Pub Date : 2025-10-01DOI: 10.1016/j.lanhl.2025.100773
Jian Hua Tay BSc , Duarte Barros MSc , Weilan Wang PhD , Vanessa Kristina Wazny PhD , Andrea B Maier MD
Background
Frailty is an age-related condition characterised by multisystem physiological decline, which increases vulnerability to adverse outcomes. Biomarkers of ageing might identify individuals at risk and enable early interventions. This systematic review and meta-analysis aimed to examine cross-sectional and longitudinal associations between DNA methylation-based biological age metrics (eg, DNA methylation age, epigenetic-age acceleration [EAA], and age deviation) and frailty.
Methods
In a systematic search of six databases (Embase, Cochrane Central Register of Controlled Trials, PubMed, Ovid, Scopus, and Web of Science) from Jan 1, 2011, to June 6, 2025, we identified population-based cohort studies reporting associations between DNA methylation age, EAA, or age deviation and frailty from general or disease-specific populations with a control group. Risk of bias was assessed using an adapted Newcastle–Ottawa Scale. Random-effects meta-analyses with Hartung–Knapp adjustments were performed on standardised β coefficients and SEs. Publication bias, influence, and sensitivity analyses were conducted.
Findings
From 34 437 records screened, 24 studies met the inclusion criteria (17 cross-sectional studies, one longitudinal study, and six studies that were both cross-sectional and longitudinal), encompassing 28 325 participants (14 757 [52·1%] female; median of mean age 65·2 years [IQR 62·2–69·4]). DNA methylation age and age deviation showed no association with frailty. In cross-sectional meta-analyses, higher Hannum EAA (nine studies; n=11 162; standardised β coefficient 0·06 [95% CI 0·02–0·09], I2=71·4%), PhenoAge EAA (eight studies; n=10 371; 0·07 [0·03–0·11], I2=81·7%), GrimAge EAA (eight studies; n=10 371; 0·11 [0·06–0·15], I2=90·5%), and pace of ageing (five studies; n=7895; 0·10 [0·01–0·19], I2=91·0%) were significantly associated with higher frailty. In longitudinal meta-analyses, higher GrimAge EAA (five studies; n=6143; 0·02 [0·00–0·05], I2=46·0%, p=0·0481) was significantly associated with increases in frailty, whereas PhenoAge EAA and pace of ageing were not significantly associated with frailty.
Interpretation
Higher GrimAge EAA is consistently associated with higher frailty. Future research should focus on developing and validating DNA methylation clocks that integrate molecular surrogates of health risk and are specifically trained to predict frailty in large, harmonised, longitudinal cohorts, enabling their translation into clinical practice.
{"title":"Biological age measured by DNA methylation clocks and frailty: a systematic review and meta-analysis","authors":"Jian Hua Tay BSc , Duarte Barros MSc , Weilan Wang PhD , Vanessa Kristina Wazny PhD , Andrea B Maier MD","doi":"10.1016/j.lanhl.2025.100773","DOIUrl":"10.1016/j.lanhl.2025.100773","url":null,"abstract":"<div><h3>Background</h3><div>Frailty is an age-related condition characterised by multisystem physiological decline, which increases vulnerability to adverse outcomes. Biomarkers of ageing might identify individuals at risk and enable early interventions. This systematic review and meta-analysis aimed to examine cross-sectional and longitudinal associations between DNA methylation-based biological age metrics (eg, DNA methylation age, epigenetic-age acceleration [EAA], and age deviation) and frailty.</div></div><div><h3>Methods</h3><div>In a systematic search of six databases (Embase, Cochrane Central Register of Controlled Trials, PubMed, Ovid, Scopus, and Web of Science) from Jan 1, 2011, to June 6, 2025, we identified population-based cohort studies reporting associations between DNA methylation age, EAA, or age deviation and frailty from general or disease-specific populations with a control group. Risk of bias was assessed using an adapted Newcastle–Ottawa Scale. Random-effects meta-analyses with Hartung–Knapp adjustments were performed on standardised β coefficients and SEs. Publication bias, influence, and sensitivity analyses were conducted.</div></div><div><h3>Findings</h3><div>From 34 437 records screened, 24 studies met the inclusion criteria (17 cross-sectional studies, one longitudinal study, and six studies that were both cross-sectional and longitudinal), encompassing 28 325 participants (14 757 [52·1%] female; median of mean age 65·2 years [IQR 62·2–69·4]). DNA methylation age and age deviation showed no association with frailty. In cross-sectional meta-analyses, higher Hannum EAA (nine studies; n=11 162; standardised β coefficient 0·06 [95% CI 0·02–0·09], <em>I</em><sup>2</sup>=71·4%), PhenoAge EAA (eight studies; n=10 371; 0·07 [0·03–0·11], <em>I</em><sup><em>2</em></sup>=81·7%), GrimAge EAA (eight studies; n=10 371; 0·11 [0·06–0·15], <em>I</em><sup><em>2</em></sup>=90·5%), and pace of ageing (five studies; n=7895; 0·10 [0·01–0·19], <em>I</em><sup><em>2</em></sup>=91·0%) were significantly associated with higher frailty. In longitudinal meta-analyses, higher GrimAge EAA (five studies; n=6143; 0·02 [0·00–0·05], <em>I</em><sup><em>2</em></sup>=46·0%, p=0·0481) was significantly associated with increases in frailty, whereas PhenoAge EAA and pace of ageing were not significantly associated with frailty.