The Journals of Gerontology Series A: Biological Sciences and Medical Sciences最新文献

{"title":"Joint Association of Combined Healthy Lifestyle Factors and Hearing Loss with Cognitive Impairment in China","authors":"Feifan Zhao, Zhentao Wang, Zaichao Wu, Xueling Wang, Yun Li, Yunge Gao, Kun Han, Qiongfei Yu, Cai Wu, Jie Chen, Dan Zhao, Keqing Dong, Yan Qian, Xuanyi Wu, Ying Chen, Hao Wu","doi":"10.1093/gerona/glae226","DOIUrl":"https://doi.org/10.1093/gerona/glae226","url":null,"abstract":"Background Hearing loss and lifestyle factors have been associated with cognitive impairment. We aimed to explore the joint association of combined healthy lifestyle factors and hearing loss with cognitive impairment, which has been scarcely studied. Methods This baseline study used data from the CHOICE-Cohort study (Chinese Hearing Solution for Improvement of Cognition in Elders). Hearing loss was assessed by the better-ear pure-tone average (BPTA). A composite healthy lifestyle score was built based on never smoking, never drinking, regular physical activity, and balanced diet. Cognitive impairment was diagnosed by the Mini-Mental State Examination (MMSE) score of less than 24. Results We included 17057 participants aged 60 years or older in China (mean age 69.8 [SD 6.2] years, 55.7% female). Among the participants, 48.3% (n=8234) had mild hearing loss, and 25.8% (n=4395) had moderate or greater hearing loss. The proportion of participants with healthy lifestyle scores of 0-1, 2, 3, and 4 was 14.9% (n=2539), 29.3% (n=5000), 37.4% (n=6386), and 18.4% (n=3132), respectively. 29.6% (n=5057) participants had cognitive impairment. When compared to those with normal hearing and healthy lifestyle (scores of 3-4), participants with hearing loss plus unhealthy lifestyle (scores of 0-2) exhibited approximately twofold increased risk of cognitive impairment (OR=1.92, 95% CI 1.70-2.18). Conversely, the risk was greatly attenuated by adherence to healthy lifestyle in individuals with hearing loss (OR=1.57, 95% CI 1.40-1.76). Conclusions Our findings demonstrated adherence to a broad range of healthy lifestyle factors was associated with a significantly lower risk of cognitive impairment among participants with hearing loss.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stair Climbing, Genetic Predisposition, and the Risk of Hip/Knee Osteoarthritis","authors":"Yingliang Wei, Tingjing Zhang, Haochen Wang, Jianbang Su, Minghao Yu, Yashu Liu, Lunhao Bai, Yang Xia","doi":"10.1093/gerona/glae223","DOIUrl":"https://doi.org/10.1093/gerona/glae223","url":null,"abstract":"Background Few studies have explored the association between stair climbing and osteoarthritis (OA) to determine whether the former is a protective or risk factor for the latter. This study prospectively evaluated the associations among stair climbing, genetic susceptibility, and their interaction with the risk of incident hip/knee OA. Methods The cohort analyses included 398,939 participants from the UK Biobank. Stair climbing was assessed using a questionnaire. Genetic risk scores (GRSs) consisting of 70, 83, and 87 single-nucleotide polymorphisms for hip, knee, and hip/knee OA were constructed. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations among stair climbing, genetic predisposition, and hip and/or knee OA risk. Results After 3,621,735 person-years of follow-up, 31,940 patients developed OA. Stair climbing was positively associated with incident hip/knee (P for trend<0.001) and knee (P for trend<0.0001) OA but not hip OA. After adjustments, compared with no stair climbing, climbing >150 steps/day was associated with a higher risk of hip/knee OA (HR, 1.08; 95% CI, 1.03–1.12) and knee OA (HR, 1.13; 95% CI, 1.06–1.20). Although no significant interaction between stair climbing and the GRS of OA risk was found, the above associations were only significant in participants with middle and high GRSs. Conclusion A higher frequency of stair climbing was positively associated with the risk of knee OA but not hip OA, highlighting the importance of avoiding frequent stair climbing in preventing knee OA, especially in genetically predisposed individuals.