2007 Capital 2007 Capital ConferenceConference

DementiaDementia

Colonel Brian Unwin, M.D.Colonel Brian Unwin, M.D.

Department of Family Medicine, USUHSDepartment of Family Medicine, USUHS

OBJECTIVESOBJECTIVES Know and understand:Know and understand:

The risks for and causes of The risks for and causes of dementiadementia

Evaluation of patients with Evaluation of patients with dementiadementia

General behavioral and General behavioral and pharmacologic treatment strategies pharmacologic treatment strategies

Role of community resources for Role of community resources for patient and caregiverspatient and caregivers

Geriatrics will be part of Geriatrics will be part of your practice:your practice:

Aged >65 are 14% of our population Aged >65 are 14% of our population in 2010, and 25% in 2050in 2010, and 25% in 2050

Age >85 will be 5% of our population Age >85 will be 5% of our population in 2050 in 2050

33% of our office visits, becoming 33% of our office visits, becoming 50% of our office visits50% of our office visits

Accounts for 1/3 of our health care Accounts for 1/3 of our health care dollardollar

THE DEMOGRAPHY OF THE DEMOGRAPHY OF ALZHEIMER’S DISEASE ALZHEIMER’S DISEASE

(AD)(AD) 4 million in U.S. currently4 million in U.S. currently

14 million in U.S. by 205014 million in U.S. by 2050

1 in 10 persons aged 65+ and nearly 1 in 10 persons aged 65+ and nearly half of those aged 85+ have ADhalf of those aged 85+ have AD

Life expectancy of 8-10 years after Life expectancy of 8-10 years after symptoms beginsymptoms begin

THE IMPACT OF THE IMPACT OF DEMENTIADEMENTIA

EconomicEconomic $199 billion $199 billion

annually for care annually for care and lost and lost productivityproductivity

Medicare, Medicare, Medicaid, private Medicaid, private insurance provide insurance provide only partial only partial coveragecoverage

Families bear Families bear greatest burden of greatest burden of expenseexpense

EmotionalEmotional

Direct toll on Direct toll on patientspatients

Nearly half of Nearly half of caregivers suffer caregivers suffer depressiondepression

JAGS. 1998. 46:782-783.

Dementia and Goals of Dementia and Goals of CareCare

Prolonging lifeProlonging life Preventing M&MPreventing M&M Prevent functional Prevent functional

declinedecline Slow progressionSlow progression

Decrease Decrease psychiatric/behavipsychiatric/behavioral problemsoral problems

DialysisDialysis ImmunizationsImmunizations Fall reduction Fall reduction

programprogram

Cholinesterase Cholinesterase Inhibition and Inhibition and MemantineMemantine

Pharmacologic and Pharmacologic and behavioral behavioral interventionsinterventions

JAGS. 1998. 46: 782-283.

Dementia and Goals of Dementia and Goals of CareCare

Restore and Restore and improve functionimprove function

Decrease caregiver Decrease caregiver burdenburden

Achieve a peaceful Achieve a peaceful deathdeath

Rehab after Rehab after fracturefracture

Support groups Support groups and community and community servicesservices

Hospice referralHospice referral

WHAT IS DEMENTIA?WHAT IS DEMENTIA?

DSM-IVDSM-IV DIAGNOSTIC DIAGNOSTIC CRITERIA FOR CRITERIA FOR

ALZHEIMER’S DEMENTIA ALZHEIMER’S DEMENTIA (AD):(AD):

Development of cognitive deficits manifested by Development of cognitive deficits manifested by bothboth

impaired memoryimpaired memory aphasia, apraxia, agnosia, disturbed executive functionaphasia, apraxia, agnosia, disturbed executive function

Significantly impaired social, occupational functionSignificantly impaired social, occupational function Gradual onset, continuing declineGradual onset, continuing decline Not due to CNS or other physical conditions (e.g., Not due to CNS or other physical conditions (e.g.,

Parkinson’s, delirium)Parkinson’s, delirium) Not due to an Axis I disorder (e.g., schizophrenia)Not due to an Axis I disorder (e.g., schizophrenia)

