Function In Midlife Research Articles

Circulating IL-17A and Executive Function in Middle-Aged Adults with and without Type 2 Diabetes

Abstract Background Midlife cardiovascular risk factors, such as Type 2 Diabetes Mellitus (T2DM) and obesity, are associated with a greater risk of cognitive impairment and dementia in later life, with altered peripheral inflammation postulated as a crucial mechanistic link. Yet there is a significant gap in knowledge regarding when pathogenic alterations to these systemic inflammatory responses change during the early stages of cognitive dysfunction prior to overt disease development. To assess the earliest possible signs of this link, we recruited a cohort of middle-aged cognitively-unimpaired individuals with and without uncomplicated T2DM. Methods A comprehensive neuropsychological assessment was performed at baseline and at 4-year follow-up. A panel of ten serum chemokines and cytokines were measured at both time-points using high-sensitivity assays (Eotaxin, MCP-1, MIP-1β, CXCL-10, IL-6, IL-10, IL12p70, IL-17A, IFN-γ and TNF-α). Results Overall, 136 individuals were recruited including 90 with uncomplicated midlife T2DM (age 52.6 ± 8.3; 47% female) and 46 without (age 52.9 ± 8.03; 61% female). Cognitive trajectories were stable over time and did not differ by T2DM status. Yet on cross-sectional analyses, we observed consistent evidence across timepoints between greater circulating IL-17A and poorer performance on tests of executive function/attention (β: -0.21; -0.40, -0.02, p = 0.03 at baseline; β: -0.26; -0.46, -0.05, p = 0.02 at follow-up) as well as poorer reaction time (β: 0.34; 0.12, 0.56, p = 0.003 at follow-up). These persisted on covariate adjustment and did not differ by T2DM status. Conclusion We provide exploratory evidence that greater serum IL-17A levels are associated with poorer executive function in midlife. Long-term follow-up of this and other cohorts will further elucidate this relationship to provide further mechanistic insights and potentially identify individuals at greatest risk for later cognitive decline.

Circulating Interleukin-17A is associated with executive function in middle aged adults with and without type 2 diabetes

Midlife cardiovascular risk factors such as Type 2 Diabetes (T2DM) and obesity are associated with the later development of cognitive impairment and dementia. Systemic inflammation is postulated as a crucial mechanism, yet there are few studies examining this at the earliest stages prior to overt cognitive impairment. To assess this, we recruited a cohort of middle-aged cognitively-unimpaired individuals with and without uncomplicated T2DM. Comprehensive neuropsychological assessment was performed at baseline and at 4-year follow-up. Ten serum chemokines and cytokines (Eotaxin, MCP-1, MIP-1β, CXCL10, IL-6, IL-10, IL12p70, IL-17A, IFN-γ and TNF-α) were measured at both baseline and follow-up using high-sensitivity assays. Overall, 136 participants were recruited including 90 with uncomplicated midlife T2DM (age 52.6 ± 8.3; 47% female) and 46 without (age 52.9 ± 8.03; 61% female). Cognitive trajectories were stable over time and did not differ with T2DM. Yet on cross-sectional analyses at both baseline and follow-up, greater circulating IL-17A was consistently associated with poorer performance on tests of executive function/attention (β: 0.21; −0.40, −0.02, p = 0.03 at baseline; β: 0.26; −0.46, −0.05, p = 0.02 at follow-up). Associations persisted on covariate adjustment and did not differ by T2DM status. In summary, we provide evidence that greater circulating IL-17A levels were associated with poorer executive function in midlife, independent of T2DM. Long-term follow-up of this and other cohorts will further elucidate the earliest stages in the relationship between systemic inflammation and cognitive decline to provide further mechanistic insights and potentially identify those at greatest risk for later cognitive decline.

Undergraduate students engaging in hands-on gerontology research: a participatory case study of value gained and lessons learned

ABSTRACT As the population ages, it is essential that professionals across disciplines have experience and competence working with older adults. Though experiential learning opportunities have been extensively documented as a tool to accomplish this goal, student engagement in gerontology research has not been examined in detail. This participatory case study highlights the perspectives of undergraduate student researchers involved in a hands-on pilot research study that explored connections between cognitive, physical, and everyday function in midlife and older adults while testing the feasibility of a mobile app for early detection of cognitive decline related to Alzheimer’s disease and related dementias. As participants, students (n = 11) completed a survey about their experience and participated in focus groups. As researchers, students and faculty coded open-ended survey and focus group responses. We found that students gained both personal and professional skills from their experience. Emergent themes relevant to their experience included the overarching research lab environment and study-specific conditions related to interpersonal and technical aspects. Although these findings reflect student perspectives in one case, they can be used as a guide to support future endeavors to include undergraduate students as testers in gerontology research.

