Brain aging patterns in a large and diverse cohort of 49,482 individuals.

Brain aging process is influenced by various lifestyle, environmental and genetic factors, as well as by age-related and often coexisting pathologies. Magnetic resonance imaging and artificial intelligence methods have been instrumental in understanding neuroanatomical changes that occur during aging. Large, diverse population studies enable identifying comprehensive and representative brain change patterns resulting from distinct but overlapping pathological and biological factors, revealing intersections and heterogeneity in affected brain regions and clinical phenotypes. Herein, we leverage a state-of-the-art deep-representation learning method, Surreal-GAN, and present methodological advances and extensive experimental results elucidating brain aging heterogeneity in a cohort of 49,482 individuals from 11 studies. Five dominant patterns of brain atrophy were identified and quantified for each individual by respective measures, R-indices. Their associations with biomedical, lifestyle and genetic factors provide insights into the etiology of observed variances, suggesting their potential as brain endophenotypes for genetic and lifestyle risks. Furthermore, baseline R-indices predict disease progression and mortality, capturing early changes as supplementary prognostic markers. These R-indices establish a dimensional approach to measuring aging trajectories and related brain changes. They hold promise for precise diagnostics, especially at preclinical stages, facilitating personalized patient management and targeted clinical trial recruitment based on specific brain endophenotypic expression and prognosis.

Interactive Relations of Body Mass Index, Cardiorespiratory Fitness, and Sex to Cognitive Function in Older Adults.

OBJECTIVE: The course of cognitive aging is influenced by multiple health factors. This cross-sectional study investigated the interactive relations between body mass index (BMI), maximum oxygen consumption (VO2max), and sex on neuropsychological outcomes in community-dwelling predominantly older adults. METHODS: Participants were 164 healthy adults [M (SD) = 64.6 (12.5) years, 56% men, 87% white] who participated in an investigation of cardiovascular risk factors and brain health. Multivariable regression analysis, adjusted for age, education, ethnicity, smoking, alcohol consumption, and depression, examined the interactive relations of BMI, VO2max, and sex to multiple neuropsychological outcomes. RESULTS: Significant BMI*VO2max*sex interactions for Grooved Pegboard dominant (p = .019) and nondominant (p = .005) hands revealed that men with lower VO2max (l/min) displayed worse performance with each hand as BMI increased (p's < .02). A significant BMI*sex interaction for Logical Memory-Delayed Recall (p = .036) (after adjustment for blood glucose) showed that men, but not women, with higher BMI demonstrated worse performance (p = .036). Lastly, significant main effects indicated that lower VO2max was related to poorer logical memory, and higher BMI was associated with poorer Trail Making B and Stroop interference scores (p's < .05). CONCLUSIONS: Among men, higher cardiorespiratory fitness may protect against the negative impact of greater BMI on manual dexterity and motor speed, making VO2max a target for intervention. Higher BMI is further associated with poorer executive function and verbal memory (in men), and lower VO2max is associated with poorer verbal memory.

Helicobacter pylori, persistent infection burden and structural brain imaging markers.

