithm

SEARCHING THE LITERATURE

PICO Question

bull In patients with moderate Alzheimerrsquos disease does taking a statin slow the progression of dementia compared to not taking a statin

Literature Search Methods

bull Search Engines PubMed CINAHL Cochrane Library Ovid Medline

bull Search Terms Dementia Statins Alzheimerrsquos disease treatment progression older adults

bull Limits 2004-2014 (10 years) Humans English Full text RCT Systematic Reviews

bull Evidence Guide Center for Evidence Based Medicine (CEBM)

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

Randomized Controlled Trial of Atorvastatin in Mild to Moderate Alzheimer Disease LEADe by Feldman et al in 2010

Inclusion 50-90 yo mild to mod AD ondonepezil 10mg daily for ge 3 m prior to screen LDL-C 95-195 mgdL caregiver present le 4 on modified Hachinski Ischemic Scale not requiring tx for dyslipidemia with any lipid-lowering agent cranial CT or MRI within 12 m consistent with AD medically stable no other AchEIs

RCT with double blind randomized withdrawal phase evaluating the efficacy and safety of atorvastatin in patients with mild to moderate ADDuration 72wks trial then 8-wk atorvastatin withdrawal phaseLocation Multicenter in 10 countries Total n = 640 MMSE 13-25 96 white On donepezil 10mgday ge3-m priorIntervention Atorvastatin 80mgday n=297 Age 740 plusmn 80 47 maleControl Matching placebo n= 317 Age 732 plusmn 87 49 male

Outcome measure change in cognition (ADAS-Cog) and global function (ADCS-CGIC) at 72 wks

By 3-m mean LDL-C had darr -724 mgdL (-502) in atorvastatin group amp -10 mgdL (-02) in placebo group and changes remained constant through 18-mTotal Chol amp Trig had larger darr in atorvastatin vs placebo groupDifference in Alzheimerrsquos Disease Assessment Scale ndash Cognitive Subscale (ADAS-cog) scores between groups showed a primary analysis that was not significant (p=026) and in the Alzheimerrsquos Disease Cooperative Study ndash Clinical Glocal Impression of Change (ADCS-CGIC) scores it was also not significant (p=073)

Conclusion Adding atorvastation on a background of donepezil use was not associated with any significant clinical benefits on either cognition or global functioning over 72 wks

bull Inclusions amp Exclusion criteria stated

bull Any serious adverse effects or deaths stated

bull FU at 3-month intervals through month 18

bull Population in currentstudy restricted to those who did not have an indication for statin treatment

bull Pts with significant concurrent cardiac cerebrovascular or PVD were excluded but could atorvastatin have benefited those pts with AD

bull Power analysis for sample size stated

bull P-value cut-off value listed

Level IIA (Single RCT)

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

A Randomized Double-blindPlacebo-controlled Trial of Simvastatin to Treat Alzheimer Disease by Sano et al in 2011

Inclusion gt 50 yo not on lipid lowering drugs mild to mod AD LDL gt80 mgdL or Trig lt500mgdL ge 3m of cholinesterase inhibitors and memantine use allowed medically stable

RCT double blind determining if the lipid-lowering agent simvastatin slows the progression of symptoms of AD in individuals with mild to moderate AD and normal lipid levelsDuration 18 monthsLocation Multicenter in USATotal n = 406 MMSE 12-26Intervention Simvastatin 20mgday x 6-wk then 40mgday n=204 Age 740 plusmn 96 588 femaleControl Matching placebo n= 202 Age 751 plusmn90 599 female

Outcome measure Rate of change in cognitive portion of the Alzheimerrsquos Disease Assessment Scale-Cognitive subscale (ADAS-Cog) score

Rate of change in ADAS-Cog score did not differ between groups (p=025 95 CI -00462 to 01680)No significant differences between groups in the secondary outcomes (MMSE Dependent Scale ADCS-ADL and NPI or the additional cognitive measures) or the CGICTotal Chol and LDL levels were significantly darr by the tx compared to placebo (plt0001) the darr was 23 in total Chol amp 37 in LDL HDL levels were also uarr wiith tx by 2 (p=002)Use of antidementia drugs alone or in combination did not change primary results

Conclusion Simvastatin had no effect on the progression of symptoms in individuals with mild to moderate AD despite significant lowering of cholesterol

bull Inclusions amp Exclusion criteria stated

bull Funding by NationalInstitute of Aging disclosed

bull FU at 3- 6- 12- and 18-m after baseline

bull Any serious adverse effects or deaths stated

bull P-value cut-off value not listed so assumption 005

bull This study did not address the utility of statin in pts who do not otherwise require lipid lowering at predementia stages MCI or presymptomatic AD

bull Power analysis for sample size stated

Level IIA (Single RCT)

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

Atorvastatin for the Treatment of Mild to Moderate Alzheimerrsquos Disease Preliminary Results by Sparks et al in 2005

Inclusion ge 51 yo mild to mod AD 9th

grade education le 4 on modified Hachinski Ischemic Scale and le 20 on GDS stable dose of cholinesterase inhibitors for ge 3 m allowed accompanied by caregiver good general health speak english cholesterol gt90mgdL

Double-blind placebo-controlled randomized trial to determine if tx w atorvastatin calcium affects cognitive andor behavioral decline in pts with mild to mod ADDuration 1yearLocation single site in USATotal n = 63 MMSE 12-28Intervention Atorvastatin 80mgday n=32 Age 7815 plusmn 13 375 femaleControl Matching placebo n= 31 Age 789 plusmn 12 355 female

Outcome measure change in Alzheimerrsquos Disease Assessment Scale-cognitive subscale (ADAS-Cog) amp the Clinical Global Impression of Change Scale (CGIS) scores

Both groups showed deterioration on the ADAS-cog at 3-m Placebo group continued to deteriorate app 1 pointquarter Difference in ADAS-cog scores between groups was significant at 6-m (P=0003) amp 12-m (P=0055)A trend for a difference on the CGIC between groups was achieved at both 9 (P=0058) and 12-m (P=007)MMSE score in atorvastatin group showed limited improvement after 3-m visit amp the difference between groups was not significant (Pgt10) Atorvastatin Tx had significant darr in total Chol LDL VLDL compared to placebo group (Plt01)

Conclusion Atorvastatin tx may be of some clinical benefit amp could be established as an effective therapy for AD if the current findings are substantiated by a much larger multicenter trial (Promising results)

bull Inclusions amp Exclusion criteria stated

bull FU at 3- 6- 9- and 12-month

bull Pilot studybull Very small sample

groups ndash started with 98 participants 71 were eligible 67 randomized amp 63 completed 3-m visit amp were considered eligible

bull No power analysisbull Study is 9 years oldbull Results may or may not

be applicable to other types of statins

Level IIA (Single RCT)

SUMMARY OF LITERATURE amp TREATMENT GUIDELINES

bull Primary goal improve QOL and maximize functional performance by enhancing cognition and addressing mood and behavior

bull AChEI for mild to moderate AD

bull Memantidine + AChEI (Aricept) for moderate to severe AD

bull AVOID anticholinergic medications amp LIMIT prn psychotropic medication use

bull Consider referral to hospice if FAST (Functional Assessment Staging Scale) =7

bull Statins show NO CLEAR BENEFITS in slowing the progression of dementia

bull RCTs with larger populations and longer time frame needed

bull One study was gt5 years due to limited meta-analysis or systematic reviews to support PICO

HEALTH PROMOTION MODEL Katharine Kolcabarsquos Comfort Theory

bull Born and educated in Cleveland Ohio

bull In 1987 RN to MSN degree with a specialty in gerontology Maintained head nurse position on a dementia unit while in graduate school and began theorizing about comfort

bull While pursuing her doctorate in nursing she used her course work to further develop her theory over a 10 year period

bull Extensive publications compiled in her book Comfort Theory and Practice

bull Comfort means to strengthen greatly

bull It exists in three forms Relief Ease amp Transcendence

bull Four contexts in which comfort is experienced Physical Psychospiritual Sociocultural amp Environmental

CRITIQUE

STRENGTHS Applicable to other disciplines amp settings Adaptable to each patient situation or scenario Nurse works closely with the patient Patients can engage in HSB once comfort is achieved Provides direction for quality improvement Comfort rounds with pts amp work environment

WEAKNESS Enhanced comfort does not always produce the expected outcome like health seeking behaviors Places nurses at center of concept

APPLICATION TO PRACTICE Nurses play a critical role in helping patients achieve comfort and engage in health-seeking behaviors Nurses can impact patientrsquos quality care Nurses can work with patients to come up with interventions to impact their comfort and evaluate those interventions Nurses can impact institutional integrity

APPLICATION to CASE

Health Care NeedsFeeding Assistance uarr assistance with ADLs weight loss difficulty swallowingComfort InterventionsReview med list with family educate staff on ptrsquos uarr needs feeding assistance aspiration precautions address hospice eligibility include pt in activities toileting scheduleIntervening VariablesAdvanced age terminal illness

support system (wifePOA) assisted livingEnhanced ComfortJT is being strengthened through having comfort needs addressedHealth Seeking BehaviorsWeight gain acceptancewife is more trusting and calmer peaceful deathInstitutional IntegrityApplication of CT to other cases staff investment in implementing theory