SYMPTOMS & SIGNS OF SYMPTOMS & SIGNS OF ADAD

Memory impairmentMemory impairment Gradual onset, progressive cognitive declineGradual onset, progressive cognitive decline Behavior and mood changesBehavior and mood changes Difficulty learning, retaining new Difficulty learning, retaining new

informationinformation Aphasia, apraxia, disorientation, Aphasia, apraxia, disorientation,

visuospatial dysfunctionvisuospatial dysfunction Impaired executive function, judgmentImpaired executive function, judgment Delusions, hallucinations, aggression, Delusions, hallucinations, aggression,

wanderingwandering

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

Behavioral Disturbances in Behavioral Disturbances in Dementia:Dementia:

DIFFERENTIAL DIFFERENTIAL DIAGNOSIS DIAGNOSIS

FOR DEMENTIA:FOR DEMENTIA: Alzheimer’s Alzheimer’s disease- 70%disease- 70%

Vascular Vascular dementia- 10-20%dementia- 10-20%

Dementia Dementia associated with associated with Lewy bodies Lewy bodies (associated with (associated with PD features)PD features)

Frontal lobe- Frontal lobe- Picks: <5%Picks: <5%

Other Other AlcoholAlcohol Parkinson's disease Parkinson's disease

[PD][PD] DeliriumDelirium DepressionDepression NeurosyphilisNeurosyphilis Creutzfeldt-Jakob Creutzfeldt-Jakob

(1/167,000 in U.S. (1/167,000 in U.S. annually)annually)

NPH NPH (ataxia>incontinenc(ataxia>incontinence> cognition)e> cognition)

““Normal”Normal”

NORMAL LAPSES vs NORMAL LAPSES vs DEMENTIADEMENTIA

Examples (1 of 2)Examples (1 of 2)

Forgetting a nameForgetting a name

Leaving kettle onLeaving kettle on

Finding right wordFinding right word

Forgetting date or Forgetting date or dayday

Not recognizing Not recognizing family memberfamily member

Forgetting to serve Forgetting to serve meal just preparedmeal just prepared

Substituting Substituting inappropriate wordsinappropriate words

Getting lost in ownGetting lost in own neighborhoodneighborhood

NORMAL LAPSES vs NORMAL LAPSES vs DEMENTIADEMENTIA

Examples (2 of 2)Examples (2 of 2)

Trouble balancing Trouble balancing checkbookcheckbook

Losing keys, Losing keys, glassesglasses

Getting blues in Getting blues in sad situationssad situations

Gradual changes Gradual changes with agingwith aging

Not recognizing Not recognizing numbersnumbers

Putting iron in Putting iron in freezerfreezer

Rapid mood swings Rapid mood swings for no reasonfor no reason

Sudden, dramatic Sudden, dramatic personality changepersonality change

DEPRESSION vs DEPRESSION vs DEMENTIA:DEMENTIA:

The symptoms of depression and dementia The symptoms of depression and dementia often overlapoften overlap

Late life depression can herald impending Late life depression can herald impending dementiadementia

In general, patients with primary depression:In general, patients with primary depression: Demonstrate Demonstrate motivation during cognitive testing motivation during cognitive testing Express cognitive complaints that exceed Express cognitive complaints that exceed

measured deficitsmeasured deficits Maintain language and motor skillsMaintain language and motor skills

Risk Factors for ADRisk Factors for AD AgeAge Family historyFamily history Head injuryHead injury Fewer years of Fewer years of

educationeducation Down’s SyndromeDown’s Syndrome Metabolic Metabolic

Syndrome?Syndrome? Inactivity?Inactivity? Vascular disease Vascular disease

risk factorsrisk factors

THE GENETICS OF THE GENETICS OF DEMENTIADEMENTIA

Mutations of Mutations of chromosomes 1, chromosomes 1, 14, 2114, 21 Rare early-onset Rare early-onset

(before age 60) (before age 60) familial forms of familial forms of dementiadementia

Down’s syndromeDown’s syndrome Limited Limited

indications for indications for screeningscreening

Apolipoprotein E4 Apolipoprotein E4 on chromosome 19on chromosome 19 Late-onset ADLate-onset AD APOE*4 allele APOE*4 allele risk & risk &

onset age in dose-onset age in dose-related fashionrelated fashion

APOE*2 allele may APOE*2 allele may have protective effecthave protective effect

Limited indications Limited indications for screeningfor screening

HISTORYHISTORY:: Ask both the patient Ask both the patient

& a reliable & a reliable informant about the informant about the patient’s:patient’s: Current conditionCurrent condition Medical historyMedical history Current medications Current medications