Persistent infections, whether viral, bacterial or parasitic, including Helicobacter pylori infection, have been implicated in non-communicable diseases, including dementia and other neurodegenerative diseases. In this cross-sectional study, data on 635 cognitively normal participants from the UK Biobank study (2006-21, age range: 40-70 years) were used to examine whether H. pylori seropositivity (e.g. presence of antibodies), serointensities of five H. pylori antigens and a measure of total persistent infection burden were associated with selected brain volumetric structural MRI (total, white, grey matter, frontal grey matter (left/right), white matter hyperintensity as percent intracranial volume and bi-lateral sub-cortical volumes) and diffusion-weighted MRI measures (global and tract-specific bi-lateral fractional anisotropy and mean diffusivity), after an average 9-10 years of lag time. Persistent infection burden was calculated as a cumulative score of seropositivity for over 20 different pathogens. Multivariable-adjusted linear regression analyses were conducted, whereby selected potential confounders (all measures) and intracranial volume (sub-cortical volumes) were adjusted, with stratification by Alzheimer's disease polygenic risk score tertile when exposures were H. pylori antigen serointensities. Type I error was adjusted to 0.007. We report little evidence of an association between H. pylori seropositivity and persistent infection burden with various volumetric outcomes (P > 0.007, from multivariable regression models), unlike previously reported in past research. However, H. pylori antigen serointensities, particularly immunoglobulin G against the vacuolating cytotoxin A, GroEL and outer membrane protein antigens, were associated with poorer tract-specific white matter integrity (P < 0.007), with outer membrane protein serointensity linked to worse outcomes in cognition-related tracts such as the external capsule, the anterior limb of the internal capsule and the cingulum, specifically at low Alzheimer's disease polygenic risk. Vacuolating cytotoxin A serointensity was associated with greater white matter hyperintensity volume among individuals with mid-level Alzheimer's disease polygenic risk, while among individuals with the highest Alzheimer's disease polygenic risk, the urease serointensity was consistently associated with reduced bi-lateral caudate volumes and the vacuolating cytotoxin A serointensity was linked to reduced right putamen volume (P < 0.007). Outer membrane protein and urease were associated with larger sub-cortical volumes (e.g. left putamen and right nucleus accumbens) at middle Alzheimer's disease polygenic risk levels (P < 0.007). Our results shed light on the relationship between H. pylori seropositivity, H. pylori antigen levels and persistent infection burden with brain volumetric structural measures. These data are important given the links between infectious agents and neurodegenerative diseases, including Alzheimer's disease, and can be used for the development of drugs and preventive interventions that would reduce the burden of those diseases.

Plasma neurofilament light and brain volumetric outcomes among middle-aged urban adults.

Elevated plasma neurofilament light chain (NfL) is associated with dementia though underlying mechanisms remain unknown. We examined cross-sectional relationships of time-dependent plasma NfL with selected brain structural magnetic resonance imaging (sMRI) prognostic markers of dementia. The sample was drawn from the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study, selecting participants with complete v1 (2004-2009) and v2 (2009-2013) plasma NfL exposure and ancillary sMRI data at vscan (2011-2015, n = 179, mean v1 to vscan time: 5.4 years). Multivariable-adjusted linear regression models were conducted, overall, by sex, and race, correcting for multiple testing with q-values. NfL(v1) was associated with larger WMLV (both Loge transformed), after 5-6 years' follow-up, overall (ß = +2.131 ± 0.660, b = +0.29, p = 0.001, and q = 0.0029) and among females. NfLv2 was linked to a 125 mm3 lower left hippocampal volume (p = 0.004 and q = 0.015) in reduced models, mainly among males, as was observed for annualized longitudinal change in NfL (δNfLbayes). Among African American adults, NfLv1 was inversely related to total, gray and white matter volumes. Plasma NfL may reflect future brain pathologies in middle-aged adults.

Absent Relations of Religious Coping to Telomere Length in African American and White Women and Men.

OBJECTIVES: This study investigated whether race and sex moderated the relations of religious coping to telomere length (TL), a biomarker of cellular aging implicated in race-related health disparities. METHODS: Participant data were drawn from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study, which included 252 socioeconomically diverse African American and White men and women aged (30-64 years old). Cross-sectional multivariable regression analyses examined interactive associations of religious coping, race, and sex to TL, adjusting for other sociodemographic characteristics. RESULTS: Religious coping was unrelated to TL in this sample (p's > .05). There were no notable race or sex differences. Post hoc exploratory analyses similarly found that neither secular social support coping use nor substance use coping was associated with TL. CONCLUSION: There was no evidence to support that religious coping use provided protective effects to TL in this sample of African American and White women and men. Nevertheless, future studies should use more comprehensive assessments of religious coping and intersectional identities to provide an in-depth examination of religiosity/spirituality as a potential culturally salient protective factor in cellular aging among African Americans in the context of specific chronic stressors such as discrimination.

