Vascular dementia (VaD) represents the second most frequent cause of dementia after Alzheimer’s disease (AD). Clinicopathological correlations carried out in individuals with both macroscopic and microscopic vascular lesions have shown that current clinical criteria for VaD are generally specific but not very sensitive. Further studies have shown the influence of macroscopic vascular lesions on the clinical expression of Alzheimer’s disease (AD) thus providing support for including these lesions in establishing the neuropathological diagnosis of mixed dementia (MD). However, the clinical significance of isolated microvascular cortical lesions, which are frequently observed in elderly cohorts, remains obscure. To address this issue we evaluated cognitive function as measured by the CDR in 74 elderly individuals with either microinfarcts, diffuse gliosis, white matter lesions or a combination thereof. Neuropathological examination included definition of Braak neurofibrillary tangle staging as well as a detailed analysis of microscopic vascular lesions in the frontal parietal and temporal neocortex, the hippocampal formation and subcortical and periventricular white matter. Cases with either Braak stage > III or macrosopic vascular lesions were excluded. Hippocampal microinfarcts and subcortical demyelination had the greatest impact on cognitive function; the effect of other lesions including periventricular white matter demyelination did not reach statistical significance. These results suggest that isolated microscopic ischemic pathology in the hippocampal formation and subcortical white matter should be taken into account for the diagnosis of mixed dementia.
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