HOW TO EXAMINE PATIENTS WITH DEMENTIA Serge Gauthier, MD, FRCPC McGill Centre for Studies in Aging Douglas Mental Health Research Institute

OUTLINE Usual clinical presentation of dementia Diagnostic criteria for the common degenerative dementias Natural history of AD Cases

CLINICAL PRESENTATION OF DEMENTIA Decline in intellectual abilities (memory plus one other domain) Interfering with social or occupational life

CLINICAL PRESENTATION OF DEMENTIA Decline in intellectual abilities (memory plus one other domain) Interfering with social or occupational life

CLINICAL PRESENTATION OF DEMENTIA - MEMORY Do you need reminders for appointments? Do you forget birthdays? (Women only!) Do you look for things at home? Do you remember recent conversations? Do you need to read back a page in your book to get back into the story?

CLINICAL PRESENTATION OF DEMENTIA - LANGUAGE Do you look for words? – do you say “give me the thing there…what do you call it?” Do you have trouble finishing your cross- word puzzles? Do you still do ‘Mystery words’?

CLINICAL PRESENTATION OF DEMENTIA - PRAXIS Do you still fix things in the house? Do you have trouble using your computer, using the phone? Do you have difficulties using kitchen appliances? Do you need help to get the shower running?

CLINICAL PRESENTATION OF DEMENTIA - GNOSIS Do you have difficulties recognizing people? Do you have trouble with directions when driving?

CLINICAL PRESENTATION OF DEMENTIA – EXECUTIVE ABILITIES Do you need help playing a card game? Do you find it difficult to plan a meal for the family? Do you need help to pay your bills on time? Do you need help to take your pills?

CLINICAL PRESENTATION OF DEMENTIA Decline in intellectual abilities (memory plus one other domain) Interfering with social or occupational life

CLINICAL PRESENTATION OF DEMENTIA – MOST SENSITIVE ADLs Using phone and other means of communication Planning an outing and completing it efficiently Using medication safely Using money appropriately

CLINICAL PRESENTATION OF DEMENTIA – MOOD AND BEHAVIOR Apathy (more quiet, socially withdrawn) Anxiety & depression (worries about the future, about money) False beliefs (blames spouse when looking for things) Irritability (when spouse takes over finances, when making mistakes)

CLINICAL PRESENTATION OF DEMENTIA There may be little insight and reporting is done by family Patients are nearly always brought in by someone There is often need for additional information (other family member, SW or OT going to the house)

ASSESSMENT OF DEMENTIA IN CLINICAL PRACTICE History with reliable informant is key to diagnosis Physical & neurological examination MMSE & MoCA Recommended blood work: CBC, TSH, lytes, Ca, glycemia. Brain CT or MRI without enhancement optional but done in most cases.

MoCA ►One-page ► 30-point scale ► 10 minutes to administer

OUTLINE Usual clinical presentation of dementia Diagnostic criteria for the common degenerative dementias Natural history of AD Cases

DIAGNOSTIC CRITERIA FOR PROBABLE AD (90% accuracy) Dementia established clinically, eg deficit in two or more areas or cognition, interfering with daily life, progressing gradually No disturbance of consciousness Onset between 40 and 90 (below 65: early onset) Absence of other brain or systemic disease that could account for the dementia

PROPOSAL FOR MODIFIED NINCDS-AA DIAGNOSTIC CRITERIA – AD DEMENTIA (McKhann et al, A&D 7, 263-9, 2011) No age specification Memory decline not mandatory for the two cognitive domains affected Changes in personality, impaired motivation or initiative as a possible domain Probable AD: documented cognitive decline or positive biomarker

BIOMARQUERS FOR AD * Amyloid build up - CSF Aß42 (low) - PET amyloid (high) * Evidence of neuronal injury - CSF tau (high) - MRI (atrophy) - PET-FDG (hypometabolism)

DIAGNOSTIC CRITERIA FOR DEMENTIA PROBABLY DUE TO AD USING BIOMARKERS (Modified from McKhann et al, 2011) Aß Neuronal injury Probable AD with + + high likelihood Probable AD with + or untested untested or + intermediate likelihood Probable AD dementia untested or conflicting results Possible AD dementia + + (atypical clinical presentation) * Unlikely AD dementia - -

CRITERIAS FOR VASCULAR DEMENTIA (VaD) Decline in two or more cognitive abilities interfering with daily life but not caused by the physical effects of stroke Evidence of stroke by history, physical exam or brain imaging Temporal relationship between dementia and stroke (within 3 months of a stroke)

CRITERIAS FOR DEMENTIA WITH LEWY BODIES (DLB) Progressive intellectual decline interfering with daily life One or two of * fluctuations of cognition * visual hallucinations * spontaneous parkinsonism * Supportive features: REM Behavior Disorder, neuroleptic hypersensitivity

CRITERIAS FOR PARKINSON DISEASE DEMENTIA (PDD) Idiopathic PD (2 of rigidity, bradykinesia, resting tremor) Impairment of attention, executive and visuo-spatial abilities Often with visual hallucinations

OUTLINE Usual clinical presentation of dementia Diagnostic criteria for the common degenerative dementias Natural history of AD Cases

PROGRESSION OF SYMPTOMS IN ALZHEIMER’S DISEASE Lovestone & Gauthier 2000

STAGING OF AD: THE GLOBAL DETERIORATION SCALE (Reisberg) 1, 2: normal or minimal cognitive complaints 3: early cognitive impairment (MCI) 4, 5: mild to moderate dementia 6, 7: severe dementia

OUTLINE Usual clinical presentation of dementia Diagnostic criteria for the common degenerative dementias Natural history of AD Cases

CASE 1 Woman age 82 with progressive memory decline over 2 years False beliefs of “people stealing things from her” MMSE 23/30 Good general health “Normal for age” head CT scan

CASE 1 Likely diagnosis? Any extra tests?

CASE 2 Man age 82 needing reminders for appointments, forgetting conversations, once could not find his car on the street, over 2 years MMSE 22/30 Diabetes type 2; labile HBP CT with mild WMC (capping) and one lacunar infarct in right external capsule

CASE 2 Likely diagnosis? Any extra tests?

CASE 3 Woman age 72 needing reminders for appointments, forgetting conversations for 1 year Thinks that there are other persons in her house. Sets table for extra people. MMSE 24/30 CT mild cortical atrophy

CASE 3 Likely diagnosis? Any extra tests?

CASE 3 PET-FDG with occipital hypometabolism If available: DAT scan

CASE 4 Man age 40 making mistakes at work (forgets orders from customers) for 1 year Irritable at home since wife has to supervise finances. Mother had AD died at age 45. MMSE 21/30 CT mild cortical atrophy

CASE 4 Likely diagnosis? Any extra tests?

CASE 4 PS1 mutation confirms EOFAD.

CASE 5 Man age 52 making mistakes at work (pharmacist) for 1 year Irritable since partner at work has to supervise him. Makes inapropriate jokes in restaurants. Mother had a dementia, died at age 60. MMSE 26/30 CT mild cortical atrophy especially right anterior temporal

CASE 5 Likely diagnosis? Any extra tests?

CASE 5 PET-FDG right fronto-temporal hypometabolism SPECT right fronto-temporal hypometabolism Genetic testing confirms a progranulin mutation