GeroScience最新文献

{"title":"Synergistic effects of plasma S100B and MRI measures of cerebrovascular disease on cognition in older adults","authors":"Colleen Pappas, Christopher E. Bauer, Valentinos Zachariou, T. J. Libecap, Beatriz Rodolpho, Tiffany L. Sudduth, Peter T. Nelson, Gregory A. Jicha, Anika MS Hartz, Xingfeng Shao, Danny J. J. Wang, Brian T. Gold","doi":"10.1007/s11357-024-01498-1","DOIUrl":"https://doi.org/10.1007/s11357-024-01498-1","url":null,"abstract":"<p>There is growing interest in studying vascular contributions to cognitive impairment and dementia (VCID) and developing biomarkers to identify at-risk individuals. A combination of biofluid and neuroimaging markers may better profile early stage VCID than individual measures. Here, we tested this possibility focusing on plasma levels of S100 calcium-binding protein B (S100B), which has been linked with blood–brain-barrier (BBB) integrity, and neuroimaging measures assessing BBB function (water exchange rate across the BBB (k_w)) and cerebral small vessel disease (white matter hyperintensities (WMHs)). A total of 74 older adults without dementia had plasma samples collected and underwent cognitive assessment. A subsample had neuroimaging data including diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL) for assessment of BBB k_w and T2-weighted fluid-attenuated inversion recovery (FLAIR) for quantification of WMHs. Results indicated that higher plasma S100B levels were associated with poorer episodic memory performance (<i>β</i> = − .031, SE = .008, <i>p</i> &lt; .001). Moreover, significant interactions were observed between plasma S100B levels and parietal lobe BBB k_w (interaction <i>β</i> = .095, SE = .042, <i>p</i> = .028) and between plasma S100B levels and deep WMH volume (interaction <i>β</i> = − .025, SE = .009, <i>p</i> = .007) for episodic memory. Individuals with the poorest memory performance showed both high plasma S100B and either low BBB k_w in the parietal lobe or increased deep WMH burden. Taken together, our results provide support for the combined use of biofluid and neuroimaging markers in the study of VCID.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"25 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143125378","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":"A cohort study reveals shared and distinct serum metabolic biomarkers for major adverse cardiovascular events in middle-aged and older adults","authors":"Yi Ren, Bo Chen, Honggang Zhang, Shaoyong Xu","doi":"10.1007/s11357-025-01544-6","DOIUrl":"https://doi.org/10.1007/s11357-025-01544-6","url":null,"abstract":"&lt;p&gt;We assessed the association of serum metabolites with the occurrence of major adverse cardiovascular events (MACE) in middle-aged and elderly individuals, explored the value of metabolomics in predicting MACE, and compared the distinctions in MACE risk-related metabolic biomarkers between middle-aged and elderly groups. Among the participants of the UK Biobank who underwent baseline assessment through nuclear magnetic resonance (NMR)-based metabolomic profiling of 168 serum metabolites and had complete covariates and clinical lipid parameters, we included those without a previous diagnosis of ischemic heart disease, cerebrovascular disease, heart failure, or cardiac arrest and not on lipid-lowering medications. Relevant covariates included sociodemographic characteristics, lifestyle factors, clinical information, and fasting time. Cox regression gave adjusted hazard ratios for metabolites, including the concentrations of various lipoprotein particles, compositional profiles of different lipoproteins, ketone bodies, amino acids, fatty acids, and additional low-molecular-weight metabolic biomarkers. The least absolute shrinkage and selection operator (LASSO) regression was applied to these metabolites to screen characteristic metabolic variables. Selected feature metabolic biomarkers were added to the established model for predicting MACE risk; risk differentiation (C-statistic) and reclassification (continuous net reclassification improvement [NRI], integrated differentiation index [IDI]) were evaluated. This study included 54,561 UK Biobank participants (34,797 middle-aged adults and 19,764 elderly adults) and was followed for a median of more than 12 years. Of