9/6/2014 who is this?€¦ · 15/9/2014 · -predominantly aerobic (i.e. walking) interventions...

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Dementia Assessment: Delaying Progression

September 15, 2014

BJ Messinger-Rapport, MD

Cleveland Clinic

Who is this?

Agatha ChristieQueen of Crime!

B: 1890

England D: 1976

Age 85

1st novel:

Mysterious Affair at Styles(Poirot)

Last novel she wrote:

1973 Postern of Fate

1934 Murder on the

Orient Express Her 80’s

Alzheimer Disease

1955 Mystery Writers of AmericaGrand Master Award

Dame Commander of the British Empire

1926 Murder of

Roger Ackroyd

Murder on the Orient ExpressAgatha Christie Age 44

83 years oldPostern of Fate

What do you see in 1973 compared with 1934?

• Creative

• Desire to contribute

• Rambling

• Paucity of words

• Simpler ideas

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What Is Dementia?

• Dementia is a general term for a decline

in cognition

- severe enough to interfere with

activities of daily living.

• Dementia is not a specific disease. It's an overall term that describes a wide range of symptoms

Cognition?

• Memory – short term, long term, working memory

• Communication and language

• Ability to focus and pay attention

• Reasoning and judgment

• Visual perception

• Problem solving, Executive function

Activities of Daily Living?

Basic (BADL)

• Eating

• Bathing, grooming

• Toileting

• Dressing

- Choosing clothes

- Putting on in order

• Transfer

• Locomotion

Instrumental (IADL)

• Transportation

- Driving, other means

- Keeping appointments

• Shopping

• Homemaking

- Cooking, cleaning

- Washer, drier

• Mail, money, medications

• Telephone & other technology

• Caregiving, pet care

Stages of dementia

• Mild

- Intact Basic ADL; impaired ≥ 1 IADL*

• Common: meds, appointments

• Moderate:

- Impaired in ≥ 1 IADL + ≥ 1 BADL

• Common: grooming

• Severe:

- Impaired in most IADL, BADL

BADL are the “basic” ADL; IADL are the “complex” ADL

Impact of MILD dementia

• Moderate memory, mild functional deficits

• Doctors, family may miss the diagnosis

• Needs assistance or oversight in

- Medication management

- Appointments

- Finances, Big decisions

• MAY continue to drive

- If allows periodic safety evaluation

Conversation in mild AD

• Current events

- Socially appropriate

- Vague- lots bad things, war

- Trouble naming recent presidents

• 10 years ago- the 911 incident

- “Bombing”, many killed. Date/year?

- May not recall plane -> Pentagon.

- May recall plane down in PA.

• Pearl Harbor

- Date? Combatants? Which war? Ships?

- Likely to remember it all!

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Impact of MODERATE dementia

• Moderate to severe memory loss

• Moderate functional deficits

• Can “pass” at a party

• Requires daily prompting or assistance

- Grooming; Bathing (prompting)

- Dressing (choosing clothes)

- Meal prep (disconnected stove)

• No driving

Impact of SEVERE dementia

• Only fragments of memory remain

• Severe functional deficits

• Cannot “pass” for normal even briefly

• 24 x 7 care

- Where? Depends upon

• Finances, Personality

• Family emotional, physical resources

Does a person go from “normal aging” to “dementia”

overnight?• If stroke, traumatic brain injury,

- Can be overnight!

- Ex: Classic vascular dementia

• If Alzheimer’s disease

- Progressive, gradual

- 20 years….

• If mixed (vascular, Alzheimer disease)

- Progressive but bumpy

Dementia types

• Alzheimer's disease

• Vascular Dementia

• Mixed

• Post-infectious (meningitis)

• Parkinson’s disease or parkinsonism

• Trauma

• Often only distinguishable early in the disease

Genetics & Alzheimer’s Disease

• Early onset dementia- destined

APP, PS1, PS2

• Late onset dementia- influence only

ApoE e4

- Onset, intensity influenced by

• Lifestyle, comorbidities

Typical occurrence of manifestations

of Alzheimer's disease.

Sloane, AAFP, 1998

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Mild Cognitive Impairment

U of California Irvine ADRC

Who is likely to progress from MCI to Dementia?

• Small hippocampal volumes

- MRI

• Decreased blood flow to posterior cingulate gyrus

- PET, amyloid scans

• Certain CSF markers

- High tau protein, Low beta amyloid (1-24)

NONE COLLECTED TYPICALLY DURING ROUTINE CARE

Risk Factors for worsening cognitive impairment

Fixed

• Male

• Advanced age

• Lower Education

• APOEe4 genotype

• Smoking, alcohol

• Lifestyle

- Socialization

- Cognitive stimulation

- Physical exercise

• Diet

• Certain drugs

• Vascular disease

• Medical conditions

Potentially Modifiable

Medical conditions associated with impaired cognition

• Sleep apnea

• Atrial fibrillation

• Heart Failure

• Diabetes

• Stroke

• Hypertension

Pharmacological Interventions

Mild Cognitive

Impairment

Mild Dementia

ModerateDementia

SevereDementia

No FDA-

approved drug therapies

currently

available

Cholinesterase

inhibitors

Cholinesterase

inhibitors

NMDA-

antagonists

Cholinesterase

inhibitors

NMDA-

antagonists

Pharmacological InterventionsMedication Side effects

Acetylcholinesterase inhibitors:

