Microinfarcts in an older population-representative brain donor cohort (MRC CFAS): Prevalence, relation to dementia and mobility, and implications for the evaluation of cerebral Small Vessel Disease.

INTRODUCTION: Microinfarcts, small ischaemic foci common in ageing brain, are associated with dementia and gait dysfunction. We determined their relationship with dementia, mobility and cerebrovascular disease in an older population-representative brain donor cohort. These data on microinfarcts were evaluated in relation to pathological assessments of clinically significant cerebral small vessel disease (SVD). METHODS: Microinfarcts were assessed in the MRC Cognitive Function and Ageing Study (n = 331). Nine brain areas were staged according to the number of areas affected. RESULTS: 36% of brains showed at least 1 microinfarct. Higher cortical microinfarct stage was associated with dementia at death (OR 1.41, 95% CI 1.02; 1.96, P = 0.038), whilst cortical and subcortical microinfarct stages were associated with impaired mobility (OR 1.36, 95% CI 1.05-1.74; P 0.018) and falls (OR 1.96, 95% CI 1.11-3.43; P = 0.02). Adding data on microinfarcts to a definition of SVD, based on white matter lesions (WMLs), lacunes and significant arteriosclerosis, were assessed by comparing area under ROC curve (AUC) with and without microinfarcts. SVD was significantly related to dementia status with or without inclusion of microinfarcts. Modelling potential pathological definitions of SVD to predict dementia or impaired mobility indicated optimal prediction using combined assessment of WMLs, lacunes and microinfarcts. CONCLUSION: Cortical (dementia) and subcortical microinfarcts (impaired mobility) are related to diverse clinical outcomes. Optimal pathological assessment of significant SVD in brain ageing is achieved based on WMLs, lacunes and microinfarcts and may not require subjective assessment of the extent and severity of arteriosclerosis

Population variation in oxidative stress and astrocyte DNA damage in relation to Alzheimer-type pathology in the ageing brain

Increasing evidence suggests a role for oxidative damage to DNA in brain ageing and in neurodegenerative disorders, including Alzheimer's disease. Most studies have focussed on the reduced capacity for DNA repair by neurones, and have not taken into account the effect of oxidative stress on astrocytes, and their contribution to pathology

Neuropsychological tests for the diagnosis of Alzheimer’s disease dementia and other dementias: a generic protocol for cross-sectional and delayed-verification studies

This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the cross-sectional diagnostic accuracy of [index test] at various thresholds for ADD and other dementias [target condition] in [target population].ORTo determine the accuracy of [index test] at various thresholds for diagnosing ADD and other dementias [target condition] in [target population] after a follow-up period (delayed-verification studies).To investigate the heterogeneity of test accuracy in the included studies.To highlight the quality and quantity of research evidence available on the effectiveness of the index test in the target population.To identify gaps in the evidence and determine where further research is required