Post-stroke Dementia: A review with clinical tips and pearls Rick Swartz HBSc , MD, PhD FRCP(C)

2. Post-stroke Dementia: A review with clinical tips and pearls Rick Swartz HBSc, MD, PhD FRCP(C) Division of Neurology, Department of Medicine Director, University of Toronto Stroke Program Sunnybrook HSC, University of Toronto Nov 9th, 2013

3. Disclosures • Ad board: Bristol-Myers Squibb • Will discuss off-label use of AChE-inhibitors – no relationships • Stroke neurologist.

4. Learning Objectives • To highlight the definitions, frequency, causes and impact of post-stroke cognitive impairment • To review recent clinical guidelines, tips and pearls to help identify, assess and manage post-stroke dementia

5. TIP #1: Definitions are problematic (everyone knows, no-one can define) Love Young Stroke Dementia…

6. Defining Stroke • PEARL: “Stroke” is a concept, not a diagnosis. • Damage to brain tissue due to alterations in blood flow. • Ischemic (85%), hemorrhagic (15%) • OTHERS: SAH, Venous sinus thrombosis • Full diagnosis requires subtyping, localization and etiological assessment: • e.g. L MCA territory infarct with L M1 occlusion from cardioembolic source (atrial fibrillation) R.H. Swartz, University of Toronto

7. Post-Stroke • Stroke is an important concept: • 1 stroke every 10 minutes in Canada • #1 leading cause of adult neurological disability • 3rd leading cause of death worldwide • Overall, ~20% fatal; 60-75% some disability • ~50,000 Canadians annually have strokes resulting in death or serious disability. • The toll of stroke is more than motor and speech… R.H. Swartz, University of Toronto

8. Dementia • PEARL: Dementia is a syndrome, not a diagnosis. • “Headache” • “Shortness of breath” • Multiple causes • Degenerative (AD, DLB, PD) • Non-degenerative (stroke, trauma, infectious, autoimmune) • Multiple pathologies (amyloid, tau, alpha-synuclein, ubiquitin, necrosis/gliosis…) R.H. Swartz, University of Toronto

9. Dementia: Top 4 Neurodegenerations • Alzheimer’s Disease – amyloidopathy (70%) • Vascular Dementia – vasculopathy (5-10%) • Lewy Body Disease – synucleinopathy (15%) • Frontal Temporal Degeneration – tauopathy (5-10%) • Mixed Disease common: e.g. AD/CVD; AD/LBD • VaD, AD & mixed ~80% of all dementias R.H.Swartz, University of Toronto

10. Definition of Dementia DSM IV (R) • Memory impairment • At least one of: • Language difficulty; • Apraxia; • Visuospatialdifficulty; • Executive dysfunction • Impaired occupational or social functioning • Decline from previous level of functioning

11. NEW Definition of Dementia - DSM5 • Demotes the centrality/requirement of memory • Replaces “dementia”with Major and Minor Neurocognitive Disorder, depending on degree of autonomy in ADL’s www.dsm5.org

12. Definitions and Terms • Vascular Dementia • Vascular Cognitive Impairment • MCI – v • V-CIND (cognitive impairment no dementia) • Major Neurocognitive Disorder (DSM5) • Minor Mild Neurocognitive disorder (!?) R.H.Swartz, University of Toronto

13. VCI (Gorelick, Stroke 2011) R.H.Swartz, University of Toronto

14. VCI (Gorelick, Stroke 2011) R.H.Swartz, University of Toronto

15. VCI (Gorelick, Stroke 2011) R.H.Swartz, University of Toronto

16. VCI TIA! (Gorelick, Stroke 2011) R.H.Swartz, University of Toronto

17. TIP #2: We are getting older.

18. 1999 2030 Males Females Males Females Age Age 100+ 100+ 80 80 60 60 8 6 4 2 0 2 4 6 8 8 6 4 2 0 2 4 6 8 40 40 Percentage of population Percentage of population 20 20 0 0 • Both stroke and dementia are increasing problems in aging society(dementia 1/12 over 65; 1/3 over 85) • Aging is a risk for all forms of stroke and dementia • More parents than children! United Nations 1999 R.H.Swartz, University of Toronto

19. The Boomer Bulge 2001 2011 2021

20. Prevalence • AD prevalence doubles every 4.3 years • VaD prevalence doubles every 5.3 years • Covert vessel disease: 23% lacunes; 95% hyperintensities), both associated with increased risk of stroke and dementia R.H.Swartz, University of Toronto

21. TIP #3: Strokes are bad for your brain Mechanisms of dementia: Strategic infarct Multi-infarct SIVD (Subcortical ischemic vascular dementia) Specific diseases (CADASIL, CAA)