A prospective study of per- and polyfluoroalkyl substances (PFAS) and women’s cognitive function in midlife

A prospective study of per- and polyfluoroalkyl substances (PFAS) and women’s cognitive function in midlife

Cross-sectional associations between temporal patterns and composition of upright and stepping events with physical function in midlife: Insights from the 1970 British Cohort Study.

Age-related decline in physical functioning has significant implications for health in later life but declines begin earlier in midlife. Physical activity (PA) volume is associated with physical function, but the importance of the pattern in which PA is accumulated is unclear. This study investigates associations between patterns of PA accumulation, including the composition, variation, and temporal distribution of upright and stepping events, with physical function in midlife. Participants (n = 4378) from the 1970 British Cohort Study wore an activPAL3 accelerometer on the thigh for 7 consecutive days. Exposure measures included a suite of metrics describing the frequency, duration, and composition of upright events, as well as the duration and volume (total steps) of stepping events. In addition, patterns of accumulation of upright and sedentary events were examined including how fragmented/transient they were (upright-to-sedentary transition probability [USTP]) and their burstiness (the tendency for events to be clustered together followed by longer interevent times). Physical function outcomes included grip strength (GS), balance, and SF-36 physical functioning subscale (SF-36pf). Cross-sectional analyses included multivariable linear regression models to assess associations, adjusting for covariates including overall PA volume (mean daily step count). Higher upright event burstiness was associated with higher GS, and higher USTP was associated with lower GS. Duration and step volume of stepping events were positively associated with SF-36pf in females. Step-weighted cadence was positively associated with SF-36pf and balance. Contradictory findings were also present (e.g., more transient stepping events were associated with better GS) particularly for GS in males. Inconsistencies between sexes were observed across some associations. Our study reveals that diverse patterns of PA accumulation exhibit distinct associations with various measures of physical function in midlife, irrespective of the overall volume. Contradictory findings and inconsistency between sexes warrant further investigation. Patterns of PA accumulation, in addition to volume, should be considered in future PA research. Longitudinal studies are required to determine whether a given volume of activity accumulated in different patterns, impacts associations between PA and health outcomes.

Lifestyle for brain health and cognitive functioning in midlife to early late-life New Zealanders: Utility of the LIBRA index.

There is enormous potential to improve brain health and reduce the risk of cognitive decline and dementia based on modifiable risk factors. The Lifestyle for Brain Health (LIBRA) index was developed to quantify modifiable dementia risk or room for brain health improvement. The objective of the study was to investigate the utility of the LIBRA index in relation to cognitive functioning in a midlife to early late-life sample of New Zealanders. A subsample (n=1001) of the longitudinal New Zealand Health, Work and Retirement (NZHWR) study completed face-to-face cognitive assessments using the 'Kiwi' Addenbrooke's Cognitive Examination-Revised (ACE-R)in 2010 and again in 2012, in addition to completing biennial NZHWR surveys on socioeconomic, health and wellbeing aspects. The LIBRA index was calculated incorporating information on 8 out of 12 modifiable health and lifestyle factors for dementia. Unadjusted and adjusted regression models and mixed effects models were used to inspect associations of LIBRA with cognitive functioning, cognitive impairment, and cognitive decline. The analytical sample (n=881 [88.0%], after considering exclusion criteria and missing data) had a mean age of 63.1 (SD=6.5) years, 53.3% were female, 26.2% were Māori, and 61.7% were highly educated. Higher LIBRA scores (indicating higher modifiable dementia risk) were associated with lower cognitive functioning (B=-0.33, 95% CI=-0.52;-0.15, p<0.001) and a higher likelihood of cognitive impairment (OR=1.22, 95% CI=1.04; 1.42, p=0.013), but did not predict cognitive decline over 2years (B=-0.03, 95% CI=-0.22; 0.16, p=0.766), adjusted for age, age2, gender, education, and ethnicity. The LIBRA index indicated promising utility for quantifying modifiable dementia risk in midlife and early late-life New Zealanders. For local use, refinement of the LIBRA index should consider cultural differences in health and lifestyle risk factors, and further investigate its utility with a wider range of modifiable factors over a longer observation period.

