Cross-sectional Associations Research Articles

Cross-Sectional and Longitudinal Association of Clinical and Neurocognitive Factors With Apathy in Patients With Parkinson Disease.

A robust understanding of the natural history of apathy in Parkinson disease (PD) is foundational for developing effective clinical management tools. However, large longitudinal studies are lacking while the literature is inconsistent about even cross-sectional associations. We aimed to determine the longitudinal predictors of apathy development in a large cohort of people with PD and its cross-sectional associations and trajectories over time, using sophisticated Bayesian modeling techniques. People with PD followed up in the longitudinal New Zealand Parkinson's progression project were included. Apathy was defined using the neuropsychiatric inventory subscale ≥4, and analyses were also repeated using a less stringent cutoff of ≥1. Both MoCA and comprehensive neuropsychological testing were used as appropriate to the model. Depression was assessed using the hospital anxiety and depression scale. Cross-sectional Bayesian regressions were conducted, and a multistate predictive model was used to identify factors that predict the initial onset of apathy in nonapathetic PD, while also accounting for the competing risk of death. The relationship between apathy presence and mortality was also investigated. Three hundred forty-six people with PD followed up for up to 14 years across a total of 1,392 sessions were included. Apathy occurrence did not vary significantly across the disease course (disease duration odds ratio [OR] = 0.55, [95% CI 0.28-1.12], affecting approximately 11% or 22% of people at any time depending on the NPI cutoff used. Its presence was associated with a significantly higher risk of death after controlling for all other factors (hazard ratio [HR] = 2.92 [1.50-5.66]). Lower cognition, higher depression levels, and greater motor severity predicted apathy development in those without motivational deficits (HR [cognition] = 0.66 [0.48-0.90], HR [depression] = 1.45 [1.04-2.02], HR [motor severity] = 1.37 [1.01-1.86]). Cognition and depression were also associated with apathy cross-sectionally, along with male sex and possibly lower dopaminergic therapy level, but apathy still occurred across the full spectrum of each variable (OR [cognition] = 0.58 [0.44-0.76], OR [depression] = 1.43 [1.04-1.97], OR [female sex] = 0.45 [0.22-0.92], and OR [levodopa equivalent dose] = 0.78 [0.59-1.04]. Apathy occurs across the PD time course and is associated with higher mortality. Depressive symptoms and cognitive impairment in particular predict its future development in those with normal motivation.

Cross-sectional and longitudinal associations between late-life depressive symptoms and cognitive deficits: 20-year follow-up of the Kuakini Honolulu-Asia aging study

ObjectiveTo examine depressed affect, somatic complaints, and positive affect as longitudinal predictors of fluid, crystallized and global cognitive performance in the Kuakini Honolulu-Asia Aging Study (HAAS), a large prospective cohort study of Japanese-American men. MethodsWe assessed 3,088 dementia-free Kuakini-HAAS participants aged 71–93 (77.1 ± 4.2) years at baseline (1991–1993). Depressive symptoms were evaluated by the Center for Epidemiologic Studies Depression (CES-D) Scale. Baseline CES-D depression subscales (depressed and positive affects; somatic complaints) were computed. The Cognitive Abilities Screening Instrument (CASI) measured cognitive performance on a 100-point scale; fluid and crystallized cognitive abilities were derived from CASI factor analysis. Cognition was also evaluated at 4 follow-up examinations over a 20-year period. Multiple regression assessed baseline CES-D subscales as predictors of cognitive change. The baseline covariates analyzed were CASI, age, education, prevalent stroke, APOE ε4 presence, and the longevity-associated FOXO3 genotype. ResultsCross-sectionally, baseline CES-D subscales were related to cognitive measures; e.g., higher depressed affect was associated with lower crystallized ability (β = −0.058, p ≤ 0.01), and somatic complaints were linked to poorer fluid ability (β = −0.045, p ≤ 0.05) and to worse global cognitive function as measured by total CASI score (β = −0.038, p ≤ 0.05). However, depression subscales did not significantly or consistently predict fluid ability, crystallized ability, or global cognitive performance over time. ConclusionPsychological and physical well-being were associated with contemporaneous but not subsequent cognitive functioning. Assessment of depressive symptoms may identify individuals who are likely to benefit from interventions to improve mood and somatic health and thereby maintain or enhance cognition.

Plasma Insulin Predicts Early Amyloid-β Pathology Changes in Alzheimer's Disease.

