Pub Date : 2026-04-01Epub Date: 2025-07-27DOI: 10.1016/j.jagp.2025.07.006
Ziping Wang Ph.D. , Yan Deng Ph.D. , Liangkai Chen Ph.D. , Benchao Li Ph.D. , Wei Bao Ph.D. , Ting Wang Ph.D. , Shuang Rong Ph.D.
Objective
Methylmalonic acid (MMA) accumulation, as a novel link between aging and cancer progression, had attracted widespread attention. However, there was limited evidence focusing on its association with age-related cognitive decline in elderly people. Further evidence for this will help provide new perspective on preventing cognitive disorders such as dementia.
Methods
Overall, 2,760 older adults (mean age: 69.46 years, female: 50.98%) from the National Health and Nutrition Examination Survey were included. Serum MMA concentrations were measured by gas chromatography/mass spectrophotometry. Four cognitive domains (immediate memory, delayed memory, language function, attention) were evaluated through a battery of neuropsychological tests. The global cognition was assessed by a composite z score. And the subjective cognitive decline was examined via self-reports. The weighted linear regression and logistic regression model were performed to evaluate the relationship of MMA with cognition.
Results
Individuals with higher MMA levels tended to have poorer cognitive function, especially in the language function and attention domain. In the logistic regression model, compared to participants with MMA <170 nmol/L, those with MMA ≥250 nmol/L have the ORs (95% confidence interval) of 1.53 (1.15, 2.04) for poor global cognition, 1.56 (1.09, 2.23) for language function, and 1.48 (1.02, 2.15) for attention. In the multivariable linear regression model, the β coefficients (95% confidence intervals) of MMA were −1.84 (−3.44, −0.25) for global cognitive score and −2.06 (−3.38, −0.74) for attention.
Conclusion
The circulating MMA was inversely associated with global cognition, language function, and attention in older adults. The underlying causality and biological mechanisms warrant further exploration.
{"title":"Association Between Serum Methylmalonic Acid and Poor Cognitive Performance","authors":"Ziping Wang Ph.D. , Yan Deng Ph.D. , Liangkai Chen Ph.D. , Benchao Li Ph.D. , Wei Bao Ph.D. , Ting Wang Ph.D. , Shuang Rong Ph.D.","doi":"10.1016/j.jagp.2025.07.006","DOIUrl":"10.1016/j.jagp.2025.07.006","url":null,"abstract":"<div><h3>Objective</h3><div>Methylmalonic acid (MMA) accumulation, as a novel link between aging and cancer progression, had attracted widespread attention. However, there was limited evidence focusing on its association with age-related cognitive decline in elderly people. Further evidence for this will help provide new perspective on preventing cognitive disorders such as dementia.</div></div><div><h3>Methods</h3><div>Overall, 2,760 older adults (mean age: 69.46 years, female: 50.98%) from the National Health and Nutrition Examination Survey were included. Serum MMA concentrations were measured by gas chromatography/mass spectrophotometry. Four cognitive domains (immediate memory, delayed memory, language function, attention) were evaluated through a battery of neuropsychological tests. The global cognition was assessed by a composite z score. And the subjective cognitive decline was examined via self-reports. The weighted linear regression and logistic regression model were performed to evaluate the relationship of MMA with cognition.</div></div><div><h3>Results</h3><div>Individuals with higher MMA levels tended to have poorer cognitive function, especially in the language function and attention domain. In the logistic regression model, compared to participants with MMA <170 nmol/L, those with MMA ≥250 nmol/L have the ORs (95% confidence interval) of 1.53 (1.15, 2.04) for poor global cognition, 1.56 (1.09, 2.23) for language function, and 1.48 (1.02, 2.15) for attention. In the multivariable linear regression model, the β coefficients (95% confidence intervals) of MMA were −1.84 (−3.44, −0.25) for global cognitive score and −2.06 (−3.38, −0.74) for attention.</div></div><div><h3>Conclusion</h3><div>The circulating MMA was inversely associated with global cognition, language function, and attention in older adults. The underlying causality and biological mechanisms warrant further exploration.</div></div>","PeriodicalId":55534,"journal":{"name":"American Journal of Geriatric Psychiatry","volume":"34 4","pages":"Pages 474-485"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144986952","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}
Pub Date : 2026-04-01Epub Date: 2025-03-01DOI: 10.1016/j.jagp.2025.02.012
Malcolm Forbes M.B.B.S. , Tayler Watson M.B.B.S. , Duncan J. Topliss M.D. , Mojtaba Lotfaliany Ph.D. , Mohammadreza Mohebbi Ph.D. , Robyn L. Woods Ph.D. , John J. McNeil Ph.D. , Michael Berk MBB.Ch.
