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.