JTrsquos PLAN OF CAREDIFFERENTIALS VaD Dementia with Lewy Bodies Frontotemporal dementiaEVALUATION Comprehensive physical and neurologic exam Assess functional status and evaluate mental status Labs CBC TSH B12 Folate metabolic screenPLANbull STOP Simvastatin 10mg PO bedtime amp Change Citalopram to 20mg PO QDbull No hospice referral ndash Needs to have lt 6m To livebull FAST ge 7A amp ASPNA or upper UTI or septicemia or multiple PU (stage 34) or

recurrent fever on ABX or weight loss gt10 in past 6 m Alb lt25bull Review Advance directive with POAbull Involve and encourage JT to participates in cares and activitiesbull One can of Ensure with every mealbull Aspiration precautionsbull Record weekly weightbull FU in 3-4 weeks or earlier if status change

REFERENCES

Alzheimerrsquos Association (2014) Alzheimerrsquos facts and figures Retrieved from httpwwwalzorgalzheimers_disease_facts_and_figuresasp

Alzheimerrsquos Association (2014) Medications for memory loss Retrieved from

httpwwwalzorgalzheimers_disease_standard_prescriptionsasp

Alzheimerrsquos Foundation of America (2014) About Alzheimerrsquos Retrieved from httpwwwalzfdnorgAboutAlzheimerscosthtml

American Geriatrics Society (2013) A guide to dementia diagnosis and treatment Retrieved from

httpwwwamericangeriatricsorgfilesdocumentsdementia_pocket_cardpdf

Buttaro T M Trybulski J Bailey P P amp Sandberg-Cook J (2013) Primary care A collaborative practice (4th ed) St Louis MO Elsevier

Centers for Medicare amp Medicaid Services (2013) Superseded local coverage determination (LCD) Hospice determining terminal status (L32015)

Retrieved from httpwwwcmsgovmedicare-coverage-databasedetailslcd-

detailsaspxLCDId=32015ampContrId=236ampver=14ampContrVer=2ampCntrctrSelected=2362ampCntrctr=236ampname=CGS+Administrators2c+LL

C+(150042c+HHH+MAC)amps=11ampDocType=Activeampbc=AggAAAIAAAAAAA3d3damp

SEARCHING THE LITERATURE

PICO Question

bull In patients with moderate Alzheimerrsquos disease does taking a statin slow the progression of dementia compared to not taking a statin

Literature Search Methods

bull Search Engines PubMed CINAHL Cochrane Library Ovid Medline

bull Search Terms Dementia Statins Alzheimerrsquos disease treatment progression older adults

bull Limits 2004-2014 (10 years) Humans English Full text RCT Systematic Reviews

bull Evidence Guide Center for Evidence Based Medicine (CEBM)

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

Randomized Controlled Trial of Atorvastatin in Mild to Moderate Alzheimer Disease LEADe by Feldman et al in 2010

Inclusion 50-90 yo mild to mod AD ondonepezil 10mg daily for ge 3 m prior to screen LDL-C 95-195 mgdL caregiver present le 4 on modified Hachinski Ischemic Scale not requiring tx for dyslipidemia with any lipid-lowering agent cranial CT or MRI within 12 m consistent with AD medically stable no other AchEIs

RCT with double blind randomized withdrawal phase evaluating the efficacy and safety of atorvastatin in patients with mild to moderate ADDuration 72wks trial then 8-wk atorvastatin withdrawal phaseLocation Multicenter in 10 countries Total n = 640 MMSE 13-25 96 white On donepezil 10mgday ge3-m priorIntervention Atorvastatin 80mgday n=297 Age 740 plusmn 80 47 maleControl Matching placebo n= 317 Age 732 plusmn 87 49 male

Outcome measure change in cognition (ADAS-Cog) and global function (ADCS-CGIC) at 72 wks

By 3-m mean LDL-C had darr -724 mgdL (-502) in atorvastatin group amp -10 mgdL (-02) in placebo group and changes remained constant through 18-mTotal Chol amp Trig had larger darr in atorvastatin vs placebo groupDifference in Alzheimerrsquos Disease Assessment Scale ndash Cognitive Subscale (ADAS-cog) scores between groups showed a primary analysis that was not significant (p=026) and in the Alzheimerrsquos Disease Cooperative Study ndash Clinical Glocal Impression of Change (ADCS-CGIC) scores it was also not significant (p=073)

Conclusion Adding atorvastation on a background of donepezil use was not associated with any significant clinical benefits on either cognition or global functioning over 72 wks

bull Inclusions amp Exclusion criteria stated

bull Any serious adverse effects or deaths stated

bull FU at 3-month intervals through month 18

bull Population in currentstudy restricted to those who did not have an indication for statin treatment

bull Pts with significant concurrent cardiac cerebrovascular or PVD were excluded but could atorvastatin have benefited those pts with AD

bull Power analysis for sample size stated

bull P-value cut-off value listed

Level IIA (Single RCT)

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

A Randomized Double-blindPlacebo-controlled Trial of Simvastatin to Treat Alzheimer Disease by Sano et al in 2011

Inclusion gt 50 yo not on lipid lowering drugs mild to mod AD LDL gt80 mgdL or Trig lt500mgdL ge 3m of cholinesterase inhibitors and memantine use allowed medically stable

RCT double blind determining if the lipid-lowering agent simvastatin slows the progression of symptoms of AD in individuals with mild to moderate AD and normal lipid levelsDuration 18 monthsLocation Multicenter in USATotal n = 406 MMSE 12-26Intervention Simvastatin 20mgday x 6-wk then 40mgday n=204 Age 740 plusmn 96 588 femaleControl Matching placebo n= 202 Age 751 plusmn90 599 female

Outcome measure Rate of change in cognitive portion of the Alzheimerrsquos Disease Assessment Scale-Cognitive subscale (ADAS-Cog) score

Rate of change in ADAS-Cog score did not differ between groups (p=025 95 CI -00462 to 01680)No significant differences between groups in the secondary outcomes (MMSE Dependent Scale ADCS-ADL and NPI or the additional cognitive measures) or the CGICTotal Chol and LDL levels were significantly darr by the tx compared to placebo (plt0001) the darr was 23 in total Chol amp 37 in LDL HDL levels were also uarr wiith tx by 2 (p=002)Use of antidementia drugs alone or in combination did not change primary results

Conclusion Simvastatin had no effect on the progression of symptoms in individuals with mild to moderate AD despite significant lowering of cholesterol

bull Inclusions amp Exclusion criteria stated

bull Funding by NationalInstitute of Aging disclosed

bull FU at 3- 6- 12- and 18-m after baseline

bull Any serious adverse effects or deaths stated

bull P-value cut-off value not listed so assumption 005

bull This study did not address the utility of statin in pts who do not otherwise require lipid lowering at predementia stages MCI or presymptomatic AD

bull Power analysis for sample size stated

Level IIA (Single RCT)

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

Atorvastatin for the Treatment of Mild to Moderate Alzheimerrsquos Disease Preliminary Results by Sparks et al in 2005

Inclusion ge 51 yo mild to mod AD 9th

grade education le 4 on modified Hachinski Ischemic Scale and le 20 on GDS stable dose of cholinesterase inhibitors for ge 3 m allowed accompanied by caregiver good general health speak english cholesterol gt90mgdL

Double-blind placebo-controlled randomized trial to determine if tx w atorvastatin calcium affects cognitive andor behavioral decline in pts with mild to mod ADDuration 1yearLocation single site in USATotal n = 63 MMSE 12-28Intervention Atorvastatin 80mgday n=32 Age 7815 plusmn 13 375 femaleControl Matching placebo n= 31 Age 789 plusmn 12 355 female

Outcome measure change in Alzheimerrsquos Disease Assessment Scale-cognitive subscale (ADAS-Cog) amp the Clinical Global Impression of Change Scale (CGIS) scores

Both groups showed deterioration on the ADAS-cog at 3-m Placebo group continued to deteriorate app 1 pointquarter Difference in ADAS-cog scores between groups was significant at 6-m (P=0003) amp 12-m (P=0055)A trend for a difference on the CGIC between groups was achieved at both 9 (P=0058) and 12-m (P=007)MMSE score in atorvastatin group showed limited improvement after 3-m visit amp the difference between groups was not significant (Pgt10) Atorvastatin Tx had significant darr in total Chol LDL VLDL compared to placebo group (Plt01)

Conclusion Atorvastatin tx may be of some clinical benefit amp could be established as an effective therapy for AD if the current findings are substantiated by a much larger multicenter trial (Promising results)

bull Inclusions amp Exclusion criteria stated

bull FU at 3- 6- 9- and 12-month

bull Pilot studybull Very small sample

groups ndash started with 98 participants 71 were eligible 67 randomized amp 63 completed 3-m visit amp were considered eligible

bull No power analysisbull Study is 9 years oldbull Results may or may not

be applicable to other types of statins

Level IIA (Single RCT)

