tbuckley/cabot-search huggingface dataset:
Essential Nutrients, Added Sugar Intake, and Epigenetic Age in Midlife Black and White Women
Authors: Dorothy T. Chiu, Elissa June Hamlat, Joshua Zhang, Elissa S. Epel, Barbara A. Laraia
Journal: JAMA Network Open (2024)

Importance Nutritive compounds play critical roles in DNA replication, maintenance, and repair, and also serve as antioxidant and anti-inflammatory agents. Sufficient dietary intakes support genomic stability and preserve health. Objective To investigate the associations of dietary patterns, including intakes of essential nutrients and added sugar, and diet quality scores of established and new nutrient indices with epigenetic age in a diverse cohort of Black and White women at midlife. Design, Setting, and Participants This cross-sectional study included analyses (2021-2023) of past women participants of the 1987-1997 National Heart, Lung, and Blood Institute Growth and Health Study (NGHS), which examined cardiovascular health in a community cohort of Black and White females aged between 9 and 19 years. Of these participants who were recruited between 2015 and 2019 from NGHS’s California site, 342 females had valid completed diet and epigenetic assessments. The data were analyzed from October 2021 to November 2023. Exposure Diet quality scores of established nutrient indices (Alternate Mediterranean Diet [aMED], Alternate Healthy Eating Index [AHEI]–2010); scores for a novel, a priori–developed Epigenetic Nutrient Index [ENI]; and mean added sugar intake amounts were derived from 3-day food records. Main Outcomes and Measures GrimAge2, a second-generation epigenetic clock marker, was calculated from salivary DNA. Hypotheses were formulated after data collection. Healthier diet indicators were hypothesized to be associated with younger epigenetic age. Results A total of 342 women composed the analytic sample (mean [SD] age, 39.2 [1.1] years; 171 [50.0%] Black and 171 [50.0%] White participants). In fully adjusted models, aMED (β, −0.41; 95% CI, −0.69 to −0.13), AHEI-2010 (β, −0.05; 95% CI, −0.08 to −0.01), and ENI (β, −0.17; 95% CI, −0.29 to −0.06) scores, and added sugar intake (β, 0.02; 95% CI, 0.01-0.04) were each significantly associated with GrimAge2 in expected directions. In combined analyses, the aforementioned results with GrimAge2 were preserved with the association estimates for aMED and added sugar intake retaining their statistical significance. Conclusions and Relevance In this cross-sectional study, independent associations were observed for both healthy diet and added sugar intake with epigenetic age. To our knowledge, these are among the first findings to demonstrate associations between added sugar intake and epigenetic aging using second-generation epigenetic clocks and one of the first to extend analyses to a diverse population of Black and White women at midlife. Promoting diets aligned with chronic disease prevention recommendations and replete with antioxidant or anti-inflammatory and pro-epigenetic health nutrients while emphasizing low added sugar consumption may support slower cellular aging relative to chronological age, although longitudinal analyses are needed.
Blood–brain barrier alterations and their impact on Parkinson’s disease pathogenesis and therapy
Authors: Kristina Lau, Rebecca Kotzur, Franziska Richter
Journal: Translational Neurodegeneration (2024)

There is increasing evidence for blood-brain barrier (BBB) alterations in Parkinson's disease (PD), the second most common neurodegenerative disorder with rapidly rising prevalence. Altered tight junction and transporter protein levels, accumulation of α-synuclein and increase in inflammatory processes lead to extravasation of blood molecules and vessel degeneration. This could result in a self-perpetuating pathophysiology of inflammation and BBB alteration, which contribute to neurodegeneration. Toxin exposure or α-synuclein over-expression in animal models has been shown to initiate similar pathologies, providing a platform to study underlying mechanisms and therapeutic interventions. Here we provide a comprehensive review of the current knowledge on BBB alterations in PD patients and how rodent models that replicate some of these changes can be used to study disease mechanisms. Specific challenges in assessing the BBB in patients and in healthy controls are discussed. Finally, a potential role of BBB alterations in disease pathogenesis and possible implications for therapy are explored. The interference of BBB alterations with current and novel therapeutic strategies requires more attention. Brain region-specific BBB alterations could also open up novel opportunities to target specifically vulnerable neuronal subpopulations.
Telehealth Parenting Program and Salivary Epigenetic Biomarkers in Preschool Children With Developmental Delay
Authors: Sarah M. Merrill, Christina Hogan, Anne K. Bozack, Andres Cardenas, Jonathan S. Comer, Daniel M. Bagner, April Highlander, Justin Parent
Journal: JAMA Network Open (2024)