these, there are 1799 middle-aged individuals and 2527 elderly individuals incident of MACE (ischemic heart disease, stroke, and cardiovascular deaths). After adjusting for relevant covariates, Cox regression yielded metabolic biomarkers associated with the occurrence of MACE in the population (false discovery rate controlled &lt;i&gt;P&lt;/i&gt; &lt; 0.05). In the elderly, the metabolites associated with increased MACE risk were notably diminished compared to the middle-aged; and the elderly group underscored the protective function of medium and small HDL and their constituents, docosahexaenoic acid, and glycine. The more comprehensive model, which additionally includes the feature metabolic biomarkers, demonstrated enhanced discriminatory power and predictive accuracy for MACE occurrence among middle-aged individuals, evidenced by improved C-statistics (from 0.711 [95% CI 0.699–0.722] to 0.723 [0.711–0.734]), a continuous NRI of 0.247 [0.207–0.315], and an absolute IDI of 0.005 [0.004–0.008]. Its evaluation value is superior to that in the elderly. Our study explored the association of circulating metabolites with MACE risk in middle-aged and elderly adults and made comparisons. Metabolomic insights have revealed biomarkers associated with new-onset MACE in different age populations, highlightin","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"61 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143125087","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":"Fecal microbiota transplant from long-living Ames dwarf mice alters the microbial composition and biomarkers of liver health in normal mice","authors":"Sarah A. Ashiqueali, Natalie Hayslip, Diptaraj S. Chaudhari, Augusto Schneider, Xiang Zhu, Blazej Rubis, Corey E. Seavey, Md Tanjim Alam, Ridwan Hussein, Sarah A. Noureddine, Ewelina Golusinska-Kardach, Pawel Pazdrowski, Hariom Yadav, Michal M. Masternak","doi":"10.1007/s11357-025-01539-3","DOIUrl":"https://doi.org/10.1007/s11357-025-01539-3","url":null,"abstract":"<p>Aging is associated with intestinal dysbiosis, a condition characterized by diminished microbial biodiversity and inflammation. This leads to increased vulnerability to extraintestinal manifestations such as autoimmune, metabolic, and neurodegenerative conditions thereby accelerating mortality. As such, modulation of the gut microbiome is a promising way to extend healthspan. In this study, we explore the effects of fecal microbiota transplant (FMT) from long-living Ames dwarf donors to their normal littermates, and vice versa, on the recipient gut microbiota and liver transcriptome. Importantly, our previous studies highlight differences between the microbiome of Ames dwarf mice relative to their normal siblings, potentially contributing to their extended lifespan and remarkable healthspan. Our findings demonstrate that FMT from Ames dwarf mice to normal mice significantly alters the recipient’s gut microbiota, potentially reprogramming bacterial functions related to healthy aging, and changes the liver transcriptome, indicating improved metabolic health. Particularly, the microbiome of Ames dwarf mice, characterized by a higher abundance of beneficial bacterial families such as <i>Peptococcaceae</i>, <i>Oscillospiraceae</i>, and <i>Lachnospiraceae</i>, appears to play a crucial role in modulating these effects. Alongside, our mRNA sequencing and RT-PCR validation reveals that FMT may contribute to the significant downregulation of <i>p21</i>, <i>Elovl3</i>, and <i>Insig2</i>, genes involved with cellular senescence and liver metabolic pathways. Our data suggest a regulatory axis exists between the gut and liver, highlighting the potential of microbiome-targeted therapies in promoting healthy aging. Future research should focus on functional validation of altered microbial communities and explore the underlying biomolecular pathways that confer geroprotection.