22. Multiple Lacunae Binswanger’s /CADASIL VCI: A Heterogeneous Disorder Cardiovascular Risk Factors Hypertension Diabetes Genetics Hypercholesterolemia Heart Disease Damage to Cerebral Vasculature Multiple Distinct Pathologies Large Vessel Infarcts Small Vessel Infarcts Hypoperfusion Hemorrhage • Strategic Single Infarcts • Multi-infarct Dementia • Chronic SDH • SAH • ICH • Global (e.g., cardiac arrest) • Hypotension Final Common Pathway Damage to critical cortical and subcortical structures Damage/interruption of subcortical circuits and projections Cholinergic transmission VCI/VaD Courtesy of R Schindler

23. Strategic Infarct dementia 72 yr old man presented with sudden onset confusion Short term Memory Loss, anomia and executive dysfunction persisted R.H.Swartz, U of T.

24. Multi-Infarct dementia • Mailman at age 39 suffered • Right and left hemisphere strokes. • Bilateral carotid occlusions, R vertebral and basilar stenosis on angiography. • At age 61 seen in memory clinic for forgetfulness, anomia, difficulty with comprehension • MMSE 23/30 • good function in ADL’s; unable to work • hospital volunteer 3x/week, bingo, shopping • developed seizures, partially controlled on meds and died in status epilepticus at age 64

25. Final Diagnosis • Above: MRI shows watershedstrokes • Left:Autopsy shows ischemic infarcts: neuronal loss and gliosis. No Alzheimer’s Disease

26. Subcortical Ischemic Vascular Disease –Cognitive Syndrome EXECUTIVE DYSFUNCTION • Impaired goal formulation, initiation, planning, organizing, sequencing, executing, set-shifting and maintenance, abstraction. MEMORY DEFICIT (may be mild) • Impaired recall, relative intact recognition, less severe forgetting, benefit from cues.

27. 81 y.o. man 23 y.o.e. Dx: AD w CVD MMSE: 27/30 78 y.o. woman 12 y.o.e. Dx: AD w CVD MMSE: 25/30 Clock Drawing(Set hands to 10 after 11) 75 y.o. woman 16 y.o.e. Dx: VaD MMSE: 26/30

28. SIVD - Arteries and Arterioles

29. Obliteration and occlusion Tortuosity, coiling Increased resistance Decreased autoregulation Endothelial changes BBB changes Perivascular changes CADASIL Small Vessel Disease

30. Arteriolar Tortuosity Thore et al Exp Neuro 2007

31. SIVD – Early Clinical Features • Gait disorder, imbalance • Urinary frequency and incontinence • Dysarthria, dysphagia • Emotional incontinence • Extrapyramidal signs (hypokinesia, rigidity) • Depression and mood changes

32. SIVD; Leukoairiosis; Binswanger’s…

33. Post-stroke Dementia PREVALENCE PEARLS: • 10% stroke patients have dementia BEFORE • 10% more get dementia after a first stroke • 1/3 have dementia after recurrent strokes • New dementia after a stroke increases from 7% at 1 year to 48% by 25 years. Pendlebury and Rothwell Lancet Neurol 2009;8(11):1006-18. R.H.Swartz, University of Toronto

34. The Overt Disease: Post-Stroke Dementia • Some form of VCI even more common: • By 3 months post-stroke , 65% cognitively impaired • Co-morbidities common: • Depressive symptoms post-stroke occur in 25-50%4,5 • Obstructive Sleep Apnea present in up to 60% post-stroke 1. Tatemichi et al. Neurology. 1992 2. Desmond et al. Stroke. 2002 3. Pohjasvaara et al. Stroke. 1997 4. Pohjasvaara et al. Stroke. 1998 5. Herrmann et al. Stroke. 1998

35. TIP #4: Cognitive impairment is a vascular risk factor.

36. Post-stroke Cognitive Impairment: • Increases mortality(61% vs 25%)1,2 • Increases morbidity, long-term dependence • Impairs recovery • Increases stroke recurrence risk • … And vascular risk factors are associated with poor cognition 1. Tatemichi et al. Neurology. 1992 2. Desmond et al. Stroke. 2002 R.H. Swartz, University of Toronto

37. Post-stroke Cognitive Decline • Midlife vascular risk factors increase the risk of dementia in later life • Treatment of risk factors in mid-life lowers the risk of dementia and cognitive decline • PEARL: The ONLY neuroprotective strategies proven to prevent dementia are those that reduce vascular risk – especially treatment of midlife hypertension. R.H.Swartz, University of Toronto

