GeroScience最新文献

{"title":"Effects of home-based exercise with or without cognitive training on cognition and mobility in cardiac patients: A randomized clinical trial","authors":"Florent Besnier, Emma Gabrielle Dupuy, Christine Gagnon, Thomas Vincent, Tudor Vrinceanu, Caroll-Ann Blanchette, Josep Iglesies-Grau, Kathia Saillant, Malorie Chabot-Blanchet, Sylvie Belleville, Martin Juneau, Paolo Vitali, Mathieu Gayda, Anil Nigam, Louis Bherer","doi":"10.1007/s11357-025-01530-y","DOIUrl":"https://doi.org/10.1007/s11357-025-01530-y","url":null,"abstract":"<p>This randomized controlled trial compared the effects of home-based exercise, with or without cognitive training, on cognition and physical function in individuals aged 50 years and older with stable CVD during the COVID-19 pandemic. 122 patients (67.3 ± 7.9 years, 71% men) with stable CVD (77% coronary heart disease) were randomly assigned (1:1) to (1) Home-based physical exercise alone, or (2) Home-based physical exercise combined with cognitive training. Cognition (executive functions (primary outcome), processing speed, episodic memory, and working memory) and physical functions were assessed remotely at baseline, 3 months, and 6 months. Adjusted mean changes from baseline to 3 months and 6 months for executive functions, episodic memory, working memory, sit-to-stand test, gait speed, and timed up-and-go test were significant in the overall sample (<i>p</i> &lt; 0.05). Furthermore, executive functions, episodic memory, sit-to-stand test, and timed up-and-go performances were significantly improved at 6 months in both groups when analyzed separately although no group differences were observed. Mean exercise dose differed significantly between the 2 groups: 1413 vs 953 METs.min⁻¹ week⁻¹ respectively for the exercise and combined group (<i>p</i> &lt; 0.01). Mean cognitive training duration was 25.6 ± 16.6 min.week⁻¹ for the combined intervention group. Results remained unchanged after accounting for the exercise dose. In adults affected by CVD, a remote combined intervention integrating sequential cognitive and exercise training yields comparable enhancements in executive function, episodic memory, and physical performances compared to exercise training alone. ClinicalTrials.gov: NCT04661189.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3>\u0000","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"20 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal relationships between depressive symptoms, functional impairment, and physical activity in later late life.","authors":"Lisa Y Xiong, Madeline Wood Alexander, Hugo Cogo-Moreira, Che-Yuan Wu, Michael Eid, Nathan Herrmann, Damien Gallagher, Jodi D Edwards, Krista L Lanctôt, Susan Marzolini, David A Bennett, Jennifer S Rabin, Walter Swardfager","doi":"10.1007/s11357-024-01282-1","DOIUrl":"10.1007/s11357-024-01282-1","url":null,"abstract":"<p><p>The purpose of this study was to investigate relationships between depressive symptoms, functional disability, and physical activity over time in community-dwelling older adults. The Religious Order Study and Rush Memory and Aging Project are longitudinal cohort studies based in the United States which began recruitment in 1994 and 1997, respectively. This analysis included 1611 participants (27.4% male, 92.9% White, 74.7% cognitively normal) who were included at age 80 and followed until age 90. Depressive symptoms were assessed using the modified Center for Epidemiologic Studies Depression scale. Functional disability was assessed using the Instrumental Activities of Daily Living (IADL) scale. Physical activity was self-reported hours of weekly exercise. Reciprocal temporal relationships between these variables were investigated using a random intercept cross-lagged panel model, which decomposes observed variables into stable between-person ('trait') and variable within-person ('state') components to estimate the directional effects between variables over time. Traits for depressive symptoms, IADL disability, and physical activity were correlated. IADL disability showed autoregressive effects; disability starting at age 82 strongly predicted subsequent disability. Consistent autoregressive effects were not observed for depressive symptoms nor physical activity. Several small cross-lagged effects between states were observed for IADL disability and physical activity, as well as for IADL disability and depressive symptoms. There were no direct effects between depressive symptoms and physical activity, but several paths through IADL disability were observed between ages 82 and 88. Functional disability played an important role in octogenarians, highlighting the importance of maintaining functional independence later in life.