Children with developmental delays are at a heightened risk of experiencing mental health challenges, and this risk is exacerbated among racially minoritized children who face disproportionate adversity. Understanding the impact of parenting interventions on biological markers associated with these risks is crucial for mitigating long-term health disparities. To examine the effect of 20 weeks of an internet-based parent-child interaction training (iPCIT) program on biomarkers associated with aging and chronic inflammation among preschoolers with developmental delay at 12-month follow-up. An observational secondary analysis of data from a randomized clinical trial conducted from March 17, 2016, to December 15, 2020, to assess changes in salivary DNA methylation (DNAm)-derived biomarkers following iPCIT intervention. Participants were recruited from 3 Part C early intervention sites in a large southeastern US city. Eligible participants included children recruited within 3 months of their third birthday who had a Child Behavior Checklist Externalizing Problems T score greater than 60 and provided saliva in at least 1 study wave. Data analysis was conducted May 2023 to April 2024. Participants received either iPCIT (a telehealth therapeutic intervention focused on enhancing the parent-child relationship and addressing behavioral challenges in young children) or referrals as usual. DNAm at the 12-month follow-up was assessed using the Infinium HumanMethylationEPIC Bead Chip Assay to derive biomarkers DunedinPACE, C-reactive protein (CRP), and interleukin-6 (IL-6). Analyses were intent-to-treat and used path analysis. A total of 71 children (mean [SD] age, 36.27 [0.61] months 51 male [71.8%] and 20 female [28.2%]) were analyzed, of whom 34 received iPCIT and 37 received referrals as usual. The iPCIT group had a slower pace of aging (β = 0.26; 95% CI, 0.06 to 0.50; P = .03) and less DNAm-derived CRP (β = 0.27; 95% CI, 0.05 to 0.49; P = .01) relative to the control condition at the 12-month follow-up. These associations remained significant after accounting for baseline DNAm score, child demographics, and symptom severity, and were independent of predicted buccal epithelial cell proportion for both DunedinPACE and CRP. There was no association with DNAm-derived IL-6 (β = 0.14; 95% CI, -0.08 to 0.36; P = .21). In this study of a parenting intervention, iPCIT, the association of intervention with decreased molecular markers of inflammation and biological aging suggests their potential to modify aspects of the biological embedding of stress. Understanding the systemic biological impact of such interventions offers insights into addressing health disparities and promoting resilience among vulnerable populations. ClinicalTrials.gov Identifier: NCT03260816.
Fecal Microbiota Transplantation for Treatment of Parkinson Disease
Authors: Filip Scheperjans, Reeta Levo, Berta Bosch, Mitja Lääperi, Pedro A. B. Pereira, Olli-Pekka Smolander, Velma T. E. Aho, Nora Vetkas, Lotta Toivio, Veera Kainulainen, Tatyana D. Fedorova, Perttu Lahtinen, Rebekka Ortiz, Valtteri Kaasinen, Reetta Satokari, Perttu Arkkila
Journal: JAMA Neurology (2024)

