Publications by authors named "Michele K Evans"

240 Publications

Mitochondria as extracellular vesicle cargo in aging.

Aging (Albany NY) 2021 07 20;undefined(undefined). Epub 2021 Jul 20.

Laboratory of Epidemiology and Population Science, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.

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http://dx.doi.org/10.18632/aging.203358DOI Listing
July 2021

Race, APOE genotypes, and cognitive decline among middle-aged urban adults.

Alzheimers Res Ther 2021 Jun 30;13(1):120. Epub 2021 Jun 30.

Laboratory of Epidemiology and Population Sciences, NIH Biomedical Research Center, National Institute on Aging, IRP, 251 Bayview Blvd., Suite 100, Room #: 04B118, Baltimore, MD, 21224, USA.

Background: Associations of Apolipoprotein (APOE) ε2 or ε4 (APOE2 or APOE4) dosages with cognitive change may differ across racial groups.

Methods: Longitudinal data on 1770 middle-aged White and African American adults was compiled from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS 2004-2013) study. APOE2 and APOE4 dosages were the two main exposures, while v and annual rate of change in cognitive performance (between v and v) on 11 test scores were the main outcomes of interest (v1: 2004-2009 and v2: 2009-2013). Mixed-effects linear regression models were conducted adjusting for socio-demographic, lifestyle, and health-related potential confounders. Race (African American vs. White) and sex within racial groups were main effect modifiers.

Results: Upon adjustment for multiple testing and potential confounders, APOE4 allelic dosage was associated with faster decline on a test of verbal memory among Whites only (CVLT-List A: γ = - 0.363 ± 0.137, p = 0.008), but not among African Americans. In contrast, among African American women, APOE4 dosage was linked to slower decline on a test of attention (BTA: γ = + 0.106 ± 0.035, p = 0.002), while no association was detected among African American men. APOE2 and APOE4 dosages showed inconsistent results in other domains of cognition overall and across racial groups that did not survive correction for multiple testing.

Conclusions: In conclusion, APOE4 dosage was associated with faster decline on a test of verbal memory among Whites only, while exhibiting a potential protective effect among African American women in the domain of attention. Further longitudinal studies are needed to replicate our race and sex-specific findings.
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http://dx.doi.org/10.1186/s13195-021-00855-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247163PMC
June 2021

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

Neurobiol Aging 2021 May 21;105:229-240. Epub 2021 May 21.

Department of Psychology, University of Maryland Baltimore County, Catonsville, MD, USA; Geriatric Research Education and Clinical Center, Baltimore VA Medical Center, Baltimore, MD, USA; Division of Gerontology & Geriatric Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.

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 (v; 2004-2009) and/or v (2009-2013) data; while diffusion tensor magnetic resonance imaging (dMRI) outcome data were collected at HANDLS SCAN visit (v: 2011-2015, n = 214, mean follow-up from v ±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 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.
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http://dx.doi.org/10.1016/j.neurobiolaging.2021.05.004DOI Listing
May 2021

Affirming NIH's commitment to addressing structural racism in the biomedical research enterprise.

Cell 2021 Jun;184(12):3075-3079

Immediate Office of the Director (IMOD)/OD, NIH, Bethesda, MD 20892, USA.

NIH has acknowledged and committed to ending structural racism. The framework for NIH's approach, summarized here, includes understanding barriers; developing robust health disparities/equity research; improving its internal culture; being transparent and accountable; and changing the extramural ecosystem so that diversity, equity, and inclusion are reflected in funded research and the biomedical workforce.
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http://dx.doi.org/10.1016/j.cell.2021.05.014DOI Listing
June 2021

Caregiver Status and Diet Quality in Community-Dwelling Adults.

Nutrients 2021 May 26;13(6). Epub 2021 May 26.

Department of Behavioral Health and Nutrition, University of Delaware, Newark, DE 19716, USA.

Objective: We investigated cross-sectional and longitudinal associations of diet quality with middle-aged caregiver status.

Methods: Caregiving in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (57.7% women, 62% African American (AA)) was measured at waves 3 (2009-2013) and 4 (2013-2017) (mean follow-up time 4.1 years). Diet quality was assessed by the Healthy Eating Index 2010 (HEI-2010) derived from two separate 24 h diet recalls. Multivariable ordinary least square regression was performed for cross-sectional analyses of the association of wave 4 caregiving with wave 4 HEI-2010. Wave 3 caregiving was examined both cross-sectionally and with annual rate of change in HEI using mixed-effects linear regression Models. Multivariable models were adjusted for age, sex, and poverty status.