Plasma neurofilament light as blood marker for poor brain white matter integrity among middle-aged urban adults.

Plasma neurofilament light chain (NfL)'s link to dementia may be mediated through white matter integrity (WMI). In this study, we examined plasma NfL's relationships with diffusion tensor magnetic resonance imaging markers: global and cortical white matter fractional anisotropy (FA) and trace (TR). Plasma NfL measurements at 2 times (v1: 2004-2009 and v2: 2009-2013) and ancillary dMRI (vscan: 2011-2015) were considered (n = 163, mean time v1 to vscan = 5.4 years and v2 to vscan: 1.1 years). Multivariable-adjusted regression models, correcting for multiple-testing revealed that, overall, higher NfLv1 was associated with greater global TR (ß ± SE: +0.0000560 ± 0.0000186, b = 0.27, p = 0.003, q = 0.012), left frontal WM TR (ß ± SE: + 0.0000706 ± 0.0000201, b ± 0.30, p = 0.001, q = 0.0093) and right frontal WM TR (ß ± SE: + 0.0000767 ± 0.000021, b ± 0.31, p < 0.001, q = 0.0093). These associations were mainly among males and White adults. Among African American adults only, NfLv2 was associated with greater left temporal lobe TR. "Tracking high" in NfL was associated with reduced left frontal FA (Model 2, body mass index-adjusted: ß ± SE:-0.01084 ± 0.00408, p = 0.009). Plasma NfL is a promising biomarker predicting future brain white matter integrity (WMI) in middle-aged adults.

Five dominant dimensions of brain aging are identified via deep learning: associations with clinical, lifestyle, and genetic measures.

Brain aging is a complex process influenced by various lifestyle, environmental, and genetic factors, as well as by age-related and often co-existing pathologies. MRI and, more recently, AI methods have been instrumental in understanding the neuroanatomical changes that occur during aging in large and diverse populations. However, the multiplicity and mutual overlap of both pathologic processes and affected brain regions make it difficult to precisely characterize the underlying neurodegenerative profile of an individual from an MRI scan. Herein, we leverage a state-of-the art deep representation learning method, Surreal-GAN, and present both methodological advances and extensive experimental results that allow us to elucidate the heterogeneity of brain aging in a large and diverse cohort of 49,482 individuals from 11 studies. Five dominant patterns of neurodegeneration were identified and quantified for each individual by their respective (herein referred to as) R-indices. Significant associations between R-indices and distinct biomedical, lifestyle, and genetic factors provide insights into the etiology of observed variances. Furthermore, baseline R-indices showed predictive value for disease progression and mortality. These five R-indices contribute to MRI-based precision diagnostics, prognostication, and may inform stratification into clinical trials.

White matter integrity as a mediator between socioeconomic status and executive function.

Introduction: Lower socioeconomic status (SES) is associated with poorer executive function, but the neural mechanisms of this association remain unclear. As healthy brain communication is essential to our cognitive abilities, white matter integrity may be key to understanding socioeconomic disparities. Methods: Participants were 201 African American and White adults (ages 33-72) from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) SCAN study. Diffusion tensor imaging was used to estimate regional fractional anisotropy as a measure of white matter integrity. Adjusting for age, analyses examined if integrity of the anterior limb of the internal capsule (ALIC), external capsule (EC), superior longitudinal fasciculus (SLF), and cingulum mediated SES-executive function relations. Results: Lower SES was related to poorer cognitive performance and white matter integrity. Lower Trails B performance was related to poorer integrity of the ALIC, EC, and SLF, and lower Stroop performance was associated with poorer integrity of the ALIC and EC. ALIC mediated the SES-Trails B relation, and EC mediated the SES-Trails B and SES-Stroop relations. Sensitivity analyses revealed that (1) adjustment for race rendered the EC mediations non-significant, (2) when using poverty status and continuous education as predictors, results were largely the same, (3) at least some of the study's findings may generalize to processing speed, (4) mediations are not age-dependent in our sample, and (5) more research is needed to understand the role of cardiovascular risk factors in these models. Discussion: Findings demonstrate that poorer white matter integrity helps explain SES disparities in executive function and highlight the need for further clarification of the biopsychosocial mechanisms of the SES-cognition association.