SUMMARY OF LITERATURE amp TREATMENT GUIDELINES

bull Primary goal improve QOL and maximize functional performance by enhancing cognition and addressing mood and behavior

bull AChEI for mild to moderate AD

bull Memantidine + AChEI (Aricept) for moderate to severe AD

bull AVOID anticholinergic medications amp LIMIT prn psychotropic medication use

bull Consider referral to hospice if FAST (Functional Assessment Staging Scale) =7

bull Statins show NO CLEAR BENEFITS in slowing the progression of dementia

bull RCTs with larger populations and longer time frame needed

bull One study was gt5 years due to limited meta-analysis or systematic reviews to support PICO

HEALTH PROMOTION MODEL Katharine Kolcabarsquos Comfort Theory

bull Born and educated in Cleveland Ohio

bull In 1987 RN to MSN degree with a specialty in gerontology Maintained head nurse position on a dementia unit while in graduate school and began theorizing about comfort

bull While pursuing her doctorate in nursing she used her course work to further develop her theory over a 10 year period

bull Extensive publications compiled in her book Comfort Theory and Practice

bull Comfort means to strengthen greatly

bull It exists in three forms Relief Ease amp Transcendence

bull Four contexts in which comfort is experienced Physical Psychospiritual Sociocultural amp Environmental

CRITIQUE

STRENGTHS Applicable to other disciplines amp settings Adaptable to each patient situation or scenario Nurse works closely with the patient Patients can engage in HSB once comfort is achieved Provides direction for quality improvement Comfort rounds with pts amp work environment

WEAKNESS Enhanced comfort does not always produce the expected outcome like health seeking behaviors Places nurses at center of concept

APPLICATION TO PRACTICE Nurses play a critical role in helping patients achieve comfort and engage in health-seeking behaviors Nurses can impact patientrsquos quality care Nurses can work with patients to come up with interventions to impact their comfort and evaluate those interventions Nurses can impact institutional integrity

APPLICATION to CASE

Health Care NeedsFeeding Assistance uarr assistance with ADLs weight loss difficulty swallowingComfort InterventionsReview med list with family educate staff on ptrsquos uarr needs feeding assistance aspiration precautions address hospice eligibility include pt in activities toileting scheduleIntervening VariablesAdvanced age terminal illness

support system (wifePOA) assisted livingEnhanced ComfortJT is being strengthened through having comfort needs addressedHealth Seeking BehaviorsWeight gain acceptancewife is more trusting and calmer peaceful deathInstitutional IntegrityApplication of CT to other cases staff investment in implementing theory

JTrsquos PLAN OF CAREDIFFERENTIALS VaD Dementia with Lewy Bodies Frontotemporal dementiaEVALUATION Comprehensive physical and neurologic exam Assess functional status and evaluate mental status Labs CBC TSH B12 Folate metabolic screenPLANbull STOP Simvastatin 10mg PO bedtime amp Change Citalopram to 20mg PO QDbull No hospice referral ndash Needs to have lt 6m To livebull FAST ge 7A amp ASPNA or upper UTI or septicemia or multiple PU (stage 34) or

recurrent fever on ABX or weight loss gt10 in past 6 m Alb lt25bull Review Advance directive with POAbull Involve and encourage JT to participates in cares and activitiesbull One can of Ensure with every mealbull Aspiration precautionsbull Record weekly weightbull FU in 3-4 weeks or earlier if status change

REFERENCES

Alzheimerrsquos Association (2014) Alzheimerrsquos facts and figures Retrieved from httpwwwalzorgalzheimers_disease_facts_and_figuresasp

Alzheimerrsquos Association (2014) Medications for memory loss Retrieved from

httpwwwalzorgalzheimers_disease_standard_prescriptionsasp

Alzheimerrsquos Foundation of America (2014) About Alzheimerrsquos Retrieved from httpwwwalzfdnorgAboutAlzheimerscosthtml

American Geriatrics Society (2013) A guide to dementia diagnosis and treatment Retrieved from

httpwwwamericangeriatricsorgfilesdocumentsdementia_pocket_cardpdf

Buttaro T M Trybulski J Bailey P P amp Sandberg-Cook J (2013) Primary care A collaborative practice (4th ed) St Louis MO Elsevier

Centers for Medicare amp Medicaid Services (2013) Superseded local coverage determination (LCD) Hospice determining terminal status (L32015)

Retrieved from httpwwwcmsgovmedicare-coverage-databasedetailslcd-

detailsaspxLCDId=32015ampContrId=236ampver=14ampContrVer=2ampCntrctrSelected=2362ampCntrctr=236ampname=CGS+Administrators2c+LL

C+(150042c+HHH+MAC)amps=11ampDocType=Activeampbc=AggAAAIAAAAAAA3d3damp

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

Randomized Controlled Trial of Atorvastatin in Mild to Moderate Alzheimer Disease LEADe by Feldman et al in 2010

Inclusion 50-90 yo mild to mod AD ondonepezil 10mg daily for ge 3 m prior to screen LDL-C 95-195 mgdL caregiver present le 4 on modified Hachinski Ischemic Scale not requiring tx for dyslipidemia with any lipid-lowering agent cranial CT or MRI within 12 m consistent with AD medically stable no other AchEIs

RCT with double blind randomized withdrawal phase evaluating the efficacy and safety of atorvastatin in patients with mild to moderate ADDuration 72wks trial then 8-wk atorvastatin withdrawal phaseLocation Multicenter in 10 countries Total n = 640 MMSE 13-25 96 white On donepezil 10mgday ge3-m priorIntervention Atorvastatin 80mgday n=297 Age 740 plusmn 80 47 maleControl Matching placebo n= 317 Age 732 plusmn 87 49 male

Outcome measure change in cognition (ADAS-Cog) and global function (ADCS-CGIC) at 72 wks

By 3-m mean LDL-C had darr -724 mgdL (-502) in atorvastatin group amp -10 mgdL (-02) in placebo group and changes remained constant through 18-mTotal Chol amp Trig had larger darr in atorvastatin vs placebo groupDifference in Alzheimerrsquos Disease Assessment Scale ndash Cognitive Subscale (ADAS-cog) scores between groups showed a primary analysis that was not significant (p=026) and in the Alzheimerrsquos Disease Cooperative Study ndash Clinical Glocal Impression of Change (ADCS-CGIC) scores it was also not significant (p=073)

Conclusion Adding atorvastation on a background of donepezil use was not associated with any significant clinical benefits on either cognition or global functioning over 72 wks

bull Inclusions amp Exclusion criteria stated

bull Any serious adverse effects or deaths stated

bull FU at 3-month intervals through month 18

bull Population in currentstudy restricted to those who did not have an indication for statin treatment

bull Pts with significant concurrent cardiac cerebrovascular or PVD were excluded but could atorvastatin have benefited those pts with AD

bull Power analysis for sample size stated

bull P-value cut-off value listed

Level IIA (Single RCT)

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

A Randomized Double-blindPlacebo-controlled Trial of Simvastatin to Treat Alzheimer Disease by Sano et al in 2011

Inclusion gt 50 yo not on lipid lowering drugs mild to mod AD LDL gt80 mgdL or Trig lt500mgdL ge 3m of cholinesterase inhibitors and memantine use allowed medically stable

RCT double blind determining if the lipid-lowering agent simvastatin slows the progression of symptoms of AD in individuals with mild to moderate AD and normal lipid levelsDuration 18 monthsLocation Multicenter in USATotal n = 406 MMSE 12-26Intervention Simvastatin 20mgday x 6-wk then 40mgday n=204 Age 740 plusmn 96 588 femaleControl Matching placebo n= 202 Age 751 plusmn90 599 female

Outcome measure Rate of change in cognitive portion of the Alzheimerrsquos Disease Assessment Scale-Cognitive subscale (ADAS-Cog) score

Rate of change in ADAS-Cog score did not differ between groups (p=025 95 CI -00462 to 01680)No significant differences between groups in the secondary outcomes (MMSE Dependent Scale ADCS-ADL and NPI or the additional cognitive measures) or the CGICTotal Chol and LDL levels were significantly darr by the tx compared to placebo (plt0001) the darr was 23 in total Chol amp 37 in LDL HDL levels were also uarr wiith tx by 2 (p=002)Use of antidementia drugs alone or in combination did not change primary results

Conclusion Simvastatin had no effect on the progression of symptoms in individuals with mild to moderate AD despite significant lowering of cholesterol

bull Inclusions amp Exclusion criteria stated

bull Funding by NationalInstitute of Aging disclosed

bull FU at 3- 6- 12- and 18-m after baseline

bull Any serious adverse effects or deaths stated

bull P-value cut-off value not listed so assumption 005

bull This study did not address the utility of statin in pts who do not otherwise require lipid lowering at predementia stages MCI or presymptomatic AD

bull Power analysis for sample size stated

Level IIA (Single RCT)

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

Atorvastatin for the Treatment of Mild to Moderate Alzheimerrsquos Disease Preliminary Results by Sparks et al in 2005

