Diagnosis and Initial Diagnosis and Initial Management of Management of

DementiaDementia

Nicolas Szecket & Shabbir AlibhaiNicolas Szecket & Shabbir AlibhaiUpdates by Sharif Missiha, PGY2Updates by Sharif Missiha, PGY2

AIMGP, MSHAIMGP, MSHDecember 9, 2004December 9, 2004

ObjectivesObjectives

Definition of dementiaDefinition of dementia

Basic work-up of dementiaBasic work-up of dementia

Role of neuroimagingRole of neuroimaging

““Cognitive-enhancing” drug therapyCognitive-enhancing” drug therapy

Ethical issues in dementiaEthical issues in dementia

Selected References - Selected References - DiagnosisDiagnosis

Practice Parameter: Diagnosis of dementia. Practice Parameter: Diagnosis of dementia. Report of the Quality Standards Report of the Quality Standards Subcommittee of the American Academy of Subcommittee of the American Academy of Neurology. Neurology 2001; 56:1143-53Neurology. Neurology 2001; 56:1143-53

Folstein MF, Folstein SE, McHugh PR. “Mini-Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading mental state”. A practical method for grading the cognitive state of patients for the clinician. the cognitive state of patients for the clinician. J Psychiat Res 1975; 12:189-98. J Psychiat Res 1975; 12:189-98.

Selected References - Selected References - TreatmentTreatment

Canadian Consensus Conference on Dementia. Canadian Consensus Conference on Dementia. Management of dementing disorders. Can Med Management of dementing disorders. Can Med Assoc J 1999; 160(12 Suppl)Assoc J 1999; 160(12 Suppl)

Mayeux R, Sano M. Treatment of Alzheimer’s Mayeux R, Sano M. Treatment of Alzheimer’s disease. N Engl J Med 1999; 341:1670-79disease. N Engl J Med 1999; 341:1670-79

Practice parameter: Management of dementia. Practice parameter: Management of dementia. Report of the Quality Standards Subcommittee Report of the Quality Standards Subcommittee of the American Academy of Neurology. of the American Academy of Neurology. Neurology 2001; 56:1154-66.Neurology 2001; 56:1154-66.

The CaseThe Case

82 y.o. female recently discharged from 82 y.o. female recently discharged from GIM with CAPGIM with CAP

Episodes of fluctuating LOC and Episodes of fluctuating LOC and confusion at initial hospital presentationconfusion at initial hospital presentation

Resolved in hospital with treatment of Resolved in hospital with treatment of pneumonia/hypoxia and low-dose pneumonia/hypoxia and low-dose HaloperidolHaloperidol

The CaseThe Case

PMHPMH

COPD x 5 yearsCOPD x 5 years

Type II Diabetes MellitusType II Diabetes Mellitus

OsteoarthritisOsteoarthritis

MedicationsMedications

pufferspuffers

Glyburide 2.5 mg BIDGlyburide 2.5 mg BID

Tylenol PRNTylenol PRN

The CaseThe Case

Lives with daughterLives with daughter

Progressive memory loss over 2 yearsProgressive memory loss over 2 years

Patient repeats herself, occasionally Patient repeats herself, occasionally disorienteddisoriented

Forgets to take some of her medicationsForgets to take some of her medications

Daughter is concerned about mother having Daughter is concerned about mother having ‘senile dementia’ and asks you to “check it ‘senile dementia’ and asks you to “check it out”out”

The CaseThe Case

Physical ExaminationPhysical Examination

BP 130/70 HR 80 reg RR 18BP 130/70 HR 80 reg RR 18

Cardio/resp exam normalCardio/resp exam normal

Abdominal exam normalAbdominal exam normal

Neurological exam no focal deficits, absent Neurological exam no focal deficits, absent ankle jerks, downgoing toesankle jerks, downgoing toes

Question 1Question 1

Does this woman have dementia?Does this woman have dementia?