Synergistic Associations of Depressive Symptoms and Executive Functions With Longitudinal Trajectories of Diabetes Biomarkers Among Urban-Dwelling Adults Without Diabetes.

OBJECTIVE: Depressive symptoms and executive functions (EFs) have recently emerged as novel risk factors for type 2 diabetes, but it is unknown if these factors interact to influence diabetes pathophysiology across the life span. We examined the synergistic associations of depressive symptoms and EFs with longitudinal trajectories of diabetes diagnostic criteria among middle-aged and older adults without diabetes. METHODS: Participants were 1257 African American and White, urban-dwelling adults from the Healthy Aging in Neighborhoods of Diversity across the Life Span study who were assessed up to three times over a 13-year period (2004-2017). At baseline, participants completed the Center for Epidemiological Studies-Depression scale and measures of EFs-Trail Making Test Part B, verbal fluency, and Digit Span Backward-for a composite EFs score, and provided blood samples at each follow-up for glycated hemoglobin and fasting serum glucose. RESULTS: A total of 155 and 220 individuals developed diabetes or prediabetes at wave 3 and wave 4, respectively. Linear mixed-effects regression models adjusting for sociodemographic factors, diabetes risk factors, and antidepressant medications revealed significant three-way interactions of Center for Epidemiological Studies-Depression, EFs, and age on change in glycated hemoglobin (b = -0.0001, p = .005) and in fasting serum glucose (b = -0.0004, p < .001), such that among individuals with lower but not higher EFs, elevated depressive symptoms were associated with steeper age-related increases in diabetes biomarkers over time. CONCLUSIONS: Depressive symptoms and lower EFs may interactively accelerate trajectories of key diagnostic criteria, thereby increasing the risk for earlier diabetes incidence. Identifying individuals in this high-risk group may be an important clinical priority for earlier intervention, which has the promise of preventing or delaying this debilitating disease.

Microvascular dysfunction and neurovascular uncoupling are exacerbated in peripheral artery disease, increasing the risk of cognitive decline in older adults.

Peripheral artery disease (PAD) is a vascular pathology with high prevalence among the aging population. PAD is associated with decreased cognitive performance, but the underlying mechanisms remain obscure. Normal brain function critically depends on an adequate adjustment of cerebral blood supply to match the needs of active brain regions via neurovascular coupling (NVC). NVC responses depend on healthy microvascular endothelial function. PAD is associated with significant endothelial dysfunction in peripheral arteries, but its effect on NVC responses has not been investigated. This study was designed to test the hypothesis that NVC and peripheral microvascular endothelial function are impaired in PAD. We enrolled 11 symptomatic patients with PAD and 11 age- and sex-matched controls. Participants were evaluated for cognitive performance using the Cambridge Neuropsychological Test Automated Battery and functional near-infrared spectroscopy to assess NVC responses during the cognitive n-back task. Peripheral microvascular endothelial function was evaluated using laser speckle contrast imaging. We found that cognitive performance was compromised in patients with PAD, evidenced by reduced visual memory, short-term memory, and sustained attention. We found that NVC responses and peripheral microvascular endothelial function were significantly impaired in patients with PAD. A positive correlation was observed between microvascular endothelial function, NVC responses, and cognitive performance in the study participants. Our findings support the concept that microvascular endothelial dysfunction and neurovascular uncoupling contribute to the genesis of cognitive impairment in older PAD patients with claudication. Longitudinal studies are warranted to test whether the targeted improvement of NVC responses can prevent or delay the onset of PAD-associated cognitive decline.NEW & NOTEWORTHY Peripheral artery disease (PAD) was associated with significantly decreased cognitive performance, impaired neurovascular coupling (NVC) responses in the prefrontal cortex (PFC), left and right dorsolateral prefrontal cortices (LDLPFC and RDLPFC), and impaired peripheral microvascular endothelial function. A positive correlation between microvascular endothelial function, NVC responses, and cognitive performance may suggest that PAD-related cognitive decrement is mechanistically linked, at least in part, to generalized microvascular endothelial dysfunction and subsequent impairment of NVC responses.