</div></div><div><h3>Interpretation</h3><div>Higher GrimAge EAA is consistently associated with higher frailty. Future research should focus on developing and validating DNA methylation clocks that integrate molecular surrogates of health risk and are specifically trained to predict frailty in large, harmonised, longitudinal cohorts, enabling their translation into clinical practice.</div></div><div><h3>Funding</h3><div>National University of Singapore.</div></div>","PeriodicalId":34394,"journal":{"name":"Lancet Healthy Longevity","volume":"6 10","pages":"Article 100773"},"PeriodicalIF":14.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145483225","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}
Pub Date : 2025-10-01DOI: 10.1016/j.lanhl.2025.100767
Hanadi A Oughli MD , Nicholas J Ainsworth MD PhD , Prof Meryl A Butters PhD , Patrick J Brown PhD , Marie Anne Gebara MD , Torie R Gettinger PhD , Prof Jordan F Karp MD , Helen Lavretsky MD MS , Emily Lenard LMSW , Prof J Philip Miller AB , Prof Benoit H Mulsant MD MS , Ginger E Nicol MD , Prof Charles F Reynolds 3rd MD , Michael Yingling MS , Prof Eric J Lenze MD , OPTIMUM Research Group
<div><h3>Background</h3><div>The cognitive effects of various antidepressant strategies for treatment-resistant depression in older adults are unclear. We aimed to evaluate acute cognitive changes associated with various pharmacotherapy treatment strategies for treatment-resistant depression in older adults.</div></div><div><h3>Methods</h3><div>We did a prespecified secondary analysis of the OPTIMUM trial, which was a pragmatic, randomised, comparative effectiveness trial of various augmentation or switch pharmacotherapy strategies, enrolling adults aged 60 years or older with treatment-resistant depression. Participants were recruited from five academic medical centres (four in the USA and one in Canada). In Step 1 (n=391), participants were randomly assigned 1:1:1 to augmentation of their antidepressant with aripiprazole (to a maximum of 15 mg per day) or bupropion (to a maximum of 450 mg per day) or to a switch to bupropion (same dose as the bupropion-augmentation group). In Step 2 (n=182), participants who were ineligible for Step 1 or did not reach remission in this step were randomly assigned 1:1 to augmentation with lithium (titrated to attain a plasma concentration range of 0·4–0·8 mEq/L) or to a switch to nortriptyline (to reach a therapeutic plasma concentration of 80–120 ng/mL). Each step lasted 10 weeks, with 12 months of follow-up after completion of Step 1 or Step 2. The primary outcome was cognitive function at the end of Step 1 and Step 2, as evaluated with the National Institutes of Health (NIH) Toolbox Fluid Cognition Composite Score, part of the NIH Toolbox Cognition Battery. The primary outcome was analysed in the intention-to-treat population. An exploratory post-hoc analysis conducted in both the intention-to-treat and per-protocol populations examined changes in the individual cognitive tasks constituting the Fluid Cognition Composite Score. OPTIMUM was registered with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (<span><span>NCT02960763</span><svg><path></path></svg></span>) and is complete.</div></div><div><h3>Findings</h3><div>Between Feb 22, 2017, and Dec 31, 2019, 742 participants were enrolled in the OPTIMUM study. In Step 1, 619 (83%) participants were randomly assigned to aripiprazole augmentation (n=211), bupropion augmentation (n=206), or a switch to bupropion monotherapy (n=202); cognitive data were available for 128, 136, and 127 participants, respectively. 248 participants were enrolled in Step 2 and randomly assigned to lithium augmentation (n=127) or to a switch to nortriptyline monotherapy (n=121); cognitive data were available for 89 and 93 participants, respectively. Over 10 weeks, there were no significant differences between pharmacotherapy strategies in the Fluid Cognition Composite Score. In Step 1, a time × group interaction was observed for the Flanker Inhibitory Control and Attention test (<em>F</em>[2,266]=3·97; p=0·020), with a contrast analysis showing that aripiprazole au