Results: Cross-sectional analyses at wave 4 demonstrate an inverse association of frequent caregiving ("Daily or Weekly" vs. "Never") for grandchildren with HEI-2010 total score (i.e., lower diet quality) among Whites (β = -2.83 ± 1.19, = 0.03, Model 2) and AAs (β = -1.84 ± 0.79, = 0.02,). The "cross-sectional" analysis pertaining to grandchildren caregiving frequency suggested that frequent caregiving (i.e., "Daily or Weekly" vs. "Never" (β = -2.90 ± 1.17, = 0.04)) only among Whites was inversely related to HEI-2010 total score. Total HEI-2010 score was also related to caring (Model 1), for the elderly over "5 years vs. Never" among Whites (-7.31 ± 3.54, = 0.04, Model 2). Longitudinally, we found slight potential improvement in diet quality over time ("Daily or Weekly" vs. Never by TIME interaction: +0.88 ± 0.38, = 0.02) with frequent caregiving among Whites, but not so among AAs.

Conclusions: Frequent caring for grandchildren had an inverse relationship with the diet quality of White and AA urban middle-aged caregivers, while caring for elderly was inversely linked to diet quality among Whites only. Longitudinal studies should address the paucity of research on caregivers' nutritional quality.
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http://dx.doi.org/10.3390/nu13061803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227086PMC
May 2021

Healthy Behaviors Associated with Changes in Mental and Physical Strength in Urban African American and White Adults.

Nutrients 2021 May 27;13(6). Epub 2021 May 27.

Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, 251 Bayview Blvd. Suite 100, Baltimore, MD 21224, USA.

Over time, adherence to healthy behaviors may improve physical and mental strength which is essential for successful aging. A plausible mechanism is the reduction of inflammation. Research on the association of risky health behaviors on change in strength with age is limited. This study examined changes in the inflammatory potential of the diet, smoking, illicit drug use with changes in strength in a racially and socioeconomically diverse adult sample from the Healthy Aging in Neighborhoods of Diversity Across the Life Span study. The dietary inflammatory index (DII) was calculated from 35 food components derived from multiple 24-h dietary recalls. Strength was evaluated by handgrip strength (HGS), SF-12 PCS and SF-12 MCS (physical and mental component scores). Repeated measures analyses were used to examine associations. At baseline, mean age was 48.4 ± 0.25 years, 56% of the sample were women, and 58% African American. Significant 4-way interactions were found between age, race, socioeconomic status, and DII for women, on change in HGS ( < 0.05) and in SF-12 PCS ( < 0.05) and for men, in change in SF-12 PCS ( < 0.05). Improvements in SF-12 MCS were associated with all three health behaviors as main effects. This study provided evidence that changes towards improving healthy behaviors, diet with anti-inflammatory potential, not smoking cigarettes and not using illicit drugs, were associated with improved strength. Health professionals, especially registered dietitians and health coaches, should create lifestyle interventions to reduce inflammation targeting change in more than one risky health behavior.
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http://dx.doi.org/10.3390/nu13061824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226642PMC
May 2021

The trans-ancestral genomic architecture of glycemic traits.

Nat Genet 2021 06 31;53(6):840-860. Epub 2021 May 31.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
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http://dx.doi.org/10.1038/s41588-021-00852-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958PMC
June 2021

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

PLoS One 2021 19;16(5):e0251174. Epub 2021 May 19.

Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251174PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133471PMC
May 2021

Multi-ancestry genome-wide gene-sleep interactions identify novel loci for blood pressure.