Inclusion ge 51 yo mild to mod AD 9th

grade education le 4 on modified Hachinski Ischemic Scale and le 20 on GDS stable dose of cholinesterase inhibitors for ge 3 m allowed accompanied by caregiver good general health speak english cholesterol gt90mgdL

Double-blind placebo-controlled randomized trial to determine if tx w atorvastatin calcium affects cognitive andor behavioral decline in pts with mild to mod ADDuration 1yearLocation single site in USATotal n = 63 MMSE 12-28Intervention Atorvastatin 80mgday n=32 Age 7815 plusmn 13 375 femaleControl Matching placebo n= 31 Age 789 plusmn 12 355 female

Outcome measure change in Alzheimerrsquos Disease Assessment Scale-cognitive subscale (ADAS-Cog) amp the Clinical Global Impression of Change Scale (CGIS) scores

Both groups showed deterioration on the ADAS-cog at 3-m Placebo group continued to deteriorate app 1 pointquarter Difference in ADAS-cog scores between groups was significant at 6-m (P=0003) amp 12-m (P=0055)A trend for a difference on the CGIC between groups was achieved at both 9 (P=0058) and 12-m (P=007)MMSE score in atorvastatin group showed limited improvement after 3-m visit amp the difference between groups was not significant (Pgt10) Atorvastatin Tx had significant darr in total Chol LDL VLDL compared to placebo group (Plt01)

Conclusion Atorvastatin tx may be of some clinical benefit amp could be established as an effective therapy for AD if the current findings are substantiated by a much larger multicenter trial (Promising results)

bull Inclusions amp Exclusion criteria stated

bull FU at 3- 6- 9- and 12-month

bull Pilot studybull Very small sample

groups ndash started with 98 participants 71 were eligible 67 randomized amp 63 completed 3-m visit amp were considered eligible

bull No power analysisbull Study is 9 years oldbull Results may or may not

be applicable to other types of statins

Level IIA (Single RCT)

SUMMARY OF LITERATURE amp TREATMENT GUIDELINES

bull Primary goal improve QOL and maximize functional performance by enhancing cognition and addressing mood and behavior

bull AChEI for mild to moderate AD

bull Memantidine + AChEI (Aricept) for moderate to severe AD

bull AVOID anticholinergic medications amp LIMIT prn psychotropic medication use

bull Consider referral to hospice if FAST (Functional Assessment Staging Scale) =7

bull Statins show NO CLEAR BENEFITS in slowing the progression of dementia

bull RCTs with larger populations and longer time frame needed

bull One study was gt5 years due to limited meta-analysis or systematic reviews to support PICO

HEALTH PROMOTION MODEL Katharine Kolcabarsquos Comfort Theory

bull Born and educated in Cleveland Ohio

bull In 1987 RN to MSN degree with a specialty in gerontology Maintained head nurse position on a dementia unit while in graduate school and began theorizing about comfort

bull While pursuing her doctorate in nursing she used her course work to further develop her theory over a 10 year period

bull Extensive publications compiled in her book Comfort Theory and Practice

bull Comfort means to strengthen greatly

bull It exists in three forms Relief Ease amp Transcendence

bull Four contexts in which comfort is experienced Physical Psychospiritual Sociocultural amp Environmental

CRITIQUE

STRENGTHS Applicable to other disciplines amp settings Adaptable to each patient situation or scenario Nurse works closely with the patient Patients can engage in HSB once comfort is achieved Provides direction for quality improvement Comfort rounds with pts amp work environment

WEAKNESS Enhanced comfort does not always produce the expected outcome like health seeking behaviors Places nurses at center of concept

APPLICATION TO PRACTICE Nurses play a critical role in helping patients achieve comfort and engage in health-seeking behaviors Nurses can impact patientrsquos quality care Nurses can work with patients to come up with interventions to impact their comfort and evaluate those interventions Nurses can impact institutional integrity

APPLICATION to CASE

Health Care NeedsFeeding Assistance uarr assistance with ADLs weight loss difficulty swallowingComfort InterventionsReview med list with family educate staff on ptrsquos uarr needs feeding assistance aspiration precautions address hospice eligibility include pt in activities toileting scheduleIntervening VariablesAdvanced age terminal illness

support system (wifePOA) assisted livingEnhanced ComfortJT is being strengthened through having comfort needs addressedHealth Seeking BehaviorsWeight gain acceptancewife is more trusting and calmer peaceful deathInstitutional IntegrityApplication of CT to other cases staff investment in implementing theory

JTrsquos PLAN OF CAREDIFFERENTIALS VaD Dementia with Lewy Bodies Frontotemporal dementiaEVALUATION Comprehensive physical and neurologic exam Assess functional status and evaluate mental status Labs CBC TSH B12 Folate metabolic screenPLANbull STOP Simvastatin 10mg PO bedtime amp Change Citalopram to 20mg PO QDbull No hospice referral ndash Needs to have lt 6m To livebull FAST ge 7A amp ASPNA or upper UTI or septicemia or multiple PU (stage 34) or

recurrent fever on ABX or weight loss gt10 in past 6 m Alb lt25bull Review Advance directive with POAbull Involve and encourage JT to participates in cares and activitiesbull One can of Ensure with every mealbull Aspiration precautionsbull Record weekly weightbull FU in 3-4 weeks or earlier if status change

REFERENCES

Alzheimerrsquos Association (2014) Alzheimerrsquos facts and figures Retrieved from httpwwwalzorgalzheimers_disease_facts_and_figuresasp

Alzheimerrsquos Association (2014) Medications for memory loss Retrieved from

httpwwwalzorgalzheimers_disease_standard_prescriptionsasp

Alzheimerrsquos Foundation of America (2014) About Alzheimerrsquos Retrieved from httpwwwalzfdnorgAboutAlzheimerscosthtml

American Geriatrics Society (2013) A guide to dementia diagnosis and treatment Retrieved from

httpwwwamericangeriatricsorgfilesdocumentsdementia_pocket_cardpdf

Buttaro T M Trybulski J Bailey P P amp Sandberg-Cook J (2013) Primary care A collaborative practice (4th ed) St Louis MO Elsevier

Centers for Medicare amp Medicaid Services (2013) Superseded local coverage determination (LCD) Hospice determining terminal status (L32015)

Retrieved from httpwwwcmsgovmedicare-coverage-databasedetailslcd-

detailsaspxLCDId=32015ampContrId=236ampver=14ampContrVer=2ampCntrctrSelected=2362ampCntrctr=236ampname=CGS+Administrators2c+LL

C+(150042c+HHH+MAC)amps=11ampDocType=Activeampbc=AggAAAIAAAAAAA3d3damp

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

A Randomized Double-blindPlacebo-controlled Trial of Simvastatin to Treat Alzheimer Disease by Sano et al in 2011

Inclusion gt 50 yo not on lipid lowering drugs mild to mod AD LDL gt80 mgdL or Trig lt500mgdL ge 3m of cholinesterase inhibitors and memantine use allowed medically stable

RCT double blind determining if the lipid-lowering agent simvastatin slows the progression of symptoms of AD in individuals with mild to moderate AD and normal lipid levelsDuration 18 monthsLocation Multicenter in USATotal n = 406 MMSE 12-26Intervention Simvastatin 20mgday x 6-wk then 40mgday n=204 Age 740 plusmn 96 588 femaleControl Matching placebo n= 202 Age 751 plusmn90 599 female

Outcome measure Rate of change in cognitive portion of the Alzheimerrsquos Disease Assessment Scale-Cognitive subscale (ADAS-Cog) score

Rate of change in ADAS-Cog score did not differ between groups (p=025 95 CI -00462 to 01680)No significant differences between groups in the secondary outcomes (MMSE Dependent Scale ADCS-ADL and NPI or the additional cognitive measures) or the CGICTotal Chol and LDL levels were significantly darr by the tx compared to placebo (plt0001) the darr was 23 in total Chol amp 37 in LDL HDL levels were also uarr wiith tx by 2 (p=002)Use of antidementia drugs alone or in combination did not change primary results

Conclusion Simvastatin had no effect on the progression of symptoms in individuals with mild to moderate AD despite significant lowering of cholesterol

bull Inclusions amp Exclusion criteria stated

bull Funding by NationalInstitute of Aging disclosed

bull FU at 3- 6- 12- and 18-m after baseline

bull Any serious adverse effects or deaths stated

bull P-value cut-off value not listed so assumption 005

bull This study did not address the utility of statin in pts who do not otherwise require lipid lowering at predementia stages MCI or presymptomatic AD

bull Power analysis for sample size stated

Level IIA (Single RCT)

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

Atorvastatin for the Treatment of Mild to Moderate Alzheimerrsquos Disease Preliminary Results by Sparks et al in 2005

Inclusion ge 51 yo mild to mod AD 9th

grade education le 4 on modified Hachinski Ischemic Scale and le 20 on GDS stable dose of cholinesterase inhibitors for ge 3 m allowed accompanied by caregiver good general health speak english cholesterol gt90mgdL