& medication history& medication history Patterns of alcohol Patterns of alcohol

use or abuseuse or abuse Living arrangementsLiving arrangements

PHYSICALPHYSICAL Examine:Examine:

Neurologic statusNeurologic status Mental statusMental status Functional statusFunctional status Hearing/vision lossHearing/vision loss

Include:Include: Quantified screens for Quantified screens for

cognition and cognition and depression depression

e.g., Folstein’s e.g., Folstein’s MMSE, Clock DrawMMSE, Clock Draw

Neuropsychologic Neuropsychologic testing for uncertain testing for uncertain casescases

Clock Draw TestClock Draw Test

Instructions:Instructions: ““Draw the face of a clock, putting the Draw the face of a clock, putting the

numbers in correct position. I’ll then numbers in correct position. I’ll then ask you to indicate a time after you are ask you to indicate a time after you are done.”done.”

Ask the patient to draw in the hands at Ask the patient to draw in the hands at ten minutes after eleven or twenty ten minutes after eleven or twenty minutes after eight.minutes after eight.

Clock Draw TestClock Draw Test

Scoring:Scoring: Draws closed circle: 1 pointDraws closed circle: 1 point Places numbers in correct position: 1 Places numbers in correct position: 1

pointpoint Includes all 12 correct numbers: 1 pointIncludes all 12 correct numbers: 1 point Places hands in correct position: 1 pointPlaces hands in correct position: 1 point

Interpretation:Interpretation: Clinical judgment MUST be appliedClinical judgment MUST be applied Cognitively impaired people typically Cognitively impaired people typically

don’t draw a perfect clockdon’t draw a perfect clock

Clock Draw Clock Draw InterpretationInterpretation

CDT of 4 approximates a MMSE of CDT of 4 approximates a MMSE of near 30 or mild cognitive impairmentnear 30 or mild cognitive impairment

CDT of 2 puts patient in the moderate CDT of 2 puts patient in the moderate impairment of MMSE scores of high impairment of MMSE scores of high teens.teens.

CDT of 1 reflects moderate-to-severe CDT of 1 reflects moderate-to-severe scores on MMSE (low teens)scores on MMSE (low teens)

Abnormal results suggests need for Abnormal results suggests need for further assessmentfurther assessment

Clock Draw Examples:Clock Draw Examples:

Mini-Mental State Exam Mini-Mental State Exam (MMSE):(MMSE):

30-point scale to evaluate orientation, 30-point scale to evaluate orientation, concentration, verbal and visual-spatial concentration, verbal and visual-spatial skillsskills

Not necessarily the “gold standard,” but Not necessarily the “gold standard,” but most commonly recognized.most commonly recognized.

Subject to level of educational attainment, Subject to level of educational attainment, language barriers, and vision/hearing language barriers, and vision/hearing requirementsrequirements

““Early” stages typically score 21-30, Early” stages typically score 21-30, “moderate” 11-20, and end-stage 0-10“moderate” 11-20, and end-stage 0-10

Function and Mental Function and Mental Status:Status:

What labs to do?What labs to do?

LABORATORYLABORATORY::

Laboratory tests should Laboratory tests should include:include: Complete blood cell countComplete blood cell count Blood chemistriesBlood chemistries Liver function testsLiver function tests Consider HIV testingConsider HIV testing Serologic tests for:Serologic tests for:

Syphilis, TSH, B12 levelSyphilis, TSH, B12 level

To image or not to To image or not to image…image…

IMAGINGIMAGING:: Use imaging when:Use imaging when:

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

hydrocephalushydrocephalus

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

TREATMENT & TREATMENT & MANAGEMENT:MANAGEMENT:

Primary goals: Primary goals: To enhance quality of lifeTo enhance quality of life Maximize functional performance by Maximize functional performance by

improving improving CognitionCognition MoodMood BehaviorBehavior

Primary GoalsPrimary Goals Help the caregiverHelp the caregiver Treat depression (patient and caregiver)Treat depression (patient and caregiver) Advanced planning (Living Will and Advanced planning (Living Will and

DPOA)DPOA) Patient and caregiver educationPatient and caregiver education Social Work ServicesSocial Work Services Respite servicesRespite services Honest assessment of abilities (i.e., Honest assessment of abilities (i.e.,

driving, finances, etc.)driving, finances, etc.)