Mol Psychiatry 2021 Apr 15. Epub 2021 Apr 15.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups in two stages using 2 degree of freedom (df) joint test followed by 1df test of interaction effects. Primary multi-ancestry analysis in 62,969 individuals in stage 1 identified three novel gene by sleep interactions that were replicated in an additional 59,296 individuals in stage 2 (stage 1 + 2 P < 5 × 10), including rs7955964 (FIGNL2/ANKRD33) that increases BP among long sleepers, and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) that increase BP among short sleepers (P < 5 × 10). Secondary ancestry-specific analysis identified another novel gene by long sleep interaction at rs111887471 (TRPC3/KIAA1109) in individuals of African ancestry (P = 2 × 10). Combined stage 1 and 2 analyses additionally identified significant gene by long sleep interactions at 10 loci including MKLN1 and RGL3/ELAVL3 previously associated with BP, and significant gene by short sleep interactions at 10 loci including C2orf43 previously associated with BP (P < 10). 2df test also identified novel loci for BP after modeling sleep that has known functions in sleep-wake regulation, nervous and cardiometabolic systems. This study indicates that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation.
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http://dx.doi.org/10.1038/s41380-021-01087-0DOI Listing
April 2021

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

J Alzheimers Dis 2021 ;81(2):711-727

Department of Psychology, University of Maryland, Baltimore County, Catonsville, MD, USA.

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.
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http://dx.doi.org/10.3233/JAD-201386DOI Listing
January 2021

Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry.

Am J Hum Genet 2021 04 12;108(4):564-582. Epub 2021 Mar 12.

The Charles R. Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.
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http://dx.doi.org/10.1016/j.ajhg.2021.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059339PMC
April 2021

Vitamin D status and its longitudinal association with changes in patterns of sleep among middle-aged urban adults.

J Affect Disord 2021 03 29;282:858-868. Epub 2020 Dec 29.

Laboratory of Epidemiology and Population Sciences, NIA/NIH/IRP, Baltimore, MD.

Objective: We examined relationships of vitamin D status with over time changes in patterns of sleep in a longitudinal study of Whites and African-American urban middle-aged adults, while further testing effect modification by age group, sex and race and the potential roles of dietary and supplemental vitamin D.

Methods: Data on 1,760 middle-aged participants in the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS study: Age range at v: 33-71y, mean±SD:53.0±8.8, % women: 58.4%, % African-American:60.3%) were used, with complete baseline 25-hydroxyvitamin D [25(OH)D] serum concentration data, initial selected covariates and mediators, and initial and/or follow-up data on five sub-scales (sleep duration, daytime dysfunction, sleep disturbance, sleep latency and sleep quality) of the Pittsburgh Sleep Quality Index. Mean±SD time between initial and follow-up visits: 4.1±1.5 years. Time-interval multiple mixed-effects linear regression models were used.

Results: Upon multiple testing adjustment, among Whites, initial 25(OH)D was associated with better sleep duration [25(OH)D × TIME γ±SE: -0.027±0.011, P=0.017] and sleep quality [25(OH)D × TIME γ±SE: -0.026±0.010, P=0.008] over time, with heterogeneity by race found for both relationships (P<0.05 for 25(OH)D × TIME × Race in the un-stratified model). These relationships remained unaltered after further adjustment for dietary and supplemental vitamin D, indicating that this association may be largely explained by sunlight exposure.

Limitations: Limitations included small sample size, selection bias, residual confounding and lack of objective sleep measures. Conclusions Vitamin D status, possibly through mechanisms involving sunlight exposure, was linked to a potential improvement in sleep duration and quality among White urban adults.
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http://dx.doi.org/10.1016/j.jad.2020.12.145DOI Listing
March 2021

Prevalence of Guideline-Directed Medical Therapy for Cardiovascular Disease Among Baltimore City Adults in the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) Study.

J Racial Ethn Health Disparities 2021 Feb 16. Epub 2021 Feb 16.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Objective: Guideline-directed medical therapy (GDMT) has been shown to improve outcomes for people with cardiovascular disease (CVD). Our goal was to assess racial and socioeconomic differences in GDMT use among a diverse population.

Methods: We examined the cross-sectional association of race and poverty status with GDMT among 441 participants with CVD in a longitudinal cohort of urban-dwelling Black and White adults in Baltimore City, Maryland, using multivariable logistic regression. CVD status and GDMT were self-reported.

Results: The participants' mean age was 60.5 (SD 8.5) years, with 61.7% women, 64.4% Black, and 46.9% living below poverty. Of the 126 participants with coronary artery disease (CAD), 37.3%, 54.8%, and 62.7% were on aspirin, antiplatelets, and statins, respectively. Black participants with CAD were less likely to be on aspirin, OR 0.29 (95% CI 0.13-0.67), and on combination GDMT (antiplatelet and statin), OR 0.36 (0.16-0.78) compared to Whites. There were no differences by poverty status in GDMT for CAD. Fully, 222 participants reported atrial fibrillation (AF), but only 10.5% were on anticoagulation with no significant difference by race or poverty status. The use of GDMT for heart failure and stroke was also low overall, but there were no differences by race or poverty status.