Evidence suggests that type 2 diabetes (T2D) is an independent risk factor for Alzheimer's disease (AD), sharing similar pathophysiological traits like impaired insulin signaling. To test the association between plasma insulin and cerebrospinal fluid (CSF) AD pathology. A total of 304 participants were included in the Alzheimer's Disease Neuroimaging Initiative, assessing plasma insulin and CSF AD pathology. We explored the cross-sectional and longitudinal associations between plasma insulin and AD pathology and compared their associations across different AD clinical and pathological stages. In the non-demented group, amyloid-β (Aβ)+ participants (e.g., as reflected by CSF Aβ42) exhibited significantly lower plasma insulin levels compared to non-demented Aβ-participants (p < 0.001). This reduction in plasma insulin was more evident in the A+T+ group (as shown by CSF Aβ42 and pTau181 levels) when compared to the A-T- group within the non-dementia group (p = 0.002). Additionally, higher plasma insulin levels were consistently associated with more normal CSF Aβ42 levels (p < 0.001) across all participants. This association was particularly significant in the Aβ-group (p = 0.002) and among non-demented individuals (p < 0.001). Notably, baseline plasma insulin was significantly correlated with longitudinal changes in CSF Aβ42 (p = 0.006), whereas baseline CSF Aβ42 did not show a similar correlation with changes in plasma insulin over time. These findings suggest an association between plasma insulin and early Aβ pathology in the early stages of AD, indicating that plasma insulin may be a potential predictor of changes in early Aβ pathology.

Associations Between Self and Study Partner Report of Cognitive Decline With Regional Tau in a Multicohort Study.

Self-reported cognitive decline is an early behavioral manifestation of Alzheimer disease (AD) at the preclinical stage, often believed to precede concerns reported by a study partner. Previous work shows cross-sectional associations with β-amyloid (Aβ) status and self-reported and study partner-reported cognitive decline, but less is known about their associations with tau deposition, particularly among those with preclinical AD. This cross-sectional study included participants from the Anti-Amyloid Treatment in Asymptomatic AD/Longitudinal Evaluation of Amyloid Risk and Neurodegeneration studies (N = 444) and the Harvard Aging Brain Study and affiliated studies (N = 231), which resulted in a cognitively unimpaired (CU) sample of individuals with both nonelevated (Aβ-) and elevated Aβ (Aβ+). All participants and study partners completed the Cognitive Function Index (CFI). Two regional tau composites were derived by averaging flortaucipir PET uptake in the medial temporal lobe (MTL) and neocortex (NEO). Global Aβ PET was measured in Centiloids (CLs) with Aβ+ >26 CL. We conducted multiple linear regression analyses to test associations between tau PET and CFI, covarying for amyloid, age, sex, education, and cohort. We also controlled for objective cognitive performance, measured using the Preclinical Alzheimer Cognitive Composite (PACC). Across 675 CU participants (age = 72.3 ± 6.6 years, female = 59%, Aβ+ = 60%), greater tau was associated with greater self-CFI (MTL: β = 0.28 [0.12, 0.44], p < 0.001, and NEO: β = 0.26 [0.09, 0.42], p = 0.002) and study partner CFI (MTL: β = 0.28 [0.14, 0.41], p < 0.001, and NEO: β = 0.31 [0.17, 0.44], p < 0.001). Significant associations between both CFI measures and MTL/NEO tau PET were driven by Aβ+. Continuous Aβ showed an independent effect on CFI in addition to MTL and NEO tau for both self-CFI and study partner CFI. Self-CFI (β = 0.01 [0.001, 0.02], p = 0.03), study partner CFI (β = 0.01 [0.003, 0.02], p = 0.01), and the PACC (β = -0.02 [-0.03, -0.01], p < 0.001) were independently associated with MTL tau, but for NEO tau, PACC (β = -0.02 [-0.03, -0.01], p < 0.001) and study partner report (β = 0.01 [0.004, 0.02], p = 0.002) were associated, but not self-CFI (β = 0.01 [-0.001, 0.02], p = 0.10). Both self-report and study partner report showed associations with tau in addition to Aβ. Additionally, self-report and study partner report were associated with tau above and beyond performance on a neuropsychological composite. Stratification analyses by Aβ status indicate that associations between self-reported and study partner-reported cognitive concerns with regional tau are driven by those at the preclinical stage of AD, suggesting that both are useful to collect on the early AD continuum.

Study design features increase replicability in cross-sectional and longitudinal brain-wide association studies.

