Brain microinfarcts are common in aging and are associated with cognitive impairment. Watershed regions (border zones between anterior, middle, and posterior cerebral arterial territories) are considered to be more vulnerable to the effects of hypoxia-ischemia than other brain regions. However, little is known about the frequency of microinfarcts in these regions and how they relate to cognition in aging. Participants (n = 213) from the Rush Memory and Aging Project (MAP), a community-based clinical-pathologic study of aging, underwent detailed annual clinical testing, including 19 neuropsychological tests, to measure cognition proximate to death (mean age of death, 91 years; 26% men). Neuropathological examination provided measures for microinfarcts, from 2 anterior watershed regions (midfrontal cortex and adjacent white matter), one posterior watershed region (parieto-occipital cortex with underlying white matter), and 8 non-watershed regions (midtemporal, entorhinal, inferior parietal, calcarine, and anterior cingulate cortices, hippocampus, basal ganglia, and thalamus), AD pathology, and macroinfarcts. Linear regression models controlling for demographics and other age-related pathologies were used to simultaneously examine the association of watershed vs. non-watershed microinfarcts with cognition, including global cognition and 5 cognitive domains. Microinfarcts in one or more of the 11 brain regions (3 watershed; 8 non-watershed) were present in 90 (42%) participants, of which 32 (36%) showed microinfarcts in watershed regions and 73 (81%) in non-watershed regions. Microinfarcts in watershed regions were associated with lower global cognition (estimate, -0.380; SE, 0.15; p = 0.012) after controlling for demographics and age-related pathologies including Alzheimer's disease and macroscopic infarcts, whereas in the same model, non-watershed microinfarcts were not related to global cognition. Microinfarcts in watershed regions were related to all 5 cognitive domains, including visuospatial skills (estimate, -0.505; SE, 0.14; p<0.001), semantic memory (estimate, -0.418; SE, 0.18; p = 0.021), perceptual speed (estimate, -0.345; SE, 0.14; p = 0.014), and episodic memory, the presumed hallmark of clinical AD (estimate, -0.331; SE, 0.17; p = 0.047). In comparison, non-watershed microinfarcts were not associated with any of the 5 cognitive domains. These data suggest that microinfarcts in brain watershed regions contribute to age-related cognitive impairment and impairment in multiple cognitive domains. Further study of watershed microinfarcts in aging is warranted.
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