Definition of Dementia: DSM-IVDefinition of Dementia: DSM-IV

Progressive decline in memory AND at least one Progressive decline in memory AND at least one other cognitive areaother cognitive area language, orientation, attention, praxis (skilled motor language, orientation, attention, praxis (skilled motor

function), visuo-spatial, abstraction, executive functionfunction), visuo-spatial, abstraction, executive function

Impairment of social, occupational, or personal Impairment of social, occupational, or personal functionfunctionChange from baselineChange from baselineIn the absence of depression or clouding of In the absence of depression or clouding of consciousness (i.e. delerium)consciousness (i.e. delerium)

See DSM-IVSee DSM-IV

Epidemiology of DementiaEpidemiology of Dementia

From the Canadian Study of Health & Aging:From the Canadian Study of Health & Aging:2.4% of Canadians aged 65-742.4% of Canadians aged 65-7411.1% aged 75-8411.1% aged 75-8434.5% aged 85+34.5% aged 85+Affects both sexesAffects both sexesIncreasing prevalence in long-term careIncreasing prevalence in long-term careUnderdiagnosed or misdiagnosed in 20%Underdiagnosed or misdiagnosed in 20% Misperception of “normal” aging processMisperception of “normal” aging process

Can Med Assoc J 1994; 150:899-913Can Med Assoc J 1994; 150:899-913

Why Bother Making a Why Bother Making a Diagnosis?Diagnosis?

Common illness, huge burden for patient, Common illness, huge burden for patient, family, and health care systemfamily, and health care system

Potentially reversible in small numberPotentially reversible in small number

““Cognitive-enhancing” drug therapy now Cognitive-enhancing” drug therapy now availableavailable

Prognostic implications (long-term planning re Prognostic implications (long-term planning re placement, estate, advance directives, etc.)placement, estate, advance directives, etc.)

Question 1Question 1

Does this woman have dementia?Does this woman have dementia?

Possibly. Not enough information to make diagnosis

Question 2Question 2

What else should be done at the What else should be done at the initial assessment?initial assessment?

Answer:• Further dementia history• Physical exam• Mental status examination

Initial AssessmentInitial Assessment

General Dementia HistoryGeneral Dementia HistoryDate of onset/nature of symptomsDate of onset/nature of symptomsPre-morbid level of functioningPre-morbid level of functioningNature of progression (if any) - rapid/gradual Nature of progression (if any) - rapid/gradual deterioration vs. “step-wise”deterioration vs. “step-wise”Family history of dementiaFamily history of dementiaUse of CNS toxic drugsUse of CNS toxic drugsHead injury (especially recent)Head injury (especially recent)Depressive symptomsDepressive symptoms

Initial AssessmentInitial Assessment

ADLs (bathing, dressing, feeding, toileting, ADLs (bathing, dressing, feeding, toileting, transferring, ambulation)transferring, ambulation)

Instrumental ADLs (shopping, cooking, Instrumental ADLs (shopping, cooking, finances, telephone use)finances, telephone use)

Home supports (family, friends, CCAC)Home supports (family, friends, CCAC)

Safety (falls, fires, wandering, meds, Safety (falls, fires, wandering, meds, driving, violence, etc.)driving, violence, etc.)

Initial AssessmentInitial Assessment

Mental Status ExamMental Status Exam

Use standardized simple instrument (e.g. Use standardized simple instrument (e.g. Folstein’s MMSE*)Folstein’s MMSE*) MMSE cut-off MMSE cut-off << 24/30 has 75-85% sensitivity, 24/30 has 75-85% sensitivity,

70-80% specificity70-80% specificityClock-drawing may improve sensitivityClock-drawing may improve sensitivity

Less reliable for limited English, extremes of Less reliable for limited English, extremes of formal educationformal education

Make sure patient is not deliriousMake sure patient is not delirious

*J Psychiatr Res 1975; 12:189-98*J Psychiatr Res 1975; 12:189-98

Initial AssessmentInitial Assessment

Physical ExamPhysical ExamMalnutrition (Subjective Global Assessment - Malnutrition (Subjective Global Assessment - Detsky et al.)Detsky et al.)

Focal neurologic deficitsFocal neurologic deficits

Parkinsonian features (remember TRAP)Parkinsonian features (remember TRAP)

Forget “frontal release” signs (i.e. glabellar Forget “frontal release” signs (i.e. glabellar tap, snout, pout, grasp, palmo-mental, etc.) - tap, snout, pout, grasp, palmo-mental, etc.) - not helpful in diagnosisnot helpful in diagnosis

Back to the CaseBack to the Case

Progressive difficulty with cooking, Progressive difficulty with cooking, aspects of self-careaspects of self-care

Occasionally wandering, getting lostOccasionally wandering, getting lost

Forgetting names of friendsForgetting names of friends

MMSE 17/30MMSE 17/30

Probable dementia, typical features of

Alzheimer’s Disease

Question 3Question 3

What basic investigations should be What basic investigations should be done to rule out reversible causes?done to rule out reversible causes?