Brain-wide association studies (BWAS) are a fundamental tool in discovering brain-behavior associations. Several recent studies showed that thousands of study participants are required for good replicability of BWAS because the standardized effect sizes (ESs) are much smaller than the reported standardized ESs in smaller studies. Here, we perform analyses and meta-analyses of a robust effect size index using 63 longitudinal and cross-sectional magnetic resonance imaging studies from the Lifespan Brain Chart Consortium (77,695 total scans) to demonstrate that optimizing study design is critical for increasing standardized ESs and replicability in BWAS. A meta-analysis of brain volume associations with age indicates that BWAS with larger variability in covariate have larger reported standardized ES. In addition, the longitudinal studies we examined reported systematically larger standardized ES than cross-sectional studies. Analyzing age effects on global and regional brain measures from the United Kingdom Biobank and the Alzheimer's Disease Neuroimaging Initiative, we show that modifying longitudinal study design through sampling schemes improves the standardized ESs and replicability. Sampling schemes that improve standardized ESs and replicability include increasing between-subject age variability in the sample and adding a single additional longitudinal measurement per subject. To ensure that our results are generalizable, we further evaluate these longitudinal sampling schemes on cognitive, psychopathology, and demographic associations with structural and functional brain outcome measures in the Adolescent Brain and Cognitive Development dataset. We demonstrate that commonly used longitudinal models can, counterintuitively, reduce standardized ESs and replicability. The benefit of conducting longitudinal studies depends on the strengths of the between- versus within-subject associations of the brain and non-brain measures. Explicitly modeling between- versus within-subject effects avoids averaging the effects and allows optimizing the standardized ESs for each separately. Together, these results provide guidance for study designs that improve the replicability of BWAS.

The Association of Mitral Annular Calcification With Cardiovascular and Noncardiovascular Outcomes: The Multi-Ethnic Study of Atherosclerosis

Mitral annular calcification (MAC) may be a potential marker of biological aging. However, the association of MAC with non-cardiovascular measures, including bone mineral density (BMD), incident renal failure, dementia, and non-cardiovascular mortality, is not well studied in a multiracial cohort. We used data from 6,814 participants (mean age:62.2±10.2 years; 52.9%-females) without cardiovascular disease at baseline in the Multi-Ethnic Study of Atherosclerosis. MAC was assessed with non-contrast cardiac computed tomography at study baseline. Using multivariable-adjusted linear and logistic regression, we assessed cross-sectional association of MAC with BMD and walking pace. Also, using Cox proportional hazards, we evaluated the association of MAC with incident renal failure, dementia, and all-cause mortality. Additionally, we assessed the association of MAC with cardiovascular and non-cardiovascular mortality using competing risks regression. The prevalence of MAC was 9.5% and was higher in women (10.7%) than in men (8.0%). MAC was associated with low BMD (coefficient: -0.04; 95%CI: -0.06 - -0.02) with significant interaction by sex (p-interaction:0.035). MAC was, however, not associated with impaired walking pace (odds ratio:1.09; 95%CI:0.89–1.33). Compared to individuals without MAC, those with MAC had an increased risk of incident renal failure albeit nonsignificant (hazard ratio [HR]:1.18; 95%CI:0.95–1.45) but a significantly higher hazards of dementia (HR:1.36; 95%CI:1.10–1.70). Additionally, persons with MAC had a substantially higher risk of all-cause (HR:1.47; 95%CI:1.29–1.69), cardiovascular (sub-distribution HR:1.39; 95%CI:1.04–1.87), and non-cardiovascular mortality (sub-distribution HR:1.35; 95%CI:1.14–1.60), compared to those without MAC. MAC≥100 vs <100 was significantly associated with reduced BMD, incident renal failure, dementia, all-cause, cardiovascular, and non-cardiovascular mortality. In conclusion, MAC was associated with reduced BMD and dementia, as well as all-cause, cardiovascular, and non-cardiovascular mortality in this multiracial cohort. Thus, MAC may be a marker not only for atherosclerotic burden but also for other metabolic and inflammatory factors that increase the risk of non-cardiovascular outcomes and death from other causes.

Relations of optimism and purpose in life to immune markers in aging

ObjectiveOptimism and purpose in life are associated with improved health outcomes. More information is needed on biological mechanisms, including immunosenescence. We investigated if psychological well-being is associated with healthier immunosenescence-related measures including naïve and terminally differentiated CD4+ and CD8+ T cell percentages, CD4+:CD8+, and cytomegalovirus (CMV) IgG response. MethodsParticipants were adults over age 50 from the Health and Retirement Study. Optimism was measured using the Life Orientation Test Revised. Purpose in life was assessed using the subscale from the Ryff psychological well-being measure. We examined the cross-sectional associations of optimism and purpose in life with measures of T cell subsets using linear regression and with CMV IgG using ordered logit regression, controlling for potential confounding factors. ResultsThe final analytic sample ranged from 7250 to 7870. After adjusting for sociodemographic factors, a 1-SD increment in optimism was associated with the percentage of naïve CD4+ T cells increasing by 0.6 (95%CI 0.2%, 1.0%). A 1-SD increment in purpose in life was associated with the percentage of naïve CD4+ T cells increasing by 0.9 (95%CI 0.5%, 1.3%) after adjusting for sociodemographic factors and the association was maintained after further adjustments for health conditions, depression, and health behaviors. For naïve CD8+ T cell percentages, CD4:CD8 ratios, and CMV IgG antibodies, associations were seen only in models that adjusted for age. No significant associations were seen in any models for the terminally differentiated CD4+ and CD8+ T cells. ConclusionsWe found associations of optimism and purpose in life with naïve CD4+ T cell percentages.