Double-blind placebo-controlled randomized trial to determine if tx w atorvastatin calcium affects cognitive andor behavioral decline in pts with mild to mod ADDuration 1yearLocation single site in USATotal n = 63 MMSE 12-28Intervention Atorvastatin 80mgday n=32 Age 7815 plusmn 13 375 femaleControl Matching placebo n= 31 Age 789 plusmn 12 355 female

Outcome measure change in Alzheimerrsquos Disease Assessment Scale-cognitive subscale (ADAS-Cog) amp the Clinical Global Impression of Change Scale (CGIS) scores

Both groups showed deterioration on the ADAS-cog at 3-m Placebo group continued to deteriorate app 1 pointquarter Difference in ADAS-cog scores between groups was significant at 6-m (P=0003) amp 12-m (P=0055)A trend for a difference on the CGIC between groups was achieved at both 9 (P=0058) and 12-m (P=007)MMSE score in atorvastatin group showed limited improvement after 3-m visit amp the difference between groups was not significant (Pgt10) Atorvastatin Tx had significant darr in total Chol LDL VLDL compared to placebo group (Plt01)

Conclusion Atorvastatin tx may be of some clinical benefit amp could be established as an effective therapy for AD if the current findings are substantiated by a much larger multicenter trial (Promising results)

bull Inclusions amp Exclusion criteria stated

bull FU at 3- 6- 9- and 12-month

bull Pilot studybull Very small sample

groups ndash started with 98 participants 71 were eligible 67 randomized amp 63 completed 3-m visit amp were considered eligible

bull No power analysisbull Study is 9 years oldbull Results may or may not

be applicable to other types of statins

Level IIA (Single RCT)

SUMMARY OF LITERATURE amp TREATMENT GUIDELINES

bull Primary goal improve QOL and maximize functional performance by enhancing cognition and addressing mood and behavior

bull AChEI for mild to moderate AD

bull Memantidine + AChEI (Aricept) for moderate to severe AD

bull AVOID anticholinergic medications amp LIMIT prn psychotropic medication use

bull Consider referral to hospice if FAST (Functional Assessment Staging Scale) =7

bull Statins show NO CLEAR BENEFITS in slowing the progression of dementia

bull RCTs with larger populations and longer time frame needed

bull One study was gt5 years due to limited meta-analysis or systematic reviews to support PICO

HEALTH PROMOTION MODEL Katharine Kolcabarsquos Comfort Theory

bull Born and educated in Cleveland Ohio

bull In 1987 RN to MSN degree with a specialty in gerontology Maintained head nurse position on a dementia unit while in graduate school and began theorizing about comfort

bull While pursuing her doctorate in nursing she used her course work to further develop her theory over a 10 year period

bull Extensive publications compiled in her book Comfort Theory and Practice

bull Comfort means to strengthen greatly

bull It exists in three forms Relief Ease amp Transcendence

bull Four contexts in which comfort is experienced Physical Psychospiritual Sociocultural amp Environmental

CRITIQUE

STRENGTHS Applicable to other disciplines amp settings Adaptable to each patient situation or scenario Nurse works closely with the patient Patients can engage in HSB once comfort is achieved Provides direction for quality improvement Comfort rounds with pts amp work environment

WEAKNESS Enhanced comfort does not always produce the expected outcome like health seeking behaviors Places nurses at center of concept

APPLICATION TO PRACTICE Nurses play a critical role in helping patients achieve comfort and engage in health-seeking behaviors Nurses can impact patientrsquos quality care Nurses can work with patients to come up with interventions to impact their comfort and evaluate those interventions Nurses can impact institutional integrity

APPLICATION to CASE

Health Care NeedsFeeding Assistance uarr assistance with ADLs weight loss difficulty swallowingComfort InterventionsReview med list with family educate staff on ptrsquos uarr needs feeding assistance aspiration precautions address hospice eligibility include pt in activities toileting scheduleIntervening VariablesAdvanced age terminal illness

support system (wifePOA) assisted livingEnhanced ComfortJT is being strengthened through having comfort needs addressedHealth Seeking BehaviorsWeight gain acceptancewife is more trusting and calmer peaceful deathInstitutional IntegrityApplication of CT to other cases staff investment in implementing theory

JTrsquos PLAN OF CAREDIFFERENTIALS VaD Dementia with Lewy Bodies Frontotemporal dementiaEVALUATION Comprehensive physical and neurologic exam Assess functional status and evaluate mental status Labs CBC TSH B12 Folate metabolic screenPLANbull STOP Simvastatin 10mg PO bedtime amp Change Citalopram to 20mg PO QDbull No hospice referral ndash Needs to have lt 6m To livebull FAST ge 7A amp ASPNA or upper UTI or septicemia or multiple PU (stage 34) or

recurrent fever on ABX or weight loss gt10 in past 6 m Alb lt25bull Review Advance directive with POAbull Involve and encourage JT to participates in cares and activitiesbull One can of Ensure with every mealbull Aspiration precautionsbull Record weekly weightbull FU in 3-4 weeks or earlier if status change

REFERENCES

Alzheimerrsquos Association (2014) Alzheimerrsquos facts and figures Retrieved from httpwwwalzorgalzheimers_disease_facts_and_figuresasp

Alzheimerrsquos Association (2014) Medications for memory loss Retrieved from

httpwwwalzorgalzheimers_disease_standard_prescriptionsasp

Alzheimerrsquos Foundation of America (2014) About Alzheimerrsquos Retrieved from httpwwwalzfdnorgAboutAlzheimerscosthtml

American Geriatrics Society (2013) A guide to dementia diagnosis and treatment Retrieved from

httpwwwamericangeriatricsorgfilesdocumentsdementia_pocket_cardpdf

Buttaro T M Trybulski J Bailey P P amp Sandberg-Cook J (2013) Primary care A collaborative practice (4th ed) St Louis MO Elsevier

Centers for Medicare amp Medicaid Services (2013) Superseded local coverage determination (LCD) Hospice determining terminal status (L32015)

Retrieved from httpwwwcmsgovmedicare-coverage-databasedetailslcd-

detailsaspxLCDId=32015ampContrId=236ampver=14ampContrVer=2ampCntrctrSelected=2362ampCntrctr=236ampname=CGS+Administrators2c+LL

C+(150042c+HHH+MAC)amps=11ampDocType=Activeampbc=AggAAAIAAAAAAA3d3damp

Article Authors Date amp Inclusion

Description Subjects Goals Results Strengths amp Limitations Level of Evidence

Atorvastatin for the Treatment of Mild to Moderate Alzheimerrsquos Disease Preliminary Results by Sparks et al in 2005

Inclusion ge 51 yo mild to mod AD 9th

grade education le 4 on modified Hachinski Ischemic Scale and le 20 on GDS stable dose of cholinesterase inhibitors for ge 3 m allowed accompanied by caregiver good general health speak english cholesterol gt90mgdL

Double-blind placebo-controlled randomized trial to determine if tx w atorvastatin calcium affects cognitive andor behavioral decline in pts with mild to mod ADDuration 1yearLocation single site in USATotal n = 63 MMSE 12-28Intervention Atorvastatin 80mgday n=32 Age 7815 plusmn 13 375 femaleControl Matching placebo n= 31 Age 789 plusmn 12 355 female

Outcome measure change in Alzheimerrsquos Disease Assessment Scale-cognitive subscale (ADAS-Cog) amp the Clinical Global Impression of Change Scale (CGIS) scores

Both groups showed deterioration on the ADAS-cog at 3-m Placebo group continued to deteriorate app 1 pointquarter Difference in ADAS-cog scores between groups was significant at 6-m (P=0003) amp 12-m (P=0055)A trend for a difference on the CGIC between groups was achieved at both 9 (P=0058) and 12-m (P=007)MMSE score in atorvastatin group showed limited improvement after 3-m visit amp the difference between groups was not significant (Pgt10) Atorvastatin Tx had significant darr in total Chol LDL VLDL compared to placebo group (Plt01)

Conclusion Atorvastatin tx may be of some clinical benefit amp could be established as an effective therapy for AD if the current findings are substantiated by a much larger multicenter trial (Promising results)

bull Inclusions amp Exclusion criteria stated

bull FU at 3- 6- 9- and 12-month

bull Pilot studybull Very small sample

groups ndash started with 98 participants 71 were eligible 67 randomized amp 63 completed 3-m visit amp were considered eligible

bull No power analysisbull Study is 9 years oldbull Results may or may not

be applicable to other types of statins

Level IIA (Single RCT)

SUMMARY OF LITERATURE amp TREATMENT GUIDELINES

bull Primary goal improve QOL and maximize functional performance by enhancing cognition and addressing mood and behavior

bull AChEI for mild to moderate AD

bull Memantidine + AChEI (Aricept) for moderate to severe AD

bull AVOID anticholinergic medications amp LIMIT prn psychotropic medication use

bull Consider referral to hospice if FAST (Functional Assessment Staging Scale) =7

bull Statins show NO CLEAR BENEFITS in slowing the progression of dementia

bull RCTs with larger populations and longer time frame needed

bull One study was gt5 years due to limited meta-analysis or systematic reviews to support PICO

