• B Gwen Windham, Michael E Griswold, Steven R Wilkening, Dan Su, Jonathan Tingle, Laura H Coker, David Knopman, Rebecca F Gottesman, Dean Shibata, and Thomas H Mosley.
• University of Mississippi Medical Center, Jackson, Mississippi (B.G.W., T.H.M.).
• Ann. Intern. Med. 2019 Sep 17; 171 (6): 389-396.

BackgroundSmaller (<3-mm) infarctions are associated with stroke and stroke mortality, but relationships with cognitive decline are unknown.ObjectiveTo characterize the relationships of smaller, larger, and both smaller and larger infarctions in middle age with 20-year cognitive decline.DesignLongitudinal cohort study.SettingTwo ARIC (Atherosclerosis Risk in Communities) study sites with magnetic resonance imaging data (1993 to 1995) and up to 5 cognitive assessments over 20 years.ParticipantsStroke-free participants aged 50 years or older.MeasurementsInfarctions were categorized as none, smaller only, larger only (3 to 20 mm), or both smaller and larger. Global cognitive Z scores were derived from 3 cognitive tests administered up to 5 times. Mixed-effects models estimated adjusted associations between infarctions and cognitive decline. Results are the average difference in standardized cognitive decline associated with infarctions versus no infarctions.ResultsAmong 1884 participants (mean age, 62 years; 60% women; 50% black), 1611 (86%) had no infarctions, 50 (3%) had smaller infarctions only, 185 (10%) had larger infarctions only, and 35 (2%) had both. Participants with both smaller and larger infarctions had steeper cognitive decline by more than half an SD (difference, -0.57 SD [95% CI, -0.89 to -0.26 SD]) compared with those who had no infarctions. Amounts of cognitive decline associated with only smaller infarctions and only larger infarctions were similar and were not statistically different from that associated with no infarctions.LimitationFew participants had only smaller infarctions or both smaller and larger infarctions, and the data lacked counts of smaller infarctions and volumes of white matter hyperintensities.ConclusionThe substantial cognitive decline from middle age associated with having both smaller and larger infarctions, but not larger infarctions alone, suggests that the combination of smaller and larger infarctions may escalate risk for cognitive decline later in life in stroke-free persons.Primary Funding SourceNational Institutes of Health.

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