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Pleiotropic effects between cardiovascular disease risk factors and measures of cognitive and physical function in long-lived adults.

ABSTRACT: Cardiovacular disease (CVD) is the leading cause of death among older adults and is often accompanied by functional decline. It is unclear what is driving this co-occurrence, but it may be behavioral, environmental and/or genetic. We used a family-based study to estimate the phenotypic and shared genetic correlation between CVD risk factors and physical and cognitive functional measures. Participants (n = 1,881) were from the Long Life Family Study, which enrolled families based on their exceptional longevity (sample mean age = 69.4 years, 44% female). Cardiovascular disease risk factors included carotid vessel measures [intima-media thickness and inter-adventitial diameter], obesity [body mass index (BMI) and waist circumference], and hypertension [systolic and diastolic blood pressures]. Function was measured in the physical [gait speed, grip strength, chair stand] and cognitive [digital symbol substitution test, retained and working memory, semantic fluency, and trail making tests] domains. We used SOLAR to estimate the genetic, environmental, and phenotypic correlation between each pair adjusting for age, age², sex, field center, smoking, height, and weight. There were significant phenotypic correlations (range |0.05-0.22|) between CVD risk factors and physical and cognitive function (all P < 0.05). Most significant genetic correlations (range |0.21-0.62|) were between CVD risk factorsand cognitive function, although BMI and waist circumference had significant genetic correlation with gait speed and chair stand time (range |0.29-0.53|; all P < 0.05). These results suggest that CVD risk factors may share a common genetic-and thus, biologic-basis with both cognitive and physical function. This is particularly informative for research into the genetic determinants of chronic disease.

SUBMITTER: Yudkovicz JJ

PROVIDER: S-EPMC8429644 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:OBJECTIVES:To evaluate and compare the associations between microvascular and macrovascular abnormalities and cognitive and physical function DESIGN:Cross-sectional analysis of the Cardiovascular Health Study (1998-1999). SETTING:Community. PARTICIPANTS:Individuals with available data on three or more of five microvascular abnormalities (brain, retina, kidney) and three or more of six macrovascular abnormalities (brain, carotid artery, heart, peripheral artery) (N = 2,452; mean age 79.5). MEASUREMENTS:Standardized composite scores derived from three cognitive tests (Modified Mini-Mental State Examination, Digit-Symbol Substitution Test, Trail-Making Test (TMT)) and three physical tests (gait speed, grip strength, 5-time sit to stand) RESULTS:Participants with high microvascular and macrovascular burden had worse cognitive (mean score difference = -0.30, 95% confidence interval (CI) = -0.37 to -0.24) and physical (mean score difference = -0.32, 95% CI = -0.38 to -0.26) function than those with low microvascular and macrovascular burden. Individuals with high microvascular burden alone had similarly lower scores than those with high macrovascular burden alone (cognitive function: -0.16, 95% CI = -0.24 to -0.08 vs -0.13, 95% CI = -0.20 to -0.06; physical function: -0.15, 95% CI = -0.22 to -0.08 vs -0.12, 95% CI = -0.18 to -0.06). Psychomotor speed and working memory, assessed using the TMT, were only impaired in the presence of high microvascular burden. Of the 11 vascular abnormalities considered, white matter hyperintensity, cystatin C-based glomerular filtration rate, large brain infarct, and ankle-arm index were independently associated with cognitive and physical function. CONCLUSION:Microvascular and macrovascular abnormalities assessed using noninvasive tests of the brain, kidney, and peripheral artery were independently associated with poor cognitive and physical function in older adults. Future research should evaluate the usefulness of these tests in prognostication.

Project description:BACKGROUND:The Long Life Family Study (LLFS) enrolled families exhibiting exceptional longevity. The goal of this article was to determine the prevalence and predictors of remaining independent after 7 years in the oldest generation. METHODS:We examined 7-year change in physical (free of activities of daily living difficulty), cognitive (Mini-Mental State Examination score ? 24), and overall independence (physically/cognitively independent) in adults aged 90.3 ± 6.3 from LLFS's oldest generation. Potential predictors (n = 28) of remaining independent included demographics, diseases, biomarkers, anthropometrics, and physical and cognitive performance tasks and were determined using generalized estimating equations (?: p < .05). This was a discovery/exploratory analysis, so no multiple testing correction was employed and the results require independent replication. RESULTS:At baseline (n = 1442), 67.3%, 83.8%, and 79.7% were overall, physically, and cognitively independent, respectively. After 7 years, 66% died, 7.5% were lost to follow-up, and the prevalence of overall independence decreased to 59.1% in survivors (-8.2%, 95% confidence interval: -14.1%, 2.2%). Of those with baseline independence, 156/226 (69.0%) remained independent. Predictors of remaining physically independent included younger age, better Short Physical Performance Battery score and lung function, smaller waist circumference, and lower soluble receptor for advanced glycation end-product levels (p < .05). Predictors of remaining cognitively independent included no cancer history, better Digit Symbol Substitution Test performance, and higher body weight (p < .05). CONCLUSIONS:The prevalence of independence decreased by only 8.2% after 7 years, demonstrating the close correspondence between disability and mortality. Further, despite a mean baseline age of 90 years, a large proportion of survivors remained independent, suggesting this exceptional subgroup may harbor protective mechanisms.