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social Isolation and Hospitalization in Community-dwelling Older Adults by Dementia Status","authors":"Mary Louise Pomeroy, Mfon Umoh, Yiqing Qian, Gilbert Gimm, Katherine A Ornstein, Thomas K M Cudjoe","doi":"10.1093/gerona/glae224","DOIUrl":"https://doi.org/10.1093/gerona/glae224","url":null,"abstract":"Background Social isolation is a well-known risk factor for poor health outcomes, including incident dementia, yet its associations with outcomes among persons living with dementia is understudied. We examined the association between social isolation and hospitalization among a nationally representative sample of older adults with and without dementia. Methods This observational cohort study included 5,533 community-dwelling Medicare beneficiaries from the 2015 and 2016 National Health and Aging Trends Study (NHATS). Using multivariable logistic regression analyses, we examined associations between social isolation and hospitalization in the following year, examining differences by dementia status. Social isolation was measured using a 4-item typology. Dementia was identified using a pre-specified classification in NHATS. Results 20.7% of older adults were socially isolated. Social isolation was more prevalent among persons with dementia (35.4%) than among those without dementia (19.0%) (p < .001). Among persons with dementia, social isolation was associated with 1.68 greater odds of hospitalization (CI: 1.23‒2.28), translating into a 9% average increase in the predicted probability of hospitalization for persons with dementia who were socially isolated compared to those who were not (p = 0.001). In the combined sample that included persons with and without dementia, there was a significant moderation effect of dementia on the association between social isolation and hospitalization (OR: 1.70; CI: 1.19‒2.43). Conclusions For persons with dementia, social isolation is prevalent and associated with greater odds of subsequent hospitalization. Efforts to reduce acute healthcare utilization should explore ways to bolster social connection to improve health outcomes among persons with dementia.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Muscle Quality And Physical Function In Men With And Without Hiv","authors":"Jing Sun, Grace L Ditzenberger, Todd T Brown, Susan Langan, Hsing-Yu Hsu, Derek Ng, Frank J Palella, Jordan E Lake, Lawrence A Kingsley, Susan L Koletar, Wendy Post, Kristine M Erlandson","doi":"10.1093/gerona/glae229","DOIUrl":"https://doi.org/10.1093/gerona/glae229","url":null,"abstract":"Background People with HIV (PWH) experience faster physical decline than those without HIV (PWoH), despite antiretroviral therapy. We compared skeletal muscle density and area and their relationship with physical function among PWH and PWoH. Methods Quantitative computed tomography (CT) scans were performed at the L4-L5 spinal region and the thigh to evaluate muscle groups in Multicenter AIDS Cohort (MACS) participants at baseline. Using exploratory factor analysis, we summarized aggregated muscle measures based on factor loadings. Longitudinal associations between muscle area and density with gait speed and grip strength were examined using multivariable linear regression models with generalized estimating equations, adjusting for demographics, HIV serostatus, and other health metrics. Results We included 798 men (61% of PWH). The median age was 54 years (IQR: 49-59), 61% were White, 32% Black, and 10% Hispanic. Among them, 22% had a BMI over 30 kg/m2, and 14% had diabetes. Two factors emerged from the factor analysis explaining 55.9% of variance. Factor 1 (explained 32.5% of variance) encompassed all density measures. Factor 2 (explained 23.4% of variance) encompassed all area measures. Associations between muscle density and gait speed were more pronounced with aggregated measures than with individual ones. Specifically, each unit increase in overall muscle density correlated with a 0.028 meter/second increase in gait speed (95% confidence interval [CI]: 0.017, 0.038, p<0.01). Grip strength was associated with aggregated measures of both muscle density and area, with overall muscle density associated with a 1.88 kg increase in grip strength (95% CI: 1.29, 2.46, p<0.01), and overall muscle area with a 1.60 kg increase (95% CI: 1.02, 2.19, p<0.01). Conclusions Aggregated muscle density and area measurements were significantly associated with physical function. These correlations underscore the importance of interventions to enhance skeletal muscle to improve healthy aging for PWH and PWoH.