No Evidence for Cross-Sectional or Longitudinal Associations between Cognitive Flexibility Performances and Nutritional Status in a Cohort of Inpatients with Anorexia Nervosa.

According to the Cognitive-Interpersonal model of anorexia nervosa (AN), the combined influence of cognitive and socio-emotional difficulties would constitute vulnerability and maintaining factors. Poor cognitive flexibility is one of the endophenotypic candidates (i.e., a trait marker) of the disorder, but few studies have examined its association with illness symptom variations, notably weight status. The study aimed to evaluate the relationships between cognitive flexibility performances and nutritional status indices (BMI; body composition) at different times of the disorder. Cross-sectional and longitudinal associations between cognitive flexibility (TAP 2.1) and nutritional status indices, along with anxious and depressive (HAD) and eating disorder (EDE-Q) symptomatology were investigated using univariate and multivariate analyses in a cohort of AN inpatients evaluated at hospital admission (N = 167) and discharge (N = 94). We found no or negligible associations between nutritional status and HAD or EDE-Q scores or cognitive flexibility performances, either cross-sectionally or longitudinally. Cognitive performances did not significantly differ between the AN subtypes. In agreement with the Cognitive-Interpersonal model of AN, cognitive flexibility is independent of nutritional status, as well as the AN subtype. It is also independent of the levels of anxious, depressive, or ED symptomatology. A new therapeutic approach targeting cognitive flexibility and intolerance to change could benefit severely emaciated people with AN, regardless of disease subtype and level of dysphoria.

Association between bisphenol A exposure and cardiometabolic outcomes: A longitudinal approach

Increased cardiometabolic risk is associated with abnormalities in blood biomarkers profile and adiposity measurements. Some substances found in the food matrix and the environment, called endocrine-disrupting chemicals, may impair cardiometabolic health in the early and later stages of life. Bisphenol A (BPA) is a food contaminant that migrates from food contact materials and may act as an endocrine disruptor, negatively affecting human health. The present work aims to longitudinally assess the association between BPA exposure and cardiometabolic outcomes, considering data from Portuguese population-based birth cohort Generation XXI. Blood insulin (0.06stdβ; 95 %CI:0.03,0.09) and insulin resistance (0.05stdβ; 95 %CI:0.02,0.08) presented a significant longitudinal association with BPA daily exposure after adjustment for important variables and energy. The same findings were observed for fat mass (0.03stdβ; 95 %CI 0.01,0.06) and waist circumference (0.06stdβ; 95 %CI:0.04,0.08). For z-BMI, a significant cross-sectional (0.03stdβ; 95 %CI:0.01,0.04) and longitudinal (0.02stdβ; 95 %CI:0.00,0.04) association was found. This was the first study assessing the association between BPA exposure and health outcomes from childhood to adolescence. We found an association between BPA exposure and increased blood insulin level, insulin resistance, fat mass percentage, waist circumference and z-BMI. Our results point to the need to reduce exposure to BPA in the early stages of life.

Prospective effects of resilience on mental health among sexual and gender minority young people

ABSTRACT Sexual and gender minority (SGM) individuals who are assigned-female-at-birth (i.e. sexual minority women, transgender men, and gender diverse individuals [SMWTGD]) experience an increased risk for negative mental health outcomes due to minority stress related to their minoritized identity. One proposed protective factor against negative mental health outcomes is resilience, which is one’s ability to effectively achieve positive outcomes following stressful events. Past research shows cross-sectional associations between resilience and mental health in both the general population and SGM individuals. However, we know of no longitudinal research testing whether resilience prospectively predicts mental health, or whether the prospective associations between resilience and mental health differ by demographics. Self-reports of resilience, depression, anxiety, suicidality, and substance use were collected at two time-points 6 months apart from 453 SMWTGD late adolescents and young adults who reside in the Midwest region of the United States. Time 1 resilience was negatively associated with Time 2 depression, anxiety, and suicidal ideation, but not problematic substance use, controlling for Time 1 mental health. These associations were generally not moderated by demographic factors, suggesting that resilience operates consistently across most racial, sexual orientation, and gender identities within the SMWTGD community. These findings underscore the potential value of tailored interventions aimed at promoting resilience within SMWTGD.