Conclusions: Among an urban-dwelling population of adults, the use of secondary prevention of CVD was low, with lower aspirin and combination GDMT for Black participants with CAD. Efforts to improve GDMT use at the patient and provider levels may be needed to improve morbidity and mortality and reduce disparities in CVD.
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http://dx.doi.org/10.1007/s40615-021-00984-yDOI Listing
February 2021

Mitochondrial DNA in extracellular vesicles declines with age.

Aging Cell 2021 01 23;20(1):e13283. Epub 2020 Dec 23.

Laboratory of Epidemiology and Population Science, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.

The mitochondrial free radical theory of aging suggests that accumulating oxidative damage to mitochondria and mitochondrial DNA (mtDNA) plays a central role in aging. Circulating cell-free mtDNA (ccf-mtDNA) isolated from blood may be a biomarker of disease. Extracellular vesicles (EVs) are small (30-400 nm), lipid-bound vesicles capable of shuttling proteins, nucleic acids, and lipids as part of intercellular communication systems. Here, we report that a portion of ccf-mtDNA in plasma is encapsulated in EVs. To address whether EV mtDNA levels change with human age, we analyzed mtDNA in EVs from individuals aged 30-64 years cross-sectionally and longitudinally. EV mtDNA levels decreased with age. Furthermore, the maximal mitochondrial respiration of cultured cells was differentially affected by EVs from old and young donors. Our results suggest that plasma mtDNA is present in EVs, that the level of EV-derived mtDNA is associated with age, and that EVs affect mitochondrial energetics in an EV age-dependent manner.
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http://dx.doi.org/10.1111/acel.13283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811845PMC
January 2021

A Meta-Analysis of the Transferability of Bone Mineral Density Genetic Loci Associations From European to African Ancestry Populations.

J Bone Miner Res 2021 Mar 18;36(3):469-479. Epub 2020 Dec 18.

Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.

Genetic studies of bone mineral density (BMD) largely have been conducted in European populations. We therefore conducted a meta-analysis of six independent African ancestry cohorts to determine whether previously reported BMD loci identified in European populations were transferable to African ancestry populations. We included nearly 5000 individuals with both genetic data and assessments of BMD. Genotype imputation was conducted using the 1000G reference panel. We assessed single-nucleotide polymorphism (SNP) associations with femoral neck and lumbar spine BMD in each cohort separately, then combined results in fixed effects (or random effects if study heterogeneity was high, I index >60) inverse variance weighted meta-analyses. In secondary analyses, we conducted locus-based analyses of rare variants using SKAT-O. Mean age ranged from 12 to 68 years. One cohort included only men and another cohort included only women; the proportion of women in the other four cohorts ranged from 52% to 63%. Of 56 BMD loci tested, one locus, 6q25 (C6orf97, p = 8.87 × 10 ), was associated with lumbar spine BMD and two loci, 7q21 (SLC25A13, p = 2.84 × 10 ) and 7q31 (WNT16, p = 2.96 × 10 ), were associated with femoral neck BMD. Effects were in the same direction as previously reported in European ancestry studies and met a Bonferroni-adjusted p value threshold, the criteria for transferability to African ancestry populations. We also found associations that met locus-specific Bonferroni-adjusted p value thresholds in 11q13 (LRP5, p < 2.23 × 10 ), 11q14 (DCDC5, p < 5.35 × 10 ), and 17p13 (SMG6, p < 6.78 × 10 ) that were not tagged by European ancestry index SNPs. Rare single-nucleotide variants in AKAP11 (p = 2.32 × 10 ), MBL2 (p = 4.09 × 10 ), MEPE (p = 3.15 × 10 ), SLC25A13 (p = 3.03 × 10 ), STARD3NL (p = 3.35 × 10 ), and TNFRSF11A (p = 3.18 × 10 ) were also associated with BMD. The majority of known BMD loci were not transferable. Larger genetic studies of BMD in African ancestry populations will be needed to overcome limitations in statistical power and to identify both other loci that are transferable across populations and novel population-specific variants. © 2020 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4220DOI Listing
March 2021

Association of Antioxidant Vitamins A, C, E and Carotenoids with Cognitive Performance over Time: A Cohort Study of Middle-Aged Adults.