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Racial differences in the association between loneliness and cognitive impairment among older Black and White men","authors":"Bettina M Beech, Marino A Bruce, Ankita Siddhanta, Gillian L Marshall, Keith E Whitfield, Roland J Thorpe","doi":"10.1093/gerona/glae227","DOIUrl":"https://doi.org/10.1093/gerona/glae227","url":null,"abstract":"Background Loneliness is a biopsychosocial stressor linked to poor health outcomes including dementia. Few studies have focused on this association among men and even fewer have examined racial disparities in loneliness and cognitive functioning among this group. The purpose of this study was to examine racial differences in the association between loneliness and cognitive functioning among men in the 2016 wave of the Health and Retirement Study (HRS). Methods This cross-sectional study included Black and White men who completed the core questionnaire and the Leave Behind Questionnaire (n=2227). Any cognitive impairment was the primary outcome and was measured by a dichotomous variable derived from a modified version of the Telephone Interview for Cognitive Status. Loneliness was the primary independent variable and was derived from the 3-item UCLA Loneliness Scale. Modified Poisson regression models with robust standard errors were estimated to generate prevalence ratios and corresponding 95% confidence intervals. Results Black men comprised 18.4% of the study sample; however, the proportion of this group with scores indicating cognitive impairment (35.9%) doubled the corresponding percentage of white men (17.6%). Findings from race-stratified modified Poisson regression models indicated that loneliness was associated with a higher prevalence of any cognitive impairment for White men (PR=1.24, CI:1.05-1.47), but not for Black men (PR=0.92, CI:0.73-1.16). Conclusions Our results underscore the complexity of race when investigating the association between loneliness and cognitive impairment among older men. Additional studies are needed to further examine how loneliness may have racially distinct implications for cognitive outcomes among the population.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholinesterase Inhibitor Initiation Does Not Increase the Risk of Fall-Related Injury in Older Adults Treated with Beta-blockers: a self-controlled case series design","authors":"Meghan A Cupp, Sarah D Berry, Kaleen N Hayes, Lori A Daiello, Darae Ko, Melissa R Riester, Andrew R Zullo","doi":"10.1093/gerona/glae219","DOIUrl":"https://doi.org/10.1093/gerona/glae219","url":null,"abstract":"Background Prescribing cholinesterase inhibitors (ChEIs) concurrently with beta-blockers might cause syncope that increases the risk of fall-related injuries (FRIs). This self-controlled case series study assesses the risk of FRIs associated with initiating ChEIs while receiving beta-blockers among Medicare fee-for-service-insured nursing home (NH) residents in the United States. Methods We identified individuals at their first dispensing of a beta-blocker between 2016 and 2019 after at least 45 days of long-stay NH residency. Individuals were followed from the first day of beta-blocker use until beta-blocker discontinuation, Medicare disenrollment, death, or study end. ChEI initiation was classified as the first 60 days of new ChEI dispensing after 45 days of no ChEI exposure. FRIs were assessed during beta-blocker use periods and age-adjusted incidence rate ratios (IRR) for ChEI-initiation days versus other days were calculated using conditional Poisson regression models. Analyses were weighted for event-dependent observation periods due to the high risk of mortality after an FRI in this population. Subgroup analyses were conducted for several key time-fixed variables, including sex, age, ChEI type, ChEI dose, beta-blocker selectivity and beta-blocker dose. Results The FRI risk after ChEI initiation was not elevated among 837 residents who experienced an FRI while using beta-blockers (IRR=0.90 [95%CLs 0.71, 1.15]). Analyses of ChEI initiation in several subgroups yielded similar results. Conclusions There was no substantial difference in FRI risk when initiating ChEIs among older NH residents receiving beta-blocker therapy versus periods without ChEI initiation, suggesting that there is no clinically significant pharmacodynamic drug-drug interaction between beta-blockers and ChEIs.