Neighbourhood walkability and body mass index in children: Evidence from the Millennium Cohort Study in Wales

BackgroundOverweight and obesity in children continues to increase. Yet, the role of active transport, namely walking, in mitigating these trends remains unclear. This study examined the cross-sectional association between walkability and children's Body Mass Index (BMI) and how this varies by socio-economic and lifestyle characteristics. MethodsWe analysed BMI for 14-year-old children living in Wales from the UK Millennium Cohort Study. Children were categorised as healthy weight, overweight or obese using the British 1990 cut-off points. Walkability was assessed using the Wales Active Living Environments (Wal-ALE) database, categorised as 1 (least walkable environments) to 5 (most walkable environments). We applied multinomial logistic regression analysis and adjusted for ethnicity, having a limiting longstanding illness, parental BMI, socio-economic circumstances, and lifestyle characteristics. ResultsChildren were more likely to be obese if they lived in areas classed as more walkable in unadjusted analysis [Relative Risk Ratio (RRR) = 1.72 (95%CI = 1.15–2.58)] and following adjustment for ethnicity, limiting longstanding illness and parental BMI [RRR = 1.83 (95%CI = 1.12–3.00)]). Significant associations remained even after further adjustment for lifestyle characteristics and socio-economic circumstances [RRR = 1.76 (95%CI = 1.05–2.96)]. Further, children were more likely to be obese if their parents were overweight or obese and if they were living in poverty. Children were less likely to be obese if they spent 3 or more days per week in moderate-to-vigorous physical activity (MVPA) and if they ate breakfast every day vs. some days or never. ConclusionFindings demonstrate that walkable environments are not associated with lower rates of obesity in children, indicating that the relationship between the built environment and child health is complex and requires further study.

Association of serum levels of phenylalanine and tyrosine with hip fractures and frailty in older adults: The cardiovascular health study.

Protein is essential for skeletal health, but the specific amino acid compositions of protein may have differential associations with fracture risk. The aim of this study was to determine the association of serum levels of the aromatic amino acids phenylalanine and tyrosine with risk for incident hip fractures over twelve years of follow-up and cross sectional associations with frailty. We included 131 older men and women from the Cardiovascular Health Study (CHS) who sustained a hip fracture over twelve years of follow-up and 131 men and women without an incident hip fracture over this same period of time. 42% of this cohort were men and 95% were Caucasian. Weighted multivariable Cox hazards molecules were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of incident hip fracture associated with a one standard deviation (SD) higher serum level of phenylalanine or tyrosine. Relative risk regression was used to determine the cross-sectional association of these amino acids with Freid's frailty index. Neither serum levels of phenylalanine (HR 0.85 (95% CI 0.62-1.16) or tyrosine (HR 0.82 (95% CI 0.62-1.1) were significantly associated with incident hip fractures or cross sectionally with frailty (frail compared with prefrail/not frail) (HR 0.92 (95% CI 0.48-1.76) and HR (0.86 (95% CI 0.46-1.61) respectively. Phenylalanine and tyrosine are not significant contributors to hip fractures or frailty in older men and women.

Metabolite Profiles of Plant-Based Diets and Cardiometabolic Risk in the Mediators of Atherosclerosis in South Asians Living in America Study

BackgroundHealthy plant-based diets have been associated with lower risk of type 2 diabetes (T2D). Metabolomics can be leveraged to identify potential pathways through which diet influences disease risk. ObjectivesThis study aimed to identify profiles of serum metabolites reflective of plant-based diets of varying quality and examine associations with cardiometabolic risk and T2D. MethodsWe included data from 687 participants of the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort. An overall plant-based diet index (PDI), healthy PDI (hPDI), and unhealthy PDI (uPDI) were estimated from food frequency questionnaires. Serum metabolites were assayed using ultraperformance liquid chromatography mass spectrometry. Elastic net regression was used to identify sets of metabolites predictive of each diet index, and metabolite profile scores were calculated as the weighted sum of the selected metabolites. Cross-sectional associations between metabolite profile scores and cardiometabolic measures and prospective associations with incident T2D were evaluated with multivariable-adjusted linear and logistic regressions. ResultsMetabolite profiles for PDI, hPDI, and uPDI consisted of n = 51, 55, and 45 metabolites, respectively. Metabolites strongly positively correlated with diet indices included phosphatidylcholine (16:0/18:3) for PDI, phosphatidylethanolamine (20:1/20:4) and pantothenate for hPDI, and lysophosphatidylglycerol (18:2/0:0), proline, and lauric acid for uPDI. Higher metabolite profile scores for PDI and hPDI were associated with lower glycemia and lipids measures, whereas a higher uPDI metabolite score was associated with higher triglycerides and lower low density lipoprotein cholesterol and high density lipoprotein cholesterol. A higher metabolite score for hPDI was additionally associated with lower adiposity measures, higher liver fat attenuation, higher adiponectin, lower odds of overweight (odds ratio [OR]: 0.64; 95% confidence interval [CI]: 0.51, 0.81) and obesity (OR: 0.59; 95% CI: 0.48, 0.74), and lower odds of incident T2D (OR: 0.66; 95% CI: 0.45, 0.97). ConclusionsMetabolite profiles of different plant-based diets were identified. Metabolite profiles of overall and healthy plant-based diets were associated with favorable cardiometabolic risk profiles.