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"1061-1073"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mouse Social Frailty Index (mSFI): a novel behavioral assessment for impaired social functioning in aging mice.","authors":"Charles W Collinge, Maria Razzoli, Rachel Mansk, Seth McGonigle, Dudley W Lamming, Christina A Pacak, Ingrid van der Pluijm, Laura Niedernhofer, Alessandro Bartolomucci","doi":"10.1007/s11357-024-01263-4","DOIUrl":"10.1007/s11357-024-01263-4","url":null,"abstract":"<p><p>Various approaches exist to quantify the aging process and estimate biological age on an individual level. Frailty indices based on an age-related accumulation of physical deficits have been developed for human use and translated into mouse models. However, declines observed in aging are not limited to physical functioning but also involve social capabilities. The concept of \"social frailty\" has been recently introduced into human literature, but no index of social frailty exists for laboratory mice yet. To fill this gap, we developed a mouse Social Frailty Index (mSFI) consisting of seven distinct assays designed to quantify social functioning which is relatively simple to execute and is minimally invasive. Application of the mSFI in group-housed male C57BL/6 mice demonstrated a progressively elevated levels of social frailty through the lifespan. Conversely, group-housed females C57BL/6 mice manifested social frailty only at a very old age. Female mice also showed significantly lower mSFI score from 10 months of age onward when compared to males. We also applied the mSFI in male C57BL/6 mice under chronic subordination stress and in chronic isolation, both of which induced larger increases in social frailty compared to age-matched group-housed males. Lastly, we show that the mSFI is enhanced in mouse models that show accelerated biological aging such as progeroid Ercc1^-/Δ and Xpg^-/- mice of both sexes compared to age matched littermate wild types. In summary, the mSFI represents a novel index to quantify trajectories of biological aging in mice and may help elucidate links between impaired social behavior and the aging process.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"85-107"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological aging of different blood cell types.","authors":"Saara Marttila, Sonja Rajić, Joanna Ciantar, Jonathan K L Mak, Ilkka S Junttila, Laura Kummola, Sara Hägg, Emma Raitoharju, Laura Kananen","doi":"10.1007/s11357-024-01287-w","DOIUrl":"10.1007/s11357-024-01287-w","url":null,"abstract":"<p><p>Biological age (BA) captures detrimental age-related changes. The best-known and most-used BA indicators include DNA methylation-based epigenetic clocks and telomere length (TL). The most common biological sample material for epidemiological aging studies, whole blood, is composed of different cell types. We aimed to compare differences in BAs between blood cell types and assessed the BA indicators' cell type-specific associations with chronological age (CA). An analysis of DNA methylation-based BA indicators, including TL, methylation level at cg16867657 in ELOVL2, as well as the Hannum, Horvath, DNAmPhenoAge, and DunedinPACE epigenetic clocks, was performed on 428 biological samples of 12 blood cell types. BA values were different in the majority of the pairwise comparisons between cell types, as well as in comparison to whole blood (p < 0.05). DNAmPhenoAge showed the largest cell type differences, up to 44.5 years and DNA methylation-based TL showed the lowest differences. T cells generally had the \"youngest\" BA values, with differences across subsets, whereas monocytes had the \"oldest\" values. All BA indicators, except DunedinPACE, strongly correlated with CA within a cell type. Some differences such as DNAmPhenoAge-difference between naïve CD4 + T cells and monocytes were constant regardless of the blood donor's CA (range 20-80 years), while for DunedinPACE they were not. In conclusion, DNA methylation-based indicators of BA exhibit cell type-specific characteristics. Our results have implications for understanding the molecular mechanisms underlying epigenetic clocks and underscore the importance of considering cell composition when utilizing them as indicators for the success of aging interventions.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"1075-1092"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific clinical and neurobiological correlates of fatigue in older adults.","authors":"Marco Toccaceli Blasi, Alba Rosa Alfano, Martina Salzillo, Simona Buscarnera, Valeria Raparelli, Matteo Cesari, Giuseppe Bruno, Marco Canevelli","doi":"10.1007/s11357-024-01259-0","DOIUrl":"10.1007/s11357-024-01259-0","url":null,"abstract":"<p><p>Fatigue is a common and distressful symptom in older people and has been associated with adverse health outcomes. Nevertheless, its sex-specific pathophysiological underpinnings and clinical correlates have been scarcely investigated. We aimed to comprehensively explore the clinical and neurobiological determinants of fatigue in cognitively unimpaired older adults. A sex-stratified analysis was conducted to look for differences in the clinical expression of fatigue among women and men. Data on cognitively normal individuals were gathered from the Alzheimer's Disease Neuroimaging Initiative (ADNI) 2 study. Fatigue was defined based on self-report at baseline. For each participant, information on sociodemographics, comorbidities, mood, cognitive performance, frailty, and biomarkers of brain pathology was collected. Logistic regression models, stratified by sex, were conducted to explore the factors associated with fatigue. Among the 291 participants selected, 44 subjects (15.1% of the total sample) self-reported fatigue at baseline. Subjects reporting fatigue were more likely women, had higher frailty degrees, and more severe depressive symptoms than those without fatigue. Moreover, they tended to have lower MRI hippocampus volumes. Among women, those reporting fatigue exhibited higher frailty levels, worse depression, and lower MRI hippocampus volumes relative to those without fatigue. Higher frailty degrees were also observed in men reporting vs. non-reporting fatigue. In the adjusted logistic regression model, more severe depression (OR 1.64, 95% CI 1.18-2.28; p < 0.01) and lower MRI hippocampus volumes (OR 0.41, 95% CI 0.19-0.90; p = 0.03) resulted independently associated with fatigue in women, while higher frailty degrees (OR 3.10, 95% CI 1.27-7.54 per 0.1 increase in a 39-item Frailty index; p = 0.01) in men. Fatigue is a complex symptom with a sex-specific pattern of clinical and neurobiological correlates. A better understanding of the underlying mechanisms of these associations is warranted to develop sex-informed approaches for personalized treatments.