Publications by authors named "Francine Grodstein"

224 Publications

Gut Microbiota Predicts Healthy Late-Life Aging in Male Mice.

Nutrients 2021 Sep 21;13(9). Epub 2021 Sep 21.

Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Calorie restriction (CR) extends lifespan and retards age-related chronic diseases in most species. There is growing evidence that the gut microbiota has a pivotal role in host health and age-related pathological conditions. Yet, it is still unclear how CR and the gut microbiota are related to healthy aging. Here, we report findings from a small longitudinal study of male C57BL/6 mice maintained on either or mild (15%) CR diets from 21 months of age and tracked until natural death. We demonstrate that CR results in a significantly reduced rate of increase in the frailty index (FI), a well-established indicator of aging. We observed significant alterations in diversity, as well as compositional patterns of the mouse gut microbiota during the aging process. Interrogating the FI-related microbial features using machine learning techniques, we show that gut microbial signatures from 21-month-old mice can predict the healthy aging of 30-month-old mice with reasonable accuracy. This study deepens our understanding of the links between CR, gut microbiota, and frailty in the aging process of mice.
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http://dx.doi.org/10.3390/nu13093290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467910PMC
September 2021

Long-term diet quality and its change in relation to late-life subjective cognitive decline.

Am J Clin Nutr 2021 Sep 25. Epub 2021 Sep 25.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

Background: Evidence regarding the role of diet quality, especially its change, in subjective cognitive decline (SCD) is scarce.

Objectives: To examine associations of long-term diet qualities, including Alternate Mediterranean Diet (AMED), Dietary Approaches to Stop Hypertension (DASH), and Alternate Healthy Eating Index 2010 (AHEI-2010) with SCD in the Nurses' Health Study.

Methods: We followed 49,493 female registered nurses averaged 48 years from 1984 to 2014. Diet scores were derived from seven repeated food frequency questionnaires in 1984, 1986, and every four years afterward until 2006. Self-reported SCD was assessed in 2012 and 2014 by a 7-item questionnaire on memory and cognition changes. Categorical SCD score was classified as "none" (0 points, 40.8%), "moderate" (0.5-2.5 points, 46.9%), and "severe" (3-7 points, 12.3%).

Results: Multinomial and linear regression models were adjusted for total calorie, demographic characteristics, major lifestyle, and clinical factors. Comparing top vs. bottom quintiles of AMED, DASH, and AHEI-2010, multivariable-adjusted odds ratios (ORs) (95% confidence intervals, CIs) for severe vs. none SCD were 0.57 (0.51, 0.64), 0.61 (0.55, 0.68), and 0.81 (0.73, 0.90), respectively. Similar associations remained for three diet indices evaluated 28 years before SCD assessment. Compared to participants with lowest diet quality tertiles in both remote and recent years, the lowest odds of severe SCD was observed among those who maintained highest diet quality tertiles over time, with a 40%, 32%, and 20% lower odds of severe SCD for AMED, DASH, and AHEI-2010, respectively. Moreover, the odds of severe SCD was lower among those with improved diets over time; for each standard deviation higher in diet quality change, reduced risks were 11% for AMED, 5% for DASH, and 3% for AHEI-2010, respectively.

Conclusion: Our findings support beneficial roles of long-term adherence to, and improvement in healthy dietary patterns for maintenance of subjective cognition in women.
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http://dx.doi.org/10.1093/ajcn/nqab326DOI Listing
September 2021

Cognitive Activity and Onset Age of Incident Alzheimer Disease Dementia.

Neurology 2021 08 14;97(9):e922-e929. Epub 2021 Jul 14.

From the Rush Alzheimer's Disease Center (R.S.W., T.W., L.Y., F.G., D.A.B., P.A.B.), Department of Neurological Sciences (R.S.W., T.W., L.Y., F.G., D.A.B.), and Department of Psychiatry and Behavioral Sciences (R.S.W., P.A.B.), Rush University Medical Center, Chicago, IL.

Objective: To test the hypothesis that higher level of cognitive activity predicts older age at dementia onset in Alzheimer disease (AD) dementia.

Methods: As part of a longitudinal cohort study, 1,903 older persons without dementia at enrollment reported their frequency of participation in cognitively stimulating activities. They had annual clinical evaluations to diagnose dementia and AD, and the deceased underwent neuropathologic examination. In analyses, we assessed the relation of baseline cognitive activity to age at diagnosis of incident AD dementia and to postmortem markers of AD and other dementias.

Results: During a mean of 6.8 years of follow-up, 457 individuals were diagnosed with incident AD at a mean age of 88.6 (SD 6.4, range 64.1-106.5) years. In an extended accelerated failure time model, higher level of baseline cognitive activity (mean 3.2, SD 0.7) was associated with older age at AD dementia onset (estimate 0.026; 95% confidence interval 0.013-0.039). Low cognitive activity (score 2.1, 10th percentile) was associated with a mean onset age of 88.6 years compared to a mean onset age of 93.6 years associated with high cognitive activity (score 4.0, 90th percentile). Results were comparable in subsequent analyses that adjusted for potentially confounding factors. In 695 participants who died and underwent a neuropathologic examination, cognitive activity was unrelated to postmortem markers of AD and other dementias.

Conclusion: A cognitively active lifestyle in old age may delay the onset of dementia in AD by as much as 5 years.
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http://dx.doi.org/10.1212/WNL.0000000000012388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408511PMC
August 2021

The association of epigenetic clocks in brain tissue with brain pathologies and common aging phenotypes.

Neurobiol Dis 2021 09 19;157:105428. Epub 2021 Jun 19.

Rush Alzheimer's Disease Center, Chicago, IL, United States of America; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, United States of America.

