dementia.2

DementiaDementia

Arden L Aylor, MDArden L Aylor, MD

GeriatricsGeriatrics

Texas Tech UniversityTexas Tech University

Goals & ObjectivesGoals & Objectives

StatisticsStatistics Clinical FeaturesClinical Features Diagnostic CriteriaDiagnostic Criteria Assessment MethodsAssessment Methods Treatment MethodsTreatment Methods

Normal vs. Abnormal AgingNormal vs. Abnormal Aging

>40 year-old: Age Associated Memory >40 year-old: Age Associated Memory ImpairmentImpairment

Decline in Hepatic & Renal functionDecline in Hepatic & Renal function Vision changesVision changes Hearing changesHearing changes

DementiaDementia

Definition: The loss of cognitive and Definition: The loss of cognitive and intellectual function, without impairment of intellectual function, without impairment of perception or consciousness perception or consciousness

Characterized by disorientation, impaired Characterized by disorientation, impaired memory, judgment, intellect and labile memory, judgment, intellect and labile affectaffect

Did you Know…Did you Know…

Five major types of DementiaFive major types of Dementia Alzheimer’s: 60-70% Alzheimer’s: 60-70% Cerebrovascular: 15-25%Cerebrovascular: 15-25% Lewybody: 5-8%Lewybody: 5-8% Frontotemporal: 3-5% Frontotemporal: 3-5% Parkinson's with Dementia: 1-3%Parkinson's with Dementia: 1-3%

Estimated by 2040, 120 millionEstimated by 2040, 120 million

Arch Neuro, 2005Arch Neuro, 2005


Prevalence: 6-8% 60 yrs and doubles Prevalence: 6-8% 60 yrs and doubles every 5 yearsevery 5 years

80 yrs: 47-50% population suffer from 80 yrs: 47-50% population suffer from some form of dementiasome form of dementia

www.aoa.dhhs.govwww.aoa.dhhs.gov


2006 - total cost world wide exceeded 2006 - total cost world wide exceeded $220 billion $220 billion acute careacute care long-term care long-term care home health care home health care lost productivity for caregiverslost productivity for caregivers


GeneticsGenetics

The two major The two major riskrisk factors for factors for dementiadementia age age family historyfamily history

Alzheimer’s: 50% penetrance in first Alzheimer’s: 50% penetrance in first degree relatives by age 80 degree relatives by age 80

GeneticsGenetics

Alzheimer’s Alzheimer’s (AD): (AD): before age 60before age 60 genetic mutations on chromosomes 1, 14, 21genetic mutations on chromosomes 1, 14, 21

Alzheimer’s Alzheimer’s (AD): (AD): after age 60after age 60 apolipoprotein E gene apolipoprotein E gene (APOE)(APOE) on on

chromosome 19 chromosome 19

GeneticsGenetics

APOE* 4/4 allele 6x increase risk in (APOE* 4/4 allele 6x increase risk in (AD)AD)

APOE* 2 appears to be protectiveAPOE* 2 appears to be protective

Other risk factors:Other risk factors: head injury, education level, estrogen head injury, education level, estrogen

replacement after menopause, long-term replacement after menopause, long-term NSAID’s NSAID’s

Clinical FeaturesClinical Features

Memory ImpairmentMemory Impairment

Early Dementia: Early Dementia: difficulty learning and retaining new informationdifficulty learning and retaining new information

Late Dementia: Late Dementia: inability to access distant memories, impaired inability to access distant memories, impaired

judgment and executive function judgment and executive function


Dementia has a profound effect on the Dementia has a profound effect on the patient’s daily life:patient’s daily life: ADL’S ADL’S (eating, bathing, grooming)(eating, bathing, grooming) planning mealsplanning meals managing finances managing finances medicationsmedications communicationcommunication drivingdriving


Early behavior and mood changes are Early behavior and mood changes are common:common: personality alterationspersonality alterations irritabilityirritability anxiety anxiety depressiondepression

Late findings: Delusions, hallucinations, Late findings: Delusions, hallucinations, aggression and wanderingaggression and wandering


Dementia and depression often overlapDementia and depression often overlap

Depressed patients usually exhibit intact Depressed patients usually exhibit intact language and motor skillslanguage and motor skills

55% over 65 yrs with mild cognitive 55% over 65 yrs with mild cognitive impairment + depression, progress to impairment + depression, progress to moderate to severe dementia within 5 yrs moderate to severe dementia within 5 yrs