38. TIP #5: Yes we can!

39. Issues to consider • Impact on stroke recovery / rehabilitation • Impact on caregivers / environment • Impact on function, occupation, hobbies etc. (even excellent recovery can have devastating residua) • Home safety • Driving. Arg. R.H.Swartz, University of Toronto

40. Major guidelines • Canadian Stroke Best Practice Recommendations www.strokebestpractices.ca • AHA/ASA, AAN endorsed VCI recommendations R.H.Swartz, University of Toronto

42. Canadian Best Practice Recommendations for Stroke Care: Vascular Cognitive Impairment and Dementia All patients with vascular risk factors and those with clinically evident stroke or transient ischemic attack should be considered at increased risk for vascular cognitive impairment (VCI), particularly those patients with cognitive, perceptual or functional changes that are clinically evident or reported during history taking. 7.2.1 Screening and Assessment 7.2.2 Timing of Screening and Assessments 7.2.3 Management of Vascular Cognitive Impairment 7.2.4 Pharmacotherapy for Vascular Cognitive Impairment Eskes G, Salter K et al., Mar 2013 www.strokebestpractices.ca

43. 7.2.1 Screening and Assessment • Patients with significant risk factors for VCI, (HTN, DM, TIA or clinical stroke, neuroimaging findings of covert stroke or WM disease, HTN-associated damage to other target organs, atrial fibrillation, other cardiac disease, and/or sleep apnea) should be considered for VCI screening [Evidence Level A]. • Stroke patients with suspected cognitive impairment should also be screened for depression, given that depression has been found to contribute to vascular cognitive impairment. A validated screening tool for depression should be used [Evidence Level A]. Eskes G, Salter K et al., Mar 2013 www.strokebestpractices.ca

44. Tip: Screening Need Not Take Hours RECOMMENDED FIRST-LINE TOOLS: • MoCA (5-10 minutes) • NINDS-CSN Harmonization VCI Neuropsychology Protocols (60, 30, or 5 minute versions) • Bring me back in a year… DOC study completion (screening for depression, OSA, Cognitive Impairment)

45. THE MONTREAL COGNITIVE ASSESSMENT • originally developed to screen for amnestic MCI • 94 MCI patients, 93 AD patients, 90 healthy elderly • compared to Mini-Mental State Examination • MoCA 90% vs. MMSE 18% sensitive • specificity comparable Nasreddine et al., J Am Geriatr Soc. 2005

46. Montreal Cognitive Assessment (MoCA) • 30-point scale • 10 minutes to administer • One page • Using cutoff < 25, MCI was discriminated from normal • Sensitivity 80% • Specificity 91% www.mocatest.org Nasreddine et al. J AGS. 2005

47. NINDS-CSN VCI 2006 HARMONIZATION STANDARDS • screening questions • neuropsychological working group • 60 min protocol (four domains) • 30 and 5 min protocols Black et al. Stroke 2011;42:E608 Hachinski et al. Stroke 2006;37:2220

48. MoCA - good utility in stroke/TIA15 • ~10 minute administration • Still too onerous for routine clinical use • NINDS-CSN Harmonization assessment16 • 5-min cognitive screen for telephone • Delayed Recall, Verbal Fluency, 6-item Orientation • Limitations: • Lack of clearly defined cut-offs • Only one task between learning and recall • Limited executive function assessment R.H. Swartz, University of Toronto

49. 7.2.1 Screening and Assessment • Additional assessments should be undertaken to determine the nature and severity of cognitive impairments, as well as the presence of remaining cognitive abilities and strengths; • The impact of deficits on function and safety in ADL and I-ADL, and occupational and school functioning should also be assessed. c. The results of these assessments should be used to guide selection and implementation of appropriate remedial, compensatory and/or adaptive intervention strategies according to client-centered goals and current or anticipated living environment (e.g., to help with discharge planning) [Evidence Level B]. Eskes G, Salter K et al., Mar 2013 www.strokebestpractices.ca

50. 7.2.3 Management of Vascular Cognitive Impairment • Vascular risk factors (e.g., hypertension, atrial fibrillation) should be managed aggressively to achieve optimal control of the pathology underlying cognitive impairment following a stroke or TIA [Evidence Level A]. iii. Evidence for interventions for cognitive impairment is growing, although more research is required. Interventions with the patient can be broadly classified as either compensatory strategy training, or direct remediation/cognitive skill training. These approaches are not mutually exclusive, and, depending upon the impairments and goals, may be offered together [Evidence Level B]. Eskes G, Salter K et al., Mar 2013 www.strokebestpractices.ca