Importance Dysbiosis has been robustly demonstrated in Parkinson disease (PD), and fecal microbiota transplantation (FMT) has shown promising effects in preclinical PD models. Objective To assess the safety and symptomatic efficacy of colonic single-dose anaerobically prepared FMT. Design, Setting, and Participants This was a double-blind, placebo-controlled, randomized clinical trial conducted between November 2020 and June 2023 with a follow-up period of 12 months at 4 hospitals in Finland. Patients with PD aged 35 to 75 years in Hoehn &amp;amp;amp; Yahr stage 1-3 with a mild to moderate symptom burden and dysbiosis of fecal microbiota were included. Of 229 patients screened, 48 were randomized and 47 received the intervention. One patient discontinued due to worsening of PD symptoms. Two further patients were excluded before analysis and 45 were included in the intention-to-treat analysis. Intervention Participants were randomized in a 2:1 ratio to receive FMT or placebo via colonoscopy. Main Outcomes and Measures The primary end point was the change of Movement Disorder Society Unified Parkinson’s Disease Rating Scale parts I-III (part III off medication) at 6 months. Safety was assessed by recording adverse events (AEs). Results The median (IQR) age was 65 (52.5-70.0) years in the placebo group and 66 (59.25-69.75) years in the FMT group; 9 (60.0%) and 16 (53.3%) patients were male in the placebo group and the FMT group, respectively. The primary outcome did not differ between the groups (0.97 points, 95% CI, −5.10 to 7.03, P = .75). Gastrointestinal AEs were more frequent in the FMT group (16 [53%] vs 1 [7%]; P = .003). Secondary outcomes and post hoc analyses showed stronger increase of dopaminergic medication and improvement of certain motor and nonmotor outcomes in the placebo group. Microbiota changes were more pronounced after FMT but differed by donor. Nevertheless, dysbiosis status was reversed more frequently in the placebo group. Conclusions and Relevance FMT was safe but did not offer clinically meaningful improvements. Further studies—for example, through modified FMT approaches or bowel cleansing—are warranted regarding the specific impact of donor microbiota composition and dysbiosis conversion on motor and nonmotor outcomes as well as medication needs in PD. Trial Registration ClinicalTrials.gov Identifier: NCT04854291
Childhood Maltreatment and Longitudinal Epigenetic Aging
Authors: Olivia D. Chang, Helen C. S. Meier, Kathryn Maguire-Jack, Pamela Davis-Kean, Colter Mitchell
Journal: JAMA Network Open (2024)

Importance Child physical and emotional abuse and neglect may affect epigenetic signatures of accelerated aging several years after the exposure. Objective To examine the longitudinal outcomes of early-childhood and midchildhood exposures to maltreatment on later childhood and adolescent profiles of epigenetic accelerated aging. Design, Setting, and Participants This cohort study used data from the Future of Families and Child Wellbeing Study (enrolled 1998-2000), a US birth cohort study with available DNA methylation (DNAm) data at ages 9 and 15 years (assayed between 2017 and 2020) and phenotypic data at birth (wave 1), and ages 3 (wave 3), 5 (wave 4), 9 (wave 5), and 15 (wave 6) years. Data were analyzed between June 18 and December 10, 2023. Exposures Emotional aggression, physical assault, emotional neglect, and physical neglect via the Parent-Child Conflict Tactics Scale at ages 3 and 5 years. Main Outcomes and Measures Epigenetic accelerated aging (DNAmAA) was measured using 3 machine learning–derived surrogates of aging (GrimAge, PhenoAge, and DunedinPACE) and 2 machine learning–derived surrogates of age (Horvath and PedBE), residualized for age in months. Results A total of 1971 children (992 [50.3%] male) representative of births in large US cities between 1998 and 2000 were included. Physical assault at age 3 years was positively associated with DNAmAA for PhenoAge (β = 0.073; 95% CI, 0.019-0.127), and emotional aggression at age 3 years was negatively associated with PhenoAge DNAmAA (β = −0.107; 95% CI, −0.162 to −0.052). Emotional neglect at age 5 years was positively associated with PhenoAge DNAmAA (β = 0.051; 95% CI, 0.006-0.097). Cumulative exposure to physical assault between ages 3 and 5 years was positively associated with PhenoAge DNAmAA (β = 0.063; 95% CI, 0.003-0.123); emotional aggression was negatively associated with PhenoAge DNAmAA (β = −0.104; 95% CI, −0.165 to −0.043). The association of these measures with age 15 years PhenoAge DNAmAA was almost fully mediated by age 9 years PhenoAge DNAm age acceleration. Similar patterns were found for GrimAge, DunedinPACE, and PhenoAge, but only those for PhenoAge remained after adjustments for multiple comparisons. Conclusions and Relevance In this cohort study, altered patterns of DNAmAA were sensitive to the type and timing of child maltreatment exposure and appeared to be associated with more proximate biological embedding of stress.
Familial Loss of a Loved One and Biological Aging
Authors: Allison E. Aiello, Aura Ankita Mishra, Chantel L. Martin, Brandt Levitt, Lauren Gaydosh, Daniel W. Belsky, Robert A. Hummer, Debra J. Umberson, Kathleen Mullan Harris
Journal: JAMA Network Open (2024)