Arch Neuro,Arch Neuro, 2005 2005


Dementia & Agitation Dementia & Agitation undiagnosed medical problemundiagnosed medical problem pain pain depression/ anxietydepression/ anxiety deliriumdelirium environmental changesenvironmental changes

Six Diagnostic Criteria forSix Diagnostic Criteria forDementia Dementia

1.1. Multiple cognitive deficits Multiple cognitive deficits a. Memory impairmenta. Memory impairment b. One or more of the following:b. One or more of the following:

• aphasia aphasia • apraxia apraxia • agnosia agnosia • disturbance in executive function disturbance in executive function

Core Geri, 2005 Core Geri, 2005

Six Diagnostic Criteria for Six Diagnostic Criteria for DementiaDementia

2. 2. Cognitive deficits in 1a and 1b causing anCognitive deficits in 1a and 1b causing animpairment in social or occupational impairment in social or occupational

function which represents a significant function which represents a significant decline decline from a previous level from a previous level

3. 3. Course is characterized by gradual onset Course is characterized by gradual onset and continued cognitive declineand continued cognitive decline


4.4. Cognitive deficits in 1a and 1b are not due Cognitive deficits in 1a and 1b are not due to any of the following:to any of the following:

• central nervous system condition causing central nervous system condition causing progressive deficits in memory or cognitionprogressive deficits in memory or cognition

• systemic condition systemic condition • substance-induced conditionsubstance-induced condition


5.5. Deficits do not occur exclusively during the Deficits do not occur exclusively during the course of a delirium course of a delirium

6.6. Disturbance is not better accounted for by Disturbance is not better accounted for by another Axis I disorder another Axis I disorder (major depression, (major depression, schizophreniaschizophrenia))

Mild DementiaMild Dementia

Disorientation for Disorientation for datesdates

Naming difficulties Naming difficulties (anomia)(anomia)

Recent recall Recent recall problemsproblems

Difficulty copying Difficulty copying figuresfigures

Decreased insightDecreased insight Social withdrawalSocial withdrawal Irritability, mood Irritability, mood

changeschanges Problems managing Problems managing

financesfinances

Moderate DementiaModerate Dementia

Disoriented to date Disoriented to date and placeand place

Comprehension Comprehension difficulties difficulties

Impaired new learningImpaired new learning Getting lost in familiar Getting lost in familiar

areasareas Impaired calculating Impaired calculating

skillsskills

Delusions, agitation, Delusions, agitation, aggressionaggression

Stop cooking, Stop cooking, shopping, bankingshopping, banking

Restless, anxious, Restless, anxious, depresseddepressed

Problems with Problems with dressing, groomingdressing, grooming

Severe DementiaSevere Dementia

Unintelligible speechUnintelligible speech Remote memory goneRemote memory gone Inability to copy or writeInability to copy or write Loss of self careLoss of self care IncontinentIncontinent


Alzheimer’s DementiaAlzheimer’s Dementia Age: 70-75Age: 70-75 Cognition: Memory ImpairmentCognition: Memory Impairment Behavioral: Apathy, DepressionBehavioral: Apathy, Depression Neurological: IntactNeurological: Intact Prognosis: Death 8-10 yearsPrognosis: Death 8-10 years


Cerebrovascular DementiaCerebrovascular Dementia Age: 70Age: 70 Cognition: Language, Memory, Executive Cognition: Language, Memory, Executive

Function ImpairmentFunction Impairment Behavioral: Agitation, Hallucinations, Behavioral: Agitation, Hallucinations,

DepressionDepression Neurological: Frontal Release Signs, Neurological: Frontal Release Signs,

(+) Brain Imaging Studies(+) Brain Imaging Studies Prognosis: Death 5-8 yearsPrognosis: Death 5-8 years


Lewybody DementiaLewybody Dementia Age: 65Age: 65 Cognition: Memory, Executive Function & Cognition: Memory, Executive Function &

Orientation ImpairmentOrientation Impairment Behavioral: Visual Hallucinations, DepressionBehavioral: Visual Hallucinations, Depression Neurological: ParkinsonismNeurological: Parkinsonism Prognosis: Death 6-8 yearsPrognosis: Death 6-8 years


Frontotemporal DementiaFrontotemporal Dementia Age: 65Age: 65 Cognition: Executive Function ImpairmentCognition: Executive Function Impairment Behavioral: Social InhibitionBehavioral: Social Inhibition Neurological: IntactNeurological: Intact Prognosis: Death 6-8 yearsPrognosis: Death 6-8 years