Epigenetic clocks are calculated by combining DNA methylation states across select CpG sites to estimate biologic age, and have been noted as the most successful markers of biologic aging to date. Yet, limited research has considered epigenetic clocks calculated in brain tissue. We used DNA methylation states in dorsolateral prefrontal cortex specimens from 721 older participants of the Religious Orders Study and Rush Memory and Aging Project, to calculate DNA methylation age using four established epigenetic clocks: Hannum, Horvath, PhenoAge, GrimAge, and a new Cortical clock. The four established clocks were trained in blood samples (Hannum, PhenoAge, GrimAge) or using 51 human tissue and cell types (Horvath); the recent Cortical clock is the first trained in postmortem cortical tissue. Participants were recruited beginning in 1994 (Religious Orders Study) and 1997 (Memory and Aging Project), and followed annually with questionnaires and clinical evaluations; brain specimens were obtained for 80-90% of participants. Mean age at death was 88.0 (SD 6.7) years. We used linear regression, logistic regression, and linear mixed models, to examine relations of epigenetic clock ages to neuropathologic and clinical aging phenotypes, controlling for chronologic age, sex, education, and depressive symptomatology. Hannum, Horvath, PhenoAge and Cortical clock ages were related to pathologic diagnosis of Alzheimer's disease (AD), as well as to Aβ load (a hallmark pathology of Alzheimer's disease). However, associations were substantially stronger for the Cortical than other clocks; for example, each standard deviation (SD) increase in Hannum, Horvath, and PhenoAge clock age was related to approximately 30% greater likelihood of pathologic AD (all p < 0.05), while each SD increase in Cortical age was related to 90% greater likelihood of pathologic AD (odds ratio = 1.91, 95% confidence interval 1.38, 2.62). Moreover, Cortical age was significantly related to other AD pathology (eg, mean tau tangle density, p = 0.003), and to odds of neocortical Lewy body pathology (for each SD increase in Cortical age, odds ratio = 2.00, 95% confidence 1.27, 3.17), although no clocks were related to cerebrovascular neuropathology. Cortical age was the only epigenetic clock significantly associated with the clinical phenotypes examined, from dementia to cognitive decline (5 specific cognitive systems, and a global cognitive measure averaging 17 tasks) to Parkinsonian signs. Overall, our findings provide evidence of the critical necessity for bespoke clocks of brain aging for advancing research to understand, and eventually prevent, neurodegenerative diseases of aging.
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http://dx.doi.org/10.1016/j.nbd.2021.105428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373772PMC
September 2021

Vigorous physical activity and cognitive trajectory later in life: prospective association and interaction by apolipoprotein E e4 in the Nurses' Health Study.

J Gerontol A Biol Sci Med Sci 2021 Jun 14. Epub 2021 Jun 14.

MGEN Foundation for Public Health, Paris, France.

Background: The apolipoprotein E (APOE) e4 allele is a well-established genetic risk factor of brain ageing. Vigorous physical activity may be particularly important in APOE-e4 carriers, but data have been inconsistent, likely due to differences in the timing of the physical activity assessment, definition of cognitive decline and/or sample size.

Methods: We prospectively evaluated the association between vigorous physical activity and cognition assessed at least 9 years later, according to APOE-e4 carrier status. Biennially from 1986, Nurses' Health Study participants reported their leisure-time physical activities. Starting in 1995-2001 and through 2008, participants (aged 70+ years) underwent up to four repeated cognitive telephone assessments (6 tasks averaged together using z-scores).

Results: Among 7,252 women, latent process mixed models identified three major patterns of cognitive change over 6 years: high-stable, medium-stable, and decline. Taking the high-stable cognitive trajectory as the outcome reference in multinomial logistic regressions, highest tertile of vigorous physical activity (≥5.9 metabolic-equivalent[MET]-hours/week) compared to lowest tertile (≤0.9 MET-hours/week) was significantly associated with subsequent lower likelihood of the medium-stable trajectory in the global score (OR[95%CI]=0.72[0.63,0.82]), verbal memory (OR[95%CI]=0.78[0.68-0.89]) and telephone interview of cognitive status score (OR[95%CI]=0.81[0.70-0.94]). Vigorous physical activity was also associated with lower likelihood of decline in category fluency (OR[95%CI]=0.72[0.56,0.92]). We observed some evidence (p-interaction=0.06 for the global score) that the association was stronger among APOE-e4 carriers than non-carriers (OR[95%CI]=0.60[0.39,0.92] versus 0.82[0.59,1.16]).

Conclusion: Midlife vigorous physical activity was associated with better cognitive trajectories in women in their seventies, with suggestions of stronger associations among APOE-e4 carriers.
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http://dx.doi.org/10.1093/gerona/glab169DOI Listing
June 2021

Cortical proteins may provide motor resilience in older adults.

Sci Rep 2021 05 28;11(1):11311. Epub 2021 May 28.

Rush Alzheimer's Disease Center, Rush University Medical Center, 1750 West Harrison Street, Jelke Building, Suite 100, Chicago, IL, 60612, USA.

Motor resilience proteins may be a high value therapeutic target that offset the negative effects of pathologies on motor function. This study sought to identify cortical proteins associated with motor decline unexplained by brain pathologies that provide motor resilience. We studied 1226 older decedents with annual motor testing, postmortem brain pathologies and quantified 226 proteotypic peptides in prefrontal cortex. Twenty peptides remained associated with motor decline in models controlling for ten brain pathologies (FDR < 0.05). Higher levels of nine peptides and lower levels of eleven peptides were related to slower decline. A higher motor resilience protein score based on averaging the levels of all 20 peptides was related to slower motor decline, less severe parkinsonism and lower odds of mobility disability before death. Cortical proteins may provide motor resilience. Targeting these proteins in further drug discovery may yield novel interventions to maintain motor function in old age.
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http://dx.doi.org/10.1038/s41598-021-90859-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163829PMC
May 2021

Long-term Intake of Gluten and Cognitive Function Among US Women.

JAMA Netw Open 2021 May 3;4(5):e2113020. Epub 2021 May 3.

Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston.

Importance: Gluten avoidance has been suggested as having a benefit to cognitive health among the general population, given the link between gluten and cognitive impairment in patients with celiac disease. However, data are lacking in individuals without celiac disease.

Objective: To examine whether gluten intake is associated with cognitive function in women without celiac disease.

Design, Setting, And Participants: This cohort study included US women who participated in the longitudinal, population-based Nurses' Health Study II and had not previously or subsequently been diagnosed with celiac disease. Dietary data were collected from 1991 to 2015, and data on cognitive function were collected from 2014 to 2019. Data analysis was conducted from October 2020 to April 2021.

Exposures: Energy-adjusted gluten intake, cumulatively averaged across questionnaire cycles prior to cognitive assessment.

Main Outcomes And Measures: Three standardized cognitive scores assessed by the validated Cogstate Brief Battery: (1) psychomotor speed and attention score, (2) learning and working memory score, and (3) global cognition score. Higher scores indicated better performance.

Results: The cohort included 13 494 women (mean [SD] age, 60.6 [4.6] years). The mean (SD) gluten intake was 6.3 (1.6) g/d. After controlling for demographic and lifestyle risk factors in linear regression, no significant differences in standardized cognitive scores (mean [SD], 0 [1]) by quintile of gluten intake were found across highest and lowest quintiles of gluten intake (psychomotor speed and attention: -0.02; 95% CI, -0.07 to 0.03; P for trend = .22; learning and working memory: 0.02; 95% CI, -0.03 to 0.07; P for trend = .30; global cognition: -0.002; 95% CI, -0.05 to 0.05; P for trend = .78). The null associations persisted after additional adjustment for major sources of dietary gluten (ie, refined grains or whole grains), comparing decile categories of gluten intake, using gluten intake updated at each previous questionnaire cycle, or modeling changes in gluten intake. Similarly, these associations were not materially altered in sensitivity analyses that excluded women who had reported cancer or dementia diagnosis or had not completed all dietary assessments.