Primary Goals Primary Goals (continued)(continued)

Take care of the eyesTake care of the eyes Take care of the hearingTake care of the hearing Take care of the teethTake care of the teeth Some patients need Adult Protective Some patients need Adult Protective

ServicesServices

Area Agency on Area Agency on AgingAging

Cholinesterase InhibitorsCholinesterase Inhibitors Donepezil (Aricept):1996Donepezil (Aricept):1996

Delay nursing home placement and progressionDelay nursing home placement and progression 5mg q d (start) to 10mg q d5mg q d (start) to 10mg q d

Rivastigmine (Exelon):2000Rivastigmine (Exelon):2000 Global functioning and ADL preservationGlobal functioning and ADL preservation Start at 1.5mg bid to max 6mg bidStart at 1.5mg bid to max 6mg bid

Galantamine (now Razadyne (ER) formerly Galantamine (now Razadyne (ER) formerly Reminyl) (2001/2005)Reminyl) (2001/2005) Slowing progressionSlowing progression 4mg bid to max 12 mg bid4mg bid to max 12 mg bid Extended release version: 8mg/day, Extended release version: 8mg/day,

(16mg/day), 24 mg/day(16mg/day), 24 mg/day

General thoughts about General thoughts about CIsCIs

Price about the same ($120-130 per Price about the same ($120-130 per month)month)

Up to 35% of patients taking an Up to 35% of patients taking an anticholinergic!anticholinergic! JAGS. 52: 2082-2087, 2004.JAGS. 52: 2082-2087, 2004.

GI upset common, also watch for GI upset common, also watch for bradycardiabradycardia

Clinically meaningful benefit is debated Clinically meaningful benefit is debated from an EBM perspectivefrom an EBM perspective

Clinical support strongClinical support strong

PharmacologicPharmacologic

Memantine (Namenda)Memantine (Namenda) Indicated for moderate to severe dementiaIndicated for moderate to severe dementia Friendly side-effect profileFriendly side-effect profile Start at 5mg daily, target dose: 20 mg q Start at 5mg daily, target dose: 20 mg q

day day Studies suggest added benefit when used Studies suggest added benefit when used

with CIswith CIs Often used with those intolerant to CIsOften used with those intolerant to CIs Long standing use in GermanyLong standing use in Germany Debate on clinical impact/timing with use Debate on clinical impact/timing with use

of this medicationof this medication

GinkgoGinkgo

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

Antioxidants

Antioxidants beta carotene, vitamin A and vitamin E may increase mortality. JAMA 2007;297:842-857. NEJM 1997;336:1216-1222 Ann Int Med 2005;142:37-46 NEJM 2005;352:2379-2388; Am J Med 2007;120:180-184)

Dementia Dementia Therapy UpdateTherapy Update

Update on Dementia Update on Dementia MedicationsMedications

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

Challenging ArticleChallenging Article Bottom lineBottom line

Evidence of effectiveness is based on small Evidence of effectiveness is based on small effects found in poorly analyzed studieseffects found in poorly analyzed studies

AD drug studies need close scrutiny for AD drug studies need close scrutiny for methodologic errors and inflated benefitmethodologic errors and inflated benefit

Contrary to Cochrane ReviewsContrary to Cochrane Reviews conclusions were drawn “without a conclusions were drawn “without a

comprehensive assessment of the comprehensive assessment of the methodological quality of the trials.”methodological quality of the trials.”

Contrary to meta-analyses and American Contrary to meta-analyses and American Academy of NeurologyAcademy of Neurology No attempt “consider the quality of the No attempt “consider the quality of the

included trials.” included trials.”

Frustrated!Frustrated! Excellent reviewExcellent review Conflicts with Conflicts with

mentor’s experiencementor’s experience Conflicts with my Conflicts with my

hopes/limited hopes/limited experienceexperience

Re-evaluate my Re-evaluate my aggressive use of the aggressive use of the agentsagents

The need for the big, The need for the big, unbiased definitive unbiased definitive studystudy

Behavioral PharmacologyBehavioral Pharmacology

Dementia behaviors may improve Dementia behaviors may improve with cholinesterase inhibitorswith cholinesterase inhibitors

Wandering and pacing is NOT Wandering and pacing is NOT corrected with anti-psychoticscorrected with anti-psychotics

Best treated with behavior Best treated with behavior modification and caregiver education, modification and caregiver education, training and respitetraining and respite

CIs may reduce inpatient delirium CIs may reduce inpatient delirium episodesepisodes

AFP. 2003. 67: 2335-40.