Importance The link between familial loss of a loved one and long-term health decline is complex and not fully understood. Objective To test associations of losing a parent, sibling, child, or partner or spouse with accelerated biological aging. Design, Setting, and Participants Data from the National Longitudinal Study of Adolescent to Adult Health, a US population-based longitudinal cohort study, were analyzed. Participants were enrolled from 1994 to 1995 for wave 1, while in grades 7 to 12, and followed up through wave 5 in 2018. The study analyzed participant reports of loss collected at each wave from 1 to 5 over 24 years and used a banked wave 5 blood sample for subsequent DNA methylation testing and epigenetic clock calculation from 2018 to 2024. Data were analyzed from January 2022 to July 2024. Exposure Loss of biological parents or parental figures, partners or spouses, siblings, or children at waves 1 to 3 or during childhood, adolescence (aged &amp;amp;lt;18 years), or adulthood at wave 4 to wave 5 (aged 18-43 years). Main Outcomes and Measures Biological aging assessed from blood DNA methylation using the Horvath, PhenoAge, GrimAge, and DunedinPACE epigenetic clocks at wave 5. Results Data from 3963 participants were analyzed, with a weighted mean (range) age of 38.36 (36.78-39.78) years at wave 5; 2370 (50.3%) were male, 720 (15.97%) were Black, 400 (8.18%) were Hispanic, and 2642 (72.53%) were White. Nearly 40% of participants experienced loss by wave 5 when they were aged 33 to 43 years, and participants who were Black (379 participants [56.67%]), Hispanic (152 participants [41.38%]), and American Indian (18 participants [56.08%]) experienced a greater proportion of losses compared with White participants (884 participants [34.09%]). Those who experienced 2 or more losses tended to have older biological ages for several of the clocks (PhenoAge β = 0.15; 95% CI, 0.02 to 0.28; GrimAge β = 0.27; 95% CI, 0.09 to 0.45; DunedinPACE β = 0.22; 95% CI, 0.10 to 0.34) compared with those with no losses. In contrast, there were no associations with 2 or more losses for the Horvath clock (β = −0.08; 95% CI, −0.23 to 0.06). Conclusions and Relevance This study reveals associations between various measures of loss experienced from childhood to adulthood and biological aging in a diverse sample of the US population. These findings underscore the potentially enduring impact of loss on biological aging even before middle age and may contribute to understanding racial and ethnic disparities in health and mortality.
Fecal Microbiome Transplants For Parkinson Disease
Authors: Timothy R. Sampson
Journal: JAMA Neurology (2024)

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Bilateral Focused Ultrasound Thalamotomy for Tremor—Is It Really Safe?
Authors: Sameer A. Sheth, Jill L. Ostrem, Marwan Hariz
Journal: JAMA Neurology (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Psychosocial Disadvantage During Childhood and Midlife Health
Authors: Ryan L. Brown, Katie E. Alegria, Elissa Hamlat, A. Janet Tomiyama, Barbara Laraia, Eileen M. Crimmins, Terrie E. Moffitt, Elissa S. Epel
Journal: JAMA Network Open (2024)