Elucidating the Link Between Anxiety/Depression and Alzheimer’s Dementia in the Australian Imaging Biomarkers and Lifestyle (AIBL) Study

BackgroundThe associations between mood disorders (anxiety and depression) and mild cognitive impairment (MCI) or Alzheimer’s dementia (AD) remain unclear.MethodsData from the Australian Imaging, Biomarker & Lifestyle (AIBL) study were subjected to logistic regression to determine both cross-sectional and longitudinal associations between anxiety/depression and MCI/AD. Effect modification by selected covariates was analysed using the likelihood ratio test.ResultsCross-sectional analysis was performed to explore the association between anxiety/depression and MCI/AD among 2,209 participants with a mean [SD] age of 72.3 [7.4] years, of whom 55.4% were female. After adjusting for confounding variables, we found a significant increase in the odds of AD among participants with two mood disorders (anxiety: OR 1.65 [95% CI 1.04–2.60]; depression: OR 1.73 [1.12–2.69]). Longitudinal analysis was conducted to explore the target associations among 1,379 participants with a mean age of 71.2 [6.6] years, of whom 56.3% were female. During a mean follow-up of 5.0 [4.2] years, 163 participants who developed MCI/AD (refer to as PRO) were identified. Only anxiety was associated with higher odds of PRO after adjusting for covariates (OR 1.56 [1.03–2.39]). However, after additional adjustment for depression, the association became insignificant. Additionally, age, sex, and marital status were identified as effect modifiers for the target associations.ConclusionOur study provides supportive evidence that anxiety and depression impact on the evolution of MCI/AD, which provides valuable epidemiological insights that can inform clinical practice, guiding clinicians in offering targeted dementia prevention and surveillance programs to the at-risk populations.

Polycystic Ovary Syndrome, Metabolic Syndrome, and Inflammation in the Hispanic Community Health Study/Study of Latinos.

Polycystic Ovary Syndrome (PCOS) is a multifaceted endocrine disorder with reproductive and metabolic dysregulation. PCOS has been associated with inflammation and Metabolic Syndrome (MetS); however, the moderating effects of inflammation as measured by C-reactive protein (CRP) and menopause on the PCOS-MetS association have not been studied in Hispanic/Latinas with PCOS who have a higher metabolic burden. We studied the cross-sectional association between PCOS and (i) MetS in 7316 females of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), (ii) subcomponents of MetS including impaired fasting glucose (IFG) and elevated triglycerides (TGL), and (iii) effect modification by menopausal status and CRP. HCHS/SOL is a multicenter, longitudinal, and observational study of US Hispanic/Latinos. Our study sample included females from Visit 2 with self-reported PCOS and MetS (ages 23-82 years). PCOS (prevalence=18.8%) was significantly associated with MetS prevalence (OR=1.41[95% confidence interval: 1.13-1.76]), IFG and TGL (OR=1.42[1.18-1.72], OR=1.48[1.20-1.83] respectively). We observed effect modification by menopausal status (ORpre=1.46, pint=0.02; ORpost=1.34, pint=0.06) and CRP (ORelevated=1.41, pint=0.04; ORnormal=1.26, pint=0.16) on the PCOS-MetS association. We also observed a super-additive interaction between CRP and PCOS, adjusting for which resulted in an attenuated effect of PCOS on MetS (OR=1.29[0.93-1.78]). Hispanic/Latino females with PCOS had higher odds of MetS, IFG, and elevated TGL, than their peers without PCOS. Interaction analyses revealed that the odds of MetS are higher among PCOS females who have pre-menopausal status or high inflammation. Interventions in Hispanic/Latinas should target these outcomes for effective management of the disease.

