Midlife Smaller and Larger Infarctions, White Matter Hyperintensities, and 20-Year Cognitive Decline: A Cohort Study.

Background: Smaller (<3-mm) infarctions are associated with stroke and stroke mortality, but relationships with cognitive decline are unknown. Objective: To characterize the relationships of smaller, larger, and both smaller and larger infarctions in middle age with 20-year cognitive decline. Design: Longitudinal cohort study. Setting: Two ARIC (Atherosclerosis Risk in Communities) study sites with magnetic resonance imaging data (1993 to 1995) and up to 5 cognitive assessments over 20 years. Participants: Stroke-free participants aged 50 years or older. Measurements: Infarctions were categorized as none, smaller only, larger only (3 to 20 mm), or both smaller and larger. Global cognitive Z scores were derived from 3 cognitive tests administered up to 5 times. Mixed-effects models estimated adjusted associations between infarctions and cognitive decline. Results are the average difference in standardized cognitive decline associated with infarctions versus no infarctions. Results: Among 1884 participants (mean age, 62 years; 60% women; 50% black), 1611 (86%) had no infarctions, 50 (3%) had smaller infarctions only, 185 (10%) had larger infarctions only, and 35 (2%) had both. Participants with both smaller and larger infarctions had steeper cognitive decline by more than half an SD (difference, -0.57 SD [95% CI, -0.89 to -0.26 SD]) compared with those who had no infarctions. Amounts of cognitive decline associated with only smaller infarctions and only larger infarctions were similar and were not statistically different from that associated with no infarctions. Limitation: Few participants had only smaller infarctions or both smaller and larger infarctions, and the data lacked counts of smaller infarctions and volumes of white matter hyperintensities. Conclusion: The substantial cognitive decline from middle age associated with having both smaller and larger infarctions, but not larger infarctions alone, suggests that the combination of smaller and larger infarctions may escalate risk for cognitive decline later in life in stroke-free persons. Primary Funding Source: National Institutes of Health.

The PPARG Pro12Ala Polymorphism and 20-year Cognitive Decline: Race and Sex Heterogeneity.

Previous reports suggest race/ethnic and sex heterogeneity in the association between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma (PPARG) gene and cognitive decline. Tests of verbal memory, processing speed, and verbal fluency and a composite global Z-score were used to assess cognitive performance longitudinally in a large (n=11,620) biracial cohort of older adults in the Atherosclerosis Risk in Communities Neurocognitive Study from midlife to older age. Linear mixed models were used to estimate associations between the Ala12 allele and cognitive performance over 20 years of follow-up. Heterogeneity was present for rate of cognitive decline as measured by the global Z-score by race, sex, and Ala12 allele status (P=0.01 for 4-way interaction term: race×sex×time×Ala12 carrier status). Stratified analysis showed a significantly increased rate of global cognitive decline over the 20-year follow-up for carriers of the Ala12 allele compared with noncarriers among black male individuals (-0.92 SD decline vs. -0.57 SD; P=0.02) but not among black female, white male, or white female individuals. Decline in global cognitive function among black male Ala12 carriers was primarily driven by decline in verbal memory. Our data underscore the context-dependent association between the Pro12Ala polymorphism and cognitive decline, specifically race/ethnic background and sex.

Midlife cardiovascular health and 20-year cognitive decline: Atherosclerosis Risk in Communities Study results.

INTRODUCTION: The aim was to examine associations between midlife cardiovascular health (CVH) and 20-year cognitive decline among blacks and whites. METHODS: Midlife CVH metrics (American Heart Association's Life's Simple 7) were calculated and examined in relation to midlife and 20-year change in cognitive function among 13,270 whites and blacks from the Atherosclerosis Risk in Communities Cohort Study. We used linear mixed models to estimate adjusted associations of midlife CVH with midlife cognitive status and change. RESULTS: Higher midlife (Life's Simple 7) scores and individual metrics, particularly blood pressure and glucose, were associated with better midlife cognition and reduced 20-year decline. Midlife CVH 20-year neuroprotection was more pronounced among whites than blacks. DISCUSSION: Better midlife CVH was associated with higher midlife and reduced decline in cognitive function 20 years later. However, the benefits of midlife CVH on cognition were stronger for whites than for blacks. Our findings suggest that improved midlife CVH may promote enduring cognitive health.

Prevalence and Correlates of COVID-19 Vaccine Information on Family Medicine Practices' Websites in the United States: Cross-sectional Website Content Analysis.