Parkinson’s with DementiaParkinson’s with Dementia Age: 70Age: 70 Cognition: Memory, Executive Function, Cognition: Memory, Executive Function,

Language, Orientation ImpairmentLanguage, Orientation Impairment Behavioral: Depression, HallucinationsBehavioral: Depression, Hallucinations Neurological: Parkinson’s DiseaseNeurological: Parkinson’s Disease Prognosis: Death <5 yearsPrognosis: Death <5 years

Assessment MethodsAssessment Methods

Informant interview and office evaluation are the most Informant interview and office evaluation are the most important diagnostic toolsimportant diagnostic tools

Functional Status: MMSEFunctional Status: MMSE, , Functional Activities Functional Activities Questionnaire Questionnaire (FAQ),(FAQ), Geriatric Depression Geriatric Depression Screening, Clock Drawing TestScreening, Clock Drawing Test

Laboratory: CBC, CMP, TSH, Serology for Syphilis, Laboratory: CBC, CMP, TSH, Serology for Syphilis, Vitamin B12, HIVVitamin B12, HIV

Core Geri, 2005Core Geri, 2005


Brain Imaging Brain Imaging (CT, MRI, PET)(CT, MRI, PET) atrophyatrophy space-occupying lesionsspace-occupying lesions vascular diseasevascular disease whiter matter diseasewhiter matter disease


Imaging StudiesImaging Studies Order if--Order if--

• onset before 60 yrsonset before 60 yrs

• post-acute illness less that 18 monthspost-acute illness less that 18 months

• neurologic finding are asymmetricneurologic finding are asymmetric

• gait disturbancegait disturbance

• incontinence unexplainedincontinence unexplained

Treatment and ManagementTreatment and Management

Goal: Enhance quality of life, maximize Goal: Enhance quality of life, maximize function, improve cognition, mood and function, improve cognition, mood and behaviorbehavior non-pharmacologicalnon-pharmacological pharmacologicalpharmacological

NonpharmacologicNonpharmacologic

Cognitive EnhancementCognitive Enhancement reality orientation and memory trainingreality orientation and memory training

Individual and Group TherapyIndividual and Group Therapy emotional orientated psychotherapyemotional orientated psychotherapy stimulation orientated therapystimulation orientated therapy

art and exerciseart and exercise

Other NonpharmacologicOther Nonpharmacologic

Communication with family and caregiverCommunication with family and caregiver

Medical and legal Advance DirectivesMedical and legal Advance Directives

Environmental ModificationsEnvironmental Modifications moderate stimulation onlymoderate stimulation only memory measuresmemory measures

clocks, calendars, to-do listsclocks, calendars, to-do lists

name tags, alert braceletsname tags, alert bracelets

PharmacologicPharmacologic

Individualized treatmentIndividualized treatment Monitor renal clearance and hepatic Monitor renal clearance and hepatic

metabolismmetabolism Anticholinergic medications worsen Anticholinergic medications worsen

cognitive impairment cognitive impairment ““Start low and go slow”Start low and go slow” Avoid starting multiple medications Avoid starting multiple medications


Alzheimer’s Dementia Alzheimer’s Dementia Cholinesterase Inhibitors Cholinesterase Inhibitors

• Donepezil Donepezil (Aricept)(Aricept) • Galantamine Galantamine (Razadyne)(Razadyne) • Rivastigmine Rivastigmine (Exelon)(Exelon)

Memantine Memantine (Namenda)(Namenda) SSRI’sSSRI’s


Cerebrovascular DementiaCerebrovascular Dementia Cholinesterase InhibitorsCholinesterase Inhibitors Control lipidsControl lipids Stoke preventionStoke prevention SSRI’sSSRI’s MemantineMemantine AnticonvulsantsAnticonvulsants AntipsychoticsAntipsychotics


Frontotemporal DementiaFrontotemporal Dementia No Cholinesterase InhibitorsNo Cholinesterase Inhibitors SSRI’sSSRI’s MemantineMemantine AnticonvulsantsAnticonvulsants AntipsychoticsAntipsychotics


Lewybody Dementia Lewybody Dementia (Pick’s disease)(Pick’s disease) Cholinesterase InhibitorsCholinesterase Inhibitors SSRI’sSSRI’s MemantineMemantine Levodopa/ CarbidopaLevodopa/ Carbidopa AntipsychoticAntipsychotic