Conclusions And Relevance: In this study, long-term gluten intake was not associated with cognitive scores in middle-aged women without celiac disease. Our results do not support recommendations to restrict dietary gluten to maintain cognitive function in the absence of celiac disease or established gluten sensitivity.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.13020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140370PMC
May 2021

Characteristics of Epigenetic Clocks Across Blood and Brain Tissue in Older Women and Men.

Front Neurosci 2020 7;14:555307. Epub 2021 Jan 7.

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, United States.

Epigenetic clocks are among the most promising biomarkers of aging. It is particularly important to establish biomarkers of brain aging to better understand neurodegenerative diseases. To advance application of epigenetic clocks-which were largely created with DNA methylation levels in blood samples-for use in brain, we need clearer evaluation of epigenetic clock behavior in brain, including direct comparisons of brain specimens with blood, a more accessible tissue for research. We leveraged data from the Religious Orders Study and Rush Memory and Aging Project to examine three established epigenetic clocks (Horvath, Hannum, PhenoAge clocks) and a newer clock, trained in cortical tissue. We calculated each clock in three different specimens: (1) antemortem CD4+ cells derived from blood ( = 41); (2) postmortem dorsolateral prefrontal cortex (DLPFC, = 730); and (3) postmortem posterior cingulate cortex (PCC, = 186), among older women and men, age 66-108 years at death. Across all clocks, epigenetic age calculated from blood and brain specimens was generally lower than chronologic age, although differences were smallest for the Cortical clock when calculated in the brain specimens. Nonetheless, we found that Pearson correlations of epigenetic to chronologic ages in brain specimens were generally reasonable for all clocks; correlations for the Horvath, Hannum, and PhenoAge clocks largely ranged from 0.5 to 0.7 (all < 0.0001). The Cortical clock outperformed the other clocks, reaching a correlation of 0.83 in the DLFPC ( < 0.0001) for epigenetic vs. chronologic age. Nonetheless, epigenetic age was quite modestly correlated across blood and DLPFC in 41 participants with paired samples [Pearson r from 0.21 ( = 0.2) to 0.32 ( = 0.05)], indicating that broader research in neurodegeneration may benefit from clocks using CpG sites better conserved across blood and brain. Finally, in analyses stratified by sex, by pathologic diagnosis of Alzheimer disease, and by clinical diagnosis of Alzheimer dementia, correlations of epigenetic to chronologic age remained consistently high across all groups. Future research in brain aging will benefit from epigenetic clocks constructed in brain specimens, including exploration of any advantages of focusing on CpG sites conserved across brain and other tissue types.
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http://dx.doi.org/10.3389/fnins.2020.555307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817909PMC
January 2021

Optimism and telomere length among African American adults in the Jackson Heart Study.

Psychoneuroendocrinology 2021 03 29;125:105124. Epub 2020 Dec 29.

Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA 02115, USA.

Background: Optimism is linked with greater longevity in both White and African American populations. Optimism may enhance longevity by slowing cellular aging, for which leukocyte telomere shortening is a biomarker. However, limited studies have examined the association of optimism with leukocyte telomere length among African Americans.

Methods: Data are from 723 men and 1244 women participating in the Jackson Heart Study (age = 21-93 years). We used multivariable linear regression models to conduct cross-sectional analyses examining whether higher optimism was associated with longer mean absolute leukocyte telomere length (assayed with Southern blot analysis). Models adjusted for sociodemographic characteristics, depressive symptomatology, health conditions, and health behavior-related factors. We also considered potential effect modification by key factors.

Results: In the age-adjusted model, optimism, measured as a continuous variable, was not associated with leukocyte telomere length (β = 0.01, 95%CI: -0.02, 0.04). This association remained null in the fully-adjusted model (β = 0.02, 95%CI: -0.02, 0.05) and was also null when considering optimism as a binary measure (higher vs. lower optimism). We found no evidence of effect modification by sex, age, body mass index, income, or chronic conditions.

Conclusions: Optimism was not associated with leukocyte telomere length among African American adults. Future studies should investigate alternate biological and behavioral mechanisms that may explain the optimism-health association.
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http://dx.doi.org/10.1016/j.psyneuen.2020.105124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052931PMC
March 2021

Primary and Specialty Outpatient Visits for Older Women With Urinary Incontinence: A Comparison of Nurses to the General Population.

Female Pelvic Med Reconstr Surg 2021 Sep;27(9):551-555

Division of Urogynecology, Department of Obstetrics and Gynecology at Brigham and Women's Hospital.

Objective: We evaluated patterns of outpatient visits seen for urinary incontinence (UI) among women 65 years or older in the Nurses' Health Study and the general Medicare population. We were interested in understanding whether nurses, with high health literacy, may receive more care for UI than the general population.

Methods: Medicare Fee for Service claims data for women aged 66-91 years were compared for Nurses' Health Study participants (n = 3,213) and a propensity-matched sample from general Medicare Fee for Service beneficiaries (n = 3,213) with 1 or more outpatient evaluation and management visits for UI in 2012. We examined the mean number of outpatient visits for UI and the type of provider seen, using t tests and χ2 tests. Providers were categorized as specialist and nonspecialist providers using taxonomy codes.

Results: The percentage of women 65 years or older who had an outpatient visits for UI over 12 months was 6.4% in the Nurses' Health Study cohort and 5.4% in the general population. The mean number of office visits for UI in 2012 was similar between nurses and the matched general population (mean = 1.8 vs 1.8; P = 0.3). A small percentage of women saw both nonspecialists and specialists for UI (9.3% in the Nurses' Health Study and 10.0% in the Center for Medicare Services cohorts).

Conclusions: We found that less than 7% of older women had outpatient evaluation of UI symptoms during a 12-month period, despite UI being very common in this age group. This was similar in nurses and the general population, suggesting that even high health care literacy does not increase UI care seeking.
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http://dx.doi.org/10.1097/SPV.0000000000000984DOI Listing
September 2021

Childhood Abuse and Cognitive Function in a Large Cohort of Middle-Aged Women.

Child Maltreat 2020 Nov 9:1077559520970647. Epub 2020 Nov 9.

Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.

