Rural versus Urban Residence in Adulthood and Incident Cognitive Impairment.

INTRODUCTION: Rural versus urban living is a social determinant of cognitive health. We estimated the association of rural versus urban residence in the USA with incident cognitive impairment (ICI) and assessed effect heterogeneity by sociodemographic, behavioral, and clinical factors. METHODS: The Reasons for Geographic and Racial Differences in Stroke Study (REGARDS) is a population-based prospective observational cohort of 30,239 adults, 57% female, 36% Black, aged 45+ years, sampled from 48 contiguous states in the USA in 2003-2007. We analyzed 20,878 participants who at baseline were cognitively intact with no history of stroke and had ICI assessed on average 9.4 years later. We classified participants' home addresses at baseline as urban (population ≥50,000), large rural (10,000-49,999), or small rural (≤9,999) by Rural-Urban Commuting Area codes. We defined ICI as ≥1.5 SD below the mean on at least 2 of the following tests: word list learning, word list delayed recall, and animal naming. RESULTS: Participants' home addresses were 79.8% urban, 11.7% large rural, and 8.5% small rural. ICI occurred in 1,658 participants (7.9%). Small rural residents had higher odds of ICI than urban residents, adjusted for age, sex, race, region, and education (OR = 1.34 [95% CI: 1.10, 1.64]), and after further adjustment for income, health behaviors, and clinical characteristics (OR = 1.24 [95% CI: 1.02, 1.53]). Former smoking versus never, nondrinking versus light alcohol drinking, no exercise versus ≥4 times/week, CES-D depressive symptom score of 2 versus 0, and fair versus excellent self-rated health had stronger associations with ICI in small rural areas than in urban areas. For example, in urban areas, lack of exercise was not associated with ICI (OR = 0.90 [95% CI: 0.77, 1.06]); however, lack of exercise combined with small rural residence was associated with 1.45 times the odds of ICI compared with ≥4 bouts of exercise/week in urban areas (95% CI: 1.03, 2.03). Overall, large rural residence was not associated with ICI; however, black race, hypertension, and depressive symptoms had somewhat weaker associations with ICI, and heavy alcohol drinking a stronger association with ICI, in large rural areas than in urban areas. CONCLUSION: Small rural residence was associated with ICI among USA adults. Further research to better understand why rural residents are at higher risk for developing ICI and mechanisms to ameliorate that risk will support efforts to advance rural public health.

High school quality is associated with cognition 58 years later.

We leveraged a unique school-based longitudinal cohort-the Project Talent Aging Study-to examine whether attending higher quality schools is associated with cognitive performance among older adults in the United States (mean age = 74.8). Participants (n = 2,289) completed telephone neurocognitive testing. Six indicators of high school quality, reported by principals at the time of schooling, were predictors of respondents' cognitive function 58 years later. To account for school-clustering, multilevel linear and logistic models were applied. We found that attending schools with a higher number of teachers with graduate training was the clearest predictor of later-life cognition, and school quality mattered especially for language abilities. Importantly, Black respondents (n = 239; 10.5 percentage) were disproportionately exposed to low quality high schools. Therefore, increased investment in schools, especially those that serve Black children, could be a powerful strategy to improve later life cognitive health among older adults in the United States.

Genetic Risk of Alzheimer's Disease and Sleep Duration in Non-Demented Elders.

Growing evidence has suggested an association between sleep duration and Alzheimer's disease (AD), but it is unclear if sleep duration is a manifestation of the AD disease process. We studied whether genetic liability for AD predicts sleep duration using a genetic risk score (GRS) for AD (AD-GRS), in 406,536 UK Biobank participants with European ancestry and without dementia at enrollment. Higher AD-GRS score was associated with shorter sleep (b = -0.014, 95% confidence interval [CI] = -0.022 to -0.006), especially in those aged 55+. Using AD-GRS as an instrumental variable for AD diagnosis, incipient AD reduced sleep duration by 1.87 hours (95% CI = 0.96, 2.78). Short sleep duration might be an early marker of AD. ANN NEUROL 2021;89:177-181.

Cross-national Differences in the Association Between Retirement and Memory Decline.