Parkinson’s Disease with DementiaParkinson’s Disease with Dementia Treat the Parkinson’s diseaseTreat the Parkinson’s disease No Cholinesterase Inhibitors No Cholinesterase Inhibitors SSRI’sSSRI’s MemantineMemantine AntipsychoticAntipsychotic

Cholinesterase InhibitorsCholinesterase Inhibitors

Donepezil Donepezil (Aricept)(Aricept) PrecautionsPrecautions: Nausea, vomiting, diarrhea, : Nausea, vomiting, diarrhea,

GI bleed, sick sinus syndrome, seizuresGI bleed, sick sinus syndrome, seizures InteractionsInteractions: CYP2D6 : CYP2D6 (flecainide, metopropol, (flecainide, metopropol,

codeine) codeine), used with NSAID 3-4x risk for GI , used with NSAID 3-4x risk for GI bleedbleed


Galantamine Galantamine (Razadyne)(Razadyne) PrecautionsPrecautions: AV block, seizures, bladder : AV block, seizures, bladder

obstruction, renal and hepatic, GI bleed, obstruction, renal and hepatic, GI bleed,

GI upsetGI upset InteractionsInteractions: CYP3A4 : CYP3A4 (cholinergic agonist -(cholinergic agonist -

bethanechol, ketoconazole, cimetidine, bethanechol, ketoconazole, cimetidine, erythromycin)erythromycin)


Rivastigmine Rivastigmine (new q 24 Exelon Patch)(new q 24 Exelon Patch) PrecautionsPrecautions: Nausea, vomiting, anoxia, : Nausea, vomiting, anoxia,

GI bleed, sick sinus syndrome, seizuresGI bleed, sick sinus syndrome, seizures InteractionsInteractions: CYP2D6 and CYP3A4, : CYP2D6 and CYP3A4,

potentates muscle relaxants, used with potentates muscle relaxants, used with NSAID 3-4x risk for GI bleedNSAID 3-4x risk for GI bleed

NMDA [glutamate] antagonistNMDA [glutamate] antagonist

Memantine Memantine (Namenda)(Namenda) PrecautionsPrecautions: Dizziness, headache, : Dizziness, headache,

alkalinized urine alkalinized urine (ATN, UTI)(ATN, UTI) seizures, GI seizures, GI upsetupset

InteractionsInteractions: Other NMDA antagonists : Other NMDA antagonists (amantadine, dextromethorphan),(amantadine, dextromethorphan), decreased by renally-excreted drugs decreased by renally-excreted drugs (HCTZ) (HCTZ)

Mild to Moderate DementiaMild to Moderate Dementia

Cholinesterase Inhibitors slow cognitive Cholinesterase Inhibitors slow cognitive declinedecline

Meta Analysis - Delayed nursing home Meta Analysis - Delayed nursing home placement by 1.2 yearsplacement by 1.2 years

• NNT 9.6NNT 9.6


Moderate to SevereModerate to Severe

Memantine: 1-3 year delay in progression of Memantine: 1-3 year delay in progression of symptomssymptoms NNT 16.2NNT 16.2

Memantine + Cholinesterase inhibitorMemantine + Cholinesterase inhibitor No definitive dataNo definitive data

• early combination may decrease progression early combination may decrease progression from mild to severe dementia by 4-5 years from mild to severe dementia by 4-5 years

Ann Intern Ann Intern MedMed, 2004, 2004

Research: What’s NewResearch: What’s New

Tramiprostate (Alzhemed)Tramiprostate (Alzhemed)• mechanism: Inhibits GAG & Amechanism: Inhibits GAG & Aββ protein fibrillization protein fibrillization• reduces amyloid formation and accumulation reduces amyloid formation and accumulation

Tarenflurbil (Flurizan)Tarenflurbil (Flurizan)• r-flurbiprofenr-flurbiprofen• mechanism: Selective Amyloid-Lowering Agent (SALA)mechanism: Selective Amyloid-Lowering Agent (SALA)• inhibits Ainhibits Aββ42 amyloid plaques cascade42 amyloid plaques cascade

Alzheimer’s VaccineAlzheimer’s Vaccine

ResearchResearch Other studiesOther studies

estrogen estrogen NSAIDSNSAIDS vitamin E vitamin E (increase cardiac events)(increase cardiac events) selective monoamine oxidase-B inhibitor selective monoamine oxidase-B inhibitor ginko biloba ginko biloba prophylaxis cholinesterase treatmentprophylaxis cholinesterase treatment

