Bandeen‐Roche, Karen

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.

Abstract Resilience, which relates to one's ability to respond to stressors, typically declines with age and the development of comorbid conditions in older organisms. Although progress has been made to improve our understanding of resilience in older adults, disciplines have employed different frameworks and definitions to study various aspects of older adults' response to acute or chronic stressors. “Overview of the Resilience World: State of the Science,” a bench‐to‐bedside conference on October 12–13, 2022, was sponsored by the American Geriatrics Society and National Institute on Aging. This conference, summarized in this report, explored commonalities and differences among the frameworks of resilience most commonly used in aging research in the three domains of resilience: physical, cognitive, and psychosocial. These three main domains are intertwined, and stressors in one domain can lead to effects in other domains. The themes of the conference sessions included underlying contributors to resilience, the dynamic nature of resilience throughout the life span, and the role of resilience in health equity. Although participants did not agree on a single definition of “resilience(s),” they identified common core elements of a definition that can be applied to all domains and noted unique features that are domain specific. The presentations and discussions led to recommendations for new longitudinal studies of the impact of exposures to stressors on resilience in older adults, the use of new and existing cohort study data, natural experiments (including the COVID‐19 pandemic), and preclinical models for resilience research, as well as translational research to bring findings on resilience to patient care.

Introduction: Among older adults with diabetes, cognitive dysfunction is of particular concern as it has implications for treatment adherence and diabetes self-management. The prevalence of cognitive dysfunction has not been well characterized in this population. Methods: We conducted a cross-sectional analysis of 5509 participants (1815 with diabetes) from visit 5 (2011-2013) of the ARIC Study. Diabetes was defined based on self-reported physician diagnosis, diabetes medication use, or HbA1c ≥ 6.5%. Cognitive function was measured using 8 neuropsychological tests, which were grouped into three cognitive domains representing memory, executive function, and language. Participants were categorized as having cognitive dysfunction if test scores were more than 1.5 standard deviations below age-, race-, and education-adjusted scores derived from a cognitively healthy population. We calculated crude prevalence estimates and used Poisson regression to estimate adjusted prevalence ratios (PRs), comparing cognitive dysfunction in persons with and without diabetes. We adjusted for demographic and clinical characteristics. Results: The mean age of participants was 75 years, 59% were female, 79% were white, and 33% had diabetes. In each domain, the prevalence of cognitive dysfunction among persons with diabetes ranged from 14% to 27%. Persons with diabetes were more likely than persons without diabetes to have dysfunction in multiple domains (PR = 1.29, 95% CI: 1.12, 1.49). Prevalence of cognitive dysfunction was significantly higher in persons with versus without diabetes for memory (PR=1.13, 95% CI: 1.02, 1.25), language (PR=1.24, 95% CI: 1.09, 1.45), and executive function (PR=1.10, 95% CI: 1.00, 1.22)(Figure). PRs were similar in crude models. Conclusions: The prevalence of cognitive dysfunction among older adults with diabetes is high. These results have implications for how physicians educate patients in appropriate self-management practices and for the prevention of diabetes-related complications.

Introduction: The microvascular contribution to dementia may be under-recognized because of the inability to visualize the brain microvasculature in vivo. Although the easily-imaged retinal vasculature may be a surrogate measure for that in the brain, large prospective studies of the relationship between retinal vascular signs and dementia are scarce. Hypothesis: Retinal signs are associated with greater subsequent risk of all-cause dementia and etiologic subtype over 20 years in 12482 men and women (mean age of 60 years when retinal signs were measured, 22% African American). Methods: Retinal signs were measured using fundus photography (1993-1995). Presence and etiology of dementia and mild cognitive impairment (MCI) were adjudicated using data collected in 2011-13, including a complete neuropsychological battery and brain magnetic resonance imaging (subset of participants). For participants not attending the 2011-13 visit, dementia cases were identified using the Telephone Interview for Cognitive Status–Modified or informant interview, or by hospitalization or death certificate code. Multivariable-adjusted Cox proportional hazards models and logistic regression were used to quantify the relationship of retinal signs with dementia risk and with etiologic subtype, respectively. Results: During a mean 16 years of follow-up, 1259 (10%) participants developed dementia. Moderate or severe (vs. no) retinopathy (hazard ratio [HR], 1.86; 95% CI: 1.36, 2.55) and generalized arteriolar narrowing, measured as the central retinal arteriolar equivalent (CRAE, narrowest quartile vs. widest three quartiles), (HR, 1.26; 95% CI: 1.09, 1.45) were associated with all-cause dementia. Results did not differ by diabetes, race or APOE ε4 genotype. Retinopathy was associated with cerebrovascular-related dementia and MCI (odds ratio, 2.66; 95% CI: 1.30, 5.42). Conclusions: Retinal photography captures small vascular signs in the eye that are related to increased dementia risk. Emerging techniques, such as optical coherence tomography angiography, may have the sensitivity to provide surrogate indices of microvascular lesions relevant to dementia in older adults.