Abstract P332: Metabolically Healthy Obesity is Associated With Higher Levels of Executive Function in Middle-Aged Adults: The Bogalusa Heart Study

Introduction: Obesity in midlife is associated with an increased risk of cognitive decline. It remains unclear if there is a difference in cognitive function between individuals with obesity and metabolic dysfunction (metabolically abnormal obesity - MAO) versus those with metabolically healthy obesity (MHO). We assessed the relationship between MHO (vs MAO) and cognitive function in mid-life among Black and White individuals in the Bogalusa Heart Study. Methods: The Bogalusa Heart Study is a longitudinal cohort exploring the natural history of cardiovascular disease among Black and White individuals in Bogalusa, Louisiana. This cross-sectional analysis included 659 participants with obesity, defined as BMI ≥ 30 kg/m 2 . Metabolic abnormality was defined as the presence of one or more of the following: systolic blood pressure ≥ 130 mm Hg, diastolic blood pressure ≥ 85 mm Hg, taking blood pressure lowering medication, triglycerides ≥ 150 mg/dL, HDL-C &lt; 40 mg/dL (men) or &lt; 50 mg/dL (women), taking lipid-lowering medication, fasting plasma glucose ≥ 100 mg/dL, or taking diabetes medication. Healthy metabolic status was defined as the absence of blood pressure, lipid, and glycemic abnormalities. Cognitive function was measured using a total of 9 neuropsychological tests assessing attention/information processing speed, executive function, and episodic memory. Linear regression models were used to determine the association between MHO and a demographically standardized global cognitive score and individual domain-based z-scores adjusting for smoking status and education. Results: Participants had a mean age of 47.8 ± 5.3 years, 42.7% self-identified as Black, and 64.1% were female. The prevalence of MHO was 9.9%. MHO was associated with higher levels of executive function compared with MAO (β=0.46; SE=0.19; p=0.0145). No significant differences were observed between MHO and MAO participants on global cognitive score, processing speed, or episodic memory. Conclusions: Our study found that MHO is associated with better levels of executive function in midlife. While additional studies are needed, these findings suggest that interventions that reduce metabolic abnormalities related to blood pressure, lipids, and glucose may reduce obesity-related decreases in executive function among middle-aged individuals with obesity.

Abstract P336: The Association of Coronary Artery Calcium Progression and Cognitive Function in Midlife - The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Background: Little is known about the impact of coronary artery calcium (CAC) and its progression on cognitive function in midlife, a time of importance for cognitive aging. Methods: In CARDIA, CAC was measured using computed tomography at years 15 (baseline), 20 and 25. CAC progression was defined as: (1) CAC&gt;0 at follow-up among participants with baseline CAC=0; (2) an annualized change of ≥10 units at follow-up among those with 0&lt;baseline CAC&lt;100; or (3) an annualized percent change (annualized change in CAC score divided by baseline CAC score) ≥10% among those with baseline CAC≥100. Cognitive function was measured with Digit Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test (RAVLT), Stroop Interference, Montreal Cognitive Assessment (MoCA) and Verbal Fluency (Letter and Category Fluency) at year 35. We used linear regression to estimate the difference between marginal means with 95% confidence intervals (CIs) of each cognitive test by CAC score (0 vs &gt;0) and CAC progression. Results: Among 2,341 participants (mean age 40.3 ± 3.6 years, 56% female, 43% Black at baseline), higher CAC score and CAC progression were associated with significantly lower cognitive performance in all cognitive tests. After adjustment for demographics, the association remained for CAC progression, compared to no progression, for most test scores: DSST (-2.70 95% CI: -4.05 to -1.36, p &lt; 0.001), MoCA (-0.44 95% CI: -0.74 to -0.13, p = 0.005) and verbal fluency (-0.85 95% CI: -1.57 to -0.12, p = 0.02). Similar associations were observed for higher CAC score (&gt;0 vs 0): DSST (-3.11 95% CI: -5.16 to -1.06, p = 0.003), MoCA (-0.81 95% CI: -1.28 to -0.34, p = 0.001) and RAVLT (-0.67 95% CI: -1.12 to -0.23, p = 0.003). Additional adjustment for physical activity, depressive symptoms, and APOE, and mutually for baseline CAC score and progression did not materially change the association. Conclusions: CAC score and progression were associated with lower cognitive function in midlife. CAC progression may be an independent risk factor for early cognitive aging, independent of baseline CAC score and other risk factors.

Abstract P270: Higher Long-Term Fasting Glucose Variability From Childhood is Associated With Poorer Cognitive Function in Midlife: The Bogalusa Heart Study