J Gerontol a Bio Sci MedJ Gerontol a Bio Sci Med, 2004, 2004

AntidepressantsAntidepressants

Guidelines Guidelines (American & UK Geriatric Society)(American & UK Geriatric Society) treating all patients with dementia and signs treating all patients with dementia and signs

of depression/ anxiety with an SSRI or SNRI of depression/ anxiety with an SSRI or SNRI

All SSRI are not EqualAll SSRI are not Equal

Paroxetine Paroxetine (Paxil): (Paxil): Drug interaction, anti-cholinergic Drug interaction, anti-cholinergic Fluoxetine Fluoxetine (Prozac): (Prozac): Long half life, anorexia Long half life, anorexia Sertraline Sertraline (Zoloft): (Zoloft): Good, sleepyGood, sleepy Citalopram Citalopram (Celexa):(Celexa): Good, mild hypotension Good, mild hypotension Escitlopram Escitlopram (Lexapro):(Lexapro): Good, mild hypotension Good, mild hypotension

““Sundowning”Sundowning”

Mild DementiaMild Dementia late afternoon or evening confusionlate afternoon or evening confusion

Severe DementiaSevere Dementia agitation, irritability restlessnessagitation, irritability restlessness


Etiology: Etiology: lack of clues from light/ dark cyclinglack of clues from light/ dark cycling decrease sensory inputdecrease sensory input environmental changesenvironmental changes lack of a structure daily routinelack of a structure daily routine change in caregiverschange in caregivers


RecommendationsRecommendations R/O occult medical problemsR/O occult medical problems

• infectioninfection• medication changesmedication changes

avoid dramatic changes in living environmentavoid dramatic changes in living environment encourage familiar home surroundingsencourage familiar home surroundings

Key PointsKey Points

Interviews & office evaluations are the most Interviews & office evaluations are the most important diagnostic toolsimportant diagnostic tools

Goal: Enhance quality of life, maximize function, Goal: Enhance quality of life, maximize function, improve cognition, mood and behaviorimprove cognition, mood and behavior

Not all SSRI’s are equalNot all SSRI’s are equal

Individualized treatmentIndividualized treatment mild - moderate: cholinesterase inhibitors,mild - moderate: cholinesterase inhibitors, SSRI’sSSRI’s moderate - severe: memantine, SSRI’s or moderate - severe: memantine, SSRI’s or

combinationscombinations

ReferencesReferences Cobb, Duthie, Murphy; Geriatric Review Syllabus: A Cobb, Duthie, Murphy; Geriatric Review Syllabus: A

Core curriculum in Geriatrics, 5th ed, 2005, 117-129Core curriculum in Geriatrics, 5th ed, 2005, 117-129 Peterson, Smith, Waring, Mild Cognitive Impairment, Peterson, Smith, Waring, Mild Cognitive Impairment,

Arch NeurolArch Neurol., 2005(3): 303-308., 2005(3): 303-308 Royall, Chaiodo, Polk, Subclinical Cognitive Impairment, Royall, Chaiodo, Polk, Subclinical Cognitive Impairment,

J Gerontol a Bio Sci MedJ Gerontol a Bio Sci Med, 2004;55 (9):M541-M546, 2004;55 (9):M541-M546 Grifford, Holloway, Frankel, Improving adherence to Grifford, Holloway, Frankel, Improving adherence to

dementia, dementia, A randomized Controlled Trial, Ann Intern A randomized Controlled Trial, Ann Intern MedMed, 2004;131(40):237-246, 2004;131(40):237-246

Governmental Administration on Aging & Research Governmental Administration on Aging & Research www.aoa.dhhs.gov

Alzheimer Research Forum, Alzheimer Research Forum, www.alzhforum.org/drugwww.alzhforum.org/drug

Assessment: PETAssessment: PET

Alzheimer's DiseaseAlzheimer's Disease • Parietal & Temporal Parietal & Temporal

deficits with intact deficits with intact neurologyneurology

Frontotemporal Frontotemporal • Frontal & Temporal Frontal & Temporal

deficitsdeficits

Parkinson’s with Parkinson’s with dementiadementia • Parietal deficitsParietal deficits

Vascular dementiaVascular dementia• Focal, asymmetricFocal, asymmetric

dementia.2

Health & Medicine