Stroke injury, cognitive impairment and vascular dementia

Raj N Kalaria, Rufus Akinyemi, Masafumi Ihara, Raj N Kalaria, Rufus Akinyemi, Masafumi Ihara

Abstract

The global burden of ischaemic strokes is almost 4-fold greater than haemorrhagic strokes. Current evidence suggests that 25-30% of ischaemic stroke survivors develop immediate or delayed vascular cognitive impairment (VCI) or vascular dementia (VaD). Dementia after stroke injury may encompass all types of cognitive disorders. States of cognitive dysfunction before the index stroke are described under the umbrella of pre-stroke dementia, which may entail vascular changes as well as insidious neurodegenerative processes. Risk factors for cognitive impairment and dementia after stroke are multifactorial including older age, family history, genetic variants, low educational status, vascular comorbidities, prior transient ischaemic attack or recurrent stroke and depressive illness. Neuroimaging determinants of dementia after stroke comprise silent brain infarcts, white matter changes, lacunar infarcts and medial temporal lobe atrophy. Until recently, the neuropathology of dementia after stroke was poorly defined. Most of post-stroke dementia is consistent with VaD involving multiple substrates. Microinfarction, microvascular changes related to blood-brain barrier damage, focal neuronal atrophy and low burden of co-existing neurodegenerative pathology appear key substrates of dementia after stroke injury. The elucidation of mechanisms of dementia after stroke injury will enable establishment of effective strategy for symptomatic relief and prevention. Controlling vascular disease risk factors is essential to reduce the burden of cognitive dysfunction after stroke. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.

Keywords: Alzheimer's disease; Cognitive impairment; Dementia; Microinfarcts; Neuroimaging; Post-stroke dementia; Stroke; Vascular dementia; White matter.

Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Figures

Fig. 1
Fig. 1
Localization of infarcts or tissue changes associated with development of dementia after stroke. Dementia associated with different cerebrovascular pathologies. Subtype I may result from large vessel occlusion (atherothromboembolism), artery-to-artery embolism or cardioembolism. Subtype II usually involves descriptions of arteriolosclerosis, lipohyalinosis, hypertensive, arteriosclerotic, amyloid or collagen angiopathy. Subtype III is caused by infarcts in the ‘strategic’ areas such as the thalamus and hippocampus and may involve several risk factors including cardioembolism and intracranial small vessel disease. Shaded areas in each outline coronal show locations of lesions. Small dots depict small infarcts and microinfarcts, although the size of the latter can only be appreciated from microscopical images. Currently reported studies (and unpublished data) show that the estimated % cases for the three subtypes are as follows: Subtype I, 20–40%; subtype II, 40–50% and subtype III, 10–15%. The risk factors associated with particularly Subtype I can be varied including hypertension, carotid artery disease or atherosclerosis, cardio embolism (mostly atrial fibrillation) and coronary artery disease. Subtype II may involve hypertension, diabetes mellitus, hyperlipidaemia, hyperhomocysteinaemia, chronic kidney disease, infection and obstructive sleep aponea. Lifestyle factors such as smoking, obesity and alcohol abuse are other factors. These subtypes would include dementia among post-stroke survivors who fulfil the National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherché et l'Enseignement en Neurosciences (NINDS-AIREN) criteria for probable vascular dementia.
Fig. 2
Fig. 2
Pathological changes found in stroke Subtypes I to III involving large artery and small vessel diseases in elderly stroke survivors. A, Large infarcts (arrows) in the parietal lobe of 80-year old woman with cognitive impairment. This fits the classification of Subtype I in Fig. 1. B: Lacunes (arrow) and WM lesions in external capsule in the basal ganglia of a 78-year-old man with cognitive impairment. Note also WM rarefaction in the temporal limb (star symbol). C: Perivascular spaces (dilatation) and demyelination in WM (Luxol fast blue stain). D, Microinfarct in the caudate with some perivascular dilatation (HE, Haematoxylin and Eosin). E, Small infarct in the temporal pole (HE). C-E are typical small lesions in subtype II. F, A microinfarct in the thalamus. Moderate gliosis in the surrounding region is also evident. Thalamic infarcts can occur as 0.5 cm lacunes in the coronal section in B. Magnification Bar: A and B = 2 cm; C, D and F = 50 μm, E = 100 μm.

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