Leisure-time physical activity sustained since midlife and preservation of cognitive function: The Atherosclerosis Risk in Communities Study

Introduction: We tested the hypotheses that higher levels of and persistence of midlife leisure-time physical activity (LTPA) are associated long-term with lower cognitive decline and less incident dementia. Methods: A total of 10,705 participants (mean age: 60 years) had LTPA (no, low, middle, or high) measured in 1987-1989 and 1993-1995. LTPA was assessed in relation to incident dementia and 14-year change in general cognitive performance. Results: Over a median follow-up of 17.4 years, 1063 dementia cases were observed. Compared with no LTPA, high LTPA in midlife was associated with lower incidence of dementia (hazard ratio [95% confidence interval], 0.71 [0.61, 0.86]) and lower declines in general cognitive performance (−0.07 standard deviation difference [−0.12 to −0.04]). These associations were stronger when measured against persistence of midlife LTPA over 6 years. Discussion: LTPA is a readily modifiable factor associated inversely with long-term dementia incidence and cognitive decline

The ARIC (Atherosclerosis Risk In Communities) Study: JACC Focus Seminar 3/8

ARIC (Atherosclerosis Risk In Communities) initiated community-based surveillance in 1987 for myocardial infarction and coronary heart disease (CHD) incidence and mortality and created a prospective cohort of 15,792 Black and White adults ages 45 to 64 years. The primary aims were to improve understanding of the decline in CHD mortality and identify determinants of subclinical atherosclerosis and CHD in Black and White middle-age adults. ARIC has examined areas including health disparities, genomics, heart failure, and prevention, producing more than 2,300 publications. Results have had strong clinical impact and demonstrate the importance of population-based research in the spectrum of biomedical research to improve health

Prospective Analysis of Leisure-Time Physical Activity in Midlife and Beyond and Brain Damage on MRI in Older Adults

OBJECTIVE: To test the hypothesis that greater levels of leisure-time moderate to vigorous intensity physical activity (MVPA) in midlife or late life are associated with larger gray matter volumes, less white matter disease, and fewer cerebrovascular lesions measured in late life, we utilized data from 1,604 participants enrolled in the Atherosclerosis Risk in Communities study. METHODS: Leisure-time MVPA was quantified using a past-year recall, interviewer-administered questionnaire at baseline and 25 years later and classified as none, low, middle, and high at each time point. The presence of cerebrovascular lesions, white matter hyperintensities (WMH), white matter integrity (mean fractional anisotropy [FA] and mean diffusivity [MD]), and gray matter volumes were quantified with 3T MRI in late life. The odds of cerebrovascular lesions were estimated with logistic regression. Linear regression estimated the mean differences in WMH, mean FA and MD, and gray matter volumes. RESULTS: Among 1,604 participants (mean age 53 years, 61% female, 27% Black), 550 (34%), 176 (11%), 250 (16%), and 628 (39%) reported no, low, middle, and high MVPA in midlife, respectively. Compared to no MVPA in midlife, high MVPA was associated with more intact white matter integrity in late life (mean FA difference 0.13 per SD [95% confidence interval (CI) 0.004, 0.26]; mean MD difference -0.11 per SD [95% CI -0.21, -0.004]). High MVPA in midlife was also associated with a lower odds of lacunar infarcts (odds ratio 0.68, 95% CI 0.46, 0.99). High MVPA was not associated with gray matter volumes. High MVPA compared to no MVPA in late life was associated with most brain measures. CONCLUSION: Greater levels of physical activity in midlife may protect against cerebrovascular sequelae in late life

Mid- And Late-Life Leisure-Time Physical Activity and Global Brain Amyloid Burden- And Atherosclerosis Risk in Communities (ARIC)-PET Study