Importance Low childhood socioeconomic status (SES) is a social hallmark of aging that contributes to adult health disparities and earlier morbidity and mortality. Childhood perceptions of stress are associated with child health outcomes and may contribute to premature biological aging into adulthood. Objective To describe the association of childhood SES and perceived stress with midlife insulin resistance and epigenetic age and to explore whether late adolescent adiposity mediates the observed associations. Design, Setting, and Participants The longitudinal cohort National Heart, Lung, and Blood Institute Growth and Health Study enrolled girls aged 10 years from January 1987 to May 1988, and followed them up to 19 years of age. Participants from Richmond, California, were recruited again at midlife in 2016 to assess insulin resistance and epigenetic age. Analyses were conducted from August 2, 2023, to March 18, 2024. A total of 433 participants were eligible and included in the analyses (specific sample sizes ranged across analyses from 303 to 391). Exposures Childhood levels of SES at 10 years of age (parental educational level and income) and perceived stress at 11 years of age. Main Outcomes and Measures The hypotheses tested were formulated after data collection. Outcomes included the homeostatic model assessment of insulin resistance (HOMA-IR) and the GrimAge and DunedinPACE epigenetic clocks. Waist circumference in late adolescence was tested as a mediator. Results Among the 433 participants, the mean (SD) age was 39.4 (1.2) years; 218 (50.3%) were Black and 215 (49.7%) were White; and 135 (31.2%) had parents with a college degree or higher. Higher parental educational level was associated with lower HOMA-IR (B = −0.22 [95% CI, −0.41 to −0.02]; P = .03), lower midlife GrimAge (B = −1.76 [95% CI, −2.85 to −0.66] years; P = .002), and slower midlife DunedinPACE (B = −0.03 [95% CI, −6.29 to −0.002]; P = .04). Childhood perceived stress was indirectly associated through late adolescent adiposity with midlife HOMA-IR (B = 0.01 [95% CI, 0.001-0.01]; P = .02) and midlife GrimAge (B = 0.02 [95% CI, 0.003-0.04] years; P = .01). Conclusions and Relevance In this longitudinal cohort study of midlife health and aging, childhood social hallmarks of aging were associated with midlife insulin resistance and epigenetic age (GrimAge and DunedinPACE). Future studies should identify malleable factors that may slow the impact of social hallmarks of aging.
Obesity and Early-Onset Breast Cancer and Specific Molecular Subtype Diagnosis in Black and White Women
Authors: Sarabjeet Kour Sudan, Amod Sharma, Kunwar Somesh Vikramdeo, Wade Davis, Sachin K. Deshmukh, Teja Poosarla, Nicolette P. Holliday, Pranitha Prodduturvar, Cindy Nelson, Karan P. Singh, Ajay P. Singh, Seema Singh
Journal: JAMA Network Open (2024)

Importance Epidemiologic data suggest an association of obesity with breast cancer (BC); however, obesity’s contribution to early onset and risk of diagnosis with specific molecular subtypes by race is uncertain. Objective To examine the race-specific association of body mass index with early onset and diagnosis of specific molecular subtypes. Design, Setting, and Participants This retrospective cohort study included patients with BC diagnosed between October 1, 2017, and March 31, 2022, at 3 University of South Alabama Mitchell Cancer Institute clinics. Participants were also prospectively enrolled for serum leptin measurement. Main Outcomes and Measures The primary outcome was age at BC onset and specific subtype diagnosis. The secondary outcome was race-specific differences. Odds ratios (ORs) for associations of body mass index with age at onset and subtype were estimated using the Fisher exact test. Race was self-reported. Results Of the 1085 study patients, 332 (30.6%) were Black with a median age of 58 (IQR, 50-66) years, and 753 (69.4%) were White with a median age of 63 (IQR, 53-71) years. A total of 499 patients (46.0%) had obesity, with Black women with obesity receiving more frequent BC diagnosis than their White counterparts (OR, 2.40; 95% CI, 1.87-3.15; P &amp;amp;lt; .001). In addition, Black women had a significantly higher incidence of early-onset disease (OR, 1.95; 95% CI, 1.33-2.86; P = .001) than White women, and obesity increased this risk significantly in Black women (OR, 2.92; 95% CI, 1.35-6.22; P = .006). Black women with obesity also had a significantly higher risk of luminal A BC (OR, 2.53; 95% CI, 1.81-3.56; P &amp;amp;lt; .001) and triple-negative BC (TNBC) (OR, 2.48; 95% CI, 1.43-4.22; P = .002) diagnosis than White counterparts. Black women, with or without BC, had significantly higher serum leptin levels (median [IQR], 55.3 [40.3-66.2] ng/mL and 29.1 [21.1-46.5] ng/mL, respectively, P &amp;amp;lt; .001) than White women (median [IQR], 33.4 [18.9-47.7] ng/mL and 16.5 [10.0-22.9] ng/mL, respectively), which was associated with higher odds of luminal A disease (OR, 5.25; 95% CI, 1.69-14.32, P = .003). Higher odds of early-onset disease (OR, 3.50; 95% CI, 0.43-23.15; P = .33 for trend), and TNBC diagnosis (OR, 6.00; 95% CI, 0.83-37.27; P = .14 for trend) were also seen, although these outcomes were not statistically significant. Conclusions and Relevance In this cohort study of patients with BC, obesity and high serum leptin levels were associated with an enhanced risk of early-onset BC and diagnosis of luminal A and TNBC subtypes in Black women. These findings should help in developing strategies to narrow the existing disparity gaps.