Objective
To investigate the association between thyroid-stimulating hormone (TSH) levels and depression in older adults.
Design
Prospective cohort study with an 11-year follow-up period.
Setting
Community-dwelling participants from the ASPirin in Reducing Events in the Elderly (ASPREE) randomized controlled trial and its follow-up observational study in Australia.
Participants
About 9,050 adults aged ≥70 years with baseline TSH measurements and depression assessments. Participants with thyroid cancer, baseline depression, or thyroid-altering medications were excluded.
Measurements
Depression was assessed annually using the Center for Epidemiological Studies Depression Scale (CES-D-10) using a cut score of 12, and hospital admission records. TSH was measured at baseline and year 3, categorized as low (<0.34 mU/L), normal (0.34–3.75 mU/L), or high (>3.75 mU/L).
Results
Cross-sectional analyses found no significant association between TSH levels and depression at baseline (p = 0.79) or year 3 (p = 0.054). Longitudinal analyses revealed no relationship between baseline or time-varying TSH levels and incident depression over the follow-up period (HR = 1.0, 95% CI: 0.96–1.05).
Conclusions
TSH levels are not associated with prevalent or incident depression in older community-dwelling adults. These findings should guide screening approaches for depression in older adults.
{"title":"Thyroid-Stimulating Hormone Levels and Depression in Older Adults: Cross-Sectional and Longitudinal Analyses in a Community-Dwelling Population","authors":"Malcolm Forbes M.B.B.S. , Tayler Watson M.B.B.S. , Duncan J. Topliss M.D. , Mojtaba Lotfaliany Ph.D. , Mohammadreza Mohebbi Ph.D. , Robyn L. Woods Ph.D. , John J. McNeil Ph.D. , Michael Berk MBB.Ch.","doi":"10.1016/j.jagp.2025.02.012","DOIUrl":"10.1016/j.jagp.2025.02.012","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the association between thyroid-stimulating hormone (TSH) levels and depression in older adults.</div></div><div><h3>Design</h3><div>Prospective cohort study with an 11-year follow-up period.</div></div><div><h3>Setting</h3><div>Community-dwelling participants from the ASPirin in Reducing Events in the Elderly (ASPREE) randomized controlled trial and its follow-up observational study in Australia.</div></div><div><h3>Participants</h3><div>About 9,050 adults aged ≥70 years with baseline TSH measurements and depression assessments. Participants with thyroid cancer, baseline depression, or thyroid-altering medications were excluded.</div></div><div><h3>Measurements</h3><div>Depression was assessed annually using the Center for Epidemiological Studies Depression Scale (CES-D-10) using a cut score of 12, and hospital admission records. TSH was measured at baseline and year 3, categorized as low (<0.34 mU/L), normal (0.34–3.75 mU/L), or high (>3.75 mU/L).</div></div><div><h3>Results</h3><div>Cross-sectional analyses found no significant association between TSH levels and depression at baseline (p = 0.79) or year 3 (p = 0.054). Longitudinal analyses revealed no relationship between baseline or time-varying TSH levels and incident depression over the follow-up period (HR = 1.0, 95% CI: 0.96–1.05).</div></div><div><h3>Conclusions</h3><div>TSH levels are not associated with prevalent or incident depression in older community-dwelling adults. These findings should guide screening approaches for depression in older adults.</div></div>","PeriodicalId":55534,"journal":{"name":"American Journal of Geriatric Psychiatry","volume":"34 4","pages":"Pages 544-554"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712246","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}
Pub Date : 2026-04-01Epub Date: 2026-01-24DOI: 10.1016/j.jagp.2026.01.013
Christopher C Colenda M.D., M.P.H. , David C Steffens M.D., M.H.S. , Dan G Blazer M.D., Ph.D. , Charles F Reynolds III M.D.
