Office-based Cognitive Testing: Cases

1. Office-based Cognitive Testing: Cases Paul R. Solomon, PhD Professor of Psychology /Neuroscience Williams College Visiting Professor of Neurology Boston University School of Medicine Clinical Director Boston Center for Memory Clinical Director The Memory Clinic DEMENTIA: A Comprehensive Update Boston, June 7-10, 2017

2. Disclosure (past 12 months) Grant Support: AstraZeneca, AVID, Axovant, Biogen, Cambridge Cognition, Eli Lilly, Forum Pharmaceuticals, Hoffman-LaRoche, Neuronetrix, ONNIT Labs, TransTech Pharma Consulting:, Boehringer-Ingelheim, Eli Lilly, General Electric, Neuronetrix, Novartis Royalties: Elsevier(Saunders), Psychological Assessment Resources

3. Steps in Diagnosis / Differential Diagnosis Decision that dementia is present Determination of cause of dementia (differential diagnosis)

4. Steps in Diagnosis Cognitive Eval. Decision that dementia is present Hx Cognitive Complaints Neuro Exam Lab Eval Determination of cause of dementia (differential diagnosis) Imaging Cognitive Profile

5. Approaching Differential Diagnosis • Up to 75% of cases will include AD • Start with the hypothesis that AD is the cause in full or in part • Be aware of the signs/symptoms of other common causes of dementia • Cases • Real cases • Focus on most common causes of dementia

6. Other Common Causes Of Cognitive Impairment Dementias Medication Side Effects ~5-10% FRONTAL ~5% VASCULAR ~ 15 - 25% AD ~ 75% MCI ~3-22% LEWY BODY ~ 20% NON- DEGEN DEM ~ 5% • Depression • MDD ~3% • Subsyndromal • ~ 15-27%

7. Office Based Assessment Procedures Neuropsychological Tests Informant Completed Questionnaires

8. Neuropsychological Tests Advantages Disadvantages Commonly used, many choices Requires only patient (not the caregiver) to be present Requires patient to be present Requires patient to be cooperative Requires staff time to administer

9. Informant Questionnaires Advantages Disadvantages Does not require patient to be present and / cooperative Requires minimal staff time to administer Requires caregiver to be present

10. Neuropsychological Tests: Montreal Cognitive Assessment (MOCA) Advantages Disadvantages (Nasreddine et al. JAGS, 2005) Test and Instructions freely available on the web (www.mocatest.org) Clear Instructions and scoring Translated into 30 + languages Covers multiple cognitive domains (orientation, memory, attention, language, executive function, visuospatial function) Accuracy > MMSE for AD and MCI Takes 10 minutes to administer

11. Montreal Cognitive Assessment (MOCA)

12. MOCA + 5 ≅ MMSE

13. Informant Completed Alzheimer’s Disease Caregiver Questionnaire (ADCQ) Advantages Disadvantages Test and Instructions freely available on the web (bostonmemory.com) 18 item YES / NO questionnaire Sensitivity > 90%, Specificity > 85% Minimal staff time required Requires presence of caregiver Not validated for self-report by patient Solomon et al. International Psychogeriatrics, 2003

16. Domains Evaluated MOCA ADCQ Visuospatial /Executive Naming Memory Attention Abstraction Delayed Recall Cued Recall (optional) Abstraction Recent Memory Executive Function Language Visuospatial Mood & Behavior Progression

17. Case 1Patient Profile 88-years old Female 19 years of education (2 bachelors, 1 masters degree) Taught at the public school and college level Plays the organ Plays golf

18. Medical Medical History Current Medications • Levoxyl • multivitamin + iron • cortisone injection • Metamucil • calcium • B6 • Hypothyroidism • Mild anemia • Mild arthritis Physical / Neurological Exam • Unremarkable Laboratory Results • Within normal limits

19. Imaging Studies CT scan w/o contrast Impression: Moderate cerebral atrophy No evidence of acute cortical infarction or intracranial bleed

21. History of Cognitive Complaints Onset: 3 years ago, insidious Initial symptoms: deficits in recent memory Progression: progressive - particularly in the last 1–2 years Current Complaints: Memory Repeats questions multiple times within same conversation Rapidly forgets conversations Executive Function Bills now disorganized Can no longer organize medications Language Word finding difficulties Other aspects of cognition intact

22. Cognitive Assessment • MMSE = 24 • Missed 3/3 delayed item recall • Disoriented time, place • MOCA =19 • Missed 5/5 delayed item recall • Missed 4/5 with cues • Trailmaking B impaired • Verbal Fluency impaired (8 animals / 1 minute) • Clock Drawing impaired (hands set incorrectly) • Alzheimer’s Disease Caregiver Questionnaire (ADCQ) - positive • Endorsed forgetting conversations / repeating questions • Endorsed deficits in executive function • Problems have been Progressive