{"title":"Cognitive changes in older adults receiving pharmacotherapy for treatment-resistant depression: a secondary analysis of the OPTIMUM randomised controlled trial","authors":"Hanadi A Oughli MD , Nicholas J Ainsworth MD PhD , Prof Meryl A Butters PhD , Patrick J Brown PhD , Marie Anne Gebara MD , Torie R Gettinger PhD , Prof Jordan F Karp MD , Helen Lavretsky MD MS , Emily Lenard LMSW , Prof J Philip Miller AB , Prof Benoit H Mulsant MD MS , Ginger E Nicol MD , Prof Charles F Reynolds 3rd MD , Michael Yingling MS , Prof Eric J Lenze MD , OPTIMUM Research Group","doi":"10.1016/j.lanhl.2025.100767","DOIUrl":"10.1016/j.lanhl.2025.100767","url":null,"abstract":"<div><h3>Background</h3><div>The cognitive effects of various antidepressant strategies for treatment-resistant depression in older adults are unclear. We aimed to evaluate acute cognitive changes associated with various pharmacotherapy treatment strategies for treatment-resistant depression in older adults.</div></div><div><h3>Methods</h3><div>We did a prespecified secondary analysis of the OPTIMUM trial, which was a pragmatic, randomised, comparative effectiveness trial of various augmentation or switch pharmacotherapy strategies, enrolling adults aged 60 years or older with treatment-resistant depression. Participants were recruited from five academic medical centres (four in the USA and one in Canada). In Step 1 (n=391), participants were randomly assigned 1:1:1 to augmentation of their antidepressant with aripiprazole (to a maximum of 15 mg per day) or bupropion (to a maximum of 450 mg per day) or to a switch to bupropion (same dose as the bupropion-augmentation group). In Step 2 (n=182), participants who were ineligible for Step 1 or did not reach remission in this step were randomly assigned 1:1 to augmentation with lithium (titrated to attain a plasma concentration range of 0·4–0·8 mEq/L) or to a switch to nortriptyline (to reach a therapeutic plasma concentration of 80–120 ng/mL). Each step lasted 10 weeks, with 12 months of follow-up after completion of Step 1 or Step 2. The primary outcome was cognitive function at the end of Step 1 and Step 2, as evaluated with the National Institutes of Health (NIH) Toolbox Fluid Cognition Composite Score, part of the NIH Toolbox Cognition Battery. The primary outcome was analysed in the intention-to-treat population. An exploratory post-hoc analysis conducted in both the intention-to-treat and per-protocol populations examined changes in the individual cognitive tasks constituting the Fluid Cognition Composite Score. OPTIMUM was registered with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (<span><span>NCT02960763</span><svg><path></path></svg></span>) and is complete.</div></div><div><h3>Findings</h3><div>Between Feb 22, 2017, and Dec 31, 2019, 742 participants were enrolled in the OPTIMUM study. In Step 1, 619 (83%) participants were randomly assigned to aripiprazole augmentation (n=211), bupropion augmentation (n=206), or a switch to bupropion monotherapy (n=202); cognitive data were available for 128, 136, and 127 participants, respectively. 248 participants were enrolled in Step 2 and randomly assigned to lithium augmentation (n=127) or to a switch to nortriptyline monotherapy (n=121); cognitive data were available for 89 and 93 participants, respectively. Over 10 weeks, there were no significant differences between pharmacotherapy strategies in the Fluid Cognition Composite Score. In Step 1, a time × group interaction was observed for the Flanker Inhibitory Control and Attention test (<em>F</em>[2,266]=3·97; p=0·020), with a contrast analysis showing that aripiprazole au","PeriodicalId":34394,"journal":{"name":"Lancet Healthy Longevity","volume":"6 10","pages":"Article 100767"},"PeriodicalIF":14.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145521262","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}
Time is an under-recognised social determinant of brain health, and is potentially as important as education or income for dementia risk. Temporal inequity refers to the unequal distribution of discretionary time owing to structural conditions shaping daily life. Temporal inequity encompasses insufficient time for rest, misaligned biological rhythms, fragmented leisure, and the encroachment of work or digital demands into personal time. Time poverty is a measurable manifestation, denoting insufficient time for brain health, disproportionately affecting structurally disadvantaged populations and exacerbated by performance-driven cultures. Although evidence for modifiable risk factors of dementia, such as sleep, physical activity, nutrition, and social engagement, is strong, adopting healthy behaviours requires time. In this Personal View, we integrate insights from epidemiology, neuroscience, and time-use research to argue that addressing temporal inequity is essential for brain health and dementia risk reduction. We call for temporal justice through research and policies that recognise time as both a resource and a site of inequity in ageing and dementia. Accordingly, we outline future research directions, including the development of metrics for temporal inequity, longitudinal studies linking time-use patterns to brain health outcomes, and intervention research to evaluate policies that expand equitable access to time.
