2006 Capital Conference Dementia

Colonel Brian Unwin, M.D. Department of Family Medicine, USUHS

OBJECTIVES

Know and understand:

The

risks for and causes of dementia Evaluation of patients with dementia General behavioral and pharmacologic treatment strategies Role of community resources for patient and caregivers

Geriatrics will be part of your practice:

Aged >65 are 14% of our population in 2010, and 25% in 2050 Age >85 will be 5% of our population in 2050 33% of our office visits, becoming 50% of our office visits Accounts for 1/3 of our health care dollar

THE DEMOGRAPHY OF ALZHEIMERS DISEASE (AD)

4 million in U.S. currently

14 million in U.S. by 2050 1 in 10 persons aged 65+ and nearly half of those aged 85+ have AD Life expectancy of 8-10 years after symptoms begin

THE IMPACT OF DEMENTIA

Economic

Emotional

$199 billion annually for care and lost productivity Medicare, Medicaid, private insurance provide only partial coverage Families bear greatest burden of expense

Direct toll on patients Nearly half of caregivers suffer depression

Dementia and Goals of Care

Prolonging life Preventing M&M Prevent functional decline Slow progression Decrease psychiatric/behavioral problems

Dialysis Immunizations Fall reduction program Cholinesterase Inhibition and Memantine Pharmacologic and behavioral interventions

JAGS. 1998. 46:782-783.

Dementia and Goals of Care

Restore and improve function Decrease caregiver burden Achieve a peaceful death

Rehab after fracture Support groups and community services Hospice referral

JAGS. 1998. 46: 782-283.

WHAT IS DEMENTIA?

DSM-IV DIAGNOSTIC CRITERIA FOR ALZHEIMERS DEMENTIA (AD):

Development of cognitive deficits manifested by both

impaired memory aphasia, apraxia, agnosia, disturbed executive function

Significantly impaired social, occupational function Gradual onset, continuing decline Not due to CNS or other physical conditions (e.g., Parkinsons, delirium) Not due to an Axis I disorder (e.g., schizophrenia)

SYMPTOMS & SIGNS OF AD

Memory impairment Gradual onset, progressive cognitive decline Behavior and mood changes Difficulty learning, retaining new information Aphasia, apraxia, disorientation, visuospatial dysfunction Impaired executive function, judgment Delusions, hallucinations, aggression, wandering

Behavioral Disturbances in Dementia:

J Am Ger Soc. 1996; 44(9): 1078-1081

Function and Mental Status:

DIFFERENTIAL DIAGNOSIS FOR DEMENTIA:

Alzheimers disease70% Vascular dementia10-20% Dementia associated with Lewy bodies (associated with PD features) Frontal lobe- Picks: <5%

Other

Alcohol Parkinson's disease [PD] Delirium Depression Neurosyphilis Creutzfeldt-Jakob (1/167,000 in U.S. annually) NPH (ataxia>incontinence> cognition) Normal

NORMAL LAPSES vs DEMENTIA Examples (1 of 2)

Forgetting a name Leaving kettle on

Not recognizing family member

Forgetting to serve meal just prepared Substituting inappropriate words

Finding right word

Forgetting date or day

Getting lost in own neighborhood

NORMAL LAPSES vs DEMENTIA Examples (2 of 2)

Trouble balancing checkbook Losing keys, glasses Getting blues in sad situations Gradual changes with aging

Not recognizing numbers

Putting iron in freezer

Rapid mood swings for no reason

Sudden, dramatic personality change

DEPRESSION vs DEMENTIA:

The symptoms of depression and dementia often overlap Late life depression can herald impending dementia In general, patients with primary depression:
Demonstrate motivation during cognitive testing Express cognitive complaints that exceed measured deficits Maintain language and motor skills

Risk Factors for AD

Age Family history Head injury Fewer years of education Downs Syndrome Metabolic Syndrome? Inactivity? Vascular disease risk factors

THE GENETICS OF DEMENTIA

Mutations of chromosomes 1, 14, 21

Rare early-onset (before age 60) familial forms of dementia Downs syndrome

Apolipoprotein E4 on chromosome 19

Limited indications for screening

Late-onset AD APOE*4 allele risk & onset age in dose-related fashion APOE*2 allele may have protective effect

Limited indications for screening

HISTORY:

Ask both the patient & a reliable informant about the patients:
Current condition Medical history Current medications & medication history Patterns of alcohol use or abuse Living arrangements

PHYSICAL

Examine:

Neurologic status Mental status Functional status Hearing/vision loss

Quantified screens for cognition and depression e.g., Folsteins MMSE, Clock Draw

Include:

Neuropsychologic testing for uncertain cases

Clock Draw Test

Instructions:
Draw the face of a clock, putting the numbers in correct position. Ill then ask you to indicate a time after you are done. Ask the patient to draw in the hands at ten minutes after eleven or twenty minutes after eight.

Clock Draw Test

Scoring:
Draws closed circle: 1 point Places numbers in correct position: 1 point Includes all 12 correct numbers: 1 point Places hands in correct position: 1 point

Interpretation:
Clinical judgment MUST be applied Cognitively impaired people typically dont draw a perfect clock

Clock Draw Interpretation

CDT of 4 approximates a MMSE of near 30 or mild cognitive impairment CDT of 2 puts patient in the moderate impairment of MMSE scores of high teens. CDT of 1 reflects moderate-to-severe scores on MMSE (low teens) Abnormal results suggests need for further assessment

Clock Draw Examples:

Mini-Mental State Exam (MMSE):

30-point scale to evaluate orientation, concentration, verbal and visual-spatial skills Not necessarily the gold standard, but most commonly recognized. Subject to level of educational attainment, language barriers, and vision/hearing requirements Early stages typically score 21-30, moderate 11-20, and end-stage 0-10

What labs to do?