Examining Generalizability across Different Surveys: Comparing Nutrient-Based Food Patterns and Their Cross-Sectional Associations with Cardiometabolic Health in the United States Hispanic/Latino Adults

BackgroundEthnicity, cultural background, and geographic location differ significantly within the United States Hispanic/Latino population. These variations can greatly define diet and its relationship with cardiometabolic disease, thus influencing generalizability of results. ObjectivesWe aimed to examine nutrient-based food patterns (NBFPs) of Hispanic/Latino adults and their association with cardiometabolic risk factors (dyslipidemia, hypertension, obesity, diabetes) across 2 United States population-based studies with differing sampling strategies. MethodsData were collected from Mexican or other Hispanic adult participants from 2007–2012 National Health and Nutrition Examination Survey (NHANES) (n = 3605) and 2007–2011 Hispanic Community Health Survey/Study of Latinos (HCHS/SOL, n = 14,416). NBFPs were derived using factor analysis on nutrient intake data estimated from 24-h dietary recalls and interpreted using common foods in which these nutrients are prominent. Cross-sectional associations between NBFPs (quintiles) and cardiometabolic risk factors, defined by clinical measures and self-report, were estimated using survey-weighted multivariable-adjusted logistic models, accounting for multiple testing. ResultsFive NBFPs were identified in both studies: 1) meats, 2) grains/legumes, 3) fruits/vegetables, 4) dairy, and 5) fats/oils. Associations with cardiometabolic risk factors differed by NBFP and study. In HCHS/SOL, the odds of diabetes were lower for persons in the highest quintile of meats NBFP (odds ratio [OR]: 0.73; 95% confidence interval [CI]: 0.58, 0.92) and odds were higher for those in the lowest quintile of fruits/vegetables (OR: 0.71; 95% CI: 0.55, 0.93) compared to those in the third (moderate intake) quintile. Those in the fourth quintile of dairy NBFP had higher odds of hypertension than those in the third quintile (OR: 1.31; 95% CI: 1.01, 1.70). In NHANES, the odds of hypertension were higher for those in the fourth quintile of dairy (OR: 1.88; 95% CI: 1.10, 3.24) than those in the third quintile. ConclusionsDiet–disease relationships among Hispanic/Latino adults vary according to 2 population-based studies. These differences have research and practical implications when generalizing inferences on heterogeneous underrepresented populations.

Association between self-reported visual symptoms (suggesting cataract) and self-reported fall-related injury among adults aged ≥ 65 years from five low- and middle-income countries.

Cataracts may increase risk for falls but studies on this topic from low- and middle-income countries (LMICs) are scarce. Therefore, we examined the cross-sectional association between self-reported visual symptoms (suggesting cataract) and self-reported injurious falls in nationally representative samples of adults aged ≥ 65 years from five LMICs (China, Ghana, India, Mexico, and Russia). Data from the WHO Study on global AGEing and adult health (SAGE) were analysed. Self-reported information on past 12-month fall-related injury and cataract based on symptoms were collected. Multivariable logistic regression and meta-analyses were conducted to assess associations. Data on 13,101 people aged ≥ 65 years were analysed [mean (SD) age 72.5 (11.3) years; 45.2% males]. The overall prevalence of self-reported fall-related injury and visual symptoms (suggesting cataract) were 4.9% and 29.4%, respectively. There was a positive association between self-reported visual symptoms (suggesting cataract) and fall-related injury (i.e., OR > 1) in all five countries but statistical significance was reached in three: China (OR = 1.60; 95% CI = 1.08-2.35), India (OR = 1.96; 95% CI = 1.15-3.35), and Russia (OR = 3.58; 95% CI = 2.06-6.24). The pooled OR including all five countries based on a meta-analysis was OR = 1.88 (95% CI = 1.32-2.68). Self-reported visual symptoms (suggesting cataract) were associated with higher odds for self-reported injurious falls among older adults in LMICs. Expanding availability of cataract surgery in LMICs may also have the additional benefit of reducing falls among older people.

The association between the Canadian active living environments index and glucose metabolism in a Canadian national population study

Biomarkers of glucose metabolism may reflect insulin resistance, a risk factor for diabetes and cardiovascular disease (CVD). Neighborhoods conducive to a physically active lifestyle have the potential to improve these biomarkers. We examined cross-sectional associations between walkability and blood biomarkers of glucose metabolism in 29,649 Canadian Health Measures Survey (CHMS) participants. We used generalized linear mixed models with sampling weights adjusted for province, participants’ age, sex, annual household income and educational attainment, cigarette smoking, environmental tobacco smoke, alcohol consumption, and exposure to ambient fine particulate air pollution (PM2.5). A higher value of the Canadian Active Living Environments Index, a measure of neighborhood walkability, equivalent to the magnitude of its interquartile range (IQR) of 2.4 was significantly associated with percentage differences of −0.48 (95% confidence interval (CI): 0.63, −0.32), −3.17 (95%CI: 5.27, −1.08), −3.88 (95%CI: 6.38, −1.38), and −3.36 (95%CI: 5.25, −1.47) in HbA1C, fasting insulin, HOMA-IR, and HOMA-β, respectively, for all CHMS participants. No significant effects were observed in those ≤16 years old. Canadians living in neighborhoods that facilitate active living have more favorable biomarkers of glucose metabolism, suggesting that the built environment has the potential to improve risk factors for diabetes and CVD in adults.