BACKGROUND: Primary care providers are regarded as trustworthy sources of information about COVID-19 vaccines. Although primary care practices often provide information about common medical and public health topics on their practice websites, little is known about whether they also provide information about COVID-19 vaccines on their practice websites. OBJECTIVE: This study aimed to investigate the prevalence and correlates of COVID-19 vaccine information on family medicine practices' website home pages in the United States. METHODS: We used the Centers for Medicare and Medicaid National Provider Identifier records to create a sampling frame of all family medicine providers based in the United States, from which we constructed a nationally representative random sample of 964 family medicine providers. Between September 20 and October 8, 2021, we manually examined the practice websites of these providers and extracted data on the availability of COVID-19 vaccine information, and we implemented a 10% cross-review quality control measure to resolve discordances in data abstraction. We estimated the prevalence of COVID-19 vaccine information on practice websites and website home pages and used Poisson regression with robust error variances to estimate crude and adjusted prevalence ratios for correlates of COVID-19 vaccine information, including practice size, practice region, university affiliation, and presence of information about seasonal influenza vaccines. Additionally, we performed sensitivity analyses to account for multiple comparisons. RESULTS: Of the 964 included family medicine practices, most (n=509, 52.8%) had ≥10 distinct locations, were unaffiliated with a university (n=838, 87.2%), and mentioned seasonal influenza vaccines on their websites (n=540, 56.1%). In total, 550 (57.1%) practices mentioned COVID-19 vaccines on their practices' website home page, specifically, and 726 (75.3%) mentioned COVID-19 vaccines anywhere on their practice website. As practice size increased, the likelihood of finding COVID-19 vaccine information on the home page increased (n=66, 27.7% among single-location practices, n=114, 52.5% among practices with 2-9 locations, n=66, 56.4% among practices with 10-19 locations, and n=304, 77.6% among practices with 20 or more locations, P<.001 for trend). Compared to clinics in the Northeast, those in the West and Midwest United States had a similar prevalence of COVID-19 vaccine information on website home pages, but clinics in the south had a lower prevalence (adjusted prevalence ratio 0.8, 95% CI 0.7 to 1.0; P=.02). Our results were largely unchanged in sensitivity analyses accounting for multiple comparisons. CONCLUSIONS: Given the ongoing COVID-19 pandemic, primary care practitioners who promote and provide vaccines should strongly consider utilizing their existing practice websites to share COVID-19 vaccine information. These existing platforms have the potential to serve as an extension of providers' influence on established and prospective patients who search the internet for information about COVID-19 vaccines.

Reflection on modern methods: shared-parameter models for longitudinal studies with missing data.

A primary goal of longitudinal studies is to examine trends over time. Reported results from these studies often depend on strong, unverifiable assumptions about the missing data. Whereas the risk of substantial bias from missing data is widely known, analyses exploring missing-data influences are commonly done either ad hoc or not at all. This article outlines one of the three primary recognized approaches for examining missing-data effects that could be more widely used, i.e. the shared-parameter model (SPM), and explains its purpose, use, limitations and extensions. We additionally provide synthetic data and reproducible research code for running SPMs in SAS, Stata and R programming languages to facilitate their use in practice and for teaching purposes in epidemiology, biostatistics, data science and related fields. Our goals are to increase understanding and use of these methods by providing introductions to the concepts and access to helpful tools.

Calibration of blood pressure measurements in the Jackson Heart Study.

BACKGROUND: In longitudinal research studies with follow-up examinations, the devices used to measure phenotypes may change over time. When a device change occurs, the two devices should be calibrated to each other to ensure that measurements are comparable. This paper details the Jackson Heart Study (JHS) blood pressure (BP) comparability study. PARTICIPANTS AND METHODS: During its second clinic exam (2005-2008), the JHS switched from a random-zero sphygmomanometer (RZS) BP measurement device to an oscillometric device (OD). During this exam, BP measurements from both an RZS and an OD were taken simultaneously in 2117 participants for the purpose of calibration. Five methods for calibrating systolic BP (SBP) and diastolic BP (DBP) were considered: ignoring the change, ordinary least squares regression, adding the average difference, Deming regression, and robust regression. RESULTS: Using the RZS and OD, the mean (SD) SBP was 125.5 (19.2) and 126.5 (19.9), respectively, and the mean (SD) DBP was 76.4 (10.6) and 74.0 (11.0), respectively. The correlation between RZS and the OD was 0.90 for SBP and 0.80 for DBP. The prevalence of high BP and hypertension and associations with albuminuria were similar when applying each of the five calibration methods. Robust regression was chosen for calibration, giving the following equations:(Equation is included in full-text article.)These equations had a higher R statistic than using calibration equations from the Coronary Artery Risk Development in Young Adults Study and the Heinz Nixdorf Recall Study. CONCLUSIONS: The JHS BP data have been calibrated using the above equations for use in future analyses.

Midlife and Late-Life Vascular Risk Factors and White Matter Microstructural Integrity: The Atherosclerosis Risk in Communities Neurocognitive Study.

BACKGROUND: Diffusion tensor imaging measures of white matter (WM) microstructural integrity appear to provide earlier indication of WM injury than WM hyperintensities; however, risk factors for poor WM microstructural integrity have not been established. Our study quantifies the association between vascular risk factors in midlife and late life with measures of late-life WM microstructural integrity. METHODS AND RESULTS: We used data from 1851 participants in ARIC (Atherosclerosis Risk in Communities Study) who completed 3-T magnetic resonance imaging, including diffusion tensor imaging, as part of the ARIC Neurocognitive Study (ARIC-NCS). We quantified the association among lipids, glucose, and blood pressure from the baseline ARIC visit (1987-1989, ages 44-65, midlife) and visit 5 of ARIC (2011-2013, ages 67-90, late life, concurrent with ARIC-NCS) with regional and overall WM mean diffusivity and fractional anisotropy obtained at ARIC visit 5 for ARIC participants. We also considered whether these associations were independent of or modified by WM hyperintensity volumes. We found that elevated blood pressure in midlife and late life and elevated glucose in midlife, but not late life, were associated with worse late-life WM microstructural integrity. These associations were independent of the degree of WM hyperintensity, and the association between glucose and WM microstructural integrity appeared stronger for those with the least WM hyperintensity. There was little support for an adverse association between lipids and WM microstructural integrity. CONCLUSIONS: Hypertension in both midlife and late life and elevated glucose in midlife are related to worse WM microstructural integrity in late life.