LABORATORY:

Laboratory tests should include:

Complete

blood cell count Blood chemistries Liver function tests Consider HIV testing Serologic tests for: Syphilis, TSH, B12 level

To image or not to image

IMAGING:

Use imaging when:

Onset occurs at age < 65 years Symptoms have occurred for < 2 years Neurologic signs are asymmetric Clinical picture suggests normal-pressure hydrocephalus

Consider:
Noncontrast computed topography head scan Magnetic resonance imaging Positron emission tomography

TREATMENT & MANAGEMENT:

Primary goals:
To enhance quality of life Maximize functional performance by improving Cognition Mood Behavior

Primary Goals

Help the caregiver Treat depression (patient and caregiver) Advanced planning (Living Will and DPOA) Patient and caregiver education Social Work Services Respite services Honest assessment of abilities (i.e., driving, finances, etc.)

Area Agency on Aging

Primary Goals (continued)

Take care of the eyes Take care of the hearing Take care of the teeth Some patients need Adult Protective Services

Cholinesterase Inhibitors

Donepezil (Aricept):1996

Delay nursing home placement and progression 5mg q d (start) to 10mg q d

Global functioning and ADL preservation Start at 1.5mg bid to max 6mg bid

Rivastigmine (Exelon):2000

Galantamine (now Razadyne (ER) formerly Reminyl) (2001/2005)

Slowing progression 4mg bid to max 12 mg bid Extended release version: 8mg/day, (16mg/day), 24 mg/day

General thoughts about CIs

Price about the same ($120-130 per month) Up to 35% of patients taking an anticholinergic!

JAGS. 52: 2082-2087, 2004.

GI upset common, also watch for bradycardia Clinically meaningful benefit is debated from an EBM perspective Clinical support strong

Pharmacologic

Memantine (Namenda)
Indicated for moderate to severe dementia Friendly side-effect profile Start at 5mg daily, target dose: 20 mg q day Studies suggest added benefit when used with CIs Often used with those intolerant to CIs Long standing use in Germany Debate on clinical impact/timing with use of this medication

Ginkgo

Approved in Germany for treatment Antioxidant properties? Usual dosing at 240mg/day Associated with platelet inhibition

Dementia Therapy Update

Update on Dementia Medications

Kaduszkiewicz H, et al. Cholinesterase inhibitors for patients with Alzheimers Disease: systematic review of randomised trials. BMJ. August 6, 2005; 331:321-7.

Challenging Article

Bottom line

Evidence of effectiveness is based on small effects found in poorly analyzed studies AD drug studies need close scrutiny for methodologic errors and inflated benefit
conclusions were drawn without a comprehensive assessment of the methodological quality of the trials.

Contrary to Cochrane Reviews

Contrary to meta-analyses and American Academy of Neurology

No attempt consider the quality of the included trials.

Frustrated!

Excellent review Conflicts with mentors experience Conflicts with my hopes/limited experience Re-evaluate my aggressive use of the agents The need for the big, unbiased definitive study

Behavioral Pharmacology

Dementia behaviors may improve with cholinesterase inhibitors Wandering and pacing is NOT corrected with anti-psychotics Best treated with behavior modification and caregiver education, training and respite CIs may reduce inpatient delirium episodes

Atypical Antipsychotics

Effectiveness of atypicals is firmly established in treating dementia-related psychosis Includes Abilify (aripiprazole), Zyprexa (olanzapine), Seroquel (quetiapine), Risperdal (risperidone), Clozaril (clozapine) and Geodon (ziprasidone) Risperidone now available in a disintegrating tablet in 0.25mg-4mg doses and a long acting injection (up to 50mg q 2 weeks)

Continue oral therapy for three weeks to get adequate level

AFP. 2003. 67: 2335-40.

Risk of Atypical Antipsychotics

Class Effect New black box warning of increased risk of death and not approved for use in dementia-related psychosis.

Risk of death 1.6-1.7 x that of placebo Over a 10 week trial. 4.5% rate of death vs. 2.6% for the placebo group. Mostly cardiovascular deaths or infectious (pneumonia) Patient (caregiver) specific risk assessment and counseling

FDA Public Health Advisory, April 11, 2005

Other agents:

Valproate for agitation- Insufficient Evidence Trazodone for agitation- Insufficient Evidence Haldol for agitation- Effective, side effects are a problem Zhiling decoction (herbal combination)- insufficient evidence Propentofylline (adenosine blocker and phosphodiesterase inhibitor)- limited evidence of benefit Lecithin- not supported Acetyl-l-carnitine (ALC)- not supported at this time
Cochrane Database of Systematic Reviews (2005)

Screening for dementia

The USPSTF concludes that the evidence is insufficient to recommend for or against routine screening for dementia in older adults.

Age and educational level influences results The problem of arbitrary cut points Functional assessment can also detect dementia (FAQ) MMSE: PPV in UNSELECTED groups is only fair Early recognition helpful We should screen when we suspect
AFP. Vol. 69(6). March 15, 2004.

Clinical considerations

Screening for depression and dementia

New tools available Depression is very common in the elderly See:

AFP 2004; 70: 1101-1110.

SUMMARY:

Dementia is common in older adults but is NOT an inherent part of aging AD is the most common type of dementia, followed by vascular dementia and dementia with Lewy bodies

Evaluation includes history with informant, physical & functional assessment, focused labs, & possibly brain imaging

SUMMARY:

Primary treatment goals:

Enhance quality of life,

Maximize function by improving cognition, mood, behavior

Treatment may use both medications and nonpharmacologic interventions Community resources should be used to support patient, family, caregivers