Background: Physical activity (PA) may slow the development of dementia by reducing the accumulation of amyloid. Objective: We tested the hypothesis that higher levels of leisure-time PA in mid- or late-life were associated with lower brain amyloid burden in late-life among 326 non-demented participants from the Atherosclerosis Risk in Communities Study of brain florbetapir positron emission tomography (ARIC-PET) ancillary. Methods: Self-reported PA was quantified using a past-year recall, interviewer-administered questionnaire in mid-life (1987-1989, aged 45-64 years) and late-life (2011-2013, aged 67-89 years). Continuous PA estimates were classified as 1) any leisure-time PA participation (yes/no); 2) meeting the 2018 United States' PA guidelines (yes/no); and 3) per 1 standard deviation (SD) higher metabolic equivalent of task (MET) minutes per week (MET min wk-1). A brain magnetic resonance imaging scan with Florbetapir PET was performed in late-life. Adjusted odds ratios (OR) of elevated amyloid burden, defined as a global cortical standardized uptake value ratio (>1.2), compared to no elevated amyloid burden were estimated according to PA measures. Results: Among the 326 participants (mean age: 76 years, 42% male, 41% Black), 52% had elevated brain amyloid burden. Mid-life leisure-time PA did not show a statistically significant lower odds of elevated late-life amyloid burden (OR = 0.71, 95% CI: 0.43-1.18). A 1 SD (970 MET. min. wk-1) higher PA level in mid-life was also not significantly associated with elevated amyloid burden (OR = 0.89, 95% CI: 0.69-1.15). Similar estimates were observed for meeting versus not meeting PA guidelines in both mid- and late-life. Conclusion: Self-reported higher mid- and late-life leisure-time PA were not significantly associated with lower amyloid burden. Data show a trend of an association, which is, however, imprecise, suggesting replication in larger studies

Low Liver Enzymes and Risk of Dementia: The Atherosclerosis Risk in Communities (ARIC) Study

Background: Low levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the low physiologic range, surrogate markers for reduced liver metabolic function, are associated with cerebral hypometabolism, impairment in neurotransmitter production and synaptic maintenance, and a higher prevalence of dementia. It is unknown whether a prospective association exists between low liver enzyme levels and incident dementia. Objective: To determine whether low levels of ALT and AST are associated with higher risk of incident dementia. Methods: Plasma ALT and AST were measured on 10,100 study participants (mean age 63.2 years, 55% female, 22% black) in 1996-1998. Dementia was ascertained from comprehensive neuropsychological assessments, annual contact, and medical record surveillance. Cox proportional hazards regression was used to estimate the association. Results: During a median follow-up of 18.3 years (maximum 21.9 years), 1,857 individuals developed dementia. Adjusted for demographic factors, incidence rates of dementia were higher at the lower levels of ALT and AST. Compared to the second quintile, ALT values <10th percentile were associated with a higher risk of dementia (hazard ratio [HR] 1.34, 95% CI 1.08-1.65). The corresponding HR was 1.22 (0.99-1.51) for AST. Conclusion: Plasma aminotransferases <10th percentile of the physiologic range at mid-life, particularly ALT, were associated with greater long-term risk of dementia, advocating for attention to the putative role of hepatic function in the pathogenesis of dementia

Association of Ischemic Stroke Incidence, Severity, and Recurrence with Dementia in the Atherosclerosis Risk in Communities Cohort Study

Importance: Ischemic stroke is associated with increased risk of dementia, but the association of stroke severity and recurrence with risk of impaired cognition is not well known. Objective: To examine the risk of dementia after incident ischemic stroke and assess how it differed by stroke severity and recurrence. Design, Setting, and Participants: The Atherosclerosis Risk in Communities (ARIC) study is an ongoing prospective cohort of 15792 community-dwelling individuals from 4 US states (Mississippi, Maryland, Minnesota, and North Carolina). Among them, 15379 participants free of stroke and dementia at baseline (1987 to 1989) were monitored through 2019. Data were analyzed from April to October 2021. Associations between dementia and time-varying ischemic stroke incidence, frequency, and severity were studied across an average of 4.4 visits over a median follow-up of 25.5 years with Cox proportional hazards models adjusted for sociodemographic characteristics, apolipoprotein E, and vascular risk factors. Exposures: Incident and recurrent ischemic strokes were classified by expert review of hospital records, with severity defined by the National Institutes of Health Stroke Scale (NIHSS; minor, ≤5; mild, 6-10; moderate, 11-15; and severe, ≥16). Main Outcomes and Measures: Dementia cases adjudicated through expert review of in-person evaluations, informant interviews, telephone assessments, hospitalization codes, and death certificates. In participants with stroke, dementia events in the first year after stroke were not counted. Results: At baseline, the mean (SD) age of participants was 54.1 (5.8) years, and 8485 of 15379 participants (55.2%) were women. A total of 4110 participants (26.7%) were Black and 11269 (73.3%) were White. A total of 1378 ischemic strokes (1155 incident) and 2860 dementia cases were diagnosed 1 year or more after incident stroke in participants with stroke, or at any point after baseline in participants without stroke, were identified through December 31, 2019. NIHSS scores were available for 1184 of 1378 ischemic strokes (85.9%). Risk of dementia increased with both the number and severity of strokes. Compared with no stroke, risk of dementia by adjusted hazard ratio was 1.76 (95% CI, 1.49-2.00) for 1 minor to mild stroke, 3.47 (95% CI, 2.23-5.40) for 1 moderate to severe stroke, 3.48 (95% CI, 2.54-4.76) for 2 or more minor to mild strokes, and 6.68 (95% CI, 3.77-11.83) for 2 or more moderate to severe strokes. Conclusions and Relevance: In this study, risk of dementia significantly increased after ischemic stroke, independent of vascular risk factors. Results suggest a dose-response association of stroke severity and recurrence with risk of dementia