Donepezil (Aricept)Rivastigmine (Exelon)

Galantamine

DiarrheaLoss of appetite/weight loss

NauseaSyncope

BradycardiaConfusion

DizzinessInsomnia or Hypersomnolence

FatigueHeadache

Memantine (Namenda) SyncopeConfusion

DizzinessHeadache

Diarrhea or ConstipationVomiting

Hypertension

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Benefit to Current Dementia Medications

• “Boost” memory

- Perform same or better on memory tests for next 6-12 months

- After 6-12 months, decline

• Patients may feel sharper

• May seem less confused, participate more in activity

• May maintain ADL 6-12 months longer

Therapeutic Gaps

• Drugs do not delay progression

• No new drug since 2003

• No FDA Therapy approved for MCI

• Currently available medications have many known common side effects

• Therefore, there is a need for

nonpharmacological interventions

NonpharmacologicalInterventions

• Most evidence for:

- Physical activity

- Cognitive exercises

- Socialization

- Mediterranean diet


• Caveats

- There is a paucity of high-quality literature exploring these interventions

- Small sample sizes

- Short-term follow-up periods

- Highly variable interventions

Physical Activity

• Increases cerebral blood flow, primarily in the frontal lobe

• Lower levels of inflammatory markers in the brain

• Lower levels of brain A-beta protein

• Increased hippocampal volume

Physical Activity

• Overall benefits

- Decreased risk of developing chronic degenerative diseases that increase risk of dementia

- Increased functional capacity

• Slower rate of functional decline in dementia patients who participate in exercise interventions

- Reduced sarcopenia

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Exercise in persons with Mild Cognitive Impairment

• 469 persons, 75+, NYC

• 124 developed dementia over 5 yrs

• Lower risk w/ leisure activities of

- Reading

- Dancing

- Playing board games

- Playing musical instruments

Verghese. NEJM. 2003

2004 National Dance Council of America !!

Dancing away the years

Answer: activity at all ages

Mi Hujo18 años; yo mismo 50 años

70 años

Physical Activity:2004 Meta-Analysis

• 30 RCTs including 2020 adults >65 yo with cognitive impairment

- Mean training duration – 23 weeks

- Average 3.6 sessions per week and 45 min/session

- Predominantly aerobic (i.e. walking) interventions

• 12 of the included studies looked at cognitive outcomes

Hayn. Arch PMR. 2004

Physical Activity:2004 Meta-Analysis

• Results:

- Exercise group showed improvements in cognitive tasks compared to control

Hayn. Arch PMR. 2004

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Physical Activity:2014 Systematic Review

• 4 RCTs of exercise interventions in cognitively impaired adults

• Exercise interventions took place over 12-24 weeks

• Interventions ranged from 3 to 7 sessions per week

Farina. 2014 Farina. 2014

Physical Activity:Other Findings

• High intensity exercise c/w stretching control �� ↑ executive functioning (Hahn

& Andel and Baker, et al)

• 1 year Tai Chi program reduced rate of progression to dementia c/w stretching control group (Lam, et al)

• 6 month exercise group c/w normal activity control group �� ↑ cognition sustained at 18 months (Lautenschlager)

Cognitive Exercises

• Cognitive stimulation:

- group activities to increase cognitive and social operation

• Cognitive training:

- teaching techniques to improve cognitive function

• Cognitive rehabilitation:

- individualized programs to target specific activities of daily life

Cognitive Interventions

• Goal

- Optimize function and well-being

- Minimize disability

- Prevent malignant social interactions

- Attempt non-pharmacologic intervention for cognitive impairment

• Historically, main focus is memory

• Differs from other interventions that target behaviors, emotions or physical function

Cognitive Exercises

• Forms available

- Computerized interventions/games (i.e. Lumosity)

- Video games (i.e. Nintendo Brain Age)

- Senior classes

- Cognitive “hobbies” (ie. crossword puzzles, sudoku, reading)

- Cognitive training with use of therapy

• Compensatory vs. restorative techniques

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Cognitive Exercises:2006 Meta-Analysis

• Aim: review literature on cognitive interventions and evaluate the effect on cognition and function

• Included 19 studies described in 17 articles –

- All subjects had a diagnosis of AD or probable AD

- 14 of 19 were randomized controlled trials

- 12 studies used primarily restorative techniques

- 7 studies used primary compensatory techniques

Sitzer. Acta Psychiatr Scand. 2006


• Results

- Overall mean effect size for all cognitive training strategies was 0.47

- Restorative approaches had higher mean ES than compensatory approaches but not significantly different

- Findings were similar when analyses were performed on the 5 highest quality studies but effect sizes were smaller