HEALTH PROMOTION MODEL Katharine Kolcabarsquos Comfort Theory

bull Born and educated in Cleveland Ohio

bull In 1987 RN to MSN degree with a specialty in gerontology Maintained head nurse position on a dementia unit while in graduate school and began theorizing about comfort

bull While pursuing her doctorate in nursing she used her course work to further develop her theory over a 10 year period

bull Extensive publications compiled in her book Comfort Theory and Practice

bull Comfort means to strengthen greatly

bull It exists in three forms Relief Ease amp Transcendence

bull Four contexts in which comfort is experienced Physical Psychospiritual Sociocultural amp Environmental

CRITIQUE

STRENGTHS Applicable to other disciplines amp settings Adaptable to each patient situation or scenario Nurse works closely with the patient Patients can engage in HSB once comfort is achieved Provides direction for quality improvement Comfort rounds with pts amp work environment

WEAKNESS Enhanced comfort does not always produce the expected outcome like health seeking behaviors Places nurses at center of concept

APPLICATION TO PRACTICE Nurses play a critical role in helping patients achieve comfort and engage in health-seeking behaviors Nurses can impact patientrsquos quality care Nurses can work with patients to come up with interventions to impact their comfort and evaluate those interventions Nurses can impact institutional integrity

APPLICATION to CASE

Health Care NeedsFeeding Assistance uarr assistance with ADLs weight loss difficulty swallowingComfort InterventionsReview med list with family educate staff on ptrsquos uarr needs feeding assistance aspiration precautions address hospice eligibility include pt in activities toileting scheduleIntervening VariablesAdvanced age terminal illness

support system (wifePOA) assisted livingEnhanced ComfortJT is being strengthened through having comfort needs addressedHealth Seeking BehaviorsWeight gain acceptancewife is more trusting and calmer peaceful deathInstitutional IntegrityApplication of CT to other cases staff investment in implementing theory

JTrsquos PLAN OF CAREDIFFERENTIALS VaD Dementia with Lewy Bodies Frontotemporal dementiaEVALUATION Comprehensive physical and neurologic exam Assess functional status and evaluate mental status Labs CBC TSH B12 Folate metabolic screenPLANbull STOP Simvastatin 10mg PO bedtime amp Change Citalopram to 20mg PO QDbull No hospice referral ndash Needs to have lt 6m To livebull FAST ge 7A amp ASPNA or upper UTI or septicemia or multiple PU (stage 34) or

recurrent fever on ABX or weight loss gt10 in past 6 m Alb lt25bull Review Advance directive with POAbull Involve and encourage JT to participates in cares and activitiesbull One can of Ensure with every mealbull Aspiration precautionsbull Record weekly weightbull FU in 3-4 weeks or earlier if status change

REFERENCES

Alzheimerrsquos Association (2014) Alzheimerrsquos facts and figures Retrieved from httpwwwalzorgalzheimers_disease_facts_and_figuresasp

Alzheimerrsquos Association (2014) Medications for memory loss Retrieved from

httpwwwalzorgalzheimers_disease_standard_prescriptionsasp

Alzheimerrsquos Foundation of America (2014) About Alzheimerrsquos Retrieved from httpwwwalzfdnorgAboutAlzheimerscosthtml

American Geriatrics Society (2013) A guide to dementia diagnosis and treatment Retrieved from

httpwwwamericangeriatricsorgfilesdocumentsdementia_pocket_cardpdf

Buttaro T M Trybulski J Bailey P P amp Sandberg-Cook J (2013) Primary care A collaborative practice (4th ed) St Louis MO Elsevier

Centers for Medicare amp Medicaid Services (2013) Superseded local coverage determination (LCD) Hospice determining terminal status (L32015)

Retrieved from httpwwwcmsgovmedicare-coverage-databasedetailslcd-

detailsaspxLCDId=32015ampContrId=236ampver=14ampContrVer=2ampCntrctrSelected=2362ampCntrctr=236ampname=CGS+Administrators2c+LL

C+(150042c+HHH+MAC)amps=11ampDocType=Activeampbc=AggAAAIAAAAAAA3d3damp

SUMMARY OF LITERATURE amp TREATMENT GUIDELINES

bull Primary goal improve QOL and maximize functional performance by enhancing cognition and addressing mood and behavior

bull AChEI for mild to moderate AD

bull Memantidine + AChEI (Aricept) for moderate to severe AD

bull AVOID anticholinergic medications amp LIMIT prn psychotropic medication use

bull Consider referral to hospice if FAST (Functional Assessment Staging Scale) =7

bull Statins show NO CLEAR BENEFITS in slowing the progression of dementia

bull RCTs with larger populations and longer time frame needed

bull One study was gt5 years due to limited meta-analysis or systematic reviews to support PICO

HEALTH PROMOTION MODEL Katharine Kolcabarsquos Comfort Theory

bull Born and educated in Cleveland Ohio

bull In 1987 RN to MSN degree with a specialty in gerontology Maintained head nurse position on a dementia unit while in graduate school and began theorizing about comfort

bull While pursuing her doctorate in nursing she used her course work to further develop her theory over a 10 year period

bull Extensive publications compiled in her book Comfort Theory and Practice

bull Comfort means to strengthen greatly

bull It exists in three forms Relief Ease amp Transcendence

bull Four contexts in which comfort is experienced Physical Psychospiritual Sociocultural amp Environmental

CRITIQUE

STRENGTHS Applicable to other disciplines amp settings Adaptable to each patient situation or scenario Nurse works closely with the patient Patients can engage in HSB once comfort is achieved Provides direction for quality improvement Comfort rounds with pts amp work environment

WEAKNESS Enhanced comfort does not always produce the expected outcome like health seeking behaviors Places nurses at center of concept

APPLICATION TO PRACTICE Nurses play a critical role in helping patients achieve comfort and engage in health-seeking behaviors Nurses can impact patientrsquos quality care Nurses can work with patients to come up with interventions to impact their comfort and evaluate those interventions Nurses can impact institutional integrity

APPLICATION to CASE

Health Care NeedsFeeding Assistance uarr assistance with ADLs weight loss difficulty swallowingComfort InterventionsReview med list with family educate staff on ptrsquos uarr needs feeding assistance aspiration precautions address hospice eligibility include pt in activities toileting scheduleIntervening VariablesAdvanced age terminal illness

support system (wifePOA) assisted livingEnhanced ComfortJT is being strengthened through having comfort needs addressedHealth Seeking BehaviorsWeight gain acceptancewife is more trusting and calmer peaceful deathInstitutional IntegrityApplication of CT to other cases staff investment in implementing theory

JTrsquos PLAN OF CAREDIFFERENTIALS VaD Dementia with Lewy Bodies Frontotemporal dementiaEVALUATION Comprehensive physical and neurologic exam Assess functional status and evaluate mental status Labs CBC TSH B12 Folate metabolic screenPLANbull STOP Simvastatin 10mg PO bedtime amp Change Citalopram to 20mg PO QDbull No hospice referral ndash Needs to have lt 6m To livebull FAST ge 7A amp ASPNA or upper UTI or septicemia or multiple PU (stage 34) or

recurrent fever on ABX or weight loss gt10 in past 6 m Alb lt25bull Review Advance directive with POAbull Involve and encourage JT to participates in cares and activitiesbull One can of Ensure with every mealbull Aspiration precautionsbull Record weekly weightbull FU in 3-4 weeks or earlier if status change

REFERENCES

Alzheimerrsquos Association (2014) Alzheimerrsquos facts and figures Retrieved from httpwwwalzorgalzheimers_disease_facts_and_figuresasp

Alzheimerrsquos Association (2014) Medications for memory loss Retrieved from

httpwwwalzorgalzheimers_disease_standard_prescriptionsasp

Alzheimerrsquos Foundation of America (2014) About Alzheimerrsquos Retrieved from httpwwwalzfdnorgAboutAlzheimerscosthtml

American Geriatrics Society (2013) A guide to dementia diagnosis and treatment Retrieved from

httpwwwamericangeriatricsorgfilesdocumentsdementia_pocket_cardpdf

Buttaro T M Trybulski J Bailey P P amp Sandberg-Cook J (2013) Primary care A collaborative practice (4th ed) St Louis MO Elsevier

Centers for Medicare amp Medicaid Services (2013) Superseded local coverage determination (LCD) Hospice determining terminal status (L32015)

Retrieved from httpwwwcmsgovmedicare-coverage-databasedetailslcd-

detailsaspxLCDId=32015ampContrId=236ampver=14ampContrVer=2ampCntrctrSelected=2362ampCntrctr=236ampname=CGS+Administrators2c+LL

C+(150042c+HHH+MAC)amps=11ampDocType=Activeampbc=AggAAAIAAAAAAA3d3damp

HEALTH PROMOTION MODEL Katharine Kolcabarsquos Comfort Theory

bull Born and educated in Cleveland Ohio

bull In 1987 RN to MSN degree with a specialty in gerontology Maintained head nurse position on a dementia unit while in graduate school and began theorizing about comfort

bull While pursuing her doctorate in nursing she used her course work to further develop her theory over a 10 year period

bull Extensive publications compiled in her book Comfort Theory and Practice

bull Comfort means to strengthen greatly

bull It exists in three forms Relief Ease amp Transcendence

bull Four contexts in which comfort is experienced Physical Psychospiritual Sociocultural amp Environmental