Cognitive decrement in older adults with symptomatic peripheral artery disease.

Peripheral artery disease (PAD) is highly prevalent, affecting up to 20% of people over 70 years of age. To test the hypothesis that PAD promotes the pathogenesis of vascular cognitive impairment (VCI), we compared cognitive function in older adults with symptomatic PAD and in participants without PAD who had a burden of comorbid conditions. Furthermore, we compared the cognitive function of these groups after adjusting for demographic and clinical characteristics, comorbid conditions, and cardiovascular risk factors. Participants with PAD (age: 69 ± 8 years; n = 58) and those without PAD (age: 62 ± 8 years; n = 30) were assessed on a battery of eight neuropsychological tests. The tests assessed attention and working memory, verbal memory, non-verbal memory, perceptuo-motor speed, and executive function. Participants were further characterized on demographic and clinical characteristics, comorbid conditions, cardiovascular risk factors, and ankle-brachial index. The PAD group had significantly lower neuropsychological scores than the non-PAD control group on all eight tests (P < .01). After adjusting for covariates, significantly worse scores in the PAD group persisted for verbal memory, measured by tests on logical memory-immediate recall (P = .022), and logical memory-delayed recall (P < .001), and for attention and working memory, measured by tests on digits forward (P < .001), and digits backward (P = .003). Participants with symptomatic PAD have substantially lower levels of performance on tests of attention, working memory, and verbal memory than participants without PAD independent of demographic characteristics and comorbid health burdens. These findings provide additional evidence in support of the concept that generalized accelerated vascular aging manifesting as symptomatic PAD in the peripheral circulation also affects the brain promoting the pathogenesis of VCI. These cognitive difficulties may also negatively impact symptomatic patient's ability to understand and adhere to behavioral and medical therapies, creating a vicious cycle. We speculate that more intensive follow-up may be needed to promote adherence to therapies and monitor cognitive decline that may affect care.

Examining the influence of mental stress on balance perturbation responses in older adults.

BACKGROUND: Reach-to-grasp responses following balance perturbations are important to fall prevention but are often ineffective in older adults. The ability to shift attention from an ongoing cognitive task to balance related processes has been shown to influence reach-to-grasp effectiveness in older adults. However, the added influence of stress and anxiety - known to negatively affect attention shifting ability - has not yet been explored in relation to recovery from balance perturbations. Given that fear and anxiety over falling is a key fall risk factor, an understanding of how such a negative mental state may affect postural reactions is important. This study aimed to investigate the effect of varied induced emotional states on reach-to-grasp balance responses in older adults. METHODS: Healthy older adults (mean age 70.5 ± 5.38 years) stood laterally between 2 handrails with contact sensors. A safety harness with an integrated loadcell was worn to prevent falls and measure the amount of harness assistance (expressed as percent body weight). With instructions to grasp one rail to restore balance, participants' balance was laterally disturbed using surface translations under three randomized conditions: no cognitive task, neutral (verb generation) task, and mental stress task with negative prompts (paced auditory serial addition). The primary outcome was frequency of protective grasps. Secondary outcomes included frequency of harness assistance during trials with grasp errors as well as wrist movement time, trajectory distance, and peak velocity. RESULTS: Perceived level of distress was highest for the mental stress task compared to no task (p < 0.001) and neutral task conditions (p = 0.008). The mental stress task resulted in the lowest percentage of protective grasps (p < 0.001) in response to balance perturbations. Closer examination of trials that resulted in grasp errors (i.e., collisions or overshoots), revealed increased harness assistance and reduced peak velocity of wrist movement (p < 0.001) under the mental stress condition compared to grasp errors that occurred under the no task or neutral task condition. DISCUSSION AND CONCLUSION: Distressing mental thoughts immediately prior to a balance perturbation lead to reduced effectiveness in reach-to-grasp balance responses compared to no or neutral cognitive tasks and should be considered as a possible fall risk factor.