- Benefits were maintained for an average of 4.5 months




• Interpretation

- Overall there cognitive therapies can lead to improvement in cognitive and functional abilities in AD patients

- Benefits may have at least a brief lasting effect


Cognitive Exercises:Other Findings

• 2012 Cochrane Review of cognitive stimulation in dementia

- Improved cognitive function in patients receiving cognitive stimulation and reality orientation that was sustained 3 months post-intervention

- Improved self-reports of QoL and well-being

- Improved communication and social interaction as noted by others

Socialization

• Engagement in group activities

• Regular conversation

• Support groups

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Socialization

• Disengagement is a risk factor for cognitive impairment and is associated with depressive symptoms

• Small quantity and low quality of social relations is associated with increased risk of death (House as cited in Fratiglioni)

Socialization: 2011 RCT

• Aim: study the impact of a socialization intervention on cognition in “lonely”elders

• Intervention: social group activities 1x/week for ~6 hours for 3 months

• Participants: elders who self-report loneliness, MMSE >19, CDR </= 1

Pitkala. AJGP. 2011

Socialization: 2011 RCT Results

• ADAS-cog was performed at baseline and 3 months

- Improved significantly more in the intervention vs. control group

• 15D measure of HRQoL measured at baseline and 1 year

- Significant difference with higher levels in the intervention group at 1 year

- Within the dimension of “mental function”, significant improvement in the intervention group only


Socialization: 2011 RCT

• Socially stimulating activities in lonely elders may help to improve cognition


Multimodal Approaches

• Interplay among the intervention strategies discussed

- Many programs are done in a group setting

- One-on-one instruction provides social engagement

- Many programs provide multiple forms of stimulation

Multimodal Approaches

• A small study tested a multimodal method of PE, cognitive interventions and community activities

- Those who participated the longest in the intervention had no significant change in CDR, MMSE score or other tests of cognition between years for the 4 years studied

Arkin. Am J of Alz Disease

and Other Dementia. 2007

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Accessing These Interventions

• Physical activity

- Silver sneakers

- Fitness centers

- Outside activities (weather-permitting!)

- Senior dance classes


• Cognitive interventions

- Cleveland Brain Emporium

- Occupational therapy

- Speech Therapy

- At home activities (games, puzzles, electronic resources, reading, school books, etc.)


• Socialization

- Senior centers located throughout the community

- Local churches, temples

- Support groups

- Volunteer opportunities

Other Interventions

• Support groups for patients and caregivers

- One study: support groups ↓ risk institutionalization (Spijker)

Dietary Modification

• Vitamin E

• Beta-carotene

• Vitamins B6, B12, and folate

• Vitamin D

• Ginkgo biloba

• Cholesterol and fatty acid

• Alcohol

• Mediterranean diet

Vitamin E andMild-Moderate AD

• 613 veterans 2007 – 2012

• Randomized to:

- Vit E (α tocopherol)

- Memantine

- Vit E + memantine

- Placeo

• Outcome: ADL score

• Result: Vit E better than placeboSano. JAMA. 2014

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Vitamin E and Risks

• No benefit, maybe reduced cognition (Lloret 2009, very small study)

• Increased risk bleeding with warfarin in AF (Pastori. JAHA 2013)

• No effect on cancer, CVD, or mortality- Fortmann. USPSTF 2013

• Vitamin E > 22 U: increased mortality slightly

(RR 1.03, CI 1 – 1.05) Bjelakov. PLOS1 2013

Vitamin E Mortality: probably increases with dose!

Miller. Annals IM. 2005

2000 Units

Vitamin E Units/ day

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Mediterranean Dietdelays onset of dementia

• Eating primarily plant-based foods- fruits and vegetables, whole grains,

- legumes and nuts

• Replacing butter with healthy fats- olive oil and canola oil

• Reduce sodium- herbs and spices to flavor foods

• Limiting red meat- no more than a few times a month

• Eating fish and poultry at least twice a week

• Drinking red wine (no more than 1 / d)

Mediterranean diet assoc w/ reduced risk AD

“Predimed” and cognition

• 522 persons mean age 74.6

• Non-demented

• Randomized, followed x 6.5 years

- MedDiet w/ EVOO or MedDiet w/nuts

- Control low-fat diet

• Result: Cognition better with

- MedDiet w/EVOO or nuts c/w low-fat

- Differences tiny

Martinez-Lapiscina. Cog Neuro. 2014

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Benefits

• Theoretically easily to implement

• Readily available in the community

• No side effects – low risk, high reward

• Can be used at any stage of cognitive impairment

Potential Barriers

• Denial or unawareness of memory deficits

• Difficulty following tasks

• Apathy

• Cost

• Limited perceived value of task

Healthy Lifestyledelays progression of cognitive

impairment

• Social Life

• Mental Engagement and Education

• Physical Activity

• Mediterranean diet

Questions?

9/6/2014 who is this?€¦ · 15/9/2014 · -predominantly aerobic (i.e. walking) interventions...

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