{"title":"Making time for brain health: recognising temporal inequity in dementia risk reduction","authors":"Susanne Röhr PhD , Simone Reppermund PhD , Annabel Matison PhD , Suraj Samtani PhD , Prof Perminder S Sachdev MD PhD","doi":"10.1016/j.lanhl.2025.100768","DOIUrl":"10.1016/j.lanhl.2025.100768","url":null,"abstract":"<div><div>Time is an under-recognised social determinant of brain health, and is potentially as important as education or income for dementia risk. Temporal inequity refers to the unequal distribution of discretionary time owing to structural conditions shaping daily life. Temporal inequity encompasses insufficient time for rest, misaligned biological rhythms, fragmented leisure, and the encroachment of work or digital demands into personal time. Time poverty is a measurable manifestation, denoting insufficient time for brain health, disproportionately affecting structurally disadvantaged populations and exacerbated by performance-driven cultures. Although evidence for modifiable risk factors of dementia, such as sleep, physical activity, nutrition, and social engagement, is strong, adopting healthy behaviours requires time. In this Personal View, we integrate insights from epidemiology, neuroscience, and time-use research to argue that addressing temporal inequity is essential for brain health and dementia risk reduction. We call for temporal justice through research and policies that recognise time as both a resource and a site of inequity in ageing and dementia. Accordingly, we outline future research directions, including the development of metrics for temporal inequity, longitudinal studies linking time-use patterns to brain health outcomes, and intervention research to evaluate policies that expand equitable access to time.</div></div>","PeriodicalId":34394,"journal":{"name":"Lancet Healthy Longevity","volume":"6 10","pages":"Article 100768"},"PeriodicalIF":14.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145309369","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}
Pub Date : 2025-10-01DOI: 10.1016/j.lanhl.2025.100776
Natalia Dowgiałło-Gornowicz
{"title":"Metabolic and bariatric surgery in septuagenarians","authors":"Natalia Dowgiałło-Gornowicz","doi":"10.1016/j.lanhl.2025.100776","DOIUrl":"10.1016/j.lanhl.2025.100776","url":null,"abstract":"","PeriodicalId":34394,"journal":{"name":"Lancet Healthy Longevity","volume":"6 10","pages":"Article 100776"},"PeriodicalIF":14.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145422959","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}
Pub Date : 2025-10-01DOI: 10.1016/j.lanhl.2025.100791
Anna Hung , Yoon Hie Kim , Juliessa M Pavon
{"title":"Testing complex interventions for polypharmacy in real-world conditions","authors":"Anna Hung , Yoon Hie Kim , Juliessa M Pavon","doi":"10.1016/j.lanhl.2025.100791","DOIUrl":"10.1016/j.lanhl.2025.100791","url":null,"abstract":"","PeriodicalId":34394,"journal":{"name":"Lancet Healthy Longevity","volume":"6 10","pages":"Article 100791"},"PeriodicalIF":14.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145446062","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}