Reversible CausesReversible Causes(3-5% of all dementias)(3-5% of all dementias)

HypothyroidismHypothyroidismDepression (“Pseudodementia”)Depression (“Pseudodementia”)Subdural HaematomaSubdural HaematomaDrug-Induced (narcotics, sedatives, anticholinergics, etc)Drug-Induced (narcotics, sedatives, anticholinergics, etc)B12 DeficiencyB12 DeficiencyAlcoholic DementiaAlcoholic DementiaMetabolic Encephalopathy (Ca, renal/liver failure) Metabolic Encephalopathy (Ca, renal/liver failure) NeurosyphilisNeurosyphilisNormal Pressure HydrocephalusNormal Pressure HydrocephalusBrain TumoursBrain TumoursSeizuresSeizures

Basic investigationsBasic investigations

• CBC

• Lytes/Creatinine

• TSH

• Glucose

• Calcium

• B12 (recommended by AAN)

CMAJ 1999; 160(12 Suppl)

Optional InvestigationsOptional Investigations

(In selected patients)(In selected patients)Serum B12 (if not done as matter of routine)Serum B12 (if not done as matter of routine)RBC Folate (e.g. alcoholic)RBC Folate (e.g. alcoholic)VDRLVDRLHIVHIVSPECT/PET perfusion scanning (research)SPECT/PET perfusion scanning (research)EEGEEGEvoked PotentialsEvoked PotentialsGenetic testing for AD or other not currently Genetic testing for AD or other not currently recommendedrecommended

*CMAJ 1999; 160(12 Suppl)*CMAJ 1999; 160(12 Suppl)

Irreversible CausesIrreversible Causes

Alzheimer’s Disease (60-70%)Alzheimer’s Disease (60-70%)

Cortical Lewy Body Disease (assoc with Cortical Lewy Body Disease (assoc with PD) (10-25%)PD) (10-25%)

Vascular (Multi-infarct) Dementia (10-Vascular (Multi-infarct) Dementia (10-20%)20%)

Fronto-Temporal Dementia (5%) Fronto-Temporal Dementia (5%)

Mixed Dementia (10-25%)Mixed Dementia (10-25%)

Miscellaneous (e.g. PSNP)Miscellaneous (e.g. PSNP)

Question 4Question 4

Should she have neuroimaging (CT Should she have neuroimaging (CT scan or MRI)?scan or MRI)?

Criteria for NeuroimagingCriteria for NeuroimagingAge <60Age <60

Rapid decline in mental or physical function (over 3-6 Rapid decline in mental or physical function (over 3-6 mo.) or short duration of dementia (<2 y.)mo.) or short duration of dementia (<2 y.)

New localizing neurologic signNew localizing neurologic sign

Recent head trauma or unexplained neurologic Recent head trauma or unexplained neurologic symptoms (e.g. headache, seizures)symptoms (e.g. headache, seizures)

History of any cancerHistory of any cancer

Anticoagulants or bleeding disorderAnticoagulants or bleeding disorder

History of incontinence or early gait disorder History of incontinence or early gait disorder

Gait disturbanceGait disturbance

Unusual/atypical presentationUnusual/atypical presentation

CMAJ 1999; 160(12 Suppl)CMAJ 1999; 160(12 Suppl)

NeuroimagingNeuroimaging

Useful in changing diagnosis and/or management Useful in changing diagnosis and/or management of 5-10% of patientsof 5-10% of patients

Contrast-enhanced CT improves yield for strokes Contrast-enhanced CT improves yield for strokes and tumours by 10-15%and tumours by 10-15%

Unclear if MRI (cost ~ $850-1000) superior to CT Unclear if MRI (cost ~ $850-1000) superior to CT (~$250-350)(~$250-350)

SPECT/PET useful in academic settings but not SPECT/PET useful in academic settings but not recommended routinelyrecommended routinely

AAN now recommends non-contrast CT or MRI in AAN now recommends non-contrast CT or MRI in initial evaluation of initial evaluation of allall patients patients

Neurology 2001; 56:1143Neurology 2001; 56:1143

Question 4Question 4

Should she have neuroimaging (CT Should she have neuroimaging (CT scan or MRI)?scan or MRI)?

Answer:

• CT head not indicatedTypical features of dementiaNo focal neurological deficitsNo high risk features

Question 5Question 5

Is there any treatment available?Is there any treatment available?