Background: Elevated fasting blood glucose(FBG) levels have been associated with poorer cognitive function. High FBG variability has also been associated with accelerated cognitive decline in late life. However, the impact of long term FBG variability from childhood on midlife cognitive function (CF) remains understudied. Hypothesis: We hypothesized that there would be an association of higher long-term FBG variability from childhood with poorer midlife CF measures. Aim: We aimed to identify the influence of higher long term FBG variability on midlife CF. Methods: We studied 1,005 midlife Bogalusa Heart Study participants (age at baseline: mean 9.4 years +/- SD 3.5 years; age at neuropsychological(NP) exam: mean 47.9 years+/- SD 5.2 years; 60.4% women(607 of 1005); 33.5 % Black(337 of 1005)) with ≥3 FBG measurements across follow up. Participants having type 2 diabetes mellitus(T2DM) were excluded. T2DM was defined as FBG ≥126 mg/dL or taking diabetes medication. Long-term visit-to visit FBG variability was measured as deviation from age predicted values (DEV) and residual SD (RSD). Using ≥3 FBG measurements, DEV and RSD were obtained from individual growth curves created by fitting random-effects models stratified by race and sex. Participants’ midlife CF was first measured with 10 NP tests, then were classified into 3 distinct NP profiles (optimal, average, and mixed-low) using cluster analysis. Multinomial logistic regression models were used to analyze the associations between long-term FBG variability parameters and NP profiles, adjusting for education status and mean of FBG measures from childhood to midlife . DEV and RSD were standardized to z-scores by race and sex before regression analysis. Tests for interaction according to race and sex were conducted. Results: After adjusting for the mean FBG level and education status, for a 1 SD increase in DEV, the odds of having a mixed-low CF increased by 57.3% (95% CI 1.244, 1.990) and the odds of an average CF increased by 36.9% (95% CI 1.144, 1.640) respectively, compared to optimal CF. After adjusting for the mean FBG level and education status, for a 1 SD increase in RSD, the odds of having a mixed-low CF increased by 56% (95% CI 1.232, 1.974) and the odds of an average CF increased by 37.7% (95% CI 1.147, 1.653), respectively, compared to optimal CF. No significant interactions between long-term FBG variability parameters and race and sex were found. Conclusions: Higher long-term FBG variability was associated with poorer midlife CF. Further studies are needed to identify the role of long-term FBG variability in the association of cardiometabolic risk factors and midlife CF.

Early-life cumulative exposure to excess bodyweight and midlife cognitive function: longitudinal analysis in three British birth cohorts

Excess bodyweight (BMI >25 kg/m2) in midlife (age 40-65 years) has been linked to future cognitive decline and an increased risk of dementia. Whether chronic exposure to excess bodyweight in the early decades of life (<40 years) is associated with compromised cognitive function by midlife, however, remains unclear. This study therefore aimed to test potential bidirectional direct and indirect pathways linking cumulative exposure to excess bodyweight and cognitive function in the early decades of life. In this longitudinal analysis, harmonised measures of BMI and cognitive function were available in 19 742 participants aged 47-53 years recruited to the 1946 National Survey of Health and Development (n=2131), the 1958 National Child Development Study (n=9385), and the 1970 British Cohort Study (n=8226). Individual BMI trajectories spanning three decades from age 10-40 years were created for each participant and excess bodyweight duration, BMI change between ages, and cumulative excess bodyweight exposure were calculated. Harmonised measures of verbal and non-verbal ability, mathematical ability, and reading ability were used to create a latent factor for childhood cognitive function, and immediate and delayed recall, animal naming, and letter-search speed tests were used for midlife cognitive function. Multivariable linear regression and structural equation models (SEM) were used to test for potential bidirectional relationships between cognition and excess bodyweight in both individual cohorts and pooled datasets while accounting for other potential early-life confounders. Increases in BMI during adolescence and greater cumulative exposure to excess bodyweight across early life were associated with lower midlife cognitive function in all cohorts (eg, pooled difference in cognitive function per 10 years excess bodyweight duration -0·10; 95% CI -0·12 to -0·08; p<0·001). Further adjustment for childhood cognitive function attenuated many of these associations towards the null (eg, pooled difference in cognitive function per 10 years excess bodyweight duration -0·04; 95% CI -0·06 to -0·02; p=0·001), however, with any remaining associations then fully attenuating once further adjusted for other early-life factors (eg, pooled difference in cognitive function per 10 years excess bodyweight duration 0, -0·03 to 0·01; p=0·38). In the reverse direction, low childhood cognition was associated with greater cumulative exposure to excess bodyweight over the next four decades, although much of this relationship was found to probably be explained via other potentially modifiable upstream early-life factors such as childhood disadvantage. SEM in all cohorts suggested the presence of modest direct and indirect pathways connecting earlier cognitive function to later excess bodyweight, but scarce evidence for an effect of early-life excess bodyweight on cognitive function by midlife. The association between cumulative exposure to excess bodyweight in early life and lower cognitive function in midlife is probably confounded by a persistently lower cognitive function from childhood. Initiatives to improve early-life factors such as childhood disadvantage and education, however, might exert dual but independent benefits on both of these factors before old age. Alzheimer's Research UK, Diabetes Research and Wellness Foundation, Diabetes UK, British Heart Foundation, and Medical Research Council.

Association Between Sleep Quantity and Quality in Early Adulthood With Cognitive Function in Midlife.