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2-(3,4-dihydroxyphenyl)ethyl 3-hydroxybutanoate (HTHB) ameliorates cognitive dysfunction via modulating gut microbiota in aged senescence-accelerated mouse prone 8 (SAMP8) mice","authors":"Le Shi, Peipei Gao, Yue Zhang, Quanyu Liu, Ranrui Hu, Zhuang Zhao, Yachong Hu, Xiaohong Xu, Yehua Shen, Jiankang Liu, Jiangang Long","doi":"10.1093/gerona/glae220","DOIUrl":"https://doi.org/10.1093/gerona/glae220","url":null,"abstract":"Numerous studies have indicated a close association between gut microbiota dysbiosis, inflammation, and cognitive impairment, highlighting their crucial role in the aging process. 2-(3,4-Dihydroxyphenyl)ethyl 3-hydroxybutanoate (HTHB), a novel derivative of hydroxytryrosol (HT), known for its metabolic and anti-inflammatory properties, was investigated for its effects on memory, inflammation, and gut microbiota in senescence-accelerated mouse prone 8 (SAMP8) mice. The study employed behavioral testing, biochemical detection and 16S RNA analysis. Results revealed that HTHB mitigated memory decline and lymphocyte aberrance, reduced inflammation in the brain cortex, intestine and peripheral system, and modulated gut microbiota dysbiosis. Interestingly, the cognitive function and serum inflammation of mice significantly correlated with differences in gut microbiota in SAMP8 mice. Furthermore, HTHB treatment exhibited an enhancement of gut barrier integrity in colon tissue in SAMP8 mice. In vitro experiments using HCT116 and DLD1 cells further evidenced that HTHB rescued the tight junction protein levels impaired by lipopolysaccharide (LPS). These finding demonstrate that HTHB effectively ameliorates cognitive dysfunction in aged mice, might by modulating gut microbiota, suppressing inflammation and promoting intestinal barrier integrity. This highlights the potential of HTHB as a therapeutic agent for age-related cognitive loss.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Higher striatal dopamine is related with lower physical performance fatigability in community-dwelling older adults","authors":"Caterina Rosano, Lana M Chahine, Emma L Gay, Paul M Coen, Nico I Bohnen, Stephanie A Studenski, Brian LoPresti, Andrea L Rosso, Theodore Huppert, Anne B Newman, Sarah K Royse, Stephen B Kritchevsky, Nancy W Glynn","doi":"10.1093/gerona/glae209","DOIUrl":"https://doi.org/10.1093/gerona/glae209","url":null,"abstract":"Background Fatigability in community-dwelling older adults is highly prevalent and disabling, but lacks a treatment. Greater nigrostriatal dopaminergic signaling can ameliorate performance fatigability in healthy young adults, but its role in community-dwelling older adults is not known. We hypothesized that higher nigrostriatal dopaminergic integrity would be associated with lower performance fatigability, independent of cardiopulmonary and musculoskeletal energetics and other health conditions. Methods In 125 older adults participating in the Study of Muscle, Mobility and Aging, performance fatigability was measured as performance deterioration during a fast 400 meter walk (% slowing down from the 2nd to the 9th lap). Nigrostriatal DA integrity was measured using (+)-[11C] dihydrotetrabenazine (DTBZ) PET imaging. The binding signal was obtained separately for the subregions regulating sensorimotor (posterior putamen), reward (ventral striatum) and executive control processes (dorsal striatum). Multivariable linear regression models of performance fatigability (dependent variable) estimated the coefficients of dopamine integrity in striatal subregions, adjusted for demographics, comorbidities, and cognition. Models were further adjusted for skeletal muscle energetics (via biopsy) and cardiopulmonary fitness (via cardiopulmonary exercise testing). Results Higher [11C]-DTBZ binding in the posterior putamen was significantly associated with lower performance fatigability (demographic-adjusted standardized Beta = -1.08, 95% CI: -1.96, -0.20); results remained independent of adjustment for other covariates, including cardiopulmonary and musculoskeletal energetics. Associations with other striatal subregions were not significant. Discussion Dopaminergic integrity in the sensorimotor striatum may influence performance fatigability in older adults without clinically overt diseases, independent of other aging systems.