Pub Date : 2025-10-01DOI: 10.1016/j.lanhl.2025.100782
Shahmir H Ali
{"title":"Care beyond caregivers: a wider spectrum of social support for older adults","authors":"Shahmir H Ali","doi":"10.1016/j.lanhl.2025.100782","DOIUrl":"10.1016/j.lanhl.2025.100782","url":null,"abstract":"","PeriodicalId":34394,"journal":{"name":"Lancet Healthy Longevity","volume":"6 10","pages":"Article 100782"},"PeriodicalIF":14.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145348939","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}
Pub Date : 2025-10-01DOI: 10.1016/j.lanhl.2025.100772
Patricia M Ortega PhD , Elena Brachimi MBBS , Ahmed R Ahmed PhD , Prof Sanjay Purkayastha MD , Christos Tsironis MD , Krishna Moorthy MD , Sherif Hakky PhD , Jonathan Cousins MBBS , Harvinder Chahal PhD , Saira Hameed PhD , Prof Tricia Tan PhD , Samantha Scholtz PhD , Karen O'Donnell BSc , Louisa Brolly BSc , Ciara Price BSc , Anna Sackey MSc , Candace Bovill-Taylor BSc , Joanne Boyle BSc , Rhian Houghton BSc , Jonathan Sullivan MSc , Chioma Izzi-Engbeaya PhD
Background
The prevalence of obesity is rising alongside population ageing, yet the long-term benefits of metabolic and bariatric surgery (MBS) in older adults is unclear. We aimed to evaluate the impact of MBS on survival in individuals aged 69 years and older with obesity.
Methods
We conducted a retrospective cohort study of patients aged 69 years and older managed in a UK tertiary bariatric centre between Jan 1, 2015, and Dec 31, 2024. Patients were eligible for inclusion if they had complete clinical data. Patients who underwent MBS were compared with matched controls who did not undergo MBS. Mahalanobis distance matching was performed (1:1) using age, BMI, American Society of Anesthesiologists grade, type 2 diabetes, and cardiovascular disease. Data were retrieved from electronic health records. The primary outcome was all-cause mortality after matching. Cox regression was used to assess survival.
Findings
Of the 186 patients, 44 (24%) underwent MBS. The median age was 71 years (IQR 70–74), 114 (61%) of 186 patients were women, 72 (39%) were men, median BMI was 41 kg/m2 (IQR 37–45), and median follow-up was 39 months (IQR 22–70). After matching, 44 MBS patients were compared with 34 control participants. Matched Kaplan–Meier analysis showed superior survival among MBS patients compared with control patients (log-rank p=0·010). MBS was associated with a 68% reduction in all-cause mortality on univariate analysis (hazard ratio 0·32 [95% CI 0·11–0·92]; p=0·036) and a 75% reduction in all-cause mortality on multivariate analysis (0·25 [0·08–0·77]; p=0·015). In MBS patients, the postoperative 30-day morbidity rate was 9%: Dindo-Clavien grade III-IV complications occurred in three (7%) of 44 patients, and one person (2%) died.
Interpretation
In a specialist setting, MBS was independently associated with improved survival in individuals aged 69 years and older, with acceptable perioperative risk. Chronological age alone should not preclude consideration for MBS. These findings support further evaluation of surgical options in well selected older adults with obesity.