Red cell distribution width, anemia and their associations with white matter integrity among middle-aged urban adults.

Anemia (blood hemoglobin [Hb] <13 g/dL among males; <12 g/dL among females) and elevated red cell distribution width (RDW) are potential risk factors for reduced brain white matter integrity (WMI), reflected by lower fractional anisotropy or increased mean diffusivity. Cross-sectional data with exposure-outcome lag time was used, whereby hematological exposures (RDW and Hb) and covariates were compiled from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study with available visit 1 (v1; 2004-2009) and/or v2 (2009-2013) data; while diffusion tensor magnetic resonance imaging (dMRI) outcome data were collected at HANDLS SCAN visit (vscan: 2011-2015, n = 214, mean follow-up from v1 ±SD: 5.6 ± 1.8 year). Multivariable-adjusted linear regression analyses were conducted, overall, stratifying by sex, and further restricting to the nonanemic for RDW exposures in part of the analyses. Among males, RDW(v1) was linked with lower global mean fractional anisotropy (standardized effect size b = -0.30, p= 0.003, q < 0.05; basic model), an association only slightly attenuated with further covariate adjustment. Anemia was not a risk factor for poor WMI, independently of RDW. Ultimately, pending further longitudinal evidence, initial RDW appears to be associated with poorer WMI among males.

Race and other sociodemographic categories are differentially linked to multiple dimensions of interpersonal-level discrimination: Implications for intersectional, health research.

OBJECTIVES: To examine whether intersections of race with other key sociodemographic categories contribute to variations in multiple dimensions of race- and non-race-related, interpersonal-level discrimination and burden in urban-dwelling African Americans and Whites. METHODS: Data from 2,958 participants aged 30-64 in the population-based Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study were used to estimate up to four-way interactions of race, age, gender, and poverty status with reports of racial and everyday discrimination, discrimination across multiple social statuses, and related lifetime discrimination burden in multiple regression models. RESULTS: We observed that: 1) African Americans experienced all forms of discrimination more frequently than Whites, but this finding was qualified by interactions of race with age, gender, and/or poverty status; 2) older African Americans, particularly African American men, and African American men living in poverty reported the greatest lifetime discrimination burden; 3) older African Americans reported greater racial discrimination and greater frequency of multiple social status-based discrimination than younger African Americans; 4) African American men reported greater racial and everyday discrimination and a greater frequency of social status discrimination than African American women; and, 5) White women reported greater frequency of discrimination than White men. All p's < .05. CONCLUSIONS: Within African Americans, older, male individuals with lower SES experienced greater racial, lifetime, and multiple social status-based discrimination, but this pattern was not observed in Whites. Among Whites, women reported greater frequency of discrimination across multiple social statuses and other factors (i.e., gender, income, appearance, and health status) than men. Efforts to reduce discrimination-related health disparities should concurrently assess dimensions of interpersonal-level discrimination across multiple sociodemographic categories, while simultaneously considering the broader socioecological context shaping these factors.

Corrigendum: Vitamin D, Folate, and Cobalamin Serum Concentrations Are Related to Brain Volume and White Matter Integrity in Urban Adults.

[This corrects the article DOI: 10.3389/fnagi.2020.00140.].

Red Cell Distribution Width, Anemia, and Brain Volumetric Outcomes Among Middle-Aged Adults.