Cognitive function at middle age is of particular public health interest, as it strongly predicts later dementia. Children who have experienced abuse subsequently have worse cognitive function than those who have not. However, it remains unclear whether the association of abuse with cognitive function persists into middle age. In 2014-2016, 14,151 women ages 49-69 years who had previously responded to a childhood abuse questionnaire completed a cognitive battery. In models adjusted for childhood socioeconomic status and head trauma, combined physical, emotional, and sexual abuse was associated with lower scores on both Learning/Working Memory (severe abuse, lower scores similar to that observed in women 4.8 years older in our data) and Psychomotor Speed/Attention (severe abuse, lower scores similar to that observed in women to 2.9 years older in our data). Adjustment for adulthood socioeconomic status and health factors (e.g., smoking, hypertension) slightly attenuated associations. In exploratory analyses further adjusted for psychological distress, associations were attenuated. Women exposed versus unexposed to childhood abuse had poorer cognitive function at mid-life. Associations were particularly strong for learning and working memory and were not accounted for by adulthood health factors. Childhood abuse should be investigated as a potential risk factor for cognitive decline and dementia in old age.
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http://dx.doi.org/10.1177/1077559520970647DOI Listing
November 2020

Brief Preoperative Screening for Frailty and Cognitive Impairment Predicts Delirium after Spine Surgery.

Anesthesiology 2020 12;133(6):1184-1191

Background: Frailty and cognitive impairment are associated with postoperative delirium, but are rarely assessed preoperatively. The study was designed to test the hypothesis that preoperative screening for frailty or cognitive impairment identifies patients at risk for postoperative delirium (primary outcome).

Methods: In this prospective cohort study, the authors administered frailty and cognitive screening instruments to 229 patients greater than or equal to 70 yr old presenting for elective spine surgery. Screening for frailty (five-item FRAIL scale [measuring fatigue, resistance, ambulation, illness, and weight loss]) and cognition (Mini-Cog, Animal Verbal Fluency) were performed at the time of the preoperative evaluation. Demographic data, perioperative variables, and postoperative outcomes were gathered. Delirium was the primary outcome detected by either the Confusion Assessment Method, assessed daily from postoperative day 1 to 3 or until discharge, if patient was discharged sooner, or comprehensive chart review. Secondary outcomes were all other-cause complications, discharge not to home, and hospital length of stay.

Results: The cohort was 75 [73 to 79 yr] years of age, 124 of 219 (57%) were male. Many scored positive for prefrailty (117 of 218; 54%), frailty (53 of 218; 24%), and cognitive impairment (50 to 82 of 219; 23 to 37%). Fifty-five patients (25%) developed delirium postoperatively. On multivariable analysis, frailty (scores 3 to 5 [odds ratio, 6.6; 95% CI, 1.96 to 21.9; P = 0.002]) versus robust (score 0) on the FRAIL scale, lower animal fluency scores (odds ratio, 1.08; 95% CI, 1.01 to 1.51; P = 0.036) for each point decrease in the number of animals named, and more invasive surgical procedures (odds ratio, 2.69; 95% CI, 1.31 to 5.50; P = 0.007) versus less invasive procedures were associated with postoperative delirium.

Conclusions: Screening for frailty and cognitive impairment preoperatively using the FRAIL scale and the Animal Verbal Fluency test in older elective spine surgery patients identifies those at high risk for the development of postoperative delirium.

Editor’s Perspective:
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http://dx.doi.org/10.1097/ALN.0000000000003523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657972PMC
December 2020

Associations between reproductive factors and biliary tract cancers in women from the Biliary Tract Cancers Pooling Project.

J Hepatol 2020 10 11;73(4):863-872. Epub 2020 May 11.

Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.

Background & Aims: Gallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear.

Methods: We pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study.

Results: During 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR ≥5 vs. 0 births 1.72; 95% CI 1.25-2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06-1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04-1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09-1.31) and EHBDC (HR 1.11; 95% CI 1.01-1.22) in Asian women only.

Conclusion: We observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography.

Lay Summary: Our findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic bile duct cancer and extrahepatic bile duct cancer. We did not see this same association in women from Western countries. Age at menopause was not associated with the risk of any biliary tract cancers.
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http://dx.doi.org/10.1016/j.jhep.2020.04.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901003PMC
October 2020

Consumption of Nuts at Midlife and Healthy Aging in Women.

J Aging Res 2020 7;2020:5651737. Epub 2020 Jan 7.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.

Background: Nut consumption may reduce age-related diseases and lead to better health and well-being in aging. Many conditions of aging develop over decades, and thus earlier lifestyle factors may particularly influence later health.

Methods: In 1998 and 2002, we administered food frequency questionnaires to assess nut consumption (peanuts, walnuts, and other nuts and peanut butter) in women in the Nurses' Health Study in their 50 s/early 60 s. In 2012, those who survived beyond 65 years with no chronic diseases, no reported memory impairment, no physical disabilities, and intact mental health were considered "healthy agers." We used multivariable logistic regression to estimate odds ratios for healthy versus usual aging, controlled for sociodemographic, behavioral, dietary, and other potential confounding factors.

Results: Of 33,931 participants at midlife, 16% became "healthy agers." After age adjustment, we observed a significant association between total nut consumption at midlife and higher odds of healthy aging, with strongest associations observed excluding peanut butter (odds ratio (OR) = 1.46, 95% confidence interval (CI) 1.32-1.62, ≥3 servings/week versus none). Findings were attenuated after further control for covariates, including overall diet quality (OR = 1.14, 95% CI 1.02-1.28, trend = 0.05). For nut types, we found statistically significantly higher odds of healthy aging across peanuts, walnuts, and other nuts after age adjustment. After full control for confounders, only walnut consumption remained associated with healthy aging ( trend = 0.0001); for example, the OR was 1.20 (95% CI 1.00-1.44) for ≥2 servings/week versus none.

Conclusions: Women consuming nuts at midlife have a greater likelihood of overall health and well-being at older ages. Nut consumption may represent a simple intervention to explore and promote healthy aging.
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http://dx.doi.org/10.1155/2020/5651737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199627PMC
January 2020

Vitamin D Intake and Progression of Urinary Incontinence in Women.

Urology 2021 Apr 7;150:213-218. Epub 2020 May 7.

Channing Division of Network Medicine Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Epidemiology, Harvard School of Public Health, Boston, MA.

Objective: To determine if vitamin D intake is associated with reduced progression of urgency urinary incontinence (UI) in women.

Methods: We used the Nurses' Health Study (NHS) I and NHSII cohorts to evaluate the association of vitamin D intake with progression of urgency UI and mixed UI, from mild-moderate to severe symptoms, from 2004 to 2012 (NHS) and 2005-2013 (NHSII). Intake of vitamin D at study baseline was categorized and updated at the start of each 2-4 year follow-up period. Multivariable-adjusted relative risks (RRs) and 95% confidence intervals (95% CI) of progression to severe UI were estimated using Cox proportional hazard models.