24. MOCA Cued Recall

25. Function • ADLs intact • IADLs mildly impaired • Living independently • Difficulty paying bills • Difficulty managing medications Impairment index = 15%

26. Differentials Alzheimer’s disease Mild Cognitive Impairment

27. Diagnosis Alzheimer’s disease - early stages

28. Diagnostic Criteria – Probable AD Dementia Present  Presenceof significant cognitive decline documented by knowledgeable informant and neuropsych. testing  Interferes with independence in everyday activities  Impairment is in a minimum of 2 domains Probable AD Dementia  Insidious onset (months / years)  Clear cut worsening  Initial deficits are in memory (amnestic) or other cognitive area ( non-amnestic) such as language, visuospatial, executive.  No evidence for other dementing disorder

29. Why is this not MCI? The Concept of MCI due to AD was introduced in the 2011 NIA-AA criteria DSM-5 refers to this as Minor Cognitive Disorder due to AD Both NIA-AA and DSM-5: Assumes that AD pathology is present and patient will eventually progress to clinical AD Recognizes that biomarkers will eventually be available (e,g., amyloid and Tau PET, volumetric MRI) and will add confidence to this diagnosis

30. MCI due to AD AD early stages

31. Differential Diagnoses

32. Case 2Patient Profile 71 year-old Female Living independently 12 years education Retired Home Health Aide (1980s) Recent death of companion

33. Medical Medical History Current Medications • Levoxyl • multivitamine + iron • cortisone injection • Metamucil • calcium • B6 Laboratory Results • Within normal limits • Hypercholesterolemia • Left hip replacement • Status post cholecystectomy • Arthritis in many joints • L5 diskectomy Physical / Neurological Exam • Parkinsonism • Rigidity

34. Imaging Studies CT scan w/o contrast Impression Generalized atrophy prominent in presylvian area Old white matter ischemic changes Old right basal ganglia lacunar infarct

36. History of Cognitive Complaints Onset: 2-3 years Initial symptoms: becoming lost in familiar setting Progression:gradual Current Complaints: Memory Mild deficits in recent memory Executive Function Difficulty managing checkbook Can no longer organize medications Attention Fluctuating

37. Cognitive Assessment • MMSE = 26 • Disoriented to place • Could not copy complex figure • MOCA = 22 • Missed 1/5 delayed item recall • Missed 0/5 with cues • Trailmaking B impaired • Clock Drawing impaired, could not copy cube • Impaired attention, digits forward • Alzheimer’s Disease Caregiver Questionnaire (ADCQ) - positive • Endorsed visuospatial problems (e.g., becoming lost) • Endorsed deficits in executive function • Problems are progressive

38. Clock Drawing(from MOCA)

39. Function • ADLs and intact • IADLs impaired • Impairment Index = 46%

40. Differentials AD MCI Lewy Body Disease

41. Diagnosis Dementia with Lewy Bodies (DLB)

42. Diagnostic Criteria Central Features (essential)  Dementia Present Impaired executive function, attention, and visuospatial ability often prominent Memory impairment may or may not be prominent initially

43. Diagnostic Criteria Core Features (2 for probable, 1 for possible LBD)  Fluctuating cognition with pronounced variation in attention and alertness Recurrent visual hallucinations, well formed and detailed -- Often or people or animals -- Often initially present around sleep/wakefulness transitions Spontaneous features of parkinsonism

44. Differential Diagnoses

45. Case 3Patient Profile 67 year-old male Retired truck driver with 12 years of education Premorbid IQ in average range

46. Medical Medical History Current Medications • Simvastatin • Lisinopril • Metroprolol • ASA 325 • Procardia • donepezil (10 mg) • Hypercholestremia • Hypertension • Enlarged prostate (not thought to be cancer) Physical / Neurological Exam • Unremarkable Laboratory Results • Within normal limits

47. Imaging Studies MRI scattered T2 hyperintensities some atrophy PET Hypometabolism in frontal lobes

48. Insert MRI scan

49. History of Cognitive Complaints Onset: 6 years ago, insidious Initial symptoms: behavioral Progression: progressive - particularly in the last 2-3years Current Complaints: Memory Recent memory deficits, especially in past year Executive Function Difficulty with financial decisions – wife now manages finances Difficulty organizing meals (no longer cooks) and household projects Language Word finding difficulties Other aspects of cognition intact

50. Cognitive Assessment • MMSE = 25 • Missed 2/3 delayed item recall • Difficulty with WORLD backwards • MOCA = 21 • Missed 3/5 delayed item recall • Missed 0/5 with cues • Trailmaking B impaired • Verbal Fluency impaired (6 animals / 1 minute) • Alzheimer’s Disease Caregiver Questionnaire (ADCQ) - positive • Endorsed forgetting conversations • Endorsed deficits in executive function • Problems are progressive