Abstract
Recent findings in the XXIst century have revealed a high frequency of microscopic cerebral lesions including microinfarcts (MI) and microbleeds (MB). In order to determine their clinical impact on cognition, we have studied more than 300 cases that were evaluated cognitively and autopsied within 1 year. We explored the correlation between global cognitive function rated according to the clinical dementia rating scale (CDR) and the presence of MI on post-mortem brain neuropathological examination of older individuals. We also assessed potential associations between MI, MB and cerebral amyloid angiopathy (CAA). MI were a strong correlate of cognitive function explaining up to 36% of CDR variablility. In mixed cases MI neuropathological scores and Braak neurofibrillary tangle stages predicted the presence of dementia with more than 80% accuracy. MB were extremely frequent (up to 93% of the cases) but less clearly related to cognition. MI were not related to CAA and many cases of MB, including lobar MB occurred in the absence of CAA. Microscopic ischemic lesions, particularly MI are powerful determinants of cognition. They represent new and highly promising therapeutic targets and should lead us to review our understanding and current paradigms in vascular and mixed dementia.