Nutrients 2020 Nov 20;12(11). Epub 2020 Nov 20.

Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, NIA/NIH/IRP, Baltimore, MD 21224, USA.

Carotenoids may strengthen the association of antioxidant vitamins A, C, and E with favorable cognitive outcomes over time, though a few prospective studies have examined this hypothesis. We evaluated the longitudinal data from 1251 participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (Age at visit 1 in 2004-2009 (v): 30-65 years). Vitamins A, C, and E dietary intakes and total and individual dietary carotenoids were computed using two 24-h recalls at v. Cognitive tests, covering global mental status and domains of memory/learning, attention, psychomotor speed, visuo-spatial, language/verbal, and executive function were conducted at v and/or v (2009-2013); mean ± SD follow-up: 4.66 ± 0.93 years. Mixed-effects linear regression models detected an interaction between vitamin E and total (and individual) carotenoids for three of 11 cognitive tests at v, with only one meeting the statistical significance upon multiple testing correction whereby vitamin E was linked with greater verbal memory performance in the uppermost total carotenoid tertile ( = +0.26 ± 0.08, = 0.002), a synergism largely driven by carotenoid lycopene. Vitamins A and C showed no consistent interactions with carotenoids. In conclusion, we provide partial evidence for synergism between vitamin E and carotenoids in relation to better baseline cognitive performance, pending further studies with time-dependent exposures and randomized trials directly examining this synergism.
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http://dx.doi.org/10.3390/nu12113558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699702PMC
November 2020

Cross-Sectional Examination of Musculoskeletal Pain and Physical Function in a Racially and Socioeconomically Diverse Sample of Adults.

J Gerontol A Biol Sci Med Sci 2021 01;76(2):368-377

Laboratory of Epidemiology & Population Sciences, National Institute on Aging, National Institute on Aging, Biomedical Research Center, Baltimore, Maryland.

Background: Musculoskeletal pain alters physiological function, which may be evidenced as early as middle age. Previous research has concluded that middle-aged adults are a high-risk group for musculoskeletal pain and report functional limitations similar to older adults. However, few studies have examined the relationships between musculoskeletal pain and physical function, using objective performance measures in a sample of racially and socioeconomically diverse adults. Thus, this study examined musculoskeletal pain in relation to physical function in middle-aged (30-64 years) White and Black adults and investigated whether the relationship varied by sociodemographic characteristics.

Methods: This cross-sectional examination incorporated data from the Healthy Aging in Neighborhoods of Diversity across the Life-Span Study. Participants (n = 875) completed measures of musculoskeletal pain and objective measures of physical performance (ie, lower and upper body strength, balance, and gait abnormalities). Physical performance measures were standardized to derive a global measure of physical function as the dependent variable.

Results: Approximately, 59% of participants identified at least 1 pain sites (n = 518). Multivariable regression analyses identified significant relationships between greater musculoskeletal pain and poorer physical function (β = -0.07, p = .031), in mid midlife (β = -0.04, p = .041; age 40-54) and late midlife (β = -0.05, p = .027; age 55-64).

Conclusions: This study observed that musculoskeletal pain was associated with poorer physical function within a diverse group of middle-aged adults. Future research should longitudinally explore whether chronic musculoskeletal pain identified at younger ages is associated with greater risk for functional limitation and dependence in later life.
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http://dx.doi.org/10.1093/gerona/glaa251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812433PMC
January 2021

The association between poverty and gene expression within peripheral blood mononuclear cells in a diverse Baltimore City cohort.

PLoS One 2020 24;15(9):e0239654. Epub 2020 Sep 24.

Department of Biology, Morgan State University, Baltimore, MD, United States of America.