OBJECTIVE: Retirement is a potential trigger for cognitive aging as it may be a stressful life event accompanied by changes in everyday activities. However, the consequences of retirement may differ across institutional contexts which shape retirement options. Comparing memory trajectories before and after retirement in 17 European countries, this study aims to identify cross-national differences in the association between retirement and memory decline. METHOD: Respondents to the longitudinal Survey of Health, Aging, and Retirement in Europe (SHARE; N = 8,646) aged 50+ who were in paid work at baseline and retired during the observation period completed up to 6 memory assessments (immediate and delayed word recall) over 13 years. Three-level (time points, individuals, and countries) linear mixed models with country-level random slopes for retirement were estimated to evaluate whether memory decline accelerated after retirement and if this association differed between countries. RESULTS: On average, retirement was associated with a moderate decrement in word recall (b = -0.273, 95% CI -0.441, -0.104) and memory decline accelerated after retirement (b = -0.044, 95% CI -0.070, -0.018). Significant between-country heterogeneity in memory decline after retirement existed (variance = 0.047, 95% CI (0.013, 0.168). Memory decline after retirement was more rapid in Italy, Greece, Czech Republic, Poland, Portugal, and Estonia compared to Northern and Central European countries. DISCUSSION: Memory decline postretirement was faster in Mediterranean and eastern European countries, which are characterized by less generous welfare systems with comparatively low pension benefits. Evaluation of resources that could protect retirees from memory decline would be valuable.

HIV Status and Antiretroviral Therapy as Predictors of Disability among Older South Africans: Overall Association and Moderation by Body Mass Index.

Objectives: Among older people living with HIV (PLWH) and comparable individuals without HIV, we evaluated whether associations of HIV and antiretroviral therapy (ART) with disability depend on body mass index (BMI). Methods: We analyzed 4552 participants in the "Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa." (HAALSI) We compared prevalence of disability (≥1 impairment in basic activities of daily living) by HIV status, ART use, and BMI category, adjusting for age, sex, education, father's occupation, country of origin, lifetime alcohol use, and primary health-care utilization. Results: Among PLWH, those underweight had 9.8% points (95% confidence interval (CI): 1.2 to 18.4) higher prevalence of disability than those with normal BMI. Among ART users, those underweight had 11.9% points (95% CI: 2.2 to 21.6) higher prevalence of disability than those with normal BMI. Conclusions: We found no evidence that weight improvement associated with ART use is likely to increase disability.

"Liquid Biopsy" of White Matter Hyperintensity in Functionally Normal Elders.

Background and Objective: In the aging brain, increased blood-brain barrier (BBB) leakage and white matter hyperintensity (WMH) on MRI are frequently presumed secondary to cerebral small vessel disease (cSVD) or endotheliopathy. We investigate this association in vivo by quantifying protein cargo from endothelial-derived exosomes (EDE), and comparing levels between two groups of functionally normal elders with and without WMH. In addition, we study associations of EDE proteins with upstream and downstream factors, such as inflammation and neurodegenerative changes, respectively. Methods: Twenty six neurologically normal older adults completed general health questionnaires, neuropsychological and physical examinations, and brain MRI. WMH was visually graded with modified Fazekas score of 2 or greater used to classify 11 subjects as cases, and 15 without WMH as controls. Plasma total exosomes were precipitated and EDEs enriched by sequential immuno-precipitations. In addition, we quantified three inflammatory cytokines from plasma and imaging variables on MRI. Group means were compared, the discriminant functions of biomarkers calculated, and the association of EDE biomarkers with plasma inflammatory markers, cognition, and imaging outcomes assessed via regression modeling. Results: Plasma levels of EDE cargo proteins GLUT1, LAT1, P-GP, and NOSTRIN were significantly higher in subjects with WMH in comparison to those without. In contrast, EDE levels of the marker with low expression in brain (VCAM1) were equal between groups. The effect sizes for each of the brain-expressed cargo proteins (GLUT1, LAT1, and P-GP) were such that age-adjusted logistic regressions revealed areas under the curve (AUC) with range of 0.82-0.89, differentiating subjects with WMH from those without. VCAM1 poorly discriminated between groups (AUC:0.55). Higher levels of all brain-expressed EDE proteins were also associated with lower cognitive function, unrelated to burden of WMH. Levels of LAT1 and P-GP were significantly inversely associated with global gray matter volumes, and EDE GLUT1, LAT-1, and P-GP concentrations were significantly associated with systemic IL-6 levels. Conclusion: In a case control study of clinically normal adults with and without WMH, concentrations of EDE proteins were significantly higher in subjects with WMH in comparison to controls. This work is a first step toward in vivo dissection of molecular changes in endothelia of functionally normal subjects with radiographic evidence of age-associated white matter disease.

Perceived Walking Speed, Measured Tandem Walk, Incident Stroke, and Mortality in Older Latino Adults: A Prospective Cohort Study.