Charting the cascade of physical activities: implications for reducing sitting time and obesity in children

ObjectiveTraditional intensity-based physical activity measures and variable-centered statistics may not fully capture the complex associations between sitting time, physical activity, and obesity indices. This study investigates the associations between device-measured sitting, standing and different modes of physical activity (i.e., slow walking, brisk-walking, cycling and high-intensity activity) and measured body mass index (BMI) in children using person-based latent profile analyses and Partial Least Squared-structural equation modeling (PLS-SEM).MethodsA total of 344 children (11.5 ± 0.81 years, boys n = 139) wore a triaxial accelerometer (Fibion®) on their thigh for eight days, and their weight and height were measured at school. Latent profile analysis formed profiles including BMI, total sitting time, and physical activities, and their associations were further studied with PLS-SEM.ResultsThe latent profile analysis indicates that high levels of physical activity always coincide with low sitting time. Both normal weight and overweight/obesity can coexist with low physical activity and prolonged sitting. The PLS-SEM results highlight a cascade-like sequence in the relationship between various types of physical activity, sitting time, and BMI. This sequence begins with light-intensity activities, such as standing, progresses to higher-intensity activities, and ultimately through reduced sitting time (sample mean= -0.01; effect size = 0.0001; p = 0.02), mediates a decline in BMI (sample mean= -0.06; effect size = 0.0036; p = 0.01). The most positive effects on sitting time and BMI occur when this pattern is adhered to consistently, suggesting that omitting steps could negatively impact the associations.ConclusionThese findings suggest that persuading children to increase physical activity incrementally, starting from low-intensity activities such as standing and slow walking to activity types with higher intensities, possibly influence BMI by mediating reduced sitting time. This approach is particularly inclusive for overweight and obese children, taking into account the potential challenges they may encounter when performing activity types with high intensity. These cross-sectional associations need to be verified with longitudinal and experimental designs.

Developmental associations between cognition and adaptive behavior in intellectual and developmental disability

BackgroundIntellectual and developmental disabilities (IDDs) are associated with both cognitive challenges and difficulties in conceptual, social, and practical areas of living, commonly referred to as adaptive behavior (DSM–5). Although cross-sectional associations between intelligence or cognition and adaptive behavior have been reported in IDD populations, no study to date has examined whether developmental changes in cognition contribute to or track with changes in adaptive behavior. The present study sought to examine associations of longitudinal developmental change in domains of cognition (NIH Toolbox Cognition Battery, NIHTB-CB) and adaptive behavior domains (Vineland Adaptive Behavior Scales-3; VABS-3) including Socialization, Communication, and Daily Living Skills (DLS) over a two year period in a large sample of children, adolescents and young adults with IDD.MethodsThree groups were recruited, including those with fragile X syndrome, Down syndrome, and other/idiopathic intellectual disability. Eligible participants (n = 263) included those who were between 6 and 26 years (mage = 15.52, sd = 5.17) at Visit 1, and who had a diagnosis of, or suspected intellectual disability (ID), including borderline ID, with a mental age of at least 3.0 years. Participants were given cognitive and adaptive behavior assessments at two time points over a two year period (m = 2.45 years, range = 1.27 to 5.56 years). In order to examine the association of developmental change between cognitive and adaptive behavior domains, bivariate latent change score (BLCS) models were fit to compare change in the three cognitive domains measured by the NIHTB-CB (Fluid Cognition, Crystallized Cognition, Total Cognition) and the three adaptive behavior domains measured by the VABS-3 (Communication, DLS, and Socialization).ResultsOver a two year period, change in cognition (both Crystallized and Total Composites) was significantly and positively associated with change in daily living skills. Also, baseline cognition level predicted growth in adaptive behavior, however baseline adaptive behavior did not predict growth in cognition in any model.ConclusionsThe present study demonstrated that developmental changes in cognition and adaptive behavior are associated in children and young adults with IDD, indicating the potential for cross-domain effects of intervention. Notably, improvements in DLS emerged as a primary area of adaptive behavior that positively related to improvements in cognition. This work provides evidence for the clinical, “real life” meaningfulness of changes in cognition detected by the NIHTB-CB in IDD, and provides empirical support for the NIHTB-CB as a fit-for-purpose performance-based outcome measure for this population.