Results: At baseline, of the 20,560 older women (age range 58-73 years) in NHS I with mild/moderate urgency or mixed UI, 21% reported oral vitamin D intake of at least 800 IU per day. Among 12,573 middle-aged women (age range 42-59) in NHS II with mild/moderate urgency or mixed UI, 17% reported oral vitamin D intake of at least 800 IU daily. From 2004 to 2012, 4853 incident cases of urgency/mixed UI progression were identified among older women. From 2005 to 2013, 1378 incident cases of urgency/mixed UI progression were identified among middle-aged women. After multivariable adjustment, no significant associations between vitamin D intake and incidence of urgency/mixed UI progression were observed in either cohort (RR = 1.10, 95% CI 0.99-1.23 in older women, RR = 0.88, 95% CI 0.71, 1.10 in middle-aged women).

Conclusion: Despite interest in vitamin D as a low-cost strategy to prevent or reduce UI, our findings indicate oral vitamin D may not reduce urgency/mixed UI progression.
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http://dx.doi.org/10.1016/j.urology.2020.04.090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647953PMC
April 2021

Long-Term Intake of Dietary Carotenoids Is Positively Associated with Late-Life Subjective Cognitive Function in a Prospective Study in US Women.

J Nutr 2020 07;150(7):1871-1879

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: A protective association of dietary carotenoids with cognitive function has been suggested, but most studies have been relatively small with limited periods of follow-up.

Objectives: We examined prospectively long-term intakes of carotenoids in relation to subjective cognitive function (SCF), a self-reported, validated indicator of cognitive dysfunction.

Methods: Among 49,493 female registered nurses with a mean age of 48 y in 1984, we used multinomial logistic regression to estimate the ORs and 95% CIs relating intakes of carotenoids to self-reported SCF in 2012 and 2014. Mean intakes of carotenoids were calculated from 7 repeated FFQs collected in 1984, 1986, and every 4 y afterwards until 2006. Self-reported SCF was assessed by a 7-item questionnaire on changes in memory and cognition; validity was supported by strong associations with Apolipoprotein E (APOE) ε4 genotype and concurrent cognitive function and cognitive decline measured by telephone-based neuropsychological tests. The mean values of scores assessed in 2012 and 2014 were categorized as "good" (0 points, 40.8%), "moderate" (0.5-2.5 points, 46.9%), and "poor" (3-7 points, 12.3%).

Results: Higher intake of total carotenoids was associated with substantially lower odds of moderate or poor cognitive function after controlling for other dietary and nondietary risk factors and total energy intake. Comparing the top with the bottom quintile of total carotenoids, the multivariable ORs were 0.86 (95% CI: 0.80, 0.93; P-trend < 0.001) for moderate SCF and 0.67 (95% CI: 0.60, 0.75; P-trend < 0.001) for poor SCF. This lower OR was also seen for carotenoids consumed 28 y before SCF assessment. Similar associations were found for total β-carotene, dietary β-carotene, α-carotene, lycopene, lutein + zeaxanthin, and β-cryptoxanthin. The significant associations for β-cryptoxanthin, lycopene, and lutein + zeaxanthin persisted after mutual adjustment for each other.

Conclusions: Our findings support a long-term beneficial role of carotenoid consumption on cognitive function in women.
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http://dx.doi.org/10.1093/jn/nxaa087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330480PMC
July 2020

Patient-Provider Discussions About Urinary Incontinence Among Older Women.

J Gerontol A Biol Sci Med Sci 2021 02;76(3):463-469

Department of Internal Medicine, University of Michigan, Ann Arbor.

Background: Urinary incontinence (UI) is prevalent in women and has been associated with decreased quality of life and institutionalization. Despite this, and the fact that several treatment options exist, few women discuss UI with clinicians. The aim of this study was to examine the proportion of middle aged and older women with urinary incontinence who have discussed UI with clinicians, focusing on female health professionals as a way to examine this question outside of issues of health care access.

Methods: Data are from the Nurses Health Studies (NHS), two ongoing observational, prospective, cohort studies. The surveys collected detailed information about UI, including frequency, amount and type. Women were also asked if they had discussed UI with a clinician. We used multivariable-adjusted logistic regression to estimate odds ratios (OR) of participants reporting discussion about UI.

Results: 94,692 women with UI aged 49-91 years old were included in this study. Of these, 34% reported that they had discussed their incontinence with a clinician. Women with daily UI had 4.4 times greater odds of discussing it with clinicians when compared to those with monthly UI (OR = 4.36, 95% confidence interval [CI] 4.06-4.69). When controlling for severity of symptoms, the oldest women, greater than eighty years, were 20% less likely to have discussed UI with their clinician, compared to the youngest women (OR = 0.81, 95% CI 0.73-0.89).

Conclusions: A minority of women with UI, even among health professionals, discuss their symptoms with clinicians. Oldest women were the least likely to discuss their UI with a provider.
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http://dx.doi.org/10.1093/gerona/glaa107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907491PMC
February 2021

Using network science tools to identify novel diet patterns in prodromal dementia.

Neurology 2020 05 22;94(19):e2014-e2025. Epub 2020 Apr 22.

From the University of Bordeaux (C.S., S.L.-A., C.H.), Inserm, Bordeaux Population Health Research Center, UMR 1219, France; Channing Division of Network Medicine (A.R.S., F.G., K.G.), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School; and Department of Epidemiology (F.G.), Harvard T.H. Chan School of Public Health, Boston, MA.

Objective: To use network science to model complex diet relationships a decade before onset of dementia in a large French cohort, the 3-City Bordeaux study.

Methods: We identified cases of dementia incident to the baseline food frequency questionnaire over 12 years of follow-up. For each case, we randomly selected 2 controls among individuals at risk at the age at case diagnosis and matched for age at diet assessment, sex, education, and season of the survey. We inferred food networks in both cases and controls using mutual information, a measure to detect nonlinear associations, and compared food consumption patterns between groups.

Results: In the nested case-control study, the mean (SD) duration of follow-up and number of visits were 5.0 (2.5) vs 4.9 (2.6) years and 4.1 (1.0) vs 4.4 (0.9) for cases (n = 209) vs controls (n = 418), respectively. While there were few differences in simple, average food intakes, food networks differed substantially between cases and controls. The network in cases was focused and characterized by charcuterie as the main hub, with connections to foods typical of French southwestern diet and snack foods. In contrast, the network of controls included several disconnected subnetworks reflecting diverse and healthier food choices.

Conclusion: How foods are consumed (and not only the quantity consumed) may be important for dementia prevention. Differences in predementia diet networks, suggesting worse eating habits toward charcuterie and snacking, were evident years before diagnosis in this cohort. Network methods, which are designed to model complex systems, may advance our understanding of risk factors for dementia.
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http://dx.doi.org/10.1212/WNL.0000000000009399DOI Listing
May 2020

Vitamin D intake and the 10-year risk of urgency urinary incontinence in women.

