The Neuropathology of Vascular Disease in the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS)

Kathryn      Richardson; Blossom      C.M. Stephan; Paul      G. Ince; Carol      Brayne; Fiona      E. Matthews; Margaret      M. Esiri on behalf of the MRC Cognitive Function and Ageing Neuropathology Study Group

Abstract

Background: Vascular disease is associated with increased risk of dementia. Vascular health worsens with age. We investigated the relationship between self-reported vascular disease and brain pathology. Methods: Brain donations to the population-based MRC Cognitive Function and Ageing Study (n=456, age range 66-103 years) were assessed using a standard protocol for Alzheimer’s Disease (AD) and cerebrovascular pathology. History of stroke, angina, diabetes, medicated hypertension and heart attack were identified from self- and proxy-report interviews, retrospective informant interviews and death certificates. Logistic regression was used to estimate associations between each health condition and dichotomised neuropathological variables adjusted for age and sex. Results: Stroke (36%), angina (23%), diabetes (12%), medicated hypertension (35%) and heart attack (22%) were frequently reported. Self-reported stroke was strongly associated with vascular, but not AD pathology. Medicated hypertension was associated with increased microinfarcts (OR=2.1, 95%CI=1.3-3.7) and less severe neocortical tangles (OR=0.5, 95%CI=0.3-0.8) and cerebral amyloid angiopathy (OR=0.5, 95%CI=0.3-0.8). Heart attack was associated with increased microinfarcts (OR=2.1, 95%CI=1.2-3.9). Conclusions: Vascular risk factors were not associated with an increased burden of AD pathology at death in old age. A positive association between indices of systemic cardiovascular health (treated hypertension and ischaemic heart disease) and cerebral microinfarcts emerged. The findings support the view that cerebral small vessel disease and cardiovascular disease are interrelated. Microinfarcts are emerging as an important correlate of age-related vascular cognitive impairment and the findings add weight to the argument for strategies to improve general cardiovascular health as a potential preventative strategy against cognitive decline in later life.

Keywords: Dementia, cardiovascular disease, stroke, angina pectoris, diabetes mellitus, hypertension, myocardial infarction, neuropathology, coronary artery disease, neurodegenerative disorders