Stroke injury, cognitive impairment and vascular dementia

AbstractThe 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

Dementia Prevalence Estimates in Sub-Saharan Africa: Comparison of two Diagnostic Criteria.

We have previously reported the prevalence of dementia in older adults living in the rural Hai district of Tanzania according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria. The aim of this study was to compare prevalence rates using the DSM-IV criteria with those obtained using the 10/66 diagnostic criteria, which is specifically designed for use in low- and middle-income countries. In phase I, 1,198 people aged 70 and older were screened for dementia. A stratified sample of 296 was then clinically assessed for dementia according to the DSM-IV criteria. In addition, data were collected according to the protocol of the 10/66 Dementia Research Group, which allowed a separate diagnosis of dementia according to these criteria to be established. The age-standardised prevalence of clinical DSM-IV dementia was 6.4% (95% confidence interval [CI] 4.9-7.9%) and of '10/66 dementia' was 21.6% (95% CI 17.5-25.7%). Education was a significant predictor of '10/66 dementia', but not of DSM-IV dementia. There are large discrepancies in dementia prevalence rates depending on which diagnostic system is used. In rural sub-Saharan Africa, it is not clear whether the association between education and dementia using the 10/66 criteria is a genuine effect or the result of an educational bias within the diagnostic instrument. Despite its possible flaws, the DSM-IV criteria represent an international standard for dementia diagnosis. The 10/66 diagnostic criteria may be more appropriate when identification of early and mild cognitive impairment is required

Blood brain barrier leakage is not a consistent feature of white matter lesions in CADASIL

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic paradigm of small vessel disease (SVD) caused by NOTCH3 mutations that stereotypically lead to the vascular accumulation of NOTCH3 around smooth muscle cells and pericytes. White matter (WM) lesions (WMLs) are the earliest and most frequent abnormalities, and can be associated with lacunar infarcts and enlarged perivascular spaces (ePVS). The prevailing view is that blood brain barrier (BBB) leakage, possibly mediated by pericyte deficiency, plays a pivotal role in the formation of WMLs. Herein, we investigated the involvement of BBB leakage and pericyte loss in CADASIL WMLs. Using post-mortem brain tissue from 12 CADASIL patients and 10 age-matched controls, we found that WMLs are heterogeneous, and that BBB leakage reflects the heterogeneity. Specifically, while fibrinogen extravasation was significantly increased in WMLs surrounding ePVS and lacunes, levels of fibrinogen leakage were comparable in WMLs without other pathology ("pure" WMLs) to those seen in the normal appearing WM of patients and controls. In a mouse model of CADASIL, which develops WMLs but no lacunes or ePVS, we detected no extravasation of endogenous fibrinogen, nor of injected small or large tracers in WMLs. Moreover, there was no evidence of pericyte coverage modification in any type of WML in either CADASIL patients or mice. These data together indicate that WMLs in CADASIL encompass distinct classes of WM changes and argue against the prevailing hypothesis that pericyte coverage loss and BBB leakage are the primary drivers of WMLs. Our results also have important implications for the interpretation of studies on the BBB in living patients, which may misinterpret evidence of BBB leakage within WM hyperintensities as suggesting a BBB related mechanism for all WMLs, when in fact this may only apply to a subset of these lesions.Peer reviewe

Small Vessel Disease and Subcortical Vascular Dementia

Atherothromboembolism and intracranial small vessel disease are considered to be the main causes of cerebrovascular injury, which may lead to cognitive impairment and vascular dementia (VaD). VaD appears to be the second most common type of dementia with prevalence estimates of 10-15%. Cortical or multi-infarct dementia and subcortical vascular dementia (SVD) are suggested to be the two main forms of VaD. The main clinical features of SVD comprise decreased motor performance, early impairment of attention and executive function with slowing of information processing. SVD results from lacunar infarcts or multiple microinfarcts in the basal ganglia, thalamus, brainstem and white matter and are associated with more than 50% of the VaD cases. White matter changes including regions of incomplete infarction are usually widespread in VaD but their contribution to impairment of subcortical regions is unclear. While most of VaD occurs sporadically only a small proportion of cases bear clear familial traits. CADASIL is likely the most common form of hereditary VaD, which arises from subcortical arteriopathy. SVD needs unambiguous definition to impact on preventative and treatment strategies, and critical for selective recruitment to clinical trials

Alzheimer\u27s disease and vascular dementia in developing countries: prevalence, management, and risk factors

Despite mortality due to communicable diseases, poverty, and human conflicts, dementia incidence is destined to increase in the developing world in tandem with the ageing population. Current data from developing countries suggest that age-adjusted dementia prevalence estimates in 65 year olds are high (≥5%) in certain Asian and Latin American countries, but consistently low (1–3%) in India and sub-Saharan Africa; Alzheimer\u27s disease accounts for 60% whereas vascular dementia accounts for ∼30% of the prevalence. Early-onset familial forms of dementia with single-gene defects occur in Latin America, Asia, and Africa. Illiteracy remains a risk factor for dementia. The APOE ε4 allele does not influence dementia progression in sub-Saharan Africans. Vascular factors, such as hypertension and type 2 diabetes, are likely to increase the burden of dementia. Use of traditional diets and medicinal plant extracts might aid prevention and treatment. Dementia costs in developing countries are estimated to be US$73 billion yearly, but care demands social protection, which seems scarce in these regions