Profile, determinants and mechanisms of cerebral injury and cognitive impairment following stroke

Abstract

One in three people over a life time will develop a stroke, dementia or both but little is known about stroke - related cognitive impairment despite current epidemiologic transition in sub - Saharan Africa. The CogFAST Study was established in Newcastle to unmask risk factors, pathological substrates and cellular mechanisms underlying cerebral injury and cognitive impairment following stroke. The overall aim of this thesis was to establish a comparative cohort in Nigerian African stroke survivors and explore mechanisms in post - mortem brains accrued from the Newcastle cohort. Two hundred and twenty Nigerian African stroke survivors were screened three months after index stroke out of whom 143 eligible participants underwent cognitive assessment in comparison with 74 stroke - free healthy controls. We found a high frequency (49.3%) of early vascular cognitive impairment and significant association with older age and low education. Pre-stroke daily fish intake and moderate – to - heavy physical activity were inversely associated. The frequency of vascular cognitive impairment no dementia (vCIND) in the cohort (39.9%) was relatively higher than earlier report from Newcastle (32%) but neuroimaging studies revealed significant findings of MTLA and correlative white matter changes in tandem with previous reports from the Newcastle cohort. Given these, we investigated neurodegenerative hippocampal Alzheimer pathology and synaptic changes, as well as frontal and temporal white matter abnormalities in post - mortem brain tissue from the Newcastle cohort. We found increased Alzheimer pathology in the post - stroke groups but largely this did not differ between the demented (PSD) and non - demented (PSND) sub - groups. However, we found significantly higher hippocampal expression of synaptic markers (vesicular glutamate transporter – 1 and Drebrin) but lower expression of microglial, astrocytic and axonal injury markers in PSND compared to PSD subjects. The protective effect of educational attainment, pre-stroke physical activity and fish intake have public brain health implications.