Project description:Emerging evidence suggests physical activity (PA) is associated with cognitive function. To overcome limitations of self-report PA measures, this study investigated the association of accelerometer-measured PA with incident cognitive impairment and longitudinal cognition among older adults.Participants were recruited from the cohort study Reasons for Geographic and Racial Differences in Stroke in the United States. Accelerometers provided PA measures, including the percentage of total accelerometer wearing time spent in moderate-to-vigorous-intensity PA (MVPA%), light-intensity PA, and sedentary time for four to seven consecutive days at baseline. Cognitive impairment was defined by the Six-Item Screener. Letter fluency, animal fluency, word list learning, and Montreal Cognitive Assessment (orientation and recall) were conducted to assess executive function and memory.Participants (N = 6452, 69.7 ± 8.5 yr, 55.3% women, 30.5% Black) with usable accelerometer and cognition measures spent extremely limited time in MVPA (1.5% ± 1.9% of accelerometer wearing time). During an average of 3 yr of follow-up, 346 cases of incident cognitive impairment were observed. After adjustments, participants in higher MVPA% quartiles had a lower risk of cognitive impairment (i.e., quartile 2: odds ratio = 0.64, 95% confidence interval = 0.48-0.84) and better maintenance in executive function (?0.03 z-score units) and memory (?0.12 z-score units) compared with quartile 1 (P < 0.05). Stratified analyses showed the same association among White adults, but higher MVPA% was associated with better maintenance of only memory among Black adults. No significance was found for light-intensity PA or sedentary time.There was a dose-response relationship between MVPA% and cognitive function in older adults, with higher levels associated with a 36% or lower risk of cognitive impairment and better maintenance of memory and executive function over time, particularly in White adults.

Project description:ImportanceHigher purpose in life is hypothesized to reduce the likelihood of developing weak grip strength and slow walking speed because purpose has been linked with a range of positive health behaviors and biological processes that are potentially protective against declining physical function. However, the association between purpose in life and objective physical function has not been examined.ObjectiveTo assess whether higher purpose in life among adequately functioning older adults is associated with lower risk of developing weak grip strength and slow walking speed over time.Design, setting, and participantsData for a longitudinal cohort study were collected in 2006 and again in 2010 from the Health and Retirement Study, a nationally representative study of US adults older than 50 years. Data analysis was conducted from November 23, 2016, to June 2, 2017.Main outcomes and measuresThe risk of developing weak grip strength (assessed as a binary yes or no outcome) or slow walking speed (yes or no) during the 4-year follow-up period. Grip strength was assessed using Smedley spring-type hand dynamometers, and walking speed was assessed by asking respondents to walk 2.5 m at their normal walking pace.ResultsIn this study, 4486 adults had grip scores at baseline indicating adequate function (2665 women and 1821 men; mean [SD] age, 63.0 [8.2] years) and 1461 adults had walking scores at baseline indicating adequate function (801 women and 660 men; mean [SD] age, 70.8 [6.5] years). After controlling for sociodemographic factors, each 1-SD increase in purpose was associated with a 13% decreased risk (95% CI, 1%-23%) of developing weak grip strength and a 14% decreased risk (95% CI, 8%-20%) of developing slow walking speed. Associations with walking speed were maintained in all covariate models (fully adjusted model: risk ratio, 0.89; 95% CI, 0.83-0.95), but associations with grip strength did not reach conventional levels of statistical significance after additionally adjusting for relevant baseline health factors, depressive symptoms, and health behaviors (fully adjusted model: risk ratio, 0.91; 95% CI, 0.80-1.04).Conclusions and relevancePurpose in life was prospectively associated with a decreased risk of developing weak grip strength and slow walking speed, although the findings were more robust for walking speed than for grip strength. These findings suggest that a sense of purpose in life, a modifiable factor, may play an important role in maintaining physical function among older adults.

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Pleiotropic effects between cardiovascular disease risk factors and measures of cognitive and physical function in long-lived adults.

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