J Steroid Biochem Mol Biol 2020 05 28;199:105601. Epub 2020 Jan 28.

Channing Division of Network Medicine Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States.

Evidence indicates that higher serum 25-hydroxy vitamin D levels may be associated with decreased prevalence of urgency urinary incontinence (UI), but the impact of vitamin D consumption on development of urgency and mixed UI is unclear. The objective was to assess whether greater vitamin D intake was associated with decreased risk of incident urgency and mixed UI over 10 years using 2 large prospective cohorts of middle-aged and older women. We analyzed 38,101 women from the Nurses' Health Study I (NHS I) and 35,190 women from NHS II who were free of UI at baseline. We followed incident UI, defined as new UI occurring at least monthly, separately by subtype (urgency, mixed, stress UI), from 2002-2012. We categorized vitamin D intake from supplements and diet. We estimated relative risk for developing UI according to vitamin D intake using Cox-proportional hazard models with adjustment for covariates. Median vitamin D intake was 580IU in the older women in NHS I (age range 56-71 at baseline) and 487IU in middle-aged women in NHS II (age range 40-57). Among women taking ≥1000IU of vitamin D, median intake in the older women was 1252IU and 1202IU in the middle-aged women. Among the older women, we found no relation of vitamin D intake to risk of developing UI, across all UI subtypes. In multivariable-adjusted analysis for middle-aged women, the relative risk of developing mixed UI among women taking >1000IU was 0.79 (0.63, 0.99) and for urgency UI was 0.88 (0.71, 1.07), versus <200IU. Risks of developing stress UI were not related to vitamin D intake categories. Overall, we did not find a relationship between vitamin D intake and UI incidence in middle-aged and older women; however, the reported intake was moderate.
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http://dx.doi.org/10.1016/j.jsbmb.2020.105601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166185PMC
May 2020

Birth month, birth season, and overall and cardiovascular disease mortality in US women: prospective cohort study.

BMJ 2019 12 18;367:l6058. Epub 2019 Dec 18.

Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA

Objectives: To evaluate the associations between birth month, birth season, and overall and cardiovascular disease mortality, and to examine the role of familial and socioeconomic factors in these associations.

Design: Prospective cohort study.

Setting: Nurses' Health Study, established in 1976, an ongoing prospective cohort study in the United States.

Participants: Female registered nurses who reported information on date of birth at study enrolment (n=116 911, 1976-2014, followed for 38 years).

Exposure: Birth month and astronomical birth season (based on solstices and equinoxes as boundaries of the season categories).

Main Outcome Measures: Age and various multivariable adjusted hazard ratios and 95% confidence intervals for the association between birth months (using November as the reference), astronomical birth season (using autumn as the reference), and overall and cardiovascular disease specific mortality were assessed using Cox proportional hazards models.

Results: Among study participants, 43 248 overall deaths were documented during 4 136 364 person years of follow-up since enrolment, including 8360 cardiovascular disease related deaths. In fully adjusted multivariable analyses, no significant association was observed between birth month, birth season, and overall mortality. Compared with women born in November, increased cardiovascular disease mortality was observed among those born from March to July (hazard ratio for March, 1.09, 95% confidence interval 0.98 to 1.21; April, 1.12, 1.00 to 1.24; May, 1.08, 0.98 to 1.20; June, 1.07, 0.96 to 1.19; and July 1.08, 0.98 to 1.20). Those born in April had the highest cardiovascular disease mortality, and those born in December had the lowest (December, 0.95, 0.85 to 1.06). The relative difference between the lowest and highest risk month was 17.89%. Women born in spring (1.10, 1.04 to 1.17) and summer (1.09, 1.03 to 1.16) had a higher cardiovascular disease mortality than women born in the autumn. Adjustment for familial and socioeconomic factors did not change these results. The relative difference between the lowest and highest risk season was 10.00%.

Conclusion: Participants born in the spring and summer (especially those born in March-July) had a slight but significant increase in cardiovascular disease specific mortality. However, no seasonal birth month effect was observed among women for overall mortality. Familial and socioeconomic factors did not appear to alter these associations. Further studies are required to confirm these findings and reveal mechanisms of these seasonal birth month effects in cardiovascular disease mortality.
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http://dx.doi.org/10.1136/bmj.l6058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190053PMC
December 2019

Long-Term Trajectories of Body Weight, Diet, and Physical Activity From Midlife Through Late Life and Subsequent Cognitive Decline in Women.

Am J Epidemiol 2020 04;189(4):305-313

Bordeaux Population Health Research Center, Institut National de la Santé et de la Recherche Médicale Unité 1219, and University of Bordeaux, Institut de Santé Publique d'Epidémiologie et de Développement, Bordeaux, France.

Healthy lifestyles are promising targets for prevention of cognitive aging, yet the optimal time windows for interventions remain unclear. We selected a case-control sample nested within the Nurses' Health Study (starting year 1976, mean age = 51 years), including 14,956 women aged ≥70 years who were free of both stroke and cognitive impairment at enrollment in a cognitive substudy (1995-2001). Cases (n = 1,496) were women with the 10% worst slopes of cognitive decline, and controls (n = 7,478) were those with slopes better than the median. We compared the trajectories of body mass index (weight (kg)/height (m)2), alternate Mediterranean diet (A-MeDi) score, and physical activity between groups, from midlife through 1 year preceding the cognitive substudy. In midlife, cases had higher body mass index than controls (mean difference (MD) = 0.59 units, 95% confidence interval (CI): 0.39, 0.80), lower physical activity (MD = -1.41 metabolic equivalent of task-hours/week, 95% CI: -2.07, -0.71), and worse A-MeDi scores (MD = -0.16 points, 95% CI: -0.26, -0.06). From midlife through later life, compared with controls, cases had consistently lower A-MeDi scores but a deceleration of weight gain and a faster decrease in physical activity. In conclusion, maintaining a healthy lifestyle since midlife may help reduce cognitive decline in aging. At older ages, both deceleration of weight gain and a decrease in physical activity may reflect early signs of cognitive impairment.
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http://dx.doi.org/10.1093/aje/kwz262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443200PMC
April 2020

Genome-Wide Association Study for Urinary and Fecal Incontinence in Women.

J Urol 2020 May 15;203(5):978-983. Epub 2019 Nov 15.

Division of Urogynecology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts.

Purpose: Urinary incontinence and fecal incontinence are common disorders in women that negatively impact quality of life. In addition to known health and lifestyle risk factors, genetics may have a role in continence. Identification of genetic variants associated with urinary incontinence and fecal incontinence could result in a better understanding of etiologic pathways, and new interventions and treatments.