CRITIQUE

STRENGTHS Applicable to other disciplines amp settings Adaptable to each patient situation or scenario Nurse works closely with the patient Patients can engage in HSB once comfort is achieved Provides direction for quality improvement Comfort rounds with pts amp work environment

WEAKNESS Enhanced comfort does not always produce the expected outcome like health seeking behaviors Places nurses at center of concept

APPLICATION TO PRACTICE Nurses play a critical role in helping patients achieve comfort and engage in health-seeking behaviors Nurses can impact patientrsquos quality care Nurses can work with patients to come up with interventions to impact their comfort and evaluate those interventions Nurses can impact institutional integrity

APPLICATION to CASE

Health Care NeedsFeeding Assistance uarr assistance with ADLs weight loss difficulty swallowingComfort InterventionsReview med list with family educate staff on ptrsquos uarr needs feeding assistance aspiration precautions address hospice eligibility include pt in activities toileting scheduleIntervening VariablesAdvanced age terminal illness

support system (wifePOA) assisted livingEnhanced ComfortJT is being strengthened through having comfort needs addressedHealth Seeking BehaviorsWeight gain acceptancewife is more trusting and calmer peaceful deathInstitutional IntegrityApplication of CT to other cases staff investment in implementing theory

JTrsquos PLAN OF CAREDIFFERENTIALS VaD Dementia with Lewy Bodies Frontotemporal dementiaEVALUATION Comprehensive physical and neurologic exam Assess functional status and evaluate mental status Labs CBC TSH B12 Folate metabolic screenPLANbull STOP Simvastatin 10mg PO bedtime amp Change Citalopram to 20mg PO QDbull No hospice referral ndash Needs to have lt 6m To livebull FAST ge 7A amp ASPNA or upper UTI or septicemia or multiple PU (stage 34) or

recurrent fever on ABX or weight loss gt10 in past 6 m Alb lt25bull Review Advance directive with POAbull Involve and encourage JT to participates in cares and activitiesbull One can of Ensure with every mealbull Aspiration precautionsbull Record weekly weightbull FU in 3-4 weeks or earlier if status change

REFERENCES

Alzheimerrsquos Association (2014) Alzheimerrsquos facts and figures Retrieved from httpwwwalzorgalzheimers_disease_facts_and_figuresasp

Alzheimerrsquos Association (2014) Medications for memory loss Retrieved from

httpwwwalzorgalzheimers_disease_standard_prescriptionsasp

Alzheimerrsquos Foundation of America (2014) About Alzheimerrsquos Retrieved from httpwwwalzfdnorgAboutAlzheimerscosthtml

American Geriatrics Society (2013) A guide to dementia diagnosis and treatment Retrieved from

httpwwwamericangeriatricsorgfilesdocumentsdementia_pocket_cardpdf

Buttaro T M Trybulski J Bailey P P amp Sandberg-Cook J (2013) Primary care A collaborative practice (4th ed) St Louis MO Elsevier

Centers for Medicare amp Medicaid Services (2013) Superseded local coverage determination (LCD) Hospice determining terminal status (L32015)

Retrieved from httpwwwcmsgovmedicare-coverage-databasedetailslcd-

detailsaspxLCDId=32015ampContrId=236ampver=14ampContrVer=2ampCntrctrSelected=2362ampCntrctr=236ampname=CGS+Administrators2c+LL

C+(150042c+HHH+MAC)amps=11ampDocType=Activeampbc=AggAAAIAAAAAAA3d3damp

CRITIQUE

STRENGTHS Applicable to other disciplines amp settings Adaptable to each patient situation or scenario Nurse works closely with the patient Patients can engage in HSB once comfort is achieved Provides direction for quality improvement Comfort rounds with pts amp work environment

WEAKNESS Enhanced comfort does not always produce the expected outcome like health seeking behaviors Places nurses at center of concept

APPLICATION TO PRACTICE Nurses play a critical role in helping patients achieve comfort and engage in health-seeking behaviors Nurses can impact patientrsquos quality care Nurses can work with patients to come up with interventions to impact their comfort and evaluate those interventions Nurses can impact institutional integrity

APPLICATION to CASE

Health Care NeedsFeeding Assistance uarr assistance with ADLs weight loss difficulty swallowingComfort InterventionsReview med list with family educate staff on ptrsquos uarr needs feeding assistance aspiration precautions address hospice eligibility include pt in activities toileting scheduleIntervening VariablesAdvanced age terminal illness

support system (wifePOA) assisted livingEnhanced ComfortJT is being strengthened through having comfort needs addressedHealth Seeking BehaviorsWeight gain acceptancewife is more trusting and calmer peaceful deathInstitutional IntegrityApplication of CT to other cases staff investment in implementing theory

JTrsquos PLAN OF CAREDIFFERENTIALS VaD Dementia with Lewy Bodies Frontotemporal dementiaEVALUATION Comprehensive physical and neurologic exam Assess functional status and evaluate mental status Labs CBC TSH B12 Folate metabolic screenPLANbull STOP Simvastatin 10mg PO bedtime amp Change Citalopram to 20mg PO QDbull No hospice referral ndash Needs to have lt 6m To livebull FAST ge 7A amp ASPNA or upper UTI or septicemia or multiple PU (stage 34) or

recurrent fever on ABX or weight loss gt10 in past 6 m Alb lt25bull Review Advance directive with POAbull Involve and encourage JT to participates in cares and activitiesbull One can of Ensure with every mealbull Aspiration precautionsbull Record weekly weightbull FU in 3-4 weeks or earlier if status change

REFERENCES

Alzheimerrsquos Association (2014) Alzheimerrsquos facts and figures Retrieved from httpwwwalzorgalzheimers_disease_facts_and_figuresasp

Alzheimerrsquos Association (2014) Medications for memory loss Retrieved from

httpwwwalzorgalzheimers_disease_standard_prescriptionsasp

Alzheimerrsquos Foundation of America (2014) About Alzheimerrsquos Retrieved from httpwwwalzfdnorgAboutAlzheimerscosthtml

American Geriatrics Society (2013) A guide to dementia diagnosis and treatment Retrieved from

httpwwwamericangeriatricsorgfilesdocumentsdementia_pocket_cardpdf

Buttaro T M Trybulski J Bailey P P amp Sandberg-Cook J (2013) Primary care A collaborative practice (4th ed) St Louis MO Elsevier

Centers for Medicare amp Medicaid Services (2013) Superseded local coverage determination (LCD) Hospice determining terminal status (L32015)

Retrieved from httpwwwcmsgovmedicare-coverage-databasedetailslcd-

detailsaspxLCDId=32015ampContrId=236ampver=14ampContrVer=2ampCntrctrSelected=2362ampCntrctr=236ampname=CGS+Administrators2c+LL

C+(150042c+HHH+MAC)amps=11ampDocType=Activeampbc=AggAAAIAAAAAAA3d3damp

APPLICATION to CASE

Health Care NeedsFeeding Assistance uarr assistance with ADLs weight loss difficulty swallowingComfort InterventionsReview med list with family educate staff on ptrsquos uarr needs feeding assistance aspiration precautions address hospice eligibility include pt in activities toileting scheduleIntervening VariablesAdvanced age terminal illness

support system (wifePOA) assisted livingEnhanced ComfortJT is being strengthened through having comfort needs addressedHealth Seeking BehaviorsWeight gain acceptancewife is more trusting and calmer peaceful deathInstitutional IntegrityApplication of CT to other cases staff investment in implementing theory

JTrsquos PLAN OF CAREDIFFERENTIALS VaD Dementia with Lewy Bodies Frontotemporal dementiaEVALUATION Comprehensive physical and neurologic exam Assess functional status and evaluate mental status Labs CBC TSH B12 Folate metabolic screenPLANbull STOP Simvastatin 10mg PO bedtime amp Change Citalopram to 20mg PO QDbull No hospice referral ndash Needs to have lt 6m To livebull FAST ge 7A amp ASPNA or upper UTI or septicemia or multiple PU (stage 34) or

recurrent fever on ABX or weight loss gt10 in past 6 m Alb lt25bull Review Advance directive with POAbull Involve and encourage JT to participates in cares and activitiesbull One can of Ensure with every mealbull Aspiration precautionsbull Record weekly weightbull FU in 3-4 weeks or earlier if status change

REFERENCES

Alzheimerrsquos Association (2014) Alzheimerrsquos facts and figures Retrieved from httpwwwalzorgalzheimers_disease_facts_and_figuresasp

Alzheimerrsquos Association (2014) Medications for memory loss Retrieved from

httpwwwalzorgalzheimers_disease_standard_prescriptionsasp

Alzheimerrsquos Foundation of America (2014) About Alzheimerrsquos Retrieved from httpwwwalzfdnorgAboutAlzheimerscosthtml

American Geriatrics Society (2013) A guide to dementia diagnosis and treatment Retrieved from

httpwwwamericangeriatricsorgfilesdocumentsdementia_pocket_cardpdf

Buttaro T M Trybulski J Bailey P P amp Sandberg-Cook J (2013) Primary care A collaborative practice (4th ed) St Louis MO Elsevier