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"1151-1160"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrical brain networks before and after transcranial pulsed shockwave stimulation in Alzheimer's patients.","authors":"Lars Wojtecki, Celine Cont, Natalie Stute, Anastasia Galli, Christina Schulte, Carlos Trenado","doi":"10.1007/s11357-024-01305-x","DOIUrl":"10.1007/s11357-024-01305-x","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disorder that dramatically affects cognitive abilities and represents the most common cause of dementia. Currently, pharmacological interventions represent the main treatment to deal with the symptoms of AD; however, alternative approaches are readily sought. Transcranial pulse stimulation (TPS) is an emerging non-invasive neuromodulation technique that uses short, repetitive shockwaves with the potential to provide a wide range of vascular, metabolic, and neurotrophic changes and that has recently been shown to improve cognitive abilities in AD. This exploratory study aims to gain insight into the neurophysiological effect of one session of TPS in AD as reflected in electroencephalographic measures, e.g., spectral power, coherence, Tsallis entropy (TE), and cross-frequency coupling (cfc). We document changes in power (frontal and occipital), coherence (frontal, occipital and temporal), and TE (temporal and frontal) as well as changes in cfc (parietal-frontal, parietal-temporal, frontal-temporal). Our results emphasize the role of electroencephalographic measures as prospective markers for the neurophysiological effect of TPS.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"953-964"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gait Speed Reserve in the general population-based 'Good Aging in Skåne' cohort study-distribution and associated factors.","authors":"Beata Lindholm, Rani Basna, Henrik Ekström, Sölve Elmståhl, Arkadiusz Siennicki-Lantz","doi":"10.1007/s11357-024-01318-6","DOIUrl":"10.1007/s11357-024-01318-6","url":null,"abstract":"<p><p>Gait Speed Reserve (GSR) expresses a difference between fast and comfortable gait speed and may have an impact on everyday functioning. It was also hypothesized as a useful proxy measure of physiological reserve. However, height-normalizing values of GSR and its associated factors have not been evaluated in a general population of older adults. Therefore, we aimed to investigate the distribution of height-normalized GSR (HN-GSR) in an elderly population-based cohort from urban and rural areas (n = 4342) aged 60-93 years and evaluate associated physiological and lifestyle factors. Using linear mixed models, we identified gender and nine modifiable factors as significantly associated with HN-GSR across four age groups. Better handgrip strength, cognition and standing balance, higher physical activity level, larger calf circumference, and less smoking had positive associations with HN-GSR, while female gender, more leg pain, higher weight and, alcohol consumption had opposite effects. The Marginal R2 imply that this model explained 26% of the variance in HN-GSR. Physical activity and handgrip strength varied across age groups in impact on HN-GSR. The differences were however comparatively minor. In this large cohort study of older adults, we proposed for the first time that factors associated with HN-GSR represented multi-domain features that are in line with previous findings reported for GSR. Measuring HN-GSR/GSR may help clinicians identify early physiological impairments or unhealthy lifestyle habits, especially among older women, and may also have safety implications in daily life. Further work is needed to find out if measuring HN-GSR/GSR may be useful in identifying adverse health outcomes and overall physiological reserve.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"965-976"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-aging interventions in geriatric mice: insights into the timing of treatment, benefits, and limitations.","authors":"Marco Malavolta","doi":"10.1007/s11357-024-01309-7","DOIUrl":"10.1007/s11357-024-01309-7","url":null,"abstract":"<p><p>Studies aimed at preventing age-associated diseases are fundamental in addressing the challenges posed by an aging population. However, biomedical and technological advancements have now reached a stage where it appears increasingly possible to repair the damage caused by severe pathologies and reverse the functional decline that accompanies aging. This perspective highlights the significance of using aging models, specifically non-transgenic geriatric mice (aged over 24 months), to study interventions aimed at reversing or ameliorating age-related pathologies. While most research typically utilizes young, adult, and mid-aged mice to investigate aging mechanisms