Growing evidence supports an association between sleep quality and risk of dementia. However, little is known about whether objectively measured sleep duration and quality influence cognition in midlife, a period of importance for understanding the direction of the association between sleep and dementia. We examined the association between sleep duration and quality, measured when participants were in their mid-30s to late 40s, and midlife cognition assessed 11 years later among Black and White adults. As part of the Coronary Artery Risk Development in Young Adults cohort study, sleep duration and quality were assessed objectively using wrist actigraphy and subjectively by Pittsburgh Sleep Quality Index (PSQI) at 2003-2005. During 2015-2016, we evaluated midlife cognition using the Digit Symbol Substitution Test (DSST), Stroop test, Rey Auditory Verbal Learning Test, Montreal Cognitive Assessment (MoCA), and Letter Fluency and Category Fluency tests. We used multivariable logistic regression to examine the association between sleep parameters and poor cognitive performance, which was defined as a score that was >1 SD below the mean score. The 526 participants (58% women and 44% Black) had a mean age of 40.1 ± 3.6 years at baseline, a mean sleep duration of 6.1 ± 1.1 hours, and mean sleep fragmentation index (calculated as the sum of the percentage of time spent moving and the percentage of immobile periods ≤1 minute) of 19.2 ± 8.1%, and 239 (45.6%) participants reported poor sleep as defined by a PSQI global score of >5. After adjustment for demographics, education, smoking, body mass index, depression, physical activity, hypertension, and diabetes, those in the highest vs lowest tertile of sleep fragmentation index had over twice the odds of having poor cognitive performance (>1 SD below the mean) on the DSST (odds ratio [OR] = 2.97; 95% CI 1.34-6.56), fluency (OR = 2.42; 95% CI 1.17-5.02), and MoCA test (OR = 2.29; 95% CI 1.06-4.94). The association between sleep fragmentation and cognitive performance did not differ by race or sex. Objective sleep duration or subjective sleep quality was not associated with cognition in midlife. Actigraphy-measured high sleep fragmentation rather than sleep duration was associated with worse cognition among middle-aged Black and White men and women. Sleep quality is important for cognitive health even as early as midlife.

Poor Diet and Lower Neuropsychological Performance in a rural setting: The Bogalusa Heart Study

AbstractBackgroundPoor diet has been associated with insidious onset dementia. The Alternate Healthy Eating Index (AHEI) can capture overall nutrient quality and individual/population eating behaviors. Higher adherence to AHEI has been associated with a lower risk of incident dementia and better cognitive function in late life. However, most evidence comes from high‐income populations from urban areas. Here, we examined the adherence to AHEI and its association with cognitive function in midlife among Black and White individuals from a community cohort in the rural, low SES area of Bogalusa, Louisiana.MethodThis cross‐sectional analysis considered 1,040 participants from the Bogalusa Heart Study (mean age 48.1 ± 61% female, 31% Black) with a complete neuropsychological (NP) assessment and food frequency questionnaires. (AHEI‐2010 score, range 0‐110). Regression models using GEE accounted for clustering effects of neighborhood factors/SES using census‐track level codes and estimated the association between quintiles (Q1‐Q5) of AHEI‐2010 and a global cognitive z‐score (GCS) and cognitive domains.ResultIndividuals in Q5 (healthiest) tended to be female (68%, p = 0.03), significantly older (49.3 ± 5, p&lt;0.001), with higher education (³ college 56%, p&lt;0.001), and AHEI‐2010 scores from 53.38‐79.2. Compared with participants in Q1. Those in Q5 had higher GCS [ß (95% CI):1.71 (0.85, 2.57); p&lt;0.001] after adjusting for age, sex, race, and the ACS‐Index of concentration at the extremes (to account for neighborhood‐level SES). Similarly, those with the healthiest diet had higher NP z‐scores within the domains of executive function, attention and speed processing information, and episodic memory. However, these associations were not significant after adjusting for education. (Table 1) For episodic memory, individuals in quintile 4 had higher NP z‐scores after adjusting for education [0.36 (0.07, 0.65); p = 0.01], and the trend across quintiles was also significant in all models and after adjusting for education [p = 0.03].ConclusionAs early as midlife, Black and White individuals from rural settings with greater adherence to healthy dietary patterns have better NP performance across different neurocognitive domains. These results strengthen previous evidence suggesting that diet quality may be a potential avenue of intervention to prevent cognitive decline and aid health disparities.