Socioeconomic status (SES), living in poverty, and other social determinants of health contribute to health disparities in the United States. African American (AA) men living below poverty in Baltimore City have a higher incidence of mortality when compared to either white males or AA females living below poverty. Previous studies in our laboratory and elsewhere suggest that environmental conditions are associated with differential gene expression (DGE) patterns in peripheral blood mononuclear cells (PBMCs). DGE have also been associated with hypertension and cardiovascular disease (CVD) and correlate with race and sex. However, no studies have investigated how poverty status associates with DGE between male and female AAs and whites living in Baltimore City. We examined DGE in 52 AA and white participants of the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) cohort, who were living above or below 125% of the 2004 federal poverty line at time of sample collection. We performed a microarray to assess DGE patterns in PBMCs from these participants. AA males and females living in poverty had the most genes differentially-expressed compared with above poverty controls. Gene ontology (GO) analysis identified unique and overlapping pathways related to the endosome, single-stranded RNA binding, long-chain fatty-acyl-CoA biosynthesis, toll-like receptor signaling, and others within AA males and females living in poverty and compared with their above poverty controls. We performed RT-qPCR to validate top differentially-expressed genes in AA males. We found that KLF6, DUSP2, RBM34, and CD19 are expressed at significantly lower levels in AA males in poverty and KCTD12 is higher compared to above poverty controls. This study serves as an additional link to better understand the gene expression response in peripheral blood mononuclear cells in those living in poverty.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239654PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7514036PMC
November 2020

The Relationship of Diet Quality with Proportion of Daily Energy Contributed by Sandwiches Varies by Age over Adulthood in Racially and Socioeconomically Diverse Adults.

Nutrients 2020 Sep 13;12(9). Epub 2020 Sep 13.

Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, 251 Bayview Blvd. Suite 100, Baltimore, MD 21224-6825, USA.

Sandwiches are considered a staple in diets of United States adults. Previous research with Healthy Aging in Neighborhoods of Diversity across the Life Span study participants revealed that 16% consume a sandwich dietary pattern providing with 44% of their daily energy. Yet, little is known about the effect of sandwiches on diet quality over time. The study objectives were to determine the relationship of energy contributed by sandwiches to diet quality in this socioeconomically and racially diverse sample categorized by age (<50 years and ≥50 years at baseline) and to describe patterns of sandwich consumption over ~12 years. The analyses included a series of linear mixed-effects regression models, with age as the time variable centered at 50 years. In each model, the main outcome was Healthy Eating Index-2010 score with up to three scores, while the main predictor was % total energy from sandwiches (0, >0-20%, >20%) measured concurrently at each visit. Diet quality of older men with income <125% poverty improved over time for those consuming >0-20% and >20% energy from sandwiches compared to young women with incomes >125% poverty who were non-reporters of sandwiches (β ± SE: 10.93 ± 5.27, = 0.01; 13.11 ± 4.96, = 0.01, respectively). The three most common sandwich types reported, in descending order, were cold cuts, beef, and poultry.
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http://dx.doi.org/10.3390/nu12092807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551748PMC
September 2020

Health Equity - Are We Finally on the Edge of a New Frontier?

Authors:
Michele K Evans

N Engl J Med 2020 Sep;383(11):997-999

From the National Institute on Aging, Baltimore.

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http://dx.doi.org/10.1056/NEJMp2005944DOI Listing
September 2020

The Polygenic and Monogenic Basis of Blood Traits and Diseases.

Cell 2020 09;182(5):1214-1231.e11

Laboratory of Epidemiology and Population Science, National Institute on Aging/NIH, Baltimore, MD, 21224, USA.

Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation.
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http://dx.doi.org/10.1016/j.cell.2020.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482360PMC
September 2020

Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations.

Cell 2020 09;182(5):1198-1213.e14

Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA 02130, USA; Department of Medicine, Division on Aging, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.

Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p < 5 × 10, including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 secretion levels in vitro. Fine-mapping prioritized variants annotated as functional and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EUR-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations and compared genetic architecture and the effect of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies.
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http://dx.doi.org/10.1016/j.cell.2020.06.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480402PMC
September 2020

Aspects of Dietary Diversity Changes across Adulthood in Racially Diverse Adults.

Nutrients 2020 Aug 15;12(8). Epub 2020 Aug 15.

Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, 251 Bayview Blvd. Suite 100, Baltimore, MD 21224, USA.