Materials And Methods: We previously generated genome-wide single nucleotide polymorphism data from Nurses' Health Studies participants. The participants provided longitudinal urinary incontinence and fecal incontinence information via questionnaires. Cases of urinary incontinence (6,120) had at least weekly urinary incontinence reported on a majority of questionnaires (3 or 4 across 12 to 16 years) while controls (4,811) consistently had little to no urinary incontinence reported. We classified cases of urinary incontinence in women into stress (1,809), urgency (1,942) and mixed (2,036) subtypes. Cases of fecal incontinence (4,247) had at least monthly fecal incontinence reported on a majority of questionnaires while controls (11,634) consistently had no fecal incontinence reported. We performed a genome-wide association study for each incontinence outcome.

Results: We identified 8 single nucleotide polymorphisms significantly associated (p <5×10) with urinary incontinence located in 2 loci, chromosomes 8q23.3 and 1p32.2. There were no genome-wide significant findings for the urinary incontinence subtype analyses. However, the significant associations for overall urinary incontinence were stronger for the urgency and mixed subtypes than for stress. While no single nucleotide polymorphism reached genome-wide significance for fecal incontinence, 4 single nucleotide polymorphisms had p <10.

Conclusions: Few studies have collected genetic data and detailed urinary incontinence and fecal incontinence information. This genome-wide association study provides initial evidence of genetic associations for urinary incontinence and merits further research to replicate our findings and identify additional risk variants.
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http://dx.doi.org/10.1097/JU.0000000000000655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659982PMC
May 2020

Impact of adverse childhood experiences on cardiovascular disease risk factors in adulthood among Mexican women.

Child Abuse Negl 2020 01 8;99:104175. Epub 2019 Nov 8.

Center for Research on Population Health, National Institute of Public Health, 7ª Cerrada Fray Pedro de Gante # 50, Mexico City, 14000, Mexico; Department of Global Health and Population, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA, 02115, United States. Electronic address:

Background: Childhood adversities are prevalent worldwide and might affect adult cardiovascular health. However, in middle-income countries such as Mexico, research on the impact of childhood adversities on cardiovascular disease (CVD) in adulthood is lacking.

Objective: To evaluate the prevalence of adverse childhood experiences (ACEs) and their association with risk factors for CVD in adult Mexican women.

Participants And Setting: The study population comprised 9853 women from the Mexican Teachers´ Cohort.

Methods: Participants responded to an online questionnaire including a 10-item instrument on ACEs and questions on CVD risk factors, between 2014 and 2017. Multivariate logistic regression models were used to evaluate the association between ACEs and adult behavioral and medical CVD risk factors.

Results: About 61% of participants reported at least one ACE and 14% reported four or more. After multivariable adjustment, women who reported ≥4 ACEs had 58% (95%CI 1.37, 1.81) higher odds of having ever smoked and 17% (95%CI 0.69, 0.99) lower odds of being physically active, compared with women who reported no ACEs. Women who reported ≥4 ACEs also had higher odds of hypertension (OR = 1.19; 95%CI 1.00, 1.43), diabetes (OR = 1.49; 95%CI 1.13, 1.96), high cholesterol (OR = 1.49; 95%CI 1.26, 1.75), and obesity (OR = 1.37; 95%CI 1.19, 1.57). In addition, individual ACE components were independently associated with several CVD risk factors.

Conclusion: ACEs are common and associated with CVD risk factors in adult Mexican women.
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http://dx.doi.org/10.1016/j.chiabu.2019.104175DOI Listing
January 2020

Interaction between apolipoprotein E genotype and hypertension on cognitive function in older women in the Nurses' Health Study.

PLoS One 2019 7;14(11):e0224975. Epub 2019 Nov 7.

Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.

Objective: To examine the interaction between APOE genotypes and both treated and untreated hypertension on cognitive function in an updated analysis of Nurses' Health Study (NHS) data.

Design: At baseline (1995-2001) and 3 biennial follow-up assessments over ~6 years, cognitive function was assessed.

Setting And Participants: 8300 NHS participants aged 70+ years underwent a cognitive battery, which comprised 6 tests including the Telephone Interview for Cognitive Status (TICS) and tests of verbal memory, category fluency, and working memory.

Measures: We estimated the mean differences in average cognitive scores across up to 4 assessments using multiple linear regression. We also tested for interaction between APOE e4 allele carrier status and hypertension overall, as well as for apparently untreated and treated hypertension.

Results: We confirmed that, compared with those with APOE e3/3 genotype, APOE e4 allele carriers scored lower by 0.55 units on the average TICS score (95%CI:-0.67,-0.43). We also observed a significantly worse average TICS score among women with untreated hypertension compared with women without hypertension (difference = -0.23, 95%CI:-0.37,-0.09), while no significant difference was observed for women with treated hypertension. Significant interaction was detected between the APOE e4 allele and untreated hypertension (p-int = 0.02 for the TICS; p-int = 0.045 for global score), but not with treated hypertension. Specifically, compared with normotensive women with the APOE e3/3 genotype, APOE e4 allele carriers with treated hypertension scored lower by 0.50 units (95%CI:-0.69,-0.31); however, the APOE e4 allele carriers with untreated hypertension scored lower by 1.02 units on the TICS score (95%CI:-1.29, -0.76). This interaction of APOE e4 and untreated hypertension was also consistently observed for the global score.

Conclusions: Women with hypertension and at least one APOE e4 allele had worse average cognitive function compared with women without hypertension with the e3/3 genotype; this difference was amplified among APOE e4 allele carriers with untreated hypertension.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224975PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6837309PMC
March 2020

The Relation of Optimism to Relative Telomere Length in Older Men and Women.

Psychosom Med 2020 Feb/Mar;82(2):165-171

From the Department of Social and Behavioral Sciences (Kim, Kubzansky) and Lee Kum Sheung Center for Health and Happiness (Kim, Kubzansky), Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Human Flourishing Program, Institute for Quantitative Social Science (Kim), Harvard University, Cambridge, Massachusetts; Vanderbilt University Medical Center (Tindle, Duncan); Nashville, Tennessee; Department of Epidemiology (SLiu), Brown University School of Public Health, Providence, RI; Department of Epidemiology (Manson, Grodstein), Harvard T.H. Chan School of Public Health; Department of Medicine (Manson), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Stanford Prevention Research Center (Springfield), Stanford University, Palo Alto, California; Miriam Hospital, Warren Alpert School of Medicine (Salmoirago-Blotcher), Brown University, Providence, Rhode Island; Department of Family Medicine and Public Health (Shadyab), University of California San Diego School of Medicine, La Jolla, California; Department of Epidemiology (BLiu), College of Public Health, University of Iowa, Iowa City, Iowa; Channing Division of Network Medicine (Grodstein, De Vivo), Brigham and Women's Hospital, Boston, Massachusetts.

