Identifying Early Cognitive Impairment 11 th Annual GTA Primary Care Symposium

1. Sharon Cohen MD FRCPC November 9, 2013 Identifying Early Cognitive Impairment11th Annual GTA Primary Care Symposium Toronto Memory Program

2. Objectives Following this talk, participants will: • Be able to differentiate between normal aging, mild cognitive impairment and dementia • Understand the rationale for detecting early cognitive impairment • Recognize appropriate situations for screening • Identify appropriate cognitive screening tools • Appreciate recommendations and options for management of early cognitive impairment S.Cohen Toronto Memory Program

3. Disclosures Research Grants, Advisory Board Member, Speaker Honoraria from: AbbVie; Baxter; Genentech; Lilly; Lundbeck; Merck; Novartis; Pfizer; Roche; Servier; TauRx S.CohenToronto Memory Program

4. Background • Individuals are increasingly concerned about their cognitive health • Life expectancy keeps rising (2009: M:79; F:84) • Aging is associated with predictable cognitive changes that are not pathological • Aging is also the main risk factor for AD S.Cohen Toronto Memory Program S.Cohen Toronto Memory Program

5. Am I developing Alzheimer’s Disease? S.Cohen Toronto Memory Program

6. Am I developing Alzheimer’s Disease? S.Cohen Toronto Memory Program

7. Pathological Signature of AD amyloid tau

8. Early Detection Allows For: • Treatment of reversible and/or exacerbating factors (e.g., depression, sleep apnea, drug side effects, thyroid deficiency) • Optimization of patient care through education, support services, medications • Planning for future care • Participation in clinical trials • Care and support for caregivers S.Cohen Toronto Memory Program

9. Who to Screen for Cognitive Impairment? Current guidelines for screening: • No for population screening • Yes for case finding • Cognition should be assessed whenever there is a concern re: cognitive decline from any of: • The Patient • An Informant • The Clinician S.Cohen Toronto Memory Program

10. Barriers to Early Detection • ≥ 50% dementia cases go unrecognized in primary care • Canadian FPs identify the main barriers to identification and management of dementia as: • Limited training on dementia • Diagnostic uncertainty • Lack of access to resources (e.g., specialists) • Lack of time PimlottNJ et al. Can Fam Physician 2009; 55(5):508-9. World Health Organization. Dementia: A Public Health Priority. 2012. Available at: http://www.who.int/mental_health/publications/dementia_report_2012. Accessed: February 27, 2013. S.Cohen Toronto Memory Program

11. Dementia Decline in two or more cognitive domains Significant impact on daily function Alzheimer’s disease the most common cause in those over age 65 S.Cohen Toronto Memory Program

12. Mild Cognitive Impairment Decline in one or more cognitive domains Daily function relatively intact Many possible underlying causes High risk for progression to dementia S.Cohen Toronto Memory Program

13. Age Associated Cognitive Decline (AACD) Starts as early as the 4th decade Decline in multiple cognitive domains - but within 1.5 SD of norm Characterized by a reduction in: Speed of recall; Reaction time; Incidental learning; Source memory; Ability to shift set/multitask S.Cohen Toronto Memory Program

14. AACD: The Good News Many aspects of cognition remain stable or improve: Semantic memory remains strong Procedural memory remains strong Insight, judgment, decision making remain strong or increase Vocabulary continues to increase S.Cohen Toronto Memory Program S.Cohen Toronto Memory Program

15. John North PhD Philosophy Age 93 S.Cohen Toronto Memory Program

16. AACD versus MCI AACD MCI Concern voiced regarding cognitive decline Objective cognitive deficits in one or more domains Relatively preserved daily function • Concern voiced regarding cognitive decline • No objective deficits on testing (scores within 1.5 SD) • Preserved daily function S.Cohen Toronto Memory Program

17. MCI versus Dementia MCI Dementia Concern re: change in cognition voiced by patient or informant Objective cognitive deficits >1.5 SD for age and education in two or more domains Daily function significantly impaired • Concern re: change in cognition voiced by patient or informant • Objective cognitive deficits >1.5 SD for age and education in one or more domains • Daily function relatively preserved S.Cohen Toronto Memory Program

18. Cognitive Assessment Options • Bedside paper and pencil test: e.g., MMSE, CDT, MoCA, Quick Screen, MIS, Mini-Cog • Detailed neuropsychological test batteries: e.g., Weschler, Stroop, Wisconsin Card Sort • Computerized screening tests: e.g., Cognigram; CogSport; Cognistat S.Cohen Toronto Memory Program

19. Paper and Pencil Screening Tools • Majority designed to screen for dementia and are insensitive for mild deficits • MMSE sensitive to moderate severity dementia but unable to distinguishing AACD from MCI from early dementia • Of bedside paper and pencil tests, only MoCA is sensitive for MCI (90% sensitivity versus 17% for MMSE in MCI) S.Cohen Toronto Memory Program