Centers for Medicare amp Medicaid Services (2013) Superseded local coverage determination (LCD) Hospice determining terminal status (L32015)

Retrieved from httpwwwcmsgovmedicare-coverage-databasedetailslcd-

detailsaspxLCDId=32015ampContrId=236ampver=14ampContrVer=2ampCntrctrSelected=2362ampCntrctr=236ampname=CGS+Administrators2c+LL

C+(150042c+HHH+MAC)amps=11ampDocType=Activeampbc=AggAAAIAAAAAAA3d3damp

JTrsquos PLAN OF CAREDIFFERENTIALS VaD Dementia with Lewy Bodies Frontotemporal dementiaEVALUATION Comprehensive physical and neurologic exam Assess functional status and evaluate mental status Labs CBC TSH B12 Folate metabolic screenPLANbull STOP Simvastatin 10mg PO bedtime amp Change Citalopram to 20mg PO QDbull No hospice referral ndash Needs to have lt 6m To livebull FAST ge 7A amp ASPNA or upper UTI or septicemia or multiple PU (stage 34) or

recurrent fever on ABX or weight loss gt10 in past 6 m Alb lt25bull Review Advance directive with POAbull Involve and encourage JT to participates in cares and activitiesbull One can of Ensure with every mealbull Aspiration precautionsbull Record weekly weightbull FU in 3-4 weeks or earlier if status change

REFERENCES

Alzheimerrsquos Association (2014) Alzheimerrsquos facts and figures Retrieved from httpwwwalzorgalzheimers_disease_facts_and_figuresasp

Alzheimerrsquos Association (2014) Medications for memory loss Retrieved from

httpwwwalzorgalzheimers_disease_standard_prescriptionsasp

Alzheimerrsquos Foundation of America (2014) About Alzheimerrsquos Retrieved from httpwwwalzfdnorgAboutAlzheimerscosthtml

American Geriatrics Society (2013) A guide to dementia diagnosis and treatment Retrieved from

httpwwwamericangeriatricsorgfilesdocumentsdementia_pocket_cardpdf

Buttaro T M Trybulski J Bailey P P amp Sandberg-Cook J (2013) Primary care A collaborative practice (4th ed) St Louis MO Elsevier

Centers for Medicare amp Medicaid Services (2013) Superseded local coverage determination (LCD) Hospice determining terminal status (L32015)

Retrieved from httpwwwcmsgovmedicare-coverage-databasedetailslcd-

detailsaspxLCDId=32015ampContrId=236ampver=14ampContrVer=2ampCntrctrSelected=2362ampCntrctr=236ampname=CGS+Administrators2c+LL

C+(150042c+HHH+MAC)amps=11ampDocType=Activeampbc=AggAAAIAAAAAAA3d3damp

REFERENCES

Alzheimerrsquos Association (2014) Alzheimerrsquos facts and figures Retrieved from httpwwwalzorgalzheimers_disease_facts_and_figuresasp

Alzheimerrsquos Association (2014) Medications for memory loss Retrieved from

httpwwwalzorgalzheimers_disease_standard_prescriptionsasp

Alzheimerrsquos Foundation of America (2014) About Alzheimerrsquos Retrieved from httpwwwalzfdnorgAboutAlzheimerscosthtml

American Geriatrics Society (2013) A guide to dementia diagnosis and treatment Retrieved from

httpwwwamericangeriatricsorgfilesdocumentsdementia_pocket_cardpdf

Buttaro T M Trybulski J Bailey P P amp Sandberg-Cook J (2013) Primary care A collaborative practice (4th ed) St Louis MO Elsevier

Centers for Medicare amp Medicaid Services (2013) Superseded local coverage determination (LCD) Hospice determining terminal status (L32015)

Retrieved from httpwwwcmsgovmedicare-coverage-databasedetailslcd-

detailsaspxLCDId=32015ampContrId=236ampver=14ampContrVer=2ampCntrctrSelected=2362ampCntrctr=236ampname=CGS+Administrators2c+LL

C+(150042c+HHH+MAC)amps=11ampDocType=Activeampbc=AggAAAIAAAAAAA3d3damp

REFERENCES

Feldman H H Doody R S Kivipelto M Sparks D L Waters D D Jones R W Breazna A (2010) Randomized controlled trial of

atorvastatin in mild to moderate Alzheimer disease LEADe Neurology 74(12) 956-964 doi101212WNL0b013e3181d6476a

Grabowski T J (2014) Clinical manifestations and diagnosis of Alzheimer disease UpToDate Retrieved from httpwwwuptodatecomhsl-

ezproxyucdenvereducontentsclinical-manifestations-and-diagnosis-of-alzheimer-

diseasesource=search_resultampsearch=Clinical+manifestations+and+diagnosis+of+Alzheimer+diseaseampselectedTitle=1~150

Hort J OrsquoBrien J T Gainotti G Pirttila T Popescu B O Rektorova I hellip Scheltens P (2010) EFNS guidelines for the diagnosis and

management of Alzheimerrsquos disease European Journal of Neurology 17(10) 1236-1248 doi101111j1468-1331201003040x

Kolcaba K (2010) Conceptual framework for comfort theory Comfort Line Retrieved from httpwwwthecomfortlinecomindexhtml

Kolcaba K Tilton C amp Drouin C (2006) Comfort theory A unifying framework to enhance the practice environment The Journal of Nursing

Administration 36(11) 538-544

REFERENCES

Kuller L (2014) Epidemiology of Alzheimer disease UpToDate Retrieved from httpwwwuptodatecomhsl-

ezproxyucdenvereducontentsepidemiology-of-alzheimer-diseasesource=search_resultampsearch=alzheimersampselectedTitle=2~150

Lexicomp (2014) Memantine Drug information UpToDate Retrieved from httpwwwuptodatecomhsl-

ezproxyucdenvereducontentsmemantine-drug-

informationsource=search_resultampsearch=Memantine3A+Drug+informationampselectedTitle=1~32

McCance K L Huether S E Brashers V L amp Rote N S (2010) Pathophysiology The biologic basis for disease in adults and children (6th ed)

Maryland Heights MO Mosby

National Institute of Aging (2014) About Alzheimerrsquos disease Alzheimerrsquos basics Retrieved from

httpwwwnianihgovalzheimerstopicsalzheimers-basics

National Institute of Aging (2014) Alzheimerrsquos disease Unraveling the mystery Retrieved from

httpwwwnianihgovalzheimerspublicationpart-2-what-happens-brain-adchanging-brain-adother-early-signs

REFERENCES

National Institute of Aging (2014) Caring for a person with Alzheimerrsquos disease Medicines to treat AD symptoms and behaviors Retrieved from

httpwwwnianihgovalzheimerspublicationmedical-side-admedicines-treat-ad-symptoms-and-behaviors

McGuinness B Craig D Bullock R Malouf R amp Passmore P (2014) Statins for the treatment of dementia Cochrane Database of Systematic

Reviews (7) doi 10100214651858CD007514pub3

Parker M E amp Smith M C (2010)Nursing theories and nursing practice (3rd ed) Philadelphia PA Davis

Qaseem A Snow V Cross T Jr Forciea M A Hopkins R Jr Shekelle P Owens D K (2008) Current pharmacologic treatment of

dementia A clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians Annals

Of Internal Medicine 148(5) 370-378

Sano M Bell K L Galasko D Galvin J E Thomas R G van Dyck C H amp Aisen P S (2011) A randomized double-blind placebo-

controlled trial of simvastatin to treat Alzheimer disease Neurology 77(6) 556-563 doi101212WNL0b013e318228bf11

REFERENCES

Sparks D L Sabbagh M N Connor D J Lopez J Launer L J Browne P hellip Ziolwolski C (2005) Atorvastatin for the treatment of mild to moderate

Alzheimer disease Preliminary results Arch Neurol 62(5) 753-757

Sosa-Ortiz A L Acosta-Castillo I amp Prince M J (2012) Epidemiology of dementias and alzheimerrsquos disease Archives of Medical Research 43(8) 600-

608 doi 101016jarcmed201211003

Stone N J Robinson J Lichtenstein A H Merz C N B Blum C B Eckel R H hellip Wilson P W F(2013) 2013 ACCAHA guideline on the treatment of

blood cholesterol to reduce atherosclerotic cardiovascular risk in adults A report of the American College of CardiologyAmerican Heart Association

task force on practice guidelines Circulation doi 10116101cir0000437738638537a

Centre for Evidence-Based Medicine (2009) Oxford centre for evidence-based medicine Levels of evidence Retrieved from httpwwwcebmnetoxford-

centre-evidence-based-medicine-levels-evidence-march-2009

Winslow B T Onysko M K Stob C M amp Hazlewood K A (2011) Treatment of Alzheimer disease American Family Physician 83(12) 1403-1412

World Health Organization (2012) Dementia A public health priority Retrieved from httpwwwwhointirishandle1066575263sthashYZ1DtTrPdpuf