Atypical AntipsychoticsAtypical Antipsychotics

Effectiveness of atypicals is firmly established Effectiveness of atypicals is firmly established in treating dementia-related psychosisin treating dementia-related psychosis

Includes Abilify (aripiprazole), Zyprexa Includes Abilify (aripiprazole), Zyprexa (olanzapine), Seroquel (quetiapine), Risperdal (olanzapine), Seroquel (quetiapine), Risperdal (risperidone), Clozaril (clozapine) and Geodon (risperidone), Clozaril (clozapine) and Geodon (ziprasidone)(ziprasidone)

Risperidone now available in a disintegrating Risperidone now available in a disintegrating tablet in 0.25mg-4mg doses and a long acting tablet in 0.25mg-4mg doses and a long acting injection (up to 50mg q 2 weeks)injection (up to 50mg q 2 weeks) Continue oral therapy for three weeks to get Continue oral therapy for three weeks to get

adequate leveladequate level

FDA Public Health Advisory, April 11, 2005

Risk of Atypical Risk of Atypical AntipsychoticsAntipsychotics

Class EffectClass Effect New black box warning of increased risk of New black box warning of increased risk of

death and “not approved for use in death and “not approved for use in dementia-related psychosis.”dementia-related psychosis.” Risk of death 1.6-1.7 x that of placeboRisk of death 1.6-1.7 x that of placebo Over a 10 week trial. 4.5% rate of death vs. Over a 10 week trial. 4.5% rate of death vs.

2.6% for the placebo group.2.6% for the placebo group. Mostly cardiovascular deaths or infectious Mostly cardiovascular deaths or infectious

(pneumonia)(pneumonia) Patient (caregiver) specific risk assessment and Patient (caregiver) specific risk assessment and

counselingcounseling

Cochrane Database of Systematic Reviews (2005)

Other agents:Other agents: Valproate for agitation- Insufficient EvidenceValproate for agitation- Insufficient Evidence Trazodone for agitation- Insufficient EvidenceTrazodone for agitation- Insufficient Evidence Haldol for agitation- Effective, side effects are Haldol for agitation- Effective, side effects are

a problema problem Zhiling decoction (herbal combination)- Zhiling decoction (herbal combination)-

insufficient evidenceinsufficient evidence Propentofylline (adenosine blocker and Propentofylline (adenosine blocker and

phosphodiesterase inhibitor)- limited evidence phosphodiesterase inhibitor)- limited evidence of benefitof benefit

Lecithin- not supportedLecithin- not supported Acetyl-l-carnitine (ALC)- not supported at this Acetyl-l-carnitine (ALC)- not supported at this

timetime

AFP. Vol. 69(6). March 15, 2004.

Screening for dementiaScreening for dementia

The USPSTF concludes that the evidence is The USPSTF concludes that the evidence is insufficient to recommend for or against insufficient to recommend for or against routine screening for dementia in older adults.routine screening for dementia in older adults. Age and educational level influences resultsAge and educational level influences results The problem of arbitrary cut pointsThe problem of arbitrary cut points Functional assessment can also detect dementia Functional assessment can also detect dementia

(FAQ)(FAQ) Clinical considerationsClinical considerations

MMSE: PPV in UNSELECTED groups is only fairMMSE: PPV in UNSELECTED groups is only fair Early recognition helpfulEarly recognition helpful We should screen when we suspectWe should screen when we suspect

Screening for depression Screening for depression and dementiaand dementia

New tools availableNew tools available Depression is very common in the Depression is very common in the

elderlyelderly See:See:

AFP 2004; 70: 1101-1110.AFP 2004; 70: 1101-1110.

SUMMARYSUMMARY::

Dementia is common in older adults but is Dementia is common in older adults but is NOT an inherent part of agingNOT an inherent part of aging

AD is the most common type of dementia, AD is the most common type of dementia, followed by vascular dementia and followed by vascular dementia and dementia with Lewy bodiesdementia with Lewy bodies

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

SUMMARYSUMMARY::

Primary treatment goals: Primary treatment goals: Enhance quality of life, Enhance quality of life, Maximize function by improving cognition, Maximize function by improving cognition,

mood, behaviormood, behavior

Treatment may use both medications and Treatment may use both medications and nonpharmacologic interventionsnonpharmacologic interventions

Community resources should be used to Community resources should be used to support patient, family, caregiverssupport patient, family, caregivers