{"title":"Memoriam for James A. Greene, MD, DLFAPA, FACPsych","authors":"Christopher C Colenda M.D., M.P.H. , David C Steffens M.D., M.H.S. , Dan G Blazer M.D., Ph.D. , Charles F Reynolds III M.D.","doi":"10.1016/j.jagp.2026.01.013","DOIUrl":"10.1016/j.jagp.2026.01.013","url":null,"abstract":"","PeriodicalId":55534,"journal":{"name":"American Journal of Geriatric Psychiatry","volume":"34 4","pages":"Pages 669-673"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146129180","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}
Pub Date : 2026-04-01Epub Date: 2025-02-26DOI: 10.1016/j.jagp.2025.02.011
Abe J.C. van der Slot M.D. , Simon P. Mooijaart M.D., Ph.D. , Jan-Willem van Dalen Ph.D. , Marieke Hoevenaar Ph.D. , Edo Richard M.D., Ph.D. , Erik J. Giltay M.D., Ph.D.
Background
The prevalence of depressive symptoms, apathy, and cognitive decline increases with age. Understanding the temporal dynamics of these symptoms could provide valuable insights into the early stages of cognitive decline, allowing for more timely and effective treatment and management.
Methods
Participants from the Prevention of Dementia by Intensive Vascular Care (preDIVA) trial cohort with baseline and ≥3 follow-up measurements were included, with a median of 7.8 (0.68) years of follow-up. Dynamic Time Warping (DTW) analysis was used to model temporal dynamics of cognition using the Mini Mental State Exam (MMSE), activities of daily living (ADL) using the Amsterdam Linear Disability Scale (ALDS), and apathy and depressive symptoms using the 15-item Geriatric Depression Scale (GDS-15) at the individual and group level.
Results
The 1,537 participants were aged 74 (2.0) years at baseline, 56.5% were female, and 19.9% had finished higher education. A decline in ADL and increase in apathy tended to precede most indicators of cognitive decline, with all apathy items (i.e. being ‘dropped activities/interests’, ‘not feeling energetic’ and ‘not doing new things’) and ADL showing significant outstrength (all p's < 0.001). Many mood-related symptoms other than apathy, and the MMSE items ‘immediate memory’, ‘verbal comprehension’ and ‘naming objects’ tended to be the last to deteriorate, showing significant instrength (all p's < 0.001).
Conclusion
An increase apathy and a decline in ADL tended to precede mood-related symptoms and cognitive impairment in older adults from the general population. These changes may thus serve as potential early warning signs of both depression and dementia, and may allow for timely intervention.