Predicted Brain Age Difference Scores at Age 56 Are Associated with Executive Function Changes Across 12 Years

AbstractBackgroundPredicted brain age difference (PBAD) scores are novel metrics which compare chronological age to age predicted from neuroimaging data. PBADs are highly relevant to Alzheimer’s disease (AD) and cognitive aging. Individuals with AD have predicted brain ages about 10 years older than their chronological age (Franke et al. 2010). Less is known about PBADs in midlife, but recent work on the sample studied here has demonstrated that PBADs are highly heritable (59‐75%), highly stable between middle‐ and early‐old age, and moderated by modifiable lifestyle behaviors earlier in midlife (age 40). The current study examined how midlife PBAD (mean age 56) predicted executive functions concurrently and longitudinally into early old age (mean age 68).MethodWe examined 779 non‐demented men in the Vietnam Era Twin Study of Aging (VETSA) who completed cognitive and neuroimaging assessments at up to three assessments (M = 56, 62, and 68 years). PBADs were based on two methods (Liem et al., 2017, Cole et al. 2019) which include information about grey matter or both gray and white matter. Executive function was based on six tasks spanning inhibition, shifting and working memory. Analyses controlled for age, diabetes, hypertension, and APOE‐ε4 dosage.ResultLatent growth models revealed that greater PBAD at age 56 (i.e., greater brain age than chronological age) was associated with worse executive functioning at baseline and greater decline in executive functioning over the following 12 years. The latter association was observed only for PBADs that included white matter (Cole et al., 2019) and persisted even when excluding N = 61 individuals with amnestic mild cognitive impairment (MCI). Subsequent analyses indicated that associations were not moderated by APOE allele status or cognitive reserve (general cognitive ability at mean age 20).ConclusionOur findings indicate that PBAD is associated with executive functioning in midlife and predicts executive function changes into early old age. They also suggest that PBADs capturing more information about brain health are better predictors of executive function decline across midlife into early‐old age. Finally, the persistence of these effects within cognitively normal subjects suggests PBADs are important predictors of cognitive decline before the onset of MCI/AD.

Fractal complexity of daily physical activity and cognitive function in a midlife cohort

High stability of fluctuation in physiological patterns across fixed time periods suggest healthy fractal complexity, while greater randomness in fluctuation patterns may indicate underlying disease processes. The importance of fractal stability in mid-life remains unexplored. We quantified fractal regulation patterns in 24-h accelerometer data and examined associations with cognitive function in midlife. Data from 5097 individuals (aged 46) from the 1970 British Cohort Study were analyzed. Participants wore thigh-mounted accelerometers for seven days and completed cognitive tests (verbal fluency, memory, processing speed; derived composite z-score). Detrended fluctuation analysis (DFA) was used to examine temporal correlations of acceleration magnitude across 25 time scales (range: 1 min–10 h). Linear regression examined associations between DFA scaling exponents (DFAe) and each standardised cognitive outcome. DFAe was normally distributed (mean ± SD: 0.90 ± 0.06; range: 0.72–1.25). In males, a 0.10 increase in DFAe was associated with a 0.30 (95% Confidence Interval: 0.14, 0.47) increase in composite cognitive z-score in unadjusted models; associations were strongest for verbal fluency (0.10 [0.04, 0.16]). Associations remained in fully-adjusted models for verbal fluency only (0.06 [0.00, 0.12]). There was no association between DFA and cognition in females. Greater fractal stability in men was associated with better cognitive function. This could indicate mechanisms through which fractal complexity may scale up to and contribute to cognitive clinical endpoints.

Childhood maltreatment and midlife cognitive functioning: A longitudinal study of the roles of social support and social isolation.

Negative consequences of childhood maltreatment have been well-documented, including poorer executive functioning and nonverbal reasoning in midlife. However, not all adults with a history of childhood maltreatment manifest these outcomes, suggesting the presence of risk and protective factors. Based on growing empirical support for the importance of social variables in understanding neuropsychological development and functioning, we examined whether social support and social isolation mediate or moderate the effects of childhood maltreatment on cognitive functioning in midlife. In the context of a prospective cohort design study, individuals with documented histories of childhood maltreatment (ages 0-11 years) and demographically matched controls were followed up and interviewed in adulthood. Social support and isolation were assessed in young adulthood (Mage = 29), and cognitive functioning was assessed in midlife (Mage = 41). Structural equation modeling was used for mediation and linear regressions for moderation. Childhood maltreatment predicted higher levels of social isolation and lower levels of social support and cognitive functioning. Only social isolation mediated the relationship between childhood maltreatment and midlife cognitive functioning, whereas childhood maltreatment interacted with social support to predict Matrix Reasoning in midlife. Social support was protective for the control group but not for those maltreated. Social isolation and social support play different roles in understanding how childhood maltreatment impacts midlife cognitive functioning. Greater social isolation predicts greater deficits in cognitive functioning overall, whereas the protective effects of social support are limited to those without a documented history of childhood maltreatment. Clinical implications are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Social isolation, lifestyle and cognitive functioning in midlife and early‐late life: Implications for risk reduction of cognitive decline and dementia