and develop preventive strategies, geriatric models provide unique insights into the efficacy and safety of treatments in conditions that mimic the complexities of multiple concurrent diseases or syndromes. This manuscript highlights the importance of considering timing responses in aging interventions, illustrated by recent findings such as those involving canagliflozin. These studies reveal that the timing of intervention can significantly influence the outcomes, highlighting aspects often overlooked. Practical challenges and resource demands associated with geriatric mouse studies including concerns related to animal husbandry and aging phenotypes are also discussed. This perspective aims to foster a deeper understanding of the potential benefits and limitations of geriatric mice models in geroscience research and emphasizes the need for continued innovation in this field to meet the critical need to develop effective treatments for age-related diseases.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"109-119"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulation of astrocytic Aquaporin-1 in the brains of oldest-old rhesus macaques: the NIA caloric restriction study.","authors":"Opal Stayer-Wilburn, Donald I Brown, Randy L Woltjer, Sathya Srinivasan, Byung S Park, Penny Shultz, Ana Vitantonio, Christina Dimovasili, Kelli L Vaughan, Matthew F Starost, Douglas Rosene, Julie A Mattison, Henryk F Urbanski, Steven G Kohama","doi":"10.1007/s11357-024-01431-6","DOIUrl":"10.1007/s11357-024-01431-6","url":null,"abstract":"<p><p>Aquaporin-1 (AQP1) is a highly conserved water-channel protein, found to be expressed by astrocytes in adult humans and non-human primates (NHPs). Upregulation of cortical AQP1 expression occurs with cancer, injury, and neurodegenerative disease, but minimal information is available about the effects of normative aging on AQP1 expression. This study leverages tissues from the oldest-old rhesus macaques, some greater than 40 years of age, from the National Institute on Aging longitudinal study of caloric restriction (CR). We tested whether AQP1 levels are altered in the NHP brain as a function of diet group, sex, and age. Sections of formaldehyde-fixed prefrontal (PFC) and temporal (TC) cortices from 36 rhesus macaques (both sexes, 22 to 44 years, + / - CR) were immunochemically stained for AQP1, then the percent area of AQP1 staining was regionally measured using ImageJ free-ware. Results showed age-related regional increases of AQP1 expression, with no effect of diet group or sex. Specifically, in the PFC, AQP1 positively-stained area increased with age in multiple subregions. For the TC subregions, AQP1 area coverage was not affected by age, despite having average levels that were greater than in the PFC. The peak expression of AQP1 in astrocytes appeared in clusters across cortical layers in a subgroup of animals 30 + years old. Astrocytic AQP1 dysregulation may contribute to progressive risk of neuropathology with aging.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"781-793"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial DNA copy number associated dementia risk by somatic mutations and frailty.","authors":"Qu Tian, David A Zweibaum, Yong Qian, Richard F Oppong, Luke C Pilling, Francesco Casanova, Janice L Atkins, David Melzer, Jun Ding, Luigi Ferrucci","doi":"10.1007/s11357-024-01355-1","DOIUrl":"10.1007/s11357-024-01355-1","url":null,"abstract":"<p><p>Mitochondrial dysfunction is linked to physical impairment and dementia. Mitochondrial DNA copy number (mtDNAcn) from blood may predict cognitive decline and dementia risk, but the effect of somatic mutations or frailty is unknown. We estimated mtDNAcn using fastMitoCalc and microheteroplasmies using mitoCaller, from Whole Genome Sequencing (WGS) data. In 189,566 participants free of dementia at study entry (mean age = 56 ± 8), we examined the association between mtDNAcn and subsequent dementia diagnosis using Cox regression. Cognition was assessed in a subset on average 8.9 years later. We examined the associations between mtDNAcn and cognitive measures using multivariable linear regression, adjusted for demographic factors, mtDNAcn-related parameters, and apolipoprotein E ε4 status. We further stratified by frailty and microheteroplasmies. Over an average follow-up of 13.2 years, 3533 participants developed dementia. Each SD higher mtDNAcn (16) was associated with 4.2% lower all-cause dementia hazard (HR = 0.958, p = 0.030), 6% lower non-AD dementia hazard (HR = 0.933, p = 0.022), and not-AD dementia hazard. The associations between mtDNAcn and all-cause dementia and non-AD dementia were stronger among those who were pre-frail or frail or with higher microheteroplasmies. Higher mtDNAcn was associated with higher DSST scores (p = 0.036) and significant only among those with higher microheteroplasmies or frailty (p = 0.029 and 0.048, respectively). mtDNAcn was also associated with delta TMT and paired associate learning only in pre-frail/frail participants (p = 0.007 and 0.045, respectively). Higher WGS-based mtDNAcn in human blood is associated with lower dementia risk, specifically non-AD dementia, and specific cognitive function. The relationships appear stronger in high somatic mutations or frailty. Future studies are warranted to investigate biological underpinnings.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"825-835"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}