{"title":"Temporal Dynamics of Depressive Symptoms, Apathy, Daily Activities, and Cognitive Decline in Older People From the General Population: A Network Analysis","authors":"Abe J.C. van der Slot M.D. , Simon P. Mooijaart M.D., Ph.D. , Jan-Willem van Dalen Ph.D. , Marieke Hoevenaar Ph.D. , Edo Richard M.D., Ph.D. , Erik J. Giltay M.D., Ph.D.","doi":"10.1016/j.jagp.2025.02.011","DOIUrl":"10.1016/j.jagp.2025.02.011","url":null,"abstract":"<div><h3>Background</h3><div>The prevalence of depressive symptoms, apathy, and cognitive decline increases with age. Understanding the temporal dynamics of these symptoms could provide valuable insights into the early stages of cognitive decline, allowing for more timely and effective treatment and management.</div></div><div><h3>Methods</h3><div>Participants from the Prevention of Dementia by Intensive Vascular Care (preDIVA) trial cohort with baseline and ≥3 follow-up measurements were included, with a median of 7.8 (0.68) years of follow-up. Dynamic Time Warping (DTW) analysis was used to model temporal dynamics of cognition using the Mini Mental State Exam (MMSE), activities of daily living (ADL) using the Amsterdam Linear Disability Scale (ALDS), and apathy and depressive symptoms using the 15-item Geriatric Depression Scale (GDS-15) at the individual and group level.</div></div><div><h3>Results</h3><div>The 1,537 participants were aged 74 (2.0) years at baseline, 56.5% were female, and 19.9% had finished higher education. A decline in ADL and increase in apathy tended to precede most indicators of cognitive decline, with all apathy items (i.e. being ‘dropped activities/interests’, ‘not feeling energetic’ and ‘not doing new things’) and ADL showing significant outstrength (all p's < 0.001). Many mood-related symptoms other than apathy, and the MMSE items ‘immediate memory’, ‘verbal comprehension’ and ‘naming objects’ tended to be the last to deteriorate, showing significant instrength (all p's < 0.001).</div></div><div><h3>Conclusion</h3><div>An increase apathy and a decline in ADL tended to precede mood-related symptoms and cognitive impairment in older adults from the general population. These changes may thus serve as potential early warning signs of both depression and dementia, and may allow for timely intervention.</div></div>","PeriodicalId":55534,"journal":{"name":"American Journal of Geriatric Psychiatry","volume":"34 4","pages":"Pages 555-567"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617890","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}
Pub Date : 2026-03-01Epub Date: 2025-10-04DOI: 10.1016/j.jagp.2025.10.001
Anderson Matheus Pereira da Silva B.Pharm. , Ocilio de Deus M.S. , Filipe Virgilio Ribeiro M.S. , Gabriel Caruso Novaes Tudella M.S. , Lucas Silva Cabeça M.S. , Levi Leal Silva M.S. , Mariana Lee Han M.S. , Julia Oliveira Franco M.S. , João Gabriel Pereira Costa M.S. , Maria da Vitória Santos do Nascimento B.Pharm. , João Vitor Andrade Fernandes M.S. , Eryvelton de Souza Franco Ph.D. , Maria Bernadete de Sousa Maia B.Pharm., Ph.D.
Background
Alzheimer’s disease (AD) dementia is the leading cause of cognitive decline in late life, yet treatment options remain limited. Lithium, widely used in bipolar disorder, has been suggested to exert neuroprotective effects through inhibition of GSK-3β and modulation of amyloid and tau pathology. We aimed to evaluate the efficacy and safety of lithium in AD dementia.
Methods
This systematic review and meta-analysis was prospectively registered in PROSPERO and conducted following PRISMA guidelines. We searched PubMed, Embase, and Cochrane Library through April 2025 for randomized controlled trials (RCTs) comparing lithium with placebo or standard therapy in patients with AD dementia or amnestic mild cognitive impairment. Outcomes included cognition (MMSE, ADAS-Cog, memory tasks), function (CDR-SB, conversion to AD), neuropsychiatric symptoms (NPI), CSF biomarkers, and safety (adverse events [AEs], serious AEs [SAEs]). Random-effects meta-analyses were complemented by Bayesian methods and trial sequential analyses.
Results
Six RCTs involving 394 participants (196 lithium, 198 placebo) met inclusion criteria. Lithium did not significantly improve global cognition (MMSE: MD −1.61, 95% CI −4.11 to 0.88; ADAS-Cog: MD −1.82, −3.05 to −0.60; both with high heterogeneity). Memory outcomes were mixed, with possible benefit for figure recall but not delayed verbal recall. No consistent benefits were observed for episodic memory, functional outcomes (CDR-SB), neuropsychiatric symptoms, or CSF biomarkers. Safety analyses showed no increased risk of SAEs; drug-related AEs were more frequent but heterogeneous across trials.
