Vascular Dementia Laura Pedelty, PhD MD The University of Illinois at Chicago and Jesse Brown VA Medical Center
none Disclosures
Objectives To review the definition of Vascular Cognitive Impairment (VCI); To understand the anatomy and pathophysiology of CNS vascular disease; To review patterns of damage leading to VCI; To review clinical presentation, risk factors for, and management of VCI
Vascular dementia: epidemiology Second most common form of dementia, after AD, in the North America and Europe Prevalence 0.6 2.1% in the general population Accounts for 10 20% of dementia cases Possibly higher in Asian populations Increasing prevalence with age Risk factors Cardiovascular risk factors (HTN, DM/metabolic syndrome, dyslipidemia) Stroke Age Low education Potentially preventable dementia
A bit of Background: What is dementia? An acquired cognitive and functional decline involving one or more cognitive domains, sufficient to interfere with independence in everyday activities, Not occurring in the context of delirium or better explained by another mental disorder Currently conceived as part of a spectrum Normal Cognition Normal cognitive aging Mild cognitive impairment Dementia Increasing cognitive and functional impairment
A bit of background: How the brain supports cognition Cognitive domains : independently testable cognitive functions associated with a defined neuroanatomical substrate: Language (dominant perisylvian) Visuoperceptive (occipital cortices) Visuospatial (parietal) Memory (mesial temporal) Attention (distributed parietal, frontal, brainstem/thalamic RAS) Executive (frontal-subcortical circuits)
A bit of background: How the vascular system supports the brain Vessels of origin: Anterior circulation (carotid arteries) Posterior circulation (vertebrobasilar) Circle of Willis Surface arteries: pial vessels Deep structures: penetrating arteries Cerebral autoregulation Blood-brain barrier
How things can go wrong: Vascular dementia (VaD) 19 th Century: Senile dementia 1894-95: Binswanger and Alzheimer describe cerebrovascular pathology underlying dementia 1896: Kraepelin descibes arteriosclerotic dementia 1907: Alzheimer describes neurodegenerative changes associated with Alzheimer s disease 1974: Hachinski introduces the concept of multi-infarct dementia 1994: NINDS-AIREN criteria for Vascular Dementia (VaD) formulated Iadecola, Neuron, 2013
How things can go wrong: VaD and VCI Definition VaD: A syndrome with evidence of clinical stroke or subclinical vascular brain injury and cognitive impairment affecting at least one cognitive domain NINDS-CSN VCI Harmonization standards: Cognitive impairment caused by or associated with vascular factors Again recognizes a spectrum, incorporating VCIND (Vascular Cognitive Impairment, No Dementia)
Diagnostic heuristics Hachinski scale 13-item scale Assesses clinical features and risk factors suggestive of vascular disease Antedates sophisticated neuroimaging DSM-V Impairment in one or more cognitive domains With evidence of cerebrovascular disease Focal neurological signs/symptoms Neuroimaging Cognitive profile Judged to be etiologically related to the dementia NINDS-AIREN criteria Evidence of: Dementia Cerebrovascular disease Clinical signs/symptoms Neuroimaging (specified patterns A relationship between the two Incorporates neuroimaging parameters Classifies VaD as definite, probable or possible
Mechanisms Iadecola, Neuron, 2013
Single-stroke dementia Pervasive multi-domain cognitive impairment following a single stroke Lesions disrupt key circuitry Frontal-subcortical circuits -> executive dysfunction; Multimodal cortical association areas -> language, memory, visuospatial deficits Clinical presentation: Abrupt onset; Deficits reflect lesion location; Elemental neurological deficits may or may not be present
Multi-infarct Dementia Progressive cognitive and functional decline due to accumulation of ischemic disease: Location, rather than volume of tissue loss is crucial Clinical presentation: Stepwise progression Often with sensory and/or motor abnormalities
Subcortical Ischemic Vascular Progressive cognitive and functional decline due to recurrent small-vessel ischemic strokes Deficits due to: Disruption of frontalsubcortical circuits; Cholinergic deficit Clinical presentation: Stepwise or gradually progressive; Motor and sensory deficits may be present; Frontal-executive dysfunction dominates the profile Dementia (SIVD)
Binswangers Disease Chronic hypoperfusion results in thinning and attenuation of the white matter without complete infarction Pathophysiology Clinical presentation: Gradually progressive onset; Subcortical dementia with psychomotor slowing, impaired executive function; Gait abnormalities and pseudobulbar affect (emotional lability) common Iadecola, Neuron, 2013
CADASIL Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Autosomal dominant syndrome Pathology Smooth muscle deterioration, granular osmiophilic deposits Leukoariosis and lacunar infarcts Clinical presentation: Early onset (age 30 50) Seizures Migraine with aura Recurrent subcortical stroke Subcortical dementia
What about bleeds? Intracerebral hemorrhage (ICH) Lobar ICH Subcortical ICH Risk factors: Hypertension Amyloid angiopathy Cognitive and functional decline due to: Local tissue destruction Deafferentation Inflammatory reaction Hydrocephalus Cerebral microbleeds (MB) Manno Mayo Clin Proc 2005
Evaluation History Vascular risk factors Stepwise progression Physical examination Cardiovascular examination Focal neurological deficits Motor Sensory Reflex Laboratory evaluation Neuroimaging (MRI) Vascular imaging Cardiac evaluation Neurocognitive evaluation Dysexecutive profile Memory: retrieval>encoding deficits Psychomotor slowing, impairment of attention
Management: control of risk factors Prevention is key! Risk factor management Atrial fibrillation Hypertension Dyslipidemia Diabetes Lifestyle changes (diet, physical activity, smoking cessation) Role and efficacy of early vs late risk factor control
Management: pharmacotherapy No specific therapies exist Cholinesterase inhibitors Donepezil: modest cognitive and global effects in VaD and mixed dementia Galantamine: modest cognitive (executive) and functional benefits, lower rate of decline in mixed (AD/VaD) dementia Rivastigmine: less clear benefits, modest benefits in some measures of executive function Memantine: unclear benefit Other agents Symptomatic treatment (e.g. comorbid depression)
Key Points Vascular dementia (VaD) is the extreme end of a spectrum of vascular cognitive impairment, cognitive and functional decline consequent on interrupted blood supply to the brain VCI is a heterogeneous phenomenon The cognitive profile is different from that of AD and reflects the pathophysiology of the syndrome VCI is a potentially preventable condition, and early intervention may be key
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