BACKGROUND: Walking speed is associated with functional status and all-cause mortality. Yet the relationship between walking speed and stroke, also a leading cause of disability, remains poorly understood, especially in older Latino adults who suffer from a significant burden of stroke. METHODS: A total of 1,486 stroke-free participants from the Sacramento Area Latino Study on Aging, aged 60 and older at baseline in 1998-1999, were followed annually through 2010. Participants reported their usual walking speed outdoors which was classified into slow, medium, or fast. We also assessed timed tandem walk ability (unable or eight or more errors vs less than eight errors). We ascertained three incident stroke endpoints: total stroke, nonfatal stroke, and fatal stroke. Using Cox proportional hazards models, we estimated hazard ratios (HRs) for stroke at different walking speed and timed tandem walk categories. RESULTS: Over an average of 6 years of follow-up (SD = 2.8), the incidence rate of total strokes was 23.2/1,000 person-years for slow walkers compared to 15.6/1,000 person-years for medium walkers, and 7.6/1,000 person-years for fast walkers. In Cox models adjusted for sociodemographics, cardiovascular risk, cognition and functional status, and self-rated health, the hazard of total stroke was 31% lower for medium walkers (HR: 0.69, 95% confidence interval [CI]: 0.47, 1.02) and 56% lower for fast walkers (HR: 0.44, 95% CI: 0.24, 0.82) compared with slow walkers. We found similar associations with timed tandem walk ability (fully adjusted HR: 0.66, 95% CI: 0.45, 0.98). CONCLUSIONS: Our findings suggest perceived walking speed captures more than self-rated health alone and is a strong risk factor for stroke risk in Latino older adults.

Associations of Trauma Exposure and Posttraumatic Stress Symptoms With Venous Thromboembolism Over 22 Years in Women.

BACKGROUND: Trauma exposure and posttraumatic stress disorder (PTSD) have been linked to myocardial infarction and stroke in women, with biological and behavioral mechanisms implicated in underlying risk. The third most common cardiovascular illness, venous thromboembolism (VTE), is a specific health risk for women. Given previous associations with other cardiovascular diseases, we hypothesized that high levels of trauma and PTSD symptoms would be associated with higher risk of incident VTE in younger and middle-aged women. METHODS AND RESULTS: We used proportional hazards models to estimate hazard ratios (HRs) and 95% CIs for new-onset VTE (960 events) over 22 years in 49 296 women in the Nurses' Health Study II. Compared to no trauma exposure, both trauma exposure and PTSD symptoms were significantly associated with increased risk of developing VTE, adjusting for demographics, family history, and childhood adiposity. Women with the most PTSD symptoms exhibited the greatest risk elevation: trauma/6 to 7 symptoms: HR=2.42 (95% CI, 1.83-3.20); trauma/4 to 5 symptoms: HR=2.00 (95% CI, 1.55-2.59); trauma/1 to 3 symptoms: HR=1.44 (95% CI, 1.12-1.84); trauma/no symptoms: HR=1.72 (95% CI, 1.43-2.08). Results were similar, although attenuated, when adjusting for VTE-relevant medications, medical conditions, and health behaviors. CONCLUSIONS: Women with the highest PTSD symptom levels had nearly a 2-fold increased risk of VTE compared to women without trauma exposure in fully adjusted models. Trauma exposure alone was also associated with elevated VTE risk. Trauma and PTSD symptoms may be associated with a hypercoagulable state. Treatment providers should be aware that women with trauma exposure and PTSD symptoms may be vulnerable to VTE.

Time Trends in Racial and Ethnic Disparities in Asthma Prevalence in the United States From the Behavioral Risk Factor Surveillance System (BRFSS) Study (1999-2011).

OBJECTIVES: We examined whether racial/ethnic disparities in the United States increased over time. METHODS: We analyzed data from 3 868 956 adults across the United States from the Behavioral Risk Factor Surveillance System from 1999 to 2011. We used random intercepts models (individuals nested in states) to examine racial/ethnic disparities and time trends in asthma lifetime and its current prevalence, adjusted for covariates. We also investigated the heterogeneity in asthma prevalence by ethnicity of the major zone of residence. RESULTS: Lifetime and current asthma prevalence were higher among non-Hispanic Black populations, with time trends highlighting increasing differences over time (b = 0.0078; 95% confidence interval [CI] = 0.0043, 0.0106). Lower odds ratios (ORs) of asthma were noted for Hispanic populations (OR = 0.74; 95% CI = 0.73, 0.76). Hispanics in states with more Puerto Rican residents reported greater risks of asthma (OR = 1.55; 95% CI = 1.24, 1.93) compared with Hispanics in states with larger numbers of Mexican or other ethnicities. CONCLUSIONS: Disparities in asthma prevalence by racial/ethnic groups increased in the last decade, with non-Hispanic Blacks and Puerto Rican Hispanics at greater risk. Interventions targeting asthma treatments need to recognize racial, ethnic, and geographic disparities.