Knowledge of various aspects of dietary diversity (DD)-an essential healthful dietary component-across adulthood is limited. This study examined three DD aspects over time in racially diverse adults. Participants were from the National Institute on Aging, Healthy Aging in Neighborhoods of Diversity across the Life Span study. DD measures were calculated at baseline ( = 2177), and first and second examination follow-ups ( = 2140 and = 2066, respectively) using two 24-h recalls. The count was based on the consumption of ≥50% of an equivalent from 21 food groups. Evenness was derived using the Berry-Index adjusted by the food's health value; dissimilarity, by Mahalanobis Distance. Mixed-effects linear regression models were conducted to test changes in DD across adulthood, adjusting for sex, race, poverty status and education as fixed effects, and adjusting for smoking, age and energy as time-dependent variables. Only dissimilarity showed significant interactions of time × race ( = 0.0005), and time × poverty status ( = 0.0325), indicating a slower rate of increase over time in dissimilarity scores among Whites compared with African-Americans and those with income >125% poverty versus <125% poverty. A significant interaction between time×energy ( < 0.0001) was noted for both evenness and dissimilarity scores. To our knowledge, this is the first study to document the differential change in dissimilarity scores by race and income over time.
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http://dx.doi.org/10.3390/nu12082455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468858PMC
August 2020

Low-Level Ionizing Radiation Induces Selective Killing of HIV-1-Infected Cells with Reversal of Cytokine Induction Using mTOR Inhibitors.

Viruses 2020 08 13;12(8). Epub 2020 Aug 13.

Laboratory of Molecular Virology, School of Systems Biology, George Mason University, Manassas, VA 20110, USA.

HIV-1 infects 39.5 million people worldwide, and cART is effective in preventing viral spread by reducing HIV-1 plasma viral loads to undetectable levels. However, viral reservoirs persist by mechanisms, including the inhibition of autophagy by HIV-1 proteins (i.e., Nef and Tat). HIV-1 reservoirs can be targeted by the "shock and kill" strategy, which utilizes latency-reversing agents (LRAs) to activate latent proviruses and immunotarget the virus-producing cells. Yet, limitations include reduced LRA permeability across anatomical barriers and immune hyper-activation. Ionizing radiation (IR) induces effective viral activation across anatomical barriers. Like other LRAs, IR may cause inflammation and modulate the secretion of extracellular vesicles (EVs). We and others have shown that cells may secrete cytokines and viral proteins in EVs and, therefore, LRAs may contribute to inflammatory EVs. In the present study, we mitigated the effects of IR-induced inflammatory EVs (i.e., TNF-α), through the use of mTOR inhibitors (mTORi; Rapamycin and INK128). Further, mTORi were found to enhance the selective killing of HIV-1-infected myeloid and T-cell reservoirs at the exclusion of uninfected cells, potentially via inhibition of viral transcription/translation and induction of autophagy. Collectively, the proposed regimen using cART, IR, and mTORi presents a novel approach allowing for the targeting of viral reservoirs, prevention of immune hyper-activation, and selectively killing latently infected HIV-1 cells.
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http://dx.doi.org/10.3390/v12080885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472203PMC
August 2020

Association between GDF15, poverty and mortality in urban middle-aged African American and white adults.

PLoS One 2020 7;15(8):e0237059. Epub 2020 Aug 7.

Laboratory of Epidemiology and Population Science, National Institute on Aging Intramural Research Program (NIA IRP), National Institutes of Health (NIH), Baltimore, Maryland, United States of America.

Mortality disparities are influenced by race and poverty. There is limited information about whether poverty influences biologic markers of mortality risk. Emerging data suggests that growth differentiation factor 15 (GDF15) is associated with mortality; however, the interplay between GDF15, sociodemographic factors and mortality is not known. We sought to evaluate the interactions between GDF15 and sex, race and poverty status on mortality. Serum GDF15 was measured in 1036 African American and white middle-aged men and women above and below 125% of the Federal poverty status from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. Multivariable adjusted Cox regression models were used to assess the association between log-transformed GDF15 (logGDF15) and 12-year mortality outcomes (all-cause, cardiovascular- and cancer-specific outcomes) and interactions with sex, race and poverty status. Likelihood ratio tests were used to assess significance of the interaction terms. Median GDF15 was 655.2 pg/mL (IQR = 575.1). During 12.2 years of follow-up, 331 died of which 94 cardiovascular- and 87 were cancer-specific deaths. One unit of increase in logGDF15 was associated with a hazard ratio for all-cause mortality, cardiovascular- and cancer-specific mortality of 2.26 (95% confidence interval [CI], 1.94-2.64), 2.74 (95%CI, 2.06-3.63) and 1.41 (95%CI, 1.00-2.00), respectively. There was an interaction between logGDF15 and poverty status on all-cause mortality (p<0.05). The GDF15×poverty status interaction term improved model calibration for all-cause mortality. Our study provides the first evidence that the effect of elevated GDF15 on all-cause mortality is modified by poverty status.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237059PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413478PMC
October 2020

Housing Instability and Health Care Engagement Among People With CKD.

