Vascular Cognitive Impairment and Dementia January 24, 2009 Saving the Brain 3rd Annual Conference Toronto, Ontario Demetrios J. Sahlas, MSc, MD, FRCPC MG DeGroote Professor in Stroke Management Associate Professor, Division of Neurology, McMaster University Central South Regional Stroke Centre, Hamilton Health Sciences

Objectives 1) To describe the different patterns of cognitive impairment that can emerge following a stroke. 2) To review the 2008 recommendations for for vascular cognitive impairment and dementia. 3) To consider management of vascular cognitive impairment and dementia.

2008 recommendations • all patients with vascular risk factors and those with clinically evident stroke or TIA should be considered at high risk for vascular cognitive impairment • broken into sections on Assessment, Timing, and Management

What is Meant by “Cognitive Impairment”? • impairment in one or more cognitive domains: – memory, language, visuospatial function, executive function, praxis

• may be mild, moderate, or severe – referred to as dementia when affects daily social or occupational function

1. How common is cognitive impairment following a stroke? a) 10% b) 33% c) 64% d) 99%

After 3 Months . . . • up to 64% of stroke patients have some degree of cognitive impairment • severe enough to meet criteria for dementia in a third of patients • risk of developing dementia in the future is also increased Hachinski et al. Stroke 2006;37:2220

2. Vascular Dementia is characterized by which of the following clinical characteristics? a) insidious onset b) stepwise decline c) response to cholinesterase inhibitors

How Does a Stroke Result in Cognitive Impairment? • large-vessel territory infarcts – rob patient of specific cognitive domains depending upon cortical region involved – can lead to multi-infarct dementia

• small-vessel (lacunar) infarcts – importance of thalamus in cognition – can lead to strategic infarct dementia

Vascular Cognitive Disorders • Multiple Infarct Dementia – multiple cortical infarcts

• Strategic Infarct Dementia • Subcortical Ischemic Vascular Dementia – lacunar infarcts and white matter disease

• Mixed Alzheimer’s Disease and Cerebrovascular Disease

Subcortical Ischemic Vascular Disease (SIVD) • chronic atherosclerotic vessel pathology – lipohyalinosis – microatheromatosis

• small vessel (such as lenticulostriate) as well as microvascular damage

Subcortical Ischemic Vascular Disease (SIVD) • vessel changes may result in subcortical ischemic white matter pathology – microinfarcts – rarefaction of myelin – glial cell pathology

A

D

Trajectories of cholinergic pathways within the cerebral hemispheres of the human brain Selden, Gitelman, Salamon-Murayama, Parrish and Mesulam, Brain 1998;121:2249-57

The neuropsychological profile found in patients with subcortical ischemic vascular disease

O'Sullivan et al. J Neurol Neurosurg Psychiatry 2004;75:441-7

What Pre-Existing Factors Predispose to Cognitive Impairment after a Stroke or TIA?

Effects of Normal Aging

Alzheimer’s or other neurodegenerative pathology Atherosclerosis (SIVD) and cerebral infarction

Braak & Braak stages of AD Stage 1

Stage 2

Transentorhinal Cortex

Entorhinal Cortex Hippocampus Proper

Stage 4

Stage 3

Nucleus Reuniens Posterior Cingulate Temporal Isocortex

Nucleus Basalis of Meynert Hypothalamus

Stage 5

Stage 6

Anterior Thalamus Isocortical Association Areas

Primary Motor & Sensory Areas Dentate Gyrus Substantia Nigra Striatum

ORANGE = LIMBIC SYSTEM STRUCTURES

The Nun Study • prevalence of dementia with AD pathology present: – stages 1-2: 22% – stages 3-4: 43% – stages 5-6: 70%

• 93% of nuns with dementia also had at least one subcortical stroke data from Snowden et al. JAMA 1997;277:813-817

The Nun Study (con’t) • only 57% with AD pathology alone were demented • 88% with both AD and CVD pathology were demented • only 2.5% of those with dementia had only cerebrovascular lesions present

data from Snowden et al. JAMA 1997;277:813-817

2008 recommendations 6.3a Assessment: – use of validated screening tools – MoCA preferable to MMSE – patients should also be screened for depression – further cognitive or neuropsychological testing, as appropriate

Why Screen for Cognitive Impairment in Stroke Patients?

Case History • 73 year-old man • brief episode of tingling involving left hand • hypertensive, obese, high cholesterol, smoker • known to harbor bilateral carotid artery stenosis

Physical Exam & CT (head) • alert, oriented, speech normal • MMSE 27/30 • neurological exam notable for sensory and visual extinction on the left • CT scan (head) demonstrates hitherto unsuspected infarct involving the right parietal lobe

NINDS-CSN VCI 2006 Harmonization Standards • screening questions • established components of ideal as well as minimum dataset • neuropsychological working group – 60 min protocol (four domains) – 30 and 5 min protocols

5-Minute Protocol • Montreal Cognitive Assessment (MoCA) – 5 word memory task (registration, recall, recognition) – 6 item orientation – 1 letter phonemic fluency

• MoCA available at www.mocatest.org

Further Evaluation • supplemental testing – rest of MoCA – semantic fluency (animal naming) – Trail Making Test – MMSE (1 hour pre- or post-)

• MoCA available at www.mocatest.org

Trails A

Trails B

2008 recommendations 6.3b Timing: – those at high risk should be assessed periodically – testing appropriate at various transition points, including upon admission or discharge to hospital, and periodically during outpatient follow-up

Diagnostic Criteria for Vascular Dementia • DSM IV (TR) • NINDS-AIREN criteria www.strokecenter.org/trials/scales/ninds-airen.html

• Hachinski Ischemic Score www.strokecenter.org/trials/scales/hachinski.html

Roman et al. Neurology 1993;43:250 Hachinski et al. Arch Neurol 1975;32:632

2008 recommendations 6.3c Management: – aggressive vascular risk factor management – referral to health care professional with specific expertise, as appropriate – comprehensive team approach – intervention strategies

Treatment with Cholinesterase Inhibitors • galantamine (Reminyl ER) 8mg a day – increase by 8mg to 24mg a day

• donepezil (Aricept) 5mg or 10mg a day • rivastigmine (Exelon) 1.5 to 6mg bid – also available as a patch Erkinjunti et al. Lancet 2002;359:1283 Black et al. Stroke 2003;34:2323

Summary • cognitive impairment is exceedingly common after stroke – up to two-thirds of patients

• subcortical ischemic vascular disease detracts from cognitive reserve and can also result in cognitive impairment – executive dysfunction

Summary • screening for cognitive impairment is now considered best practice in stroke patients • there are standard tests for accomplishing this: – 5 minute core protocol (12 pts) – MoCA +/- MMSE (both up to 30 pts) – supplemental tests

Summary • treatment with medications, such as cholinesterase inhibitors, may be helpful, although evidence is not robust • and one last word . . .

The Nun Study • participants with lacunar infarcts had especially high prevalence of dementia compared to those without infarcts • the odds ratio [OR] for dementia was 20.7 (95% CI=1.5-288.0)

(CNN) -- Eleven million Americans will have strokes this year. But they won't know it. "There are 20 silent strokes occurring in this country each year for every single symptomatic stroke that's occurring," said Dr. Jeffrey Saver, a neurologist at the University of California-Los Angeles Stroke Center. "I think that a lot of physicians and patients and families are going to be surprised by the numbers. Previous studies had suggested that silent strokes were quite common, but research conducted by Saver and his colleagues (funded by the National Institutes of Health and the American Heart Association) put a concrete number on the incidence of silent stroke. He called the figure "shocking and dramatic."