Conclusions
Lithium demonstrated an acceptable safety profile within the dosing regimens studied. However, current evidence does not support consistent cognitive or functional benefits in AD dementia. Larger, well-designed RCTs are warranted to clarify its potential therapeutic role.
{"title":"Efficacy and Safety of Lithium for Behavioral and Cognitive Symptoms in Alzheimer's Disease Dementia: A Systematic Review With Frequentist and Bayesian Meta-Analysis","authors":"Anderson Matheus Pereira da Silva B.Pharm. , Ocilio de Deus M.S. , Filipe Virgilio Ribeiro M.S. , Gabriel Caruso Novaes Tudella M.S. , Lucas Silva Cabeça M.S. , Levi Leal Silva M.S. , Mariana Lee Han M.S. , Julia Oliveira Franco M.S. , João Gabriel Pereira Costa M.S. , Maria da Vitória Santos do Nascimento B.Pharm. , João Vitor Andrade Fernandes M.S. , Eryvelton de Souza Franco Ph.D. , Maria Bernadete de Sousa Maia B.Pharm., Ph.D.","doi":"10.1016/j.jagp.2025.10.001","DOIUrl":"10.1016/j.jagp.2025.10.001","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer’s disease (AD) dementia is the leading cause of cognitive decline in late life, yet treatment options remain limited. Lithium, widely used in bipolar disorder, has been suggested to exert neuroprotective effects through inhibition of GSK-3β and modulation of amyloid and tau pathology. We aimed to evaluate the efficacy and safety of lithium in AD dementia.</div></div><div><h3>Methods</h3><div>This systematic review and meta-analysis was prospectively registered in PROSPERO and conducted following PRISMA guidelines. We searched PubMed, Embase, and Cochrane Library through April 2025 for randomized controlled trials (RCTs) comparing lithium with placebo or standard therapy in patients with AD dementia or amnestic mild cognitive impairment. Outcomes included cognition (MMSE, ADAS-Cog, memory tasks), function (CDR-SB, conversion to AD), neuropsychiatric symptoms (NPI), CSF biomarkers, and safety (adverse events [AEs], serious AEs [SAEs]). Random-effects meta-analyses were complemented by Bayesian methods and trial sequential analyses.</div></div><div><h3>Results</h3><div>Six RCTs involving 394 participants (196 lithium, 198 placebo) met inclusion criteria. Lithium did not significantly improve global cognition (MMSE: MD −1.61, 95% CI −4.11 to 0.88; ADAS-Cog: MD −1.82, −3.05 to −0.60; both with high heterogeneity). Memory outcomes were mixed, with possible benefit for figure recall but not delayed verbal recall. No consistent benefits were observed for episodic memory, functional outcomes (CDR-SB), neuropsychiatric symptoms, or CSF biomarkers. Safety analyses showed no increased risk of SAEs; drug-related AEs were more frequent but heterogeneous across trials.</div></div><div><h3>Conclusions</h3><div>Lithium demonstrated an acceptable safety profile within the dosing regimens studied. However, current evidence does not support consistent cognitive or functional benefits in AD dementia. Larger, well-designed RCTs are warranted to clarify its potential therapeutic role.</div></div>","PeriodicalId":55534,"journal":{"name":"American Journal of Geriatric Psychiatry","volume":"34 3","pages":"Pages 371-385"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145433517","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}
Pub Date : 2026-03-01Epub Date: 2025-12-06DOI: 10.1016/j.jagp.2025.11.014
Hanadi Ajam Oughli M.D.
