Hypertension is the Main Vascular Risk Factor for Cognitive Impairment, Microvascular Pathology and Brain Atrophy in Alzheimer’s Disease

INTRODUCTION: Alzheimer's Disease (AD) is the commonest pathology underlying dementia, but it frequently coexists with cerebrovascular disease (CVD). Existing literature supports a possible role for vascular risk factors (VRFs), including hypertension, diabetes and dyslipidaemia in AD pathogenesis. This study aims to determine whether VRFs contribute to typical AD pathogenesis or co-morbid CVD in mixed AD. METHODS: Well-characterised probable AD subjects participating in two large clinical trials of Hydromethylthionine were classified into "typical AD" and "mixed" patterns based on FDG-PET images. VRFs, including hypertension, diabetes and dyslipidaemia, and MRI-derived White Matter Hyperintensities (WMHs) and brain fraction (as a measure of brain atrophy) were analysed to investigate the relationship between VRFs and AD subtypes. RESULTS: Of 794 participants, 533 (67.1%) were classified as typical AD and 261 (32.8%) were classified as mixed. Among VRFs, cardiovascular risks were significantly more frequent in typical AD (59%) than in mixed subtype (47%) (p = 0.002). DISCUSSION: We found that it was mainly hypertension that differed according to subtypes. Although brain atrophy is the main driver of cognitive impairment in patients with AD subtype, the microvascular pathology in the form of WMHs was significantly higher in patients with hypertension, irrespective of subtype. CONCLUSION: Although hypertension is the main risk factor for cerebrovascular disease, contrary to our expectation, hypertension is common in typical AD than the mixed subtype, and this association is driven by the hitherto unsuspected contribution of microvascular pathology to cognitive impairment in typical AD.