{"title":"Metabolic and bariatric surgery in adults aged 69 years and older in England: a matched survival retrospective cohort study","authors":"Patricia M Ortega PhD , Elena Brachimi MBBS , Ahmed R Ahmed PhD , Prof Sanjay Purkayastha MD , Christos Tsironis MD , Krishna Moorthy MD , Sherif Hakky PhD , Jonathan Cousins MBBS , Harvinder Chahal PhD , Saira Hameed PhD , Prof Tricia Tan PhD , Samantha Scholtz PhD , Karen O'Donnell BSc , Louisa Brolly BSc , Ciara Price BSc , Anna Sackey MSc , Candace Bovill-Taylor BSc , Joanne Boyle BSc , Rhian Houghton BSc , Jonathan Sullivan MSc , Chioma Izzi-Engbeaya PhD","doi":"10.1016/j.lanhl.2025.100772","DOIUrl":"10.1016/j.lanhl.2025.100772","url":null,"abstract":"<div><h3>Background</h3><div>The prevalence of obesity is rising alongside population ageing, yet the long-term benefits of metabolic and bariatric surgery (MBS) in older adults is unclear. We aimed to evaluate the impact of MBS on survival in individuals aged 69 years and older with obesity.</div></div><div><h3>Methods</h3><div>We conducted a retrospective cohort study of patients aged 69 years and older managed in a UK tertiary bariatric centre between Jan 1, 2015, and Dec 31, 2024. Patients were eligible for inclusion if they had complete clinical data. Patients who underwent MBS were compared with matched controls who did not undergo MBS. Mahalanobis distance matching was performed (1:1) using age, BMI, American Society of Anesthesiologists grade, type 2 diabetes, and cardiovascular disease. Data were retrieved from electronic health records. The primary outcome was all-cause mortality after matching. Cox regression was used to assess survival.</div></div><div><h3>Findings</h3><div>Of the 186 patients, 44 (24%) underwent MBS. The median age was 71 years (IQR 70–74), 114 (61%) of 186 patients were women, 72 (39%) were men, median BMI was 41 kg/m<sup>2</sup> (IQR 37–45), and median follow-up was 39 months (IQR 22–70). After matching, 44 MBS patients were compared with 34 control participants. Matched Kaplan–Meier analysis showed superior survival among MBS patients compared with control patients (log-rank p=0·010). MBS was associated with a 68% reduction in all-cause mortality on univariate analysis (hazard ratio 0·32 [95% CI 0·11–0·92]; p=0·036) and a 75% reduction in all-cause mortality on multivariate analysis (0·25 [0·08–0·77]; p=0·015). In MBS patients, the postoperative 30-day morbidity rate was 9%: Dindo-Clavien grade III-IV complications occurred in three (7%) of 44 patients, and one person (2%) died.</div></div><div><h3>Interpretation</h3><div>In a specialist setting, MBS was independently associated with improved survival in individuals aged 69 years and older, with acceptable perioperative risk. Chronological age alone should not preclude consideration for MBS. These findings support further evaluation of surgical options in well selected older adults with obesity.</div></div><div><h3>Funding</h3><div>National Institute for Health and Care Research.</div></div>","PeriodicalId":34394,"journal":{"name":"Lancet Healthy Longevity","volume":"6 10","pages":"Article 100772"},"PeriodicalIF":14.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145422947","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}
Pub Date : 2025-09-01DOI: 10.1016/j.lanhl.2025.100757
Ruby Yu PhD , Derek Lai MSc , Grace Leung MSc , Lok-yan Tam BNurs , Clara Cheng MASSM , Sara Kong BSc , Cecilia Tong MSc , Matthew Yu BSc , Prof Jean Woo MD
<div><h3>Background</h3><div>Declines in intrinsic capacity have been associated with increased risks of frailty, disability, and hospitalisation. We estimated population attributable fractions (PAFs) for these outcomes with respect to intrinsic capacity-related conditions and traditional modifiable risk factors in different age groups.</div></div><div><h3>Methods</h3><div>We analysed data from a territory-wide, multicentre, community-based, prospective cohort study (2023–24) in Hong Kong. Among 22 237 Chinese adults aged 60 years and older with follow-up data, we calculated age-specific PAFs for incident frailty, instrumental activities of daily living (IADL) disability, and hospitalisation associated with 13 modifiable risk factors. These risk factors included intrinsic capacity conditions, cardiometabolic conditions, and socioeconomic and lifestyle factors, and combinations of these.</div></div><div><h3>Findings</h3><div>Between March 21, 2023, and Dec 31, 2024, 47 776 participants were recruited to the study. 41 226 (86·3%) had complete baseline data for all intrinsic capacity conditions, cardiometabolic conditions, socioeconomic and lifestyle factors, demographic covariates, and outcome variables and were therefore included in our study sample. 