AbstractBackgroundSocial isolation (SI) is considered a modifiable risk factor for cognitive decline and dementia, is associated with unhealthy lifestyle. We investigated independent and combined associations of SI and lifestyle with cognitive functioning (CF) in a midlife to early‐late life population without dementia. This informs developing more targeted preventive strategies against cognitive decline and dementia.MethodThe “LIfestyle for BRAin health” (LIBRA) score was computed for 6,203 baseline participants of the LIFE‐Adult‐Study, a population‐based German cohort. LIBRA is validated for dementia prediction in midlife to early‐late life populations, consisting of 12 modifiable factors (heart disease, kidney disease, diabetes, obesity, hypertension, hypercholesterolemia, alcohol consumption, smoking, physical inactivity, diet, depression, cognitive activity). Higher scores (‐5.9,+12.7) indicate “worse” lifestyle. SI was assessed with the short Lubben Social Network Scale (score &lt; 12). For CF, we calculated a z‐standardized composite score of the Verbal Fluency Test, the Trail Making Test A and B. Associations of SI and LIBRA with CF were investigated using generalized linear modelling. Bootstrapped structural equation modelling (SEM) tested whether LIBRA mediated the association between SI and CF. Sampling weights were applied, variables z‐standardized for SEM.ResultsParticipants were M = 57.7 (SD = 12.0, range: 40‐79) years old; 50.7% were female; 15.8% were socially isolated. SI (β: ‐.17, 95%CI[‐.24,‐.10]; Wald = 21.45, p &lt; .001) and a higher LIBRA score (β: ‐.03, 95%CI[‐.04,‐.02]; Wald = 31.49, p &lt; .001) were independently associated with lower CF; there was no interaction (β: ‐.003, 95%CI[‐.03,.02]; Wald = 0.06, p = .814; Fig.1). Bootstrapped SEM (reps = 10,000; R² = .34) indicated that LIBRA partially mediated the association between SI and CF (IE = ‐.006, 95%CI[‐.008,‐.003], p &lt; .001; proportion mediated = 8.5%; Fig.2).ConclusionCF is lower in socially isolated than socially integrated individuals without dementia. The CF difference can be partially attributed to modifiable health and lifestyle factors; however, only to a small extent. Therefore, public health initiatives aiming at preventing SI might be more effective in promoting good CF than lifestyle interventions in socially isolated individuals in midlife to early‐late life. This would likely benefit risk reduction of cognitive decline and dementia in later life.

Dietary patterns from youth to adulthood and cognitive function in midlife: The cardiovascular risk in Young Finns Study

ObjectivesDiet plays an important role in cognitive health, but the long-term association of diet early in life with cognitive function in adulthood has not, to our knowledge, been rigorously studied. The aim of this study was to examine the association of youth, adulthood, and long-term dietary patterns from youth to adulthood with cognitive function in midlife. MethodsThis was a population-based cohort study that assessed dietary intake in 1980 (baseline, participants 3–18 y of age), 1986, 2001, 2007, and 2011 and cognitive function in 2011. Six dietary patterns were derived from 48-h food recall or food frequency questionnaires using factor analysis. The dietary patterns were traditional Finnish, high-carbohydrate, vegetables and dairy products, traditional Finnish and high-carbohydrate, red meat, and healthy. Scores of long-term dietary patterns were calculated as the average between youth and adulthood. Cognitive function outcomes assessed included episodic memory and associative learning, short-term working memory and problem solving, reaction and movement time, and visual processing and sustained attention. Standardized z-scores of exposures and outcomes were used for analyses. ResultsParticipants (n = 790, mean age 11.2 y) were followed up for 31 y. Multivariable models showed that both youth and long-term vegetable and dairy products and healthy patterns were positively associated with episodic memory and associative learning scores (β = 0.080–0.111, P < 0.05 for all). Both youth and long-term traditional Finnish patterns were negatively associated with spatial working memory and problem solving (β = –0.085 and –0.097, respectively; P < 0.05 for both). Long-term high-carbohydrate and traditional Finnish and high-carbohydrate patterns were inversely associated with visual processing and sustained attention, whereas the vegetable and dairy products pattern was positively associated with this cognitive domain (β = –0.117 to 0.073, P < 0.05 for all). Adulthood high-carbohydrate and traditional Finnish and high-carbohydrate patterns were inversely associated with all cognitive domains except for reaction and movement time (β = –0.072 to –0.161, P < 0.05 for all). Both long-term and adulthood red meat pattern were positively associated with visual processing and sustained attention (β = 0.079 and 0.104, respectively; P < 0.05 for both). These effect sizes correspond to approximately 1.6 to 16.1 y of cognitive aging on these cognitive domains. ConclusionsHigher adherence to traditional Finnish, high-carbohydrate, and traditional Finnish and high-carbohydrate patterns across the early life course was associated with poorer cognitive function in midlife, whereas higher adherence to healthy and vegetable and dairy product patterns was associated with better cognitive function. The findings, if causative, highlight the importance of maintaining a healthy dietary pattern from early life to adulthood in an attempt to promote cognitive health.

Adverse childhood experiences and sexual dysfunction in midlife women: Is there a link?