{"title":"Frailty and Depression in Late Life: A Synergistic Effect","authors":"Hanadi Ajam Oughli M.D.","doi":"10.1016/j.jagp.2025.11.014","DOIUrl":"10.1016/j.jagp.2025.11.014","url":null,"abstract":"","PeriodicalId":55534,"journal":{"name":"American Journal of Geriatric Psychiatry","volume":"34 3","pages":"Pages 298-300"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879935","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}
Pub Date : 2026-03-01Epub Date: 2025-12-06DOI: 10.1016/j.jagp.2025.12.001
Robert H. Pietrzak Ph.D., M.P.H. , Peter J. Na M.D., M.P.H. , Yen Ying Lim Ph.D.
{"title":"Commentary: The Effect of Stress on All-Cause Dementia: A Longitudinal Analysis from the Australian Longitudinal Study on Women’s Health","authors":"Robert H. Pietrzak Ph.D., M.P.H. , Peter J. Na M.D., M.P.H. , Yen Ying Lim Ph.D.","doi":"10.1016/j.jagp.2025.12.001","DOIUrl":"10.1016/j.jagp.2025.12.001","url":null,"abstract":"","PeriodicalId":55534,"journal":{"name":"American Journal of Geriatric Psychiatry","volume":"34 3","pages":"Pages 281-283"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145852203","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}
Pub Date : 2026-03-01Epub Date: 2025-12-12DOI: 10.1016/j.jagp.2025.12.005
Shyam Sundar Sah M.D. , Abhishek Kumbhalwar Ph.D.
{"title":"Comment on “Housing Assistance and Health Care Access Among Older Adults With Alzheimer’s Disease and Related Dementias: Evidence From Multisource Linked Survey-Administrative Data”","authors":"Shyam Sundar Sah M.D. , Abhishek Kumbhalwar Ph.D.","doi":"10.1016/j.jagp.2025.12.005","DOIUrl":"10.1016/j.jagp.2025.12.005","url":null,"abstract":"","PeriodicalId":55534,"journal":{"name":"American Journal of Geriatric Psychiatry","volume":"34 3","pages":"Pages 395-396"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890989","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}
Pub Date : 2026-03-01Epub Date: 2025-11-08DOI: 10.1016/j.jagp.2025.11.005
Kay Khaing M.Med. , Xenia Dolja-Gore Ph.D. , Balakrishnan R. Nair M.D. , Julie Byles Ph.D. , John Attia Ph.D.
Objectives
Perceived stress has been linked to dementia, however the duration of perceived stress, as well as the timing of this exposure, on dementia has not been explored. This study aimed to assess the effect of transient versus prolonged versus persistent perceived stress and exposure to stressful life events (SLE), as well as time windows of exposure, on all-cause dementia.
Design
Cohort study.
Setting
The Australian Longitudinal Study on Women’s Health (ALSWH).
Participants
The oldest cohort (born 1921–26), and the middle cohort (born 1946–51), from the Australian Longitudinal Study on Women’s Health were used in this analysis.
Measures
Perceived stress and SLE were measured using a self-reported questionnaire. Dementia was defined as per International Classification of Disease – 10 (ICD 10) codes through linked datasets over a mean follow up of 16 years for the oldest and 20 years for the middle cohort.
Results
Transient, prolonged and persistent perceived stress were associated with increased risk of all-cause dementia (HR: 1.52, 95% CI: 1.04–2.23, HR: 1.63, 95% CI: 1.15–2.27, and HR: 1.65, 95% CI: 1.10–2.50 respectively) in the middle cohort. Higher risk of all-cause dementia was found among middle cohort exposed to four or more SLE, however the association was statistically insignificant in the fully adjusted model. Both perceived stress and SLE had no effect in the oldest cohort.
Conclusion
Transient, prolonged and persistent perceived stress were associated with higher risk of all-cause dementia in our middle cohort which suggests that stress may be a risk factor for dementia.
