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Objectives To quantify associations between inflammatory biomarkers and hippocampal volume (HV) and to examine effect modification according to sex, race, and age. Design Cross-sectional analyses using generalized estimating equations to account for familial clustering; standardized β-coefficients adjusted for age, sex, race, and education. Setting Community cohorts in Jackson, Mississippi and Rochester, Minnesota. Participants The Genetic Epidemiology Network of Arteriopathy study. Measurements C-reactive protein (CRP), interleukin-6 (IL-6), and soluble tumor necrosis factor receptors 1 (sTNFR-1) and 2 (sTNFR-2) from peripheral blood were measured in a sample of 773 non-Hispanic whites (61% women, aged 60.2 ± 9.8) and 514 African Americans (70% women, aged 63.9 ± 8.1) who also underwent brain magnetic resonance imaging. Biomarkers were standardized and compared according to sex, race and age with HV. Results In the full sample, higher sTNFR-1 and sTNFR-2 were associated with smaller HV. Each standard deviation (SD) increase in sTNFR-1 was associated with 59.1 mm3 (95% confidence interval (CI) = −101.4 to −16.7 mm3) smaller HV and each SD increase in sTNFR-2 associated with 48.8 mm3 (95% CI = −92.2 to −5.3 mm3) smaller HV. Relationships were stronger for sTNFR-2 in men (HV = −116.6 mm3 for each SD increase, 95% CI = −201.0 to −32.1) than women (HV = −26.0 per SD increase, 95% CI = −72.4–20.5) and sTNFR-1 in non-Hispanic whites (HV = −84.7 mm3 per SD increase, 95% CI = −142.2 to −27.1) than African Americans (HV = −14.1 mm3 per SD increase, 95% CI = −78.3–50.1). Associations between IL-6 or CRP and HV were not supported. Conclusion Higher levels of sTNFRs were associated cross-sectionally with smaller hippocampi. Longitudinal data are needed to determine whether these biomarkers may help to identify risk of late-life cognitive impairment.

Objectives To examine associations between inflammation and physical function and potential mediation by white matter hyperintensities (WMHs) in African Americans (AAs) and European Americans (EAs). Design Cross-sectional analysis using linear and logistic models with generalized estimating equations to account for family clustering, reporting results as regression coefficients (β) and odds ratios (ORs) adjusted for education, alcohol, exercise, body mass index, hypertension, diabetes mellitus, heart disease, cognition, ankle–brachial index, race (site), and supported interactions. Setting Genetic Epidemiology Network of Arteriopathy-Genetics of Microangiopathic Brain Injury Study cohort. Participants AA and EA sibships with two or more siblings with hypertension before age 60 (N = 1,960; 65% female, 51% AA, aged 26–91, 50% obese, 72% hypertensive). Measurements Inflammation (C-reactive protein (CRP), interleukin-6 (IL6), soluble tumor necrosis factor receptors (sTNFRs) 1 and 2, WMH volume (cm3) according to magnetic resonance imaging), walking speed (cm/s) over 25 feet, and mobility difficulty (any self-reported difficulty walking half a mile). Results In separate models, inflammatory markers were associated with walking speed (sTNFR1: β = −2.74, P < .001; sTNFR2: β = −1.23, P = .03; CRP: β = −1.95, P = .001; IL6: β = −1.24, P = .03) and mobility difficulty (sTNFR1: OR = 1.36, P = .001; sTNFR2: OR = 1.25, P = .005; CRP: OR = 1.22, P = .005; IL6: OR = 1.18, P = .02); the association between WMH volume and sTNFR1 in AA (β = 0.07, P = .06) did not reach typical statistical thresholds. WMH volume was associated with walking speed in AA (β = −3.17, P = .02) but not with mobility difficulty (OR = 1.10, P = .54). Adjusting for WMH did not change associations. Conclusion In young, middle-aged, and older adults with prevalent cardiovascular risk factors, multiple inflammatory biomarkers were associated with slower walking speed independent of microvascular disease in the brain. There was little evidence of mediation by brain WMH volume. Inflammation may contribute to physical function impairments through pathways other than brain microvascular disease, particularly in AAs.