BACKGROUND: Anemia and red cell distribution width (RDW) have been linked to poor cognitive performance, pending studies of underlying mechanisms. OBJECTIVE: We examined cross-sectional relationships of initial RDW status (v1), RDW change (δ), and anemia with brain structural magnetic resonance imaging (sMRI) markers, including global and cortical brain and hippocampal and white matter lesion (WML) volumes, 5-6 years later. METHODS: Data were used from three prospective visits within the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study with complete v1 (2004-2009) and v2 (2009-2013) exposures and ancillary sMRI data at vscan (2011-2015, n = 213, mean v1 to vscan time: 5.7 years). Multivariable-adjusted linear regression models were conducted, overall, by sex, by race, and within non-anemics, correcting for multiple testing with q-values. RESULTS: In minimally adjusted models (socio-demographics and follow-up time), anemiav1 and RDWv1 were consistently associated with smaller bilateral hippocampal volumes overall, and among females (q < 0.05), without significant sex differences. RDWv1 was related to smaller select regional cortical brain gray and white matter volumes in hematological measure-adjusted models; anemiav1 was associated with larger WML volumes only among whites. CONCLUSION: In summary, baseline anemia and RDW were consistently associated with smaller bilateral hippocampal volumes, particularly among females, while anemia was linked to larger WML volume among Whites. In hematological measure-adjusted models, baseline RDW was linked to smaller regional gray and white matter volumes. Pending studies with sMRI repeats, randomized controlled trials are needed, demonstrating associations of anemia and elevated RDW with reduced brain volumes and cognitive dysfunction.

Vitamin D, Folate, and Cobalamin Serum Concentrations Are Related to Brain Volume and White Matter Integrity in Urban Adults.

Background and objectives: Lower vitamin status has been linked to cognitive deficits, pending mechanistic elucidation. Serum 25-hydroxyvitamin D [25(OH)D], folate and cobalamin were explored against brain volumes and white matter integrity (WMI). Methods: Three prospective waves from Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study were used [Baltimore, City, MD, 2004-2015, N = 183-240 urban adults (Agev1: 30-64 years)]. Serum vitamin 25-hydroxyvitamin D [25(OH)D], folate and cobalamin concentrations were measured at visits 1 (v1: 2004-2009) and 2 (v2: 2009-2013), while structural and diffusion Magnetic Resonance Imaging (sMRI/dMRI) outcomes were measured at vscan: 2011-2015. Top 10 ranked adjusted associations were corrected for multiple testing using familywise Bonferroni (FWER <0.05) and false discovery rates (FDR, q-value < 0.10). Results: We found statistically significant (FWER < 0.05; ß±SE) direct associations of 25(OH)D(v1) with WM volumes [overall: +910 ± 336/males: +2,054 ± 599], occipital WM; [overall: +140 ± 40, males: +261 ± 67 and Agev1 > 50 years: +205 ± 54]; parietal WM; [overall: +251 ± 77, males: +486 ± 129 and Agev1 > 50 years: +393 ± 108] and left occipital pole volume [overall: +15.70 ± 3.83 and above poverty: 19.0 ± 4.3], findings replicated for 25(OH)D (v2-v1) annualized exposure, which was also linked with greater WMI (fractional anisotropy, FA) in the anterior limb of the internal capsule (ALIC); FWER < 0.05 [Overall: +0.0020 ± 0.0004; Whites: +0.0024 ± 0.0004] and in the cingulum (hippocampus) [Overall: +0.0016 ± 0.0004]. Only trends were detected for cobalamin exposures (q < 0.10), while serum folate (v1) was associated with lower mean diffusivity (MD) in ALIC, reflecting greater WMI, overall. Conclusions: Among urban adults, serum 25(OH)D status and increase were consistently linked to larger occipital and parietal WM volumes and greater region-specific WMI. Pending longitudinal replication of our findings, randomized controlled trials of vitamin D supplementation should be conducted against brain marker outcomes.

Sociodemographic patterns of pain in an urban community sample: an examination of intersectional effects of sex, race, age, and poverty status.