{"title":"The Effect of Stress on All-Cause Dementia: A Longitudinal Analysis From the Australian Longitudinal Study on Women’s Health","authors":"Kay Khaing M.Med. , Xenia Dolja-Gore Ph.D. , Balakrishnan R. Nair M.D. , Julie Byles Ph.D. , John Attia Ph.D.","doi":"10.1016/j.jagp.2025.11.005","DOIUrl":"10.1016/j.jagp.2025.11.005","url":null,"abstract":"<div><h3>Objectives</h3><div>Perceived stress has been linked to dementia, however the duration of perceived stress, as well as the timing of this exposure, on dementia has not been explored. This study aimed to assess the effect of transient versus prolonged versus persistent perceived stress and exposure to stressful life events (SLE), as well as time windows of exposure, on all-cause dementia.</div></div><div><h3>Design</h3><div>Cohort study.</div></div><div><h3>Setting</h3><div>The Australian Longitudinal Study on Women’s Health (ALSWH).</div></div><div><h3>Participants</h3><div>The oldest cohort (born 1921–26), and the middle cohort (born 1946–51), from the Australian Longitudinal Study on Women’s Health were used in this analysis.</div></div><div><h3>Measures</h3><div>Perceived stress and SLE were measured using a self-reported questionnaire. Dementia was defined as per International Classification of Disease – 10 (ICD 10) codes through linked datasets over a mean follow up of 16 years for the oldest and 20 years for the middle cohort.</div></div><div><h3>Results</h3><div>Transient, prolonged and persistent perceived stress were associated with increased risk of all-cause dementia (HR: 1.52, 95% CI: 1.04–2.23, HR: 1.63, 95% CI: 1.15–2.27, and HR: 1.65, 95% CI: 1.10–2.50 respectively) in the middle cohort. Higher risk of all-cause dementia was found among middle cohort exposed to four or more SLE, however the association was statistically insignificant in the fully adjusted model. Both perceived stress and SLE had no effect in the oldest cohort.</div></div><div><h3>Conclusion</h3><div>Transient, prolonged and persistent perceived stress were associated with higher risk of all-cause dementia in our middle cohort which suggests that stress may be a risk factor for dementia.</div></div>","PeriodicalId":55534,"journal":{"name":"American Journal of Geriatric Psychiatry","volume":"34 3","pages":"Pages 269-280"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145650814","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}
The association between the risk of dementia and different classes of antidepressants, as well as the potential influence of treatment resistance or response, remains unexplored in individuals with major depressive disorder (MDD).
Methods
Using the Taiwan National Health Insurance Research Database, 30,390 patients with MDD and 24,312 well-matched controls were enrolled between 2002 and 2004. We stratified the antidepressant-resistant depression (ART, n = 6,078) and antidepressant-responsive depression (ARP, n = 24,312) groups. Selective serotonin reuptake inhibitors (SSRIs) versus non-SSRIs, was included as a stratification factor. The risks of dementia were examined using a Cox regression model (reported as hazard ratio with 95% confidence interval).
Results
Both the ART and ARP groups had a 5–24 fold higher risk of developing dementia than the controls. ART appeared to be associated with a higher risk of developing dementia than ARP, including any dementia (13.02 [11.08–15.31] versus 7.70 [6.63–8.94] and unspecified dementia 12.81 [10.52–15.59] versus 7.33 [6.11–8.79]). Subsequent analysis demonstrated that in the ART group, individuals who were resistant to SSRIs only (12.01 [10.02–14.40]) or both SSRIs and non-SSRIs (13.87 [11.67–16.47]) appeared to have a higher risk of developing any dementia than the ARP group (7.70 [6.63–8.94]). With the ARP as reference group, patients who were only resistant to SSRIs and those who were resistant to both SSRIs and non-SSRIs had a higher risk of developing any dementia.
Conclusions
In elderly patients with MDD, the risk of dementia is higher among those who are resistant to any type of antidepressant medication.