20. Neuropsychological Testing • May assists in diagnosis of atypical cases, e.g., those with non-amnestic deficits • Lengthy test sessions; limited availability; expensive for patient • Not required for routine diagnostic work-up of dementia (CCCDTD) Chertkow H et al. Can J Neurol Sci 2001; 28(Suppl 1):28-41; Chui H, Zhang Q. Neurology 1997; 49(4):925-35; Jacova C et al. Alzheimers Dement 2007; 3(4):299-317. S.Cohen Toronto Memory Program

21. Computerized Cognitive Screening Tools • Used extensively in clinical trials for safety monitoring • Can provide more objective and reliable testing • Can incorporate flexibility in test paradigm • Can free up MD time, staff, resources S.Cohen Toronto Memory Program

22. Cognigram (CogState) • Non-verbal, computerized test using playing cards • Detects subtle cognitive change at short intervals • Designed to be culturally and educationally neutral with minimal language requirement • Sensitivity = 81% for MCI; 100% for AD • Specificity = 82% for MCI; 92% for AD • Good correlation with neuropsychological tests Darby DG et al. J Alzheimers Dis 2011; 27(3):627-37; Dingwall K, Carney S. Australas Psychiatry 2009;17(Suppl 1):S47-50; Lim YY et al. J Clin Exp Neuropsychol2012; 34(4):345-58; Maruff P et al. Presented at: AAIC 2013. S.Cohen Toronto Memory Program

23. Cognigram: Demonstration

24. Differences in Cognigram Performance in MCI, Alzheimer’s disease, and Healthy Controls Difference from healthy controls (z-scores) Lim YY et al. J Clin Exp Neuropsychol 2012; 34(4):345-58.

25. Determining Functional Impairment • The weakest link in assessing mild patients • No problem determining once BADL impaired • However, mild patients may still be independent in IADL but: • Not at their previous level • No longer performing IADL which are or would be problematic • Therefore must consider previous level as baseline • Detects subtle cognitive change at short intervals • Designed to be culturally and educationally neutral with minimal language requirements • Sensitivity = 81% for MCI; 100% for AD • Specificity = 82% for MCI; 92% for AD • Good correlation with neuropsychological tests S.Cohen Toronto Memory Program

26. A Few Words About Biomarkers Revised Diagnostic Criteria for AD (NIA-AA 2011) recognizes 3 stages of AD: Preclinical AD MCI due to AD AD Dementia Proposes use of biomarkers (3 imaging; 2 CSF) to enhance diagnostic certainty (particularly in the pre-clinical and MCI stage of disease) S.Cohen Toronto Memory Program S.Cohen Toronto Memory Program

27. PET Amyloid Imaging

30. The Window of Opportunity Primary Prevention: The long pre-symptomatic stage of AD suggests that interventions to prevent disease should start in young to mid life Secondary Prevention: Early detection of AD at a pre-symptomatic or mild stage allows for interventions prior to the development of significant brain damage and functional impairment S.Cohen Toronto Memory Program S.Cohen Toronto Memory Program

31. April 2012: FDA Approves Amyvid for Clinical Use Amyvid™ (Florbetapir F 18 Injection) The first agent approved for clinical use to detect amyloid plaque in patients under evaluation for AD Not yet available in Canada… S.Cohen Toronto Memory Program

32. Management of MCI • Requires monitoring over time due to high risk of progression (AAN; CCCD3) • Requires investigations for underlying etiology including identification and management of vascular factors (NIA-AA; CCCDTD) • Includes promotion of a brain healthy lifestyle: physical & mental activity; social engagement; dietary pattern; sleep hygiene; stress management • Consider referral for secondary prevention trials S.Cohen Toronto Memory Program

33. Recommendations for MCI/Dementia in those under 65 (“early onset dementia”) • All patients with early onset dementia should be referred to a memory clinic, preferably with access to genetic counselling & genetic testing • Physicians should be sensitive to special issues associated with early onset dementia, e.g., employment, family responsibilities, access to age appropriate support services Gauthier S et al; CCDTD4 participants. Can Geriatr J 2012; 15(4):120-6. S.Cohen Toronto Memory Program

34. Driving and MCI/Dementia: CCCD3 Recommendations • Counsel patients that driving cessation is an inevitable consequence of progressive dementias and planning for this should occur early • Cognitive tests are insufficient to judge driving ability • Gold standard: specialized on-road driving evaluation; patients have a legal right to this test • Patient with who are deemed safe to drive require re-evaluation q 6–12 months or sooner if indicated Hogan DB et al. CMAJ 2008; 179(8):787-93. S.Cohen Toronto Memory Program

35. Summary • Cognitive concerns require cognitive screening • MoCA & Cognigram are sensitive tools for MCI and early dementia • Determining functional impairment (to distinguish dementia from MCI) requires thoughtful history taking • MCI management includes monitoring, attention to risk factors, and consideration of prevention trials • Those < 65 have additional needs & should be referred • Biomarkers enhance diagnostic certainty and will be of increasing importance over the next several years S.Cohen Toronto Memory Program

36. Am I developing Alzheimer’s Disease? S.Cohen Toronto Memory Program