Pain disparities based on race, sex, age, and socioeconomic status have been well documented. This study aimed to examine interactions among these sociodemographic factors on self-reported bodily pain in an urban community sample to assess whether membership in multiple at-risk groups confers greater risk for pain independent of depressive symptomatology. Participants (N = 1173) were enrolled in the epidemiological Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study, and reported experiences of pain in various body sites. Logistic regression was used to examine independent and interactive relations of sociodemographic factors on the likelihood of reporting pain in one or more sites. A significant three-way interaction was found for race, sex, and poverty status (odds ratio [OR] = 6.04, 95% confidence interval [CI] [1.26-28.97], P = 0.025). Specifically, among Whites living in poverty, women were more likely to report pain than men (P = 0.043), suggesting a double disadvantage of being both female and living in poverty. Among those above the poverty line, African American (AA) men were less likely to report pain than White men (P = 0.024) and AA women (P = 0.019), potentially due to greater stoicism or coping skills and sources of resilience. Consistent with prior research, significant main effects revealed that older age (OR = 2.16, 95% CI [1.28-3.64], P = 0.004) and higher depressive symptoms (OR = 1.03, 95% CI [1.02-1.04], P < 0.001) were associated independently with increased likelihood of reporting pain. This study demonstrates that in an urban population, intersecting sociodemographic factors create unique social identities that impact pain, and emphasizes the need for identification of relevant mediational pathways.

Relations of Executive Function and Physical Performance in Middle Adulthood: A Prospective Investigation in African American and White Adults.

OBJECTIVES: Previous studies in older adults found robust associations between executive functions (EF) and physical performance, as well as sociodemographic variation in physical performance decline. To examine these associations earlier in the adult lifespan, we investigated relations of EF, race, and sex with age-related physical performance decline during middle adulthood. METHOD: Participants were 2,084 urban-dwelling adults (57.2% female; 57.8% African American; 37.3% living in poverty; mean baseline age = 48.1) from the Healthy Aging in Neighborhoods of Diversity across the Life Span study. Mixed-effects regression was used to examine interactive relations among EF, race, sex, and age (indexing time) with change in dominant and nondominant handgrip strength and lower extremity strength over approximately 5 years. All analyses adjusted for poverty status, and subsequently adjusted for education, body mass index, hypertension, and diabetes. RESULTS: There were no significant prospective associations between EF and decline in physical performance measures. Significant cross-sectional associations revealed that lower EF was associated with worse performance on all physical performance measures averaged across both time points (p < .05). A significant two-way interaction of Sex × Age (p = .019) revealed that men experienced greater age-related decline in lower extremity strength than women. DISCUSSION: Findings did not reveal prospective associations between EF and physical performance decline in middle adulthood. However, they identified robust cross-sectional associations between EF and physical performance, and unexpectedly greater decline in lower extremity strength in men than women. Ultimately, these findings may inform prevention and intervention strategies targeting groups at risk for poorer physical function status and decline.

Reliability and validity of the Conners' Continuous Performance Test.

The Conners' Continuous Performance Test-Second Edition (CCPT-2) is a widely used measure of attention and impulsivity, however, only a minimal amount is known about its reliability. To clarify the psychometric properties of the CCPT-2, we assessed its performance stability and related it to criterion measures. A total of 91 undergraduate students completed the CCPT-2, the State-Trait Personality Inventory (STPI), and reported on sleep during two sessions approximately one week apart. They completed the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) at session one and the Stroop Color and Word Test at session two. Findings indicated that the CCPT-2 had strong internal consistency, adequate test-retest reliability for commission errors and response time, poor test-retest reliability for omission errors, and practice effects for omission and commission errors. The CCPT-2 was largely unrelated to the BRIEF-A, Stroop Color and Word Test, and the STPI. More sleep was related to a quicker response time and more commission errors on the CCPT-2, and the BRIEF-A's Behavior Regulation Index was positively related to commission errors. Relative to the omission error component of the CCPT-2, commission errors and response time may be useful and stable measures of sustained attention and impulsivity.