背景：在重度抑郁症（MDD）患者中，痴呆风险与不同类型抗抑郁药之间的关系，以及治疗耐药性或反应的潜在影响，仍未得到研究。我们将抗抑郁药耐药抑郁（ART, n = 6078）和抗抑郁反应性抑郁（ARP, n = 24312）组进行分层。选择性5 -羟色胺再摄取抑制剂（SSRIs）与非SSRIs，被纳入分层因素。使用Cox回归模型检查痴呆的风险（报告为95%置信区间的风险比）。结果：ART和ARP组发生痴呆的风险都比对照组高5-24倍。ART似乎比ARP与更高的痴呆风险相关，包括任何痴呆(13.02[11.08-15.31]对7.70[6.63-8.94]和未指明的痴呆（12.81[10.52-15.59]对7.33[6.11-8.79]）。随后的分析表明，在ART组中，仅对SSRIs耐药（12.01[10.02-14.40]）或同时对SSRIs和非SSRIs耐药（13.87[11.67-16.47]）的个体发生痴呆的风险似乎高于ARP组（7.70[6.63-8.94]）。以ARP为参照组，仅对SSRIs耐药的患者以及对SSRIs和非SSRIs均耐药的患者患痴呆的风险更高。结论：在老年MDD患者中，对任何类型的抗抑郁药物都有抵抗力的患者患痴呆的风险更高。
{"title":"Dementia Risk Among Patients with Major Depressive Disorder: Does Antidepressant Class Matter?","authors":"Che-Sheng Chu M.D. , Tien-Wei Hsu M.D. , Ya-Mei Bai M.D., Ph.D. , Tung-Ping Su M.D., Ph.D. , Shih-Jen Tsai M.D., Ph.D. , Tzeng-Ji Chen M.D., Ph.D. , Fu-Chi Yang M.D., Ph.D. , Mu-Hong Chen M.D., Ph.D. , Chih-Sung Liang M.D.","doi":"10.1016/j.jagp.2025.07.002","DOIUrl":"10.1016/j.jagp.2025.07.002","url":null,"abstract":"<div><h3>Background</h3><div>The association between the risk of dementia and different classes of antidepressants, as well as the potential influence of treatment resistance or response, remains unexplored in individuals with major depressive disorder (MDD).</div></div><div><h3>Methods</h3><div>Using the Taiwan National Health Insurance Research Database, 30,390 patients with MDD and 24,312 well-matched controls were enrolled between 2002 and 2004. We stratified the antidepressant-resistant depression (ART, <em>n</em> = 6,078) and antidepressant-responsive depression (ARP, <em>n</em> = 24,312) groups. Selective serotonin reuptake inhibitors (SSRIs) versus non-SSRIs, was included as a stratification factor. The risks of dementia were examined using a Cox regression model (reported as hazard ratio with 95% confidence interval).</div></div><div><h3>Results</h3><div>Both the ART and ARP groups had a 5–24 fold higher risk of developing dementia than the controls. ART appeared to be associated with a higher risk of developing dementia than ARP, including any dementia (13.02 [11.08–15.31] versus 7.70 [6.63–8.94] and unspecified dementia 12.81 [10.52–15.59] versus 7.33 [6.11–8.79]). Subsequent analysis demonstrated that in the ART group, individuals who were resistant to SSRIs only (12.01 [10.02–14.40]) or both SSRIs and non-SSRIs (13.87 [11.67–16.47]) appeared to have a higher risk of developing any dementia than the ARP group (7.70 [6.63–8.94]). With the ARP as reference group, patients who were only resistant to SSRIs and those who were resistant to both SSRIs and non-SSRIs had a higher risk of developing any dementia.</div></div><div><h3>Conclusions</h3><div>In elderly patients with MDD, the risk of dementia is higher among those who are resistant to any type of antidepressant medication.</div></div>","PeriodicalId":55534,"journal":{"name":"American Journal of Geriatric Psychiatry","volume":"34 3","pages":"Pages 313-322"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796634","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}
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