22 237 (53·9%) of 41 226 participants completed follow-up assessments at least 6 months after baseline with a mean follow-up of 360·4 days (SD 71·6, median 348·0, IQR 307·0–399·0), 1398 (7·1%) of 19 777 participants had incident frailty, 1152 (6·0%) of 19 171 participants had incident IADL disability, and 2068 (11·1%) of 18 622 participants were hospitalised. Limited mobility was the leading risk factor associated across all outcomes (PAFs 9·8–25·3%). Depressive symptoms were a strong risk factor associated with frailty (PAF 19·1%). Age-stratified analyses revealed that limited mobility had the highest PAFs in adults aged 80 years and older, whereas depressive symptoms showed peak PAFs in those aged 60–69 years in most cases. Hypertension contributed to all outcomes (PAFs 8·4–19·6%) only in adults younger than 80 years. In adults aged 60–69 years physical activity was the predominant risk factor associated with frailty (PAF 21·9%) and disability (PAF 22·3%). The attributable risk of lower education with frailty increased with age, reaching its peak in adults aged 80 years and older (PAF 20·2%). Regarding the joint effects of the risk factors, intrinsic capacity decline was the factor associated with the highest overall attributable risk for all outcomes, exceeding the impact of cardiometabolic diseases and socioeconomic and lifestyle risk.</div></div><div><h3>Interpretation</h3><div>Our findings provide insights into age-specific risk factors for frailty, disability, and hospitalisation in older people, underlining the importance of targeted prevention strategies across age groups. Our findings further support a shift towards prioritising intrinsic capacity to better support healthy ageing at the popu
{"title":"Age-specific population attributable fractions for frailty, functional disability, and hospitalisation in Chinese older people: an ICOPE-based prospective cohort study","authors":"Ruby Yu PhD , Derek Lai MSc , Grace Leung MSc , Lok-yan Tam BNurs , Clara Cheng MASSM , Sara Kong BSc , Cecilia Tong MSc , Matthew Yu BSc , Prof Jean Woo MD","doi":"10.1016/j.lanhl.2025.100757","DOIUrl":"10.1016/j.lanhl.2025.100757","url":null,"abstract":"<div><h3>Background</h3><div>Declines in intrinsic capacity have been associated with increased risks of frailty, disability, and hospitalisation. We estimated population attributable fractions (PAFs) for these outcomes with respect to intrinsic capacity-related conditions and traditional modifiable risk factors in different age groups.</div></div><div><h3>Methods</h3><div>We analysed data from a territory-wide, multicentre, community-based, prospective cohort study (2023–24) in Hong Kong. Among 22 237 Chinese adults aged 60 years and older with follow-up data, we calculated age-specific PAFs for incident frailty, instrumental activities of daily living (IADL) disability, and hospitalisation associated with 13 modifiable risk factors. These risk factors included intrinsic capacity conditions, cardiometabolic conditions, and socioeconomic and lifestyle factors, and combinations of these.</div></div><div><h3>Findings</h3><div>Between March 21, 2023, and Dec 31, 2024, 47 776 participants were recruited to the study. 41 226 (86·3%) had complete baseline data for all intrinsic capacity conditions, cardiometabolic conditions, socioeconomic and lifestyle factors, demographic covariates, and outcome variables and were therefore included in our study sample. 22 237 (53·9%) of 41 226 participants completed follow-up assessments at least 6 months after baseline with a mean follow-up of 360·4 days (SD 71·6, median 348·0, IQR 307·0–399·0), 1398 (7·1%) of 19 777 participants had incident frailty, 1152 (6·0%) of 19 171 participants had incident IADL disability, and 2068 (11·1%) of 18 622 participants were hospitalised. Limited mobility was the leading risk factor associated across all outcomes (PAFs 9·8–25·3%). Depressive symptoms were a strong risk factor associated with frailty (PAF 19·1%). Age-stratified analyses revealed that limited mobility had the highest PAFs in adults aged 80 years and older, whereas depressive symptoms showed peak PAFs in those aged 60–69 years in most cases. Hypertension contributed to all outcomes (PAFs 8·4–19·6%) only in adults younger than 80 years. In adults aged 60–69 years physical activity was the predominant risk factor associated with frailty (PAF 21·9%) and disability (PAF 22·3%). The attributable risk of lower education with frailty increased with age, reaching its peak in adults aged 80 years and older (PAF 20·2%). Regarding the joint effects of the risk factors, intrinsic capacity decline was the factor associated with the highest overall attributable risk for all outcomes, exceeding the impact of cardiometabolic diseases and socioeconomic and lifestyle risk.</div></div><div><h3>Interpretation</h3><div>Our findings provide insights into age-specific risk factors for frailty, disability, and hospitalisation in older people, underlining the importance of targeted prevention strategies across age groups. Our findings further support a shift towards prioritising intrinsic capacity to better support healthy ageing at the popu","PeriodicalId":34394,"journal":{"name":"Lancet Healthy Longevity","volume":"6 9","pages":"Article 100757"},"PeriodicalIF":14.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008445","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}
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