Introduction: Cerebrovascular small vessel disease, seen on brain imaging as lacunes and white matter hyperintensities (WMH), is a substrate for dementia in older adults. Diffusion tensor imaging (DTI) is thought to provide early signs of loss of white matter (WM) integrity due to microvascular disease and predicts WM hyperintensity volume. Retinal fundus photography provides surrogate measures of cerebral microvasculature. No studies have quantified the long-term association between retinal signs and DTI measures. Hypothesis: Microvascular retinal signs measured in midlife are associated with small vessel disease measured on brain magnetic resonance imaging (MRI) 18 years later, including reduced WM microstructural integrity (lower fractional anisotrophy [FA] and greater mean diffusivity [MD] by DTI), greater WM hyperintensity volume and greater lacune prevalence. Methods: In a biracial prospective cohort study, retinal signs were measured using fundus photography (1993-1995) with 3-T magnetic resonance imaging conducted in 2011-13. Multivariable-adjusted linear regression was used to quantify the relationships of retinal signs with WM measures. Prevalence of lacunar infarcts by retinal sign status was estimated using log binomial regression. Analyses were adjusted for age [linear and quadratic terms], education, sex, race, intracranial volume, body mass index, smoking, diabetes, hypertension, and ≥1 APOE ε4 alleles. Results: In 1829 men and women (60% [N=1100] female, 27% [N=489] black race, aged 50-72 years when retinal signs were measured), a binary measure comprised of two retinal signs suggestive of arteriolar damage due to hypertension (focal arteriolar narrowing and/or arteriovenous nicking) was associated with worse (lower) FA (standardized β=-0.19, 95% confidence interval [CI]=-0.35, -0.02), worse (higher) MD (β=0.15, 95% CI=0.00, 0.30), greater WM hyperintensity volume (β=0.15, 95% CI=0.01, 0.30), and greater prevalence of lacunes (prevalence ratio=1.33, 95% CI: 0.99, 1.80). Generalized arteriolar narrowing, measured as the central retinal arteriolar equivalent (CRAE, narrowest quartile vs. widest three quartiles) was associated with worse FA (β=-0.13, 95% CI=-0.24, -0.01) and worse MD (β=0.12, 95% CI=0.01, 0.23). Results did not differ by sex, race, hypertension status or APOE ε4 genotype. No associations were found for retinopathy, but only 56 participants had retinopathy. Conclusions: Consistent with prior work, and as expected based on a common underlying pathology, retinal signs predicted WM disease and lacunar infarcts 18 years later. Novel to this study, we found that retinal signs related to arteriolar damage also predicted loss of white matter microvascular integrity measured using DTI.

AbstractIntroductionThe easily‐imaged retinal microvasculature may reflect the brain microvasculature and therefore be related to dementia.MethodsIn a population‐based study of 12,482 adults aged 50‐73 years (22% African American), we estimated the relationship of retinal characteristics from fundus photography (1993‐1995) with incident all‐cause dementia (1993‐1995 to 2011‐2013) and with etiologic subtype of dementia/mild cognitive impairment (2011‐13).ResultsA total of 1259 (10%) participants developed dementia over a mean 15.6 years. Moderate/severe (vs. no) retinopathy (hazard ratio [HR], 1.86; 95% confidence interval [CI]: 1.36–2.55) and central retinal arteriolar equivalent (narrowest quartile vs. widest three quartiles; HR, 1.26; 95% CI: 1.09–1.45) were associated with all‐cause dementia. Results were qualitatively stronger (but not statistically significantly different) in participants with diabetes. Retinopathy was associated with a joint outcome of cerebrovascular‐related, but not Alzheimer's disease–related, dementia/mild cognitive impairment (HR, 2.29; 95% CI: 1.24–4.23).DiscussionExploration of measures in the eye may provide surrogate indices of microvascular lesions relevant to dementia.