Objectives To examine the association between midlife cardiovascular health and physical performance 25 years later. Design Cohort study (Atherosclerosis Risk in Communities Study); multinomial logistic and logistic regression adjusted for demographic characteristics and clinical measures. Setting Four U.S. communities: Forsyth County, North Carolina; Washington County, Maryland; Minneapolis, Minnesota; and Jackson, Mississippi. Participants: Individuals aged 54.2 ± 5.8 at baseline (N = 15,744; 55% female, 27% black). Measurements Cardiovascular health was measured at baseline using the American Heart Association's Life's Simple 7 (LS7) score (0–14) and LS7 component categories (poor, intermediate, ideal) for each risk factor. The Short Physical Performance Battery (SPPB) was used to quantify physical function as ordinal (0–12) and categorical (low (0–6), fair (7–9), good (10–12) outcomes. Results Mean baseline LS7 score was 7.9 ± 2.4; 6,144 (39%) individuals returned 25 years later for the fifth ARIC examination, at which point the SPPB was administered. Of 5,916 individuals who completed the SPPB, 3,288 (50%) had good physical performance. Each 1-unit increase in LS7 score was associated with a 17% higher SPPB score (rate ratio (RR) = 1.17, 95% confidence interval (CI) = 1.15–1.19) and a 29% greater chance of having a late-life SPPB score of 10 or greater compared to SPPB score of less than 10 (RR = 1.29, 95% CI = 1.25–1.34). Ideal baseline glucose (RR = 2.53, 95% CI = 2.24–2.87), smoking (RR = 1.97, 95% CI = 1.81–2.15), blood pressure (RR = 1.70, 95% CI = 1.54–1.88), body mass index (RR = 1.51, 95% CI = 1.37–1.66), and physical activity (RR = 1.31, 95% CI = 1.20–1.43) had the strongest associations with late-life SPPB score, adjusting for other LS7 components. Conclusion Better cardiovascular health during midlife may lead better physical functioning in older age.

OBJECTIVES: To assess relationships between vision (contrast sensitivity, stereopsis, visual acuity) and a performance-based measure of ability to implement new medications.DESIGN: Cross-sectional analysis; prospective cohort study.SETTING: Community-based.PARTICIPANTS: Three hundred thirty-five participants aged 73 to 82 in Year 3 of the Women's Health and Aging Study 11, a representative sample of the two-thirds least-disabled community-dwelling women.MEASUREMENTS: Hopkins Medication Schedule Pillbox Ratio, a joint measure of accuracy and time, and a performance-based measure of ability to Implement a prescription. Participants received written and verbal instructions for taking two medications and were directed to place pills in a pillbox accordingly. Vision assessments: contrast sensitivity (Pelli-Robson letter sensitivity chart), stereopsis (Randot Circles), and visual acuity (Early Treatment Diabetic Retinopathy Study eye chart).RESULTS: Forty-four percent (148/335) of women incorrectly placed one or both medications. Each vision measure was positively associated with Pillbox Ratio scores and varied with cognition and time to completion. Better visual acuity, contrast sensitivity, and stereopsis were each associated with better performance in women with poor cognition who filled the pillbox quickly. Additionally, better visual acuity was associated with better performance in participants with good cognition who filled the pillbox slowly; better stereopsis was associated with better performance in participants with poor cognition who filled the pillbox slowly and whose stereoacuity was below normal.CONCLUSION: Visual acuity, contrast sensitivity, and stereopsis should be considered potential risk factors for impaired ability to implement a medication regimen in older adults. Future research should investigate the role of vision, including contrast sensitivity and stereopsis, on performance of other instrumental activities of daily living.

Objectives: To determine the agreement between self-report of chronic disease and validated evidence of disease using multiple ascertainment methods and to assess effects of cognition, education, age, and comorbidity. Design: Cross-sectional analysis. Setting: Community Baltimore, Maryland. Participants: One thousand two community-dwelling disabled women aged 65 and older. Measurements: Kappa statistics were calculated to determine the relationship between self-report of 14 diseases and standardized algorithms. Analyses were stratified using Mini-Mental State Examination score, education, number of chronic diseases, and age. Results: Kappa was excellent for hip fracture (HF), Parkinson's disease (PD), diabetes mellitus (DM), cancer, stroke, and disc disease (DD); fair to good for angina pectoris, congestive heart failure, and myocardial infarction; and poor for peripheral arterial disease, spinal stenosis, osteoporosis, arthritis, and lung disease. Overall, kappa decreased with decreasing cognition and education, increasing age, and four or more diseases. Conclusion: In disabled older women, self-report of physician diagnosis of HF, PD, DM, cancer, stroke, and DD appears valid. In general, increasing comorbidity and age and decreasing cognition and education do not reduce validity for diseases where agreement was excellent overall.