Microinfarct Pathology, Dementia, and Cognitive Systems

Abstract

BACKGROUND AND PURPOSE: Little is known about the role of microinfarcts in dementia and cognition. We examined microinfarcts and dementia, global cognition, and 5 cognitive systems in community-dwelling older persons. METHODS: Four hundred twenty-five subjects enrolled in the Religious Orders Study underwent annual clinical evaluations, including 19 neuropsychological tests and assessment for dementia, and brain autopsy (39% men; mean age at death, 87; Mini-Mental State Examination score, 21). Neuropathologic examination documented the presence, number, and location of chronic microinfarcts on 6-μm hematoxylin-eosin-stained sections from cortical and subcortical regions. Multiple regression analyses adjusted for age at death, sex, education, macroscopic infarcts, Alzheimer disease pathology, and Lewy bodies. RESULTS: Microinfarcts were present in 129 of 425 (30%) persons (54 cortical, 80 subcortical, 49 multiple); 58 of 129 (45%) of persons with microinfarcts did not exhibit macroscopic infarcts. Persons with microinfarcts had increased odds of dementia (OR, 1.77; 95% CI, 1.07-2.92), especially those persons with multiple cortical microinfarcts. Microinfarcts were also associated with lower average global cognition (estimate, -0.287; SE, 0.113; P=0.012), particularly for persons with multiple cortical microinfarcts. Microinfarcts were specifically associated with lower episodic memory (estimate, -0.279; SE, 0.138; P=0.044), semantic memory (estimate, -0.391; SE, 0.130; P=0.003), and perceptual speed (estimate, -0.400; SE, 0.117; P<0.001). In addition, single, multiple, and cortical microinfarcts were associated with worse semantic memory and perceptual speed (all P<0.028). Neither macroscopic infarcts nor AD pathology modified these associations (all P>0.154). CONCLUSIONS: Microinfarcts are common, and persons with multiple cortical microinfarcts have higher odds of dementia. Microinfarcts are also associated with lower cognition, specifically perceptual speed and semantic and episodic memory.