One in 3 children has had at least 1 adverse childhood experience (ACE), and ACEs have been associated with multiple medical and psychiatric morbidities in women later in life, including greater menopause symptom burden. To evaluate the association between ACEs and female sexual dysfunction (FSD) in midlife women. A cross-sectional analysis from DREAMS-the Data Registry on Experiences of Aging, Menopause, and Sexuality-was conducted with questionnaires completed by women aged 40 to 65years who presented to a women's health clinic at Mayo Clinic in Rochester, Minnesota, from May 2015 to December 2016. History of ACEs was obtained with the validated ACE questionnaire. FSD was assessed by the Female Sexual Function Index and the Female Sexual Distress Scale-Revised. The association between ACEs and FSD (defined as Female Sexual Function Index score ≤26.55 and Female Sexual Distress Scale-Revised score ≥11) was evaluated via a multivariable logistic regression model, adjusting for age, menopause status, hormone therapy use, anxiety, depression, relationship satisfaction, hot flash severity, and history of abuse in the past year. Women (N = 1572) had a mean age of 53.2years. Overall 59% reported having at least 1 ACE. When compared with no ACEs, a history of ≥4 ACEs significantly increased the odds of not being sexually active (odds ratio, 1.83; 95% CI, 1.30-2.57; P < .001). Among sexually active women, the proportion of women with FSD increased sequentially as the number of ACEs increased. In the univariate analysis, a history of ≥4 ACEs significantly increased the odds of FSD as compared with no ACEs (odds ratio, 2.12; 95% CI, 1.50-2.99; P < .001). The association remained statistically significant in the multivariable analysis after adjusting for confounders (odds ratio, 1.75; 95% CI, 1.15-2.68; P = .009). The findings highlight an opportunity for clinicians to screen for ACEs in women with sexual dysfunction and offer appropriate treatment and counseling as indicated. Strengths of the study include the large cohort, the use of validated tools for assessment of ACEs and FSD, and the adjustment for multiple potential confounding factors. Limitations include the cross-sectional study design, recall bias in reporting ACEs and recent abuse, and the low representation of racially and ethnically diverse women in the cohort. The study demonstrates an increased risk of sexual inactivity and sexual dysfunction in midlife women who experienced childhood adversity. The sexual dysfunction in women with ACEs seems to be independent of other factors that potentially affect female sexual function in midlife.

Dietary Patterns From Youth To Adulthood With Cognitive Function In Midlife: The Cardiovascular Risk In Young Finns Study

Dietary Patterns From Youth To Adulthood With Cognitive Function In Midlife: The Cardiovascular Risk In Young Finns Study

Abstract 31: Associations Between Cardiorespiratory Fitness (CRF) in Early Adulthood, Retention Through Midlife, and Heart Failure (HF) Stages: Findings From Coronary Artery Risk Development in Young Adults (CARDIA) Study

Introduction: Prior studies demonstrate that poor CRF in early adulthood is associated with adverse cardiac structure and function in midlife. The purpose of this study is to examine if higher early adulthood CRF and retention of CRF through midlife are associated with lower subsequent risk of subclinical or clinical HF. Methods: CARDIA participants with available data on CRF at baseline (Year [Y] 0: 1985-86), follow-up (Y7 or Y20), and HF staging data by Y30 were included. CRF was estimated using treadmill duration from a maximal, symptom-limited graded exercise test via modified Balke protocol. An adjusted linear mixed model was used to estimate treadmill duration when CRF assessment was missing at Y7 or 20. HF stages were defined using AHA HF staging criteria, including Stage 0 (no HF risk factors). Clinical HF was adjudicated by committee. Adjusted multinomial models tested associations between Y0 CRF and percent CRF retained through Y20 with HF stages at Y30, with Stage 0 as the reference. Interactions by the four race-sex groups were examined. Results: Of 2,565 individuals (25.1±3.5 y, 43% Black, 55% female), 30% (n=778), 37% (n=952), 32% (n=813), and 1% (n=32) were classified as Stages 0, A, B, or C/D by Y30 exam, respectively. Compared with Stage 0, every 1-minute increment higher CRF in early-adulthood was associated with a lower adjusted odds ratio of HF [Stage A: 0.72 (95% CI 0.68, 0.76), Stage B: 0.80 (95% CI 0.75, 0.84), Stage C/D 0.86 (95% CI 0.71, 1.04)]. Compared with Stage 0, every 1-standard deviation of % CRF retained at Y20 (midlife) was also associated with a lower odds of Stage A, B, and C/D HF at Y30 (Figure). A race-sex interaction was not observed (p-interaction 0.42). Conclusion: Higher early adulthood CRF, and greater retention of CRF through midlife, were associated with lower risk of developing subclinical or clinical HF. Strategies to maintain optimal CRF across the young adulthood to midlife transition may be important in prevention of HF.