Kidney Med 2020 May-Jun;2(3):367-368. Epub 2020 Mar 16.

Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.

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http://dx.doi.org/10.1016/j.xkme.2019.12.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380342PMC
March 2020

Covid's Color Line - Infectious Disease, Inequity, and Racial Justice.

Authors:
Michele K Evans

N Engl J Med 2020 Jul;383(5):408-410

From the National Institute on Aging, Baltimore.

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http://dx.doi.org/10.1056/NEJMp2019445DOI Listing
July 2020

Genome-Wide Association Study Meta-Analysis of Stroke in 22 000 Individuals of African Descent Identifies Novel Associations With Stroke.

Stroke 2020 08 22;51(8):2454-2463. Epub 2020 Jul 22.

Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC (C.D.L., C.L.).

Background And Purpose: Stroke is a complex disease with multiple genetic and environmental risk factors. Blacks endure a nearly 2-fold greater risk of stroke and are 2× to 3× more likely to die from stroke than European Americans.

Methods: The COMPASS (Consortium of Minority Population Genome-Wide Association Studies of Stroke) has conducted a genome-wide association meta-analysis of stroke in >22 000 individuals of African ancestry (3734 cases, 18 317 controls) from 13 cohorts.

Results: In meta-analyses, we identified one single nucleotide polymorphism (rs55931441) near the gene that reached genome-wide significance (=4.62×10) and an additional 29 variants with suggestive evidence of association (<1×10), representing 24 unique loci. For validation, a look-up analysis for a 100 kb region flanking the COMPASS single nucleotide polymorphism was performed in SiGN (Stroke Genetics Network) Europeans, SiGN Hispanics, and METASTROKE (Europeans). Using a stringent Bonferroni correction value of 2.08×10 (0.05/24 unique loci), we were able to validate associations at the locus in both SiGN (=8.18×10) and METASTROKE (=1.72×10) European populations. Overall, 16 of 24 loci showed evidence for validation across multiple populations. Previous studies have reported associations between variants in the gene and lipids, C-reactive protein, and risk of coronary artery disease and stroke. Suggestive associations with variants in the and genes represent potential novel ischemic stroke loci.

Conclusions: These findings represent the most thorough investigation of genetic determinants of stroke in individuals of African descent, to date.
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http://dx.doi.org/10.1161/STROKEAHA.120.029123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387190PMC
August 2020

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

Front Aging Neurosci 2020 25;12:140. Epub 2020 May 25.

Department of Psychology, University of Maryland, Baltimore County, MD, United States.

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). Three prospective waves from Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study were used [Baltimore, City, MD, 2004-2015, = 183-240 urban adults (Age: 30-64 years)]. Serum vitamin 25-hydroxyvitamin D [25(OH)D], folate and cobalamin concentrations were measured at visits 1 (v: 2004-2009) and 2 (v: 2009-2013), while structural and diffusion Magnetic Resonance Imaging (sMRI/dMRI) outcomes were measured at v: 2011-2015. Top 10 ranked adjusted associations were corrected for multiple testing using familywise Bonferroni (FWER <0.05) and false discovery rates (FDR, -value < 0.10). We found statistically significant (FWER < 0.05; β±SE) direct associations of 25(OH)D(v) with WM volumes [overall: +910 ± 336/males: +2,054 ± 599], occipital WM; [overall: +140 ± 40, males: +261 ± 67 and Age > 50 years: +205 ± 54]; parietal WM; [overall: +251 ± 77, males: +486 ± 129 and Age > 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 (v-v) 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 ( < 0.10), while serum folate (v) was associated with lower mean diffusivity (MD) in ALIC, reflecting greater WMI, overall. 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.
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http://dx.doi.org/10.3389/fnagi.2020.00140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261885PMC
May 2020