Classes of TherapyClasses of Therapy

Cognitive-enhancing drug therapyCognitive-enhancing drug therapy Mainly acetylcholinesterase inhibitorsMainly acetylcholinesterase inhibitors

Symptomatic management of behavioural Symptomatic management of behavioural disturbance e.g. neuroleptics, SSRIsdisturbance e.g. neuroleptics, SSRIsPotentially disease modifying agentsPotentially disease modifying agents Memantine, Vit E & Selegilene, Estrogen Memantine, Vit E & Selegilene, Estrogen

replacement, NSAIDs (more prophylaxis)replacement, NSAIDs (more prophylaxis)

Future directions (very interesting/exciting)Future directions (very interesting/exciting) Secretase modulators, immunization, chelatorsSecretase modulators, immunization, chelators

Cognitive-Enhancing Drug Cognitive-Enhancing Drug TherapyTherapy

Acetylcholinesterase InhibitorsAcetylcholinesterase Inhibitors Tacrine (Cognex - hepatotoxic)Tacrine (Cognex - hepatotoxic) Donepezil (Aricept)Donepezil (Aricept) Rivastigmine (Exelon)Rivastigmine (Exelon) Galantamine (Reminyl)Galantamine (Reminyl)

Acetylcholinesterase InhibitorsAcetylcholinesterase InhibitorsHas best current evidence of efficacyHas best current evidence of efficacyIncreases acetylcholine levels (major Increases acetylcholine levels (major depleted neurotransmitter in Alzheimer’s depleted neurotransmitter in Alzheimer’s disease)disease)May have role in other dementias (esp. Lewy May have role in other dementias (esp. Lewy Body Dementia, mixed dementia) – no real Body Dementia, mixed dementia) – no real evidenceevidenceMost evidence/experience with Donepezil Most evidence/experience with Donepezil (Aricept)(Aricept)

Donepezil (Aricept)Donepezil (Aricept)Once daily doseOnce daily doseWell tolerated (7-16% discontinuation rate, Well tolerated (7-16% discontinuation rate, only significant s/e are cholinergic – N + V, only significant s/e are cholinergic – N + V, Dx, but no serious side effects)Dx, but no serious side effects)3-6 month trial to determine benefit3-6 month trial to determine benefitCannot predict who will benefitCannot predict who will benefitCurrently covered by ODB under limited use Currently covered by ODB under limited use criteria ($5/day otherwise)criteria ($5/day otherwise)

Donepezil (Aricept)Donepezil (Aricept)(Rule of thirds)(Rule of thirds)

20-35% major benefit (reversal of cognitive 20-35% major benefit (reversal of cognitive deterioration by 6-12 months)deterioration by 6-12 months)30-40% minor benefit (stabilization of 30-40% minor benefit (stabilization of progression)progression)25-40% no benefit25-40% no benefit

The AD2000 study, the only non-drug company The AD2000 study, the only non-drug company sponsored study, found no benefit in terms of sponsored study, found no benefit in terms of disability progression or entry into institutional disability progression or entry into institutional carecare

Question 5Question 5

Is there any treatment available?Is there any treatment available?

Answer:Answer:

Options discussedOptions discussed

Started on Donepezil 5 mg ODStarted on Donepezil 5 mg OD

To be reassessed in 3 monthsTo be reassessed in 3 months

When to Refer?When to Refer?

Depending on comfort level of Internist:Depending on comfort level of Internist:

Atypical symptoms/unusual featuresAtypical symptoms/unusual features

Rapid progressionRapid progression

Behavioural disturbancesBehavioural disturbances

Initiation/monitoring of treatmentInitiation/monitoring of treatment

Associated possible depressionAssociated possible depression

Caregiver burnout/stressCaregiver burnout/stress

Ethical issues – for discussionEthical issues – for discussion

Disclosure of diagnosisDisclosure of diagnosisDriving – obligation to report in OntarioDriving – obligation to report in OntarioCaregiver burdenCaregiver burdenInstitutionalizationInstitutionalizationAdvanced directivesAdvanced directivesCultural relevance (and sensitivity on the part of the Cultural relevance (and sensitivity on the part of the physician)physician)Depression (diagnosis and treatmentDepression (diagnosis and treatment

Watch for anticholinergic SE’s from antidepressants – may Watch for anticholinergic SE’s from antidepressants – may worsen dementia symptomsworsen dementia symptoms

Behavioural disturbances and their treatmentBehavioural disturbances and their treatment