Central arterial stiffness is associated with structural brain damage and poorer cognitive performance: The ARIC study

Background Central arterial stiffening and increased pulsatility, with consequent cerebral hypoperfusion, may result in structural brain damage and cognitive impairment. Methods and Results We analyzed a cross‐sectional sample of ARIC‐NCS(Atherosclerosis Risk in Communities–Neurocognitive Study) participants (aged 67–90 years, 60% women) with measures of cognition (n=3703) and brain magnetic resonance imaging (n=1255). Central arterial hemodynamics were assessed as carotid‐femoral pulse wave velocity and pressure pulsatility (central pulse pressure). We derived factor scores for cognitive domains. Brain magnetic resonance imaging using 3‐Tesla scanners quantified lacunar infarcts; cerebral microbleeds; and volumes of white matter hyperintensities, total brain, and the Alzheimer disease signature region. We used logistic regression, adjusted for demographics, apolipoprotein E ɛ4, heart rate, mean arterial pressure, and select cardiovascular risk factors, to estimate the odds of lacunar infarcts or cerebral microbleeds. Linear regression, additionally adjusted for intracranial volume, estimated the difference in log‐transformed volumes of white matter hyperintensities, total brain, and the Alzheimer diseasesignature region. We estimated the mean difference in cognitive factor scores across quartiles of carotid‐femoral pulse wave velocity or central pulse pressure using linear regression. Compared with participants in the lowest carotid‐femoral pulse wave velocity quartile, participants in the highest quartile of carotid‐femoral pulse wave velocity had a greater burden of white matter hyperintensities (P=0.007 for trend), smaller total brain volumes (−18.30 cm 3 ; 95% CI, −27.54 to −9.07 cm 3 ), and smaller Alzheimer disease signature region volumes (−1.48 cm 3 ; 95% CI, −2.27 to −0.68 cm 3 ). These participants also had lower scores in executive function/processing speed (β=−0.04 z score; 95% CI, −0.07 to −0.01 z score) and general cognition (β=−0.09 z score; 95% CI, −0.15 to −0.03 z score). Similar results were observed for central pulse pressure. Conclusions Central arterial hemodynamics were associated with structural brain damage and poorer cognitive performance among older adults

Retinal microvascular abnormalities and risk of lacunar stroke: Atherosclerosis risk in communities study

10.1161/STROKEAHA.110.580837Stroke4171349-1355SJCC

Relationship between retinal arteriolar narrowing and myocardial perfusion: Multi-ethnic study of atherosclerosis

10.1161/HYPERTENSIONAHA.107.098343Hypertension511119-126HPRT

Hemostatic Factors and Subclinical Brain Infarction in a Community-Based Sample: The ARIC Study

[[abstract]]Background: Previous data are conflicting as to whether imbalance between hemostatic factors is associated with clinical strokes. We evaluated the association between hemostatic factor levels and subclinical lacunar infarcts in a nested sample from a subset of the Atherosclerosis Risk in Communities (ARIC) cohort. Methods: 196 cases without clinical strokes had lacunar infarcts by MRI, and 214 controls without radiographic infarcts were frequency-matched by age group and sex. Logistic regression models were fitted to assess the association between levels of hemostatic markers and case status. Results: In age-, race- and sex-adjusted models, von Willebrand factor (vWF) and D-dimer were positively associated with case status, with odds ratios for the highest vs. lowest tertile of 2.0 (95% CI 1.2-3.6) for vWF and 1.76 (95% CI 1.02-3.0) for D-dimer. Plasminogen had nonsignificant inverse associations with presence of silent lacunar infarcts. Conclusions: vWF and D-dimer were positively associated, and plasminogen was nonsignificantly inversely associated with subclinical radiographic infarct. Further studies on the role of these hemostatic factors in the development of silent lacunar infarcts may help elucidate the mechanisms behind this injury and may even point to potential targets for future intervention