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"28 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143125377","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":"Inhibition of soluble epoxide hydrolase ameliorates cerebral blood flow autoregulation and cognition in alzheimer's disease and diabetes-related dementia rat models","authors":"Chengyun Tang, Jane J. Border, Huawei Zhang, Andrew Gregory, Shan Bai, Xing Fang, Yedan Liu, Shaoxun Wang, Sung Hee Hwang, Wenjun Gao, Gilbert C. Morgan, Jhania Smith, David Bunn, Cameron Cantwell, Karen M. Wagner, Christophe Morisseau, Jun Yang, Seung Min Shin, Philip O’Herron, Zsolt Bagi, Jessica A. Filosa, Yanbin Dong, Hongwei Yu, Bruce D. Hammock, Richard J. Roman, Fan Fan","doi":"10.1007/s11357-025-01550-8","DOIUrl":"https://doi.org/10.1007/s11357-025-01550-8","url":null,"abstract":"<p>Alzheimer's Disease and Alzheimer's Disease-related dementias (AD/ADRD) pose major global healthcare challenges, with diabetes mellitus (DM) being a key risk factor. Both AD and DM-related ADRD are characterized by reduced cerebral blood flow, although the exact mechanisms remain unclear. We previously identified compromised cerebral hemodynamics as early signs in TgF344-AD and type 2 DM-ADRD (T2DN) rat models. Genome-wide studies have linked AD/ADRD to SNPs in soluble epoxide hydrolase (sEH). This study explored the effects of sEH inhibition with TPPU on cerebral vascular function and cognition in AD and DM-ADRD models. Chronic TPPU treatment improved cognition in both AD and DM-ADRD rats without affecting body weight. In DM-ADRD rats, TPPU reduced plasma glucose and HbA1c levels. Transcriptomic analysis of primary cerebral vascular smooth muscle cells from AD rats treated with TPPU revealed enhanced pathways related to cell contraction, alongside decreased oxidative stress and inflammation. Both AD and DM-ADRD rats exhibited impaired myogenic responses and autoregulation in the cerebral circulation, which were normalized with chronic sEH inhibition. Additionally, TPPU improved acetylcholine-induced vasodilation in the middle cerebral arteries (MCA) of DM-ADRD rats. Acute TPPU administration unexpectedly caused vasoconstriction in the MCA of DM-ADRD rats at lower doses. In contrast, higher doses or longer durations were required to induce effective vasodilation at physiological perfusion pressure in both control and ADRD rats. Additionally, TPPU decreased reactive oxygen species production in cerebral vessels of AD and DM-ADRD rats. These findings provide novel evidence that chronic sEH inhibition can reverse cerebrovascular dysfunction and cognitive impairments in AD/ADRD, offering a promising avenue for therapeutic development.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"122 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083768","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":"Intrinsic brain functional connectivity mediates the relationship between psychological resilience and cognitive decline in ageing","authors":"Menglu Chen, Mengxia Gao, Junji Ma, Tatia M. C. Lee","doi":"10.1007/s11357-025-01529-5","DOIUrl":"https://doi.org/10.1007/s11357-025-01529-5","url":null,"abstract":"<p>Ageing individuals often experience cognitive decline and intrinsic functional connectivity (FC) changes. Psychological resilience, a personality trait that reflects the capacity to adapt and cope with age-related challenges, plays a key role in mitigating cognitive decline. In this study involving 101 older adults, we investigated how psychological resilience influences cognitive decline measured by processing speed. Particularly, we obtained resting-state functional magnetic resonance imaging (fMRI) to assess how intrinsic FC, represented by degree centrality, modulates the relationship between resilience and processing speed. Our results indicated while psychological resilience positively predicted processing speed, this relationship was mainly driven by education. Additionally, the degree centrality of both thalamus and caudate negatively correlated with processing speed and resilience. Notably, the degree centrality of both thalamus and caudate significantly mediated the relationship between resilience and processing speed. These findings suggest that psychological resilience could protect against age-related cognitive decline via its influence on FC in the thalamus and caudate, highlighting these areas as potential intervention targets for reducing cognitive decline in ageing people.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"27 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077463","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":"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}