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial peptides from the gut microbiome of the centenarians: diversification of biosynthesis and youthful development of resistance genes","authors":"Chunrong Lu, Xiaojun Wang, Pengpeng Ye, Zhilong Lu, Jie Ma, Weifei Luo, Shuai Wang, Xiaochun Chen","doi":"10.1093/gerona/glae218","DOIUrl":"https://doi.org/10.1093/gerona/glae218","url":null,"abstract":"Antimicrobial peptides (AMPs) offer a potential solution to the antibiotic crisis owing to their antimicrobial properties, and the human gut biome may be a source of these peptides. However, the potential AMPs and antimicrobial peptide resistance genes (AMPRGs) of gut microbes in different age groups has not been thoroughly assessed. Here, we investigated the potential development of AMPs and the distribution pattern of AMPRGs in the gut microbiome at different ages by analyzing the intestinal metagenomic data of healthy individuals at different life stages (CG: centenarians group n=20; OAG: older adults group n=15; YG: young group n=15). Age-related increases were observed in the potential AMPs within the gut microbiome, with centenarians showing a greater diversity of these peptides. However, the gut microbiome of the CG group had a lower level of AMPRGs compared to that of the OAG group, and it was similar to the level found in the YG group. Additionally, conventional probiotic strains showed a significant positive correlation with certain potential AMPs and were associated with a lower detection of resistance genes. Additionally, comparing potential AMPs with existing libraries revealed limited similarity, indicating that current machine-learning models can identify novel peptides in the gut microbiota. These results indicate that longevity may benefit from diversity of AMPs and lower resistance genes. Our findings help explain the age advantage of the centenarians and identify the potential for antimicrobial peptide biosynthesis in the human gut microbiome, offering insights into the development of antimicrobial peptide resistance and the screening of probiotic strains.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA Methylation Mediates the Association between Cardiometabolic Risk Factors and Cognition: Findings from the Health and Retirement Study","authors":"Zengyi Wan, Lori B Chibnik, Linda Valeri, Timothy M Hughes, Deborah Blacker, Yuan Ma","doi":"10.1093/gerona/glae167","DOIUrl":"https://doi.org/10.1093/gerona/glae167","url":null,"abstract":"The association between cardiometabolic risk factors and cognitive function has been well documented, but the underlying mechanisms are not fully understood. This longitudinal study aimed to investigate the potential mediating role of DNA methylation in this association. We conducted the analyses in 3708 participants (mean [SD] age: 67.3 [9.49], women: 57.9%) from the Health and Retirement Study who were assessed in the 2014 to 2020 waves, had Infinium Methylation EPIC BeadChip methylation assays from the 2016 Venous Blood Study, and had cognitive assessment between 2016-2020. Causal mediation analyses were used to test the mediation role of DNA methylation in the associations between cardiometabolic risk factors and cognition, adjusting for demographic, socioeconomic, and lifestyle factors. Hypertension (-0.061 in composite cognitive z-score; 95% CI: (-0.119, -0.004)) and diabetes (-0.134; 95% CI: (-0.198, -0.071)) were significantly associated with worse cognitive function while abnormal BMI and hypercholesterolemia were not. An increased number of cardiometabolic risk factors was associated with worse cognitive function (P=0.002). DNA methylation significantly mediated the association of hypertension (mediated effect on composite cognitive z-score: -0.023; 95% CI: (-0.033, -0.014)), diabetes (-0.022; 95% CI: (-0.032, -0.014)), and obesity (-0.021; 95% CI: (-0.033, -0.011)) with cognitive function, while the mediation effect was not observed for having hypercholesterolemia. The estimated proportions mediated were 37.4% for hypertension and 16.7% for diabetes. DNA methylation may be an important mediator linking cardiometabolic risk factors to worse cognition and might even provide a potential target for dementia prevention.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141462675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}