The journals of gerontology. Series A, Biological sciences and medical sciences最新文献

{"title":"Association and Predictive Value of Biological Aging for Chronic Kidney Disease Risk in Diabetes: Cross-Cohort Validation across UK and China.","authors":"Yiting Wu, Hao Xiang, Yu Huang, Yuanyuan Zhang, Ziliang Ye, Yanjun Zhang, Sisi Yang, Xiaoqin Gan, Yiwei Zhang, Chen Dan, Xianglian Cai, Xiaolong Liang, Sheng Nie, Fan Fan Hou, Xianhui Qin","doi":"10.1093/gerona/glag120","DOIUrl":"https://doi.org/10.1093/gerona/glag120","url":null,"abstract":"<p><strong>Background: </strong>Biological aging (BA) may influence chronic kidney disease (CKD) development. We evaluated the association of accelerated BA-quantified using Klemera-Doubal method biological age (KDM-BA) and phenotypic age (PhenoAge)-with incident CKD, and assessed its predictive value beyond conventional risk factors (CKD Prediction Consortium [CKD-PC] model) in participants with diabetes.</p><p><strong>Methods: </strong>This two-country cohort study included 14,274 participants with diabetes from the UK Biobank and 7,900 from the China Renal Data System (CRDS). KDM-BA and PhenoAge were calculated from clinical biomarkers, and their acceleration (deviation from chronological age) was evaluated. Cox regression assessed associations with incident CKD, while C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) evaluated predictive performance.</p><p><strong>Results: </strong>Over median follow-ups of 13.3 (UK Biobank) and 3.3 (CRDS) years, 1,676 and 709 incident CKD cases were documented. Each standard deviation increase in KDM-BA acceleration was associated with 31% (95%CI: 23-39%) (UK) and 68% (95%CI: 58-80%) (China) higher CKD hazard. PhenoAge acceleration similarly increased CKD risk (29% and 28%, respectively). In the UK Biobank, adding KDM-BA or PhenoAge acceleration to the CKD-PC model (C-index = 0.770) led to modest but statistically significant improvements in prediction (C-index increase = 0.004 [95%CI: 0.002-0.006] and 0.003 [0.001-0.005], respectively), while leukocyte telomere length (LTL) provided no benefit (0.0001 [-0.0004, 0.0005]). Both BA measures enhanced reclassification (NRI: 0.034-0.076; IDI: 0.002-0.003). CRDS analyses yielded consistent results.</p><p><strong>Conclusion: </strong>Accelerated BA is consistently associated with higher CKD hazard in diabetes across European and Asian populations. KDM-BA and PhenoAge offer practical tools for refining CKD risk stratification.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A pragmatic Three-Component Clinical Score for Cognitive Risk Stratification in Older Adults with Multimorbidity and Frailty.","authors":"Nusrat E Mozid, Imran Hossain Monju, Shakila Sharmin, Sanjana Binte Ahmed","doi":"10.1093/gerona/glag117","DOIUrl":"https://doi.org/10.1093/gerona/glag117","url":null,"abstract":"<p><strong>Background: </strong>Simple, scalable clinical tools are needed to identify older adults with prevalent cognitive impairment in low-resource settings, yet whether parsimonious approaches can match complex phenotyping methods remains unclear. This study developed a three-component clinical score and compared its discriminative performance with latent class analysis (LCA)-derived multimorbidity phenotypes.</p><p><strong>Methods: </strong>This cross-sectional study was conducted in two districts of Bangladesh included 504 community-dwelling adults aged ≥65 years with at least one chronic disease. Frailty was assessed using the Fried phenotype, and multimorbidity was self-reported and coded using ICD-10. An additive score (0-5 points) incorporating age ≥80 years, ≥3 chronic conditions, and frailty classified participants into low (0-1), moderate (2-3), or high (4-5) risk. Outcomes included global cognition and cognitive impairment (MMSE < 25).</p><p><strong>Results: </strong>The three-component score showed acceptable discrimination for cognitive impairment (AUC = 0.72) and explained 33% of MMSE variance. LCA-derived phenotypes demonstrated poor discrimination (AUC = 0.44; difference = 0.28, p < 0.001). A monotonic gradient was observed across risk categories, impairment prevalence increased across risk categories (59%, 83%, and 96%), corresponding to a 12.8-point MMSE difference across the score range. A frailty-augmented LCA (in which frailty was added to the original disease-only LCA) combined with age yielded a modestly higher AUC (0.764), though at substantially greater analytical complexity.</p><p><strong>Conclusions: </strong>A parsimonious clinical score combining age, multimorbidity, and frailty demonstrated acceptable cross-sectional discrimination for prevalent cognitive impairment and substantially outperformed disease-only multimorbidity phenotyping. Given the cross-sectional design, conclusions pertain to prevalence-based risk stratification rather than prediction of incident cognitive decline. Subject to prospective validation, this pragmatic tool may support case-finding and cognitive risk stratification in resource-limited settings.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The influence of accelerated aging-related cardiac remodeling on cardiovascular outcomes: an observational study.","authors":"Zhi Lv, Kexin Li, Chang Liu, Peiqi Liu, Zi Kou, Mingjuan Zhang, Dengfeng Gao","doi":"10.1093/gerona/glag098","DOIUrl":"10.1093/gerona/glag098","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to investigate the associations between phenotypic age acceleration (PhenoAgeAccel) and different CVD outcomes and mortality, examine its relationship with cardiac structure and function using cardiac magnetic resonance imaging (CMR), and explore potential mediating pathways involving cardiac remodeling and cardiometabolic diseases.</p><p><strong>Methods: </strong>PhenoAgeAccel was defined as the residual of PhenoAge, derived from 9 biomarkers, regressed on chronological age. We included 31 722 UK Biobank participants (mean age 54.6 years; 48.1% male) with complete baseline biomarker and CMR data. Multiple Cox proportional hazards models were used to assess associations with CVD outcomes and mortality. Multivariable linear regression examined associations with CMR-derived cardiac measures, and multiple mediation analyses were performed to evaluate potential mediating roles.</p><p><strong>Results: </strong>Higher PhenoAgeAccel was independently associated with increased risks of any CVD, ischemic heart disease (IHD), heart failure, all-cause mