Coresh, Josef

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.

ImportanceMidlife vascular risk factors are associated with an elevated risk of dementia. However, the total contribution of vascular risk factors in midlife and late life with incident dementia is uncertain.ObjectiveTo quantify the proportion of incident dementia attributable to modifiable vascular risk factors measured in midlife and late life and to examine differences by apolipoprotein ε4 genotype, self-reported race, and sex.Design, Setting, and ParticipantsThis was a prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study using 33 years of follow-up (1987-2020). The setting included ARIC field centers (Jackson, Mississippi; Forsyth County, North Carolina; Minneapolis suburbs, Minnesota; Washington County, Maryland). Study baseline in Black and White participants with complete exposure and covariate data was set by age at risk factor measurement (45-54 years, 55-64 years, and 65-74 years). Data were analyzed from August 2023 to December 2024.ExposuresHypertension (systolic blood pressure [BP] ≥130 mm Hg, diastolic BP ≥80 mm Hg, or use of medication for BP), diabetes (fasting glucose ≥126 mg/dL, nonfasting glucose ≥200 mg/dL, self-reported physician’s diagnosis, or use of any diabetes medication), and current smoking (self-reported).Main Outcomes and MeasuresIncident dementia. Population attributable fractions were estimated by age 80 years, and separately after 80 years, from having at least 1 vascular risk factor by age at risk factor measurement.ResultsA total of 7731 participants were included in analysis of risk factors measured at age 45 to 54 years (4494 female [58%]; 2207 Black [29%]; 5524 White [71%]), 12 274 contributed to analysis of risk factors measured at age 55 to 64 years (6698 female [55%]; 2886 Black [24%]; 9388 White [76%]), and 6787 contributed to analysis of risk factors measured at age 65 to 74 years (3764 female [56%], 1375 Black [20%]; 5412 White [80%]). There were 801, 995, and 422 dementia cases by 80 years, respectively. The fraction of dementia by 80 years attributable to at least 1 vascular factor at age 45 to 54 years was 21.8% (95% CI, 14.3%-29.3%), at 55 to 64 years was 26.4% (95% CI, 19.1%-33.6%), and at 65 to 74 years was 44.0% (95% CI, 30.9%-57.2%). Attributable fractions for these factors were higher in apolipoprotein ε4 noncarriers at age 55 years and older (range, 33.3%-61.4%), Black individuals at age 45 years and older (range, 25.5%-52.9%), and female individuals at age 55 years and older (range, 29.2%-51.3%). Only 2% to 8% of dementia cases after 80 years were attributable to these factors.Conclusions and RelevanceResults of this cohort study suggest that between 22% and 44% of incident dementia cases by 80 years in the ARIC study were attributed to midlife and late-life vascular risk factors. Assuming causal relationships, maintaining optimal vascular health across the life course could mitigate a sizeable proportion of dementia risk by 80 years.

Introduction: Vascular risk factors of hypertension, diabetes, and smoking in midlife (45-64 years) and possibly early late-life (65-74 years) are associated with increased risk of dementia. Current estimates of population attributable risk for dementia assume vascular factors are independent and do not interact to increase risk of dementia, which may underestimate the combined impact of vascular risk reduction on dementia incidence. In this study, we evaluated the joint association and interaction of vascular risk factors on risk of dementia. Methods: We performed a prospective cohort analysis using the Atherosclerosis Risk in Communities Neurocognitive Study using up to 33 years of follow-up (1987-2020). We used age as baseline (45-54 years, n=7,731; 55-64 years, n=12,273; and 65-74 years, n=6,660). We defined hypertension as systolic blood pressure ≥130 mm Hg, diastolic blood pressure ≥80 mm Hg, or anti-hypertension medication use. We defined diabetes as fasting glucose level ≥126 mg/dL, non-fasting glucose ≥200 mg/dL, self-reported physician diagnosis, or use of any diabetes medication. Current smoking was self-reported. We investigated additive and multiplicative interactions for combinations of vascular risk factors on incident (adjudicated) dementia by age 80 using joint effect variables in Cox regression models stratified by age of risk factor measurement (45-54 years, 55-64 years, or 65-74 years). For interaction analyses, parameter values >1 indicate positive interaction (synergy) and values <1 indicate negative interaction (antagonism). Results: In participants with risk factors measured in these baseline age strata, there were 801 (10%), 995 (8%), and 422 (6%) cases of incident dementia by age 80, respectively. Hypertension and diabetes exhibited positive interactions on the additive and multiplicative scales in midlife (Figure 1). Diabetes and smoking in midlife had positive additive interaction (value >1, Figure 2). All vascular risk factor combinations in late-life had negative interactions on the multiplicative scale (values <1, Figures 1-3). Conclusions: Hypertension with diabetes and diabetes with smoking, all measured in midlife, interact to increase risk of dementia by age 80. The overall impact of reducing midlife vascular risk factors on incident dementia could be sizeable. These findings highlight the importance of multifactor interventions addressing combinations of vascular risk factors for dementia prevention strategies.

Background: Dementia is increasingly appreciated to have important vascular disease contributions. Albuminuria and decreased estimated glomerular filtration rate (eGFR) define chronic kidney disease (CKD) and are related to the risk of its consequences as well as microvascular disease and endothelial damage across multiple vascular beds. We extend previous studies by examining albuminuria and eGFR measured at both mid-life and older age as risk factors for dementia. Methods: We studied 10,876 adult participants in the Atherosclerosis Risk in Communities (ARIC) Study excluding participants with end-stage renal disease, stroke and incident dementia at baseline. We analyzed the adjusted relative hazard of incident dementia as a function of eGFR (linear spine with a knot at 60 ml/min per 1.73m 2 ) and log urinary albumin-creatinine-ratio (UACR) adjusting for age, sex, race, education level, Apolipoprotein E4 level, smoking, alcohol consumption, body mass index, diabetes and hypertension. We used two different baseline visits: (1) Starting in 1996-1999 (Visit 4, age 54-74 years); (2) Starting 2011-2013 (Visit 5, age 70-90 years) with follow-up to 2017. Results: We observed 2,001 dementia cases over 16 years of follow-up (446 after Visit 5). Risk of dementia increased with higher levels of albuminuria with a stronger magnitude at older-age than in midlife ( see table ). Estimated GFR was more weakly associated with dementia (p>0.05 at both baselines). The albuminuria association was consistent across sex and race (p-interaction>0.05). Conclusion: Albuminuria, a marker of kidney disease and endothelial damage, is strongly related to dementia incidence. Albuminuria’s association with dementia is stronger in late-life unlike other vascular risk factors, where the association is weaker at older age.