Palta, Priya

Importance SARS-CoV-2 infection has been linked to neurotoxic effects and cognitive deficits. Objective To determine whether decreases in cognitive function were accelerated after SARS-CoV-2 infection compared with individuals not infected. Design, Setting, and Participants Multicenter, prospective cohort study from 2016 to 2022 among 3525 participants alive on March 1, 2020, and enrolled in The Atherosclerosis Risk in Communities (ARIC) study and the Collaborative Cohort of Cohorts for COVID-19 Research study who completed a prepandemic cognitive assessment and a pandemic-era assessment of SARS-CoV-2 infection. Final analyses performed in November 2024. Exposure SARS-CoV-2 infection determined via self-report of a positive SARS-CoV-2 test or health care professional diagnosis of COVID-19, a positive SARS-CoV-2 antinucleocapsid antibody response, or presence of an administrative code for COVID-19 on medical records. Main outcomes and measures A neuropsychological battery assessed multiple cognitive domains, and a cocalibrated confirmatory factor analysis generated factor scores for global cognitive function. The primary outcome was the rate of excess change in cognitive function. Results The 3525 eligible participants had a mean (SD) age of 80.8 (4.7) years, 2085 (59.1%) were female, 752 (21.4%) were Black, and 2773 (78.6%) were White. SARS-CoV-2 infection was detected among 307 participants (8.7%), 103 of whom (33.6%) were hospitalized. Among uninfected participants, the mean annualized change in cognitive function was −0.09 (95% CI, −0.13 to −0.04). Compared with this rate, change was faster (β = −0.06; 95% CI, −0.09 to −0.02) among participants hospitalized for infection, but not different from participants who were infected but not hospitalized (β = 0.00; 95% CI, −0.02 to 0.03). The association among participants hospitalized for infection was evident in the cognitive domains of memory and executive function, but not language. Conclusions and relevance This cohort study of older participants found accelerated decreases in cognition among individuals hospitalized for SARS-CoV-2 infection, but not nonhospitalized infection, in comparison with individuals not yet infected.

Introduction: Physical activity (PA) has been identified as a protective factor for dementia, but the mechanisms linking PA to brain health are unclear. To elucidate potential pathways linking PA to brain health, we tested the hypothesis that higher levels of late-life PA are associated with a lower burden of Alzheimer’s disease (AD) pathology, cerebrovascular disease, and neurodegeneration measured through brain imaging and plasma biomarkers. Methods: ARIC-NCS participants without dementia in 2011-13 and with measures of PA, 3T brain magnetic resonance imaging (MRI), and stored plasma samples were examined (n=1,771; mean age: 76.5 years; 40.5% male; 27.6% Black). Participants were classified as meeting or not meeting 2018 aerobic PA guidelines based on a standardized interviewer-administered questionnaire. MRI biomarkers included white matter hyperintensity (WMH) volume (cm 3 ), total brain volume (TBV) (cm 3 ), and cortical thickness (CT) (mm). Plasma biomarkers of the ratio of amyloid beta 42 to 40 (Aβ42/Aβ40), phosphorylated Tau-181 (p-Tau181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were measured using Quanterix Simoa immunoassays. All biomarkers were standardized to measures in 2011-13 to facilitate comparisons. Covariate-adjusted linear regression models estimated cross-sectional associations of PA with MRI or plasma biomarkers. Covariate-adjusted linear mixed effects models quantified associations of PA with the 5-year rate of change in a subset of participants with MRI (n=669) or plasma (n=651) biomarkers at both baseline and follow-up from 2011-19 (median follow-up: 5.4 years). Results: Meeting versus not meeting aerobic PA guidelines was cross-sectionally associated with lower volumes of WMH (β = -0.16, 95% CI: -0.25, -0.07), higher TBV (β = 0.09; 95% CI: 0.05, 0.13), and lower plasma NfL (β = -0.102, 95% CI: -0.184, -0.021) ( Figure ). Late-life PA was not associated with 5-year rates of change in MRI or plasma biomarkers. Conclusions: Late-life PA was cross-sectionally associated with less neurodegeneration and cerebrovascular disease. Associations with 5-year changes in imaging and plasma biomarkers of AD pathology, cerebrovascular disease, or neurodegeneration were not statistically supported. Longitudinal biomarker studies with wearable devices that quantify other daily intensity-based movement metrics (e.g., light PA) and larger sample sizes are needed to further examine mechanisms linking PA to brain health.