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

Abstract

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.

Keywords: dementia; epidemiological neuropathology; lacunes; microinfarct; mobility; small vessel disease; vascular risk factors; white matter lesions.

Figure 1

Photomicrographs of cortical and subcortical microinfarcts/microscopic lesions. Microinfarcts (block arrows) typically appear as small localized areas of cortical rarefaction frequently in clear association with a small penetrating artery (arrow head) (a,b). In (c), the microinfarct has a linear configuration extending towards the cortical surface (block arrows). There is eosinophilia and vessel wall thickening of the penetrating arteries in the adjacent cortex typical of amyloid angiopathy (arrows). Basal ganglia lesions frequently include a cystic component with variable attenuation of the contiguous neuropil (arrowhead) (d). [Colour figure can be viewed at wileyonlinelibrary.com]