Sorting out the clinical consequences of ischemic lesions in brain aging: a clinicopathological approach

BACKGROUND: Vascular lesions are particularly common in the aged brain. However, it is still unclear whether all such lesions affect cognition. OBJECTIVES: To better explore relationships between specific characteristics of vascular lesions (type, size and location) and cognitive status. METHODS: We performed a review of currently available neuroimaging and post-mortem studies taking into account several recent clinicopathological reports in elderly individuals with varying levels of cognitive impairment. RESULTS: New data reveals the significant impact of cortical microinfarcts on intellectual function, in contrast to focal cortical and white matter gliosis which are not significantly associated with cognitive status. Structural neuroimaging studies show inconsistent data regarding the cognitive consequences of WML. Neuropathological analyses reveal that both periventricular and subcortical demyelination are associated with cognitive status in the absence of macrovascular pathology. When lacunes are present, these microvascular lesions have no independent effect on intellectual impairment. The relationship between lacunes and cognition is highly dependent on localization. Basal ganglia and thalamic lacunes correlate with cognitive decline but not lacunes in the frontal, temporal and parietal deep white matter. CONCLUSION: Recent studies suggest that some cases of dementia might be misclassified: 1. Cases with typical Alzheimer course and moderate lacunes in subcortical white matter should probably be considered pure Alzheimer's disease. 2. The presence of microscopic infarcts can markedly impact cognition but is not detectable by currently available neuroimaging techniques and the vascular component of such mixed cases may go undiagnosed. The development of urgently needed new criteria for vascular dementia should take into account the relative contribution of various types of vascular lesions that can impact cognitive function