Objective: Mounting evidence suggests that higher optimism is associated with reduced risk of age-related morbidities and premature mortality. However, possible biological mechanisms underlying these associations remain understudied. One hypothesized mechanism is a slower rate of cellular aging, which in turn delays age-related declines in health.

Methods: We used data from two large cohort studies to test the hypothesis that higher optimism is associated with longer leukocyte telomere length. With cross-sectional data from the Health and Retirement Study (HRS; n = 6417; mean age = 70 years) and the Women's Health Initiative (WHI; N = 3582; mean age = 63 years), we used linear regression models to examine the association of optimism with relative telomere length (assessed in leukocytes from saliva [HRS] or plasma [WHI]). Models adjusted for sociodemographics, depression, health status, and health behaviors.

Results: Considering both optimism and telomere length as continuous variables, we found consistently null associations in both cohorts, regardless of which covariates were included in the models. In models adjusting for demographics, depression, comorbidities, and health behaviors, optimism was not associated with mean relative telomere length (HRS: β = -0.002, 95% confidence interval = -0.014 to 0.011; WHI: β = -0.004, 95% confidence interval = -0.017 to 0.009).

Conclusions: Findings do not support mean telomere length as a mechanism that explains observed relations of optimism with reduced risk of chronic disease in older adults. Future research is needed to evaluate other potential biological markers and pathways.
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http://dx.doi.org/10.1097/PSY.0000000000000764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522724PMC
January 2021

Associations of autozygosity with a broad range of human phenotypes.

Nat Commun 2019 10 31;10(1):4957. Epub 2019 Oct 31.

Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht University, Utrecht, 3584 CX, The Netherlands.

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F) for >1.4 million individuals, we show that F is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F are confirmed within full-sibling pairs, where the variation in F is independent of all environmental confounding.
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http://dx.doi.org/10.1038/s41467-019-12283-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823371PMC
October 2019

Longitudinal study of self-reported hearing loss and subjective cognitive function decline in women.

Alzheimers Dement 2020 04 13;16(4):610-620. Epub 2020 Feb 13.

Charming Division of Network, Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.

Introduction: We investigated the relation between self-reported hearing loss and risk of subjective cognitive function (SCF) decline among women.

Methods: We conducted a longitudinal study of 20,193 women in the Nurses' Health Study aged ≥66 years who reported their hearing status and had no subjective cognitive concerns in 2012. SCF scores were assessed by a 7-item questionnaire in 2012 and 2014. SCF decline was defined as a new report of at least one cognitive concern during follow-up.

Results: Self-reported hearing loss was associated with higher risk of SCF decline. Compared with women with no hearing loss, the multivariable-adjusted odds ratios (95% confidence interval) for incident SCF score ≥1 were 1.35 (1.25, 1.47), 1.39 (1.24, 1.56), and 1.40 (1.21, 1.75) among women with mild, moderate, and severe hearing loss, respectively. Recent progression of hearing loss was associated with even higher risk.

Discussion: Self-reported hearing loss was associated with higher risk of incident subjective cognitive function decline in women.
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http://dx.doi.org/10.1016/j.jalz.2019.08.194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138704PMC
April 2020

Social Media as an Emerging Data Resource for Epidemiologic Research: Characteristics of Regular and Nonregular Social Media Users in Nurses' Health Study II.

Am J Epidemiol 2020 02;189(2):156-161

Department of Epidemiology, T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.

With advances in natural language processing and machine learning, researchers are leveraging social media as a low-cost, low-burden method for measuring various psychosocial factors. However, it is unclear whether information derived from social media is generalizable to broader populations, especially middle-aged and older adults. Using data on women aged 53-70 years from Nurses' Health Study II (2017-2018; n = 49,045), we assessed differences in sociodemographic characteristics, health conditions, behaviors, and psychosocial factors between regular and nonregular users of Facebook (Facebook, Inc., Menlo Park, California). We evaluated effect sizes with phi (φ) coefficients (categorical data) or Cohen's d (continuous data) and calculated odds ratios with 95% confidence intervals. While most comparisons between regular and nonregular users achieved statistical significance in this large sample, effect sizes were mostly "very small" (conventionally defined as φ or d <0.01) (e.g., optimism score: meanregular users = 19 vs. meannonregular users = 19 (d = -0.03); physical activity: meanregular users = 24 metabolic equivalent of task (MET)-hours/week vs. meannonregular users = 24 MET-hours/week (d = 0.01)). Some factors had slightly larger differences for regular users versus nonregular users (e.g., depression: 28% vs. 23% (φ = 0.05); odds ratio = 1.27 (95% confidence interval: 1.22, 1.33); obesity: 34% vs. 26% (φ = 0.07); odds ratio = 1.42 (95% confidence interval: 1.36, 1.48)). Results suggest that regular Facebook users were similar to nonregular users across sociodemographic and psychosocial factors, with modestly worse health regarding obesity and depressive symptoms. In future research, investigators should evaluate other demographic groups.
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http://dx.doi.org/10.1093/aje/kwz224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156136PMC
February 2020

The Prospective Association of Social Integration With Life Span and Exceptional Longevity in Women.

J Gerontol B Psychol Sci Soc Sci 2020 11;75(10):2132-2141

Department of Social and Behavioral Sciences and Happiness, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Objectives: Although stronger social relationships have been associated with reduced mortality risk in prior research, their associations with favorable health outcomes are understudied. We evaluated whether higher social integration levels were associated with longer life span and greater likelihood of achieving exceptional longevity.

Method: Women from the Nurses' Health Study completed the Berkman-Syme Social Network Index in 1992 (N = 72,322; average age = 58.80 years), and were followed through 2014 with biennial questionnaires. Deaths were ascertained from participants' families, postal authorities, and death registries. Accelerated failure time models adjusting for relevant covariates estimated percent changes in life span associated with social integration levels; logistic regressions evaluated likelihood of surviving to age 85 years or older among women who could reach that age during follow-up (N = 16,818).

Results: After controlling for baseline demographics and chronic diseases, socially integrated versus isolated women had 10% (95% confidence interval [CI] = 8.80-11.42) longer life span and 41% (95% CI = 1.28-1.54) higher odds of surviving to age 85 years. All findings remained statistically significant after further adjusting for health behaviors and depression.

Discussion: Better social integration is related to longer life span and greater likelihood of achieving exceptional longevity among midlife women. Findings suggest social integration may be an important psychosocial asset to evaluate for promoting longer, healthier lives.
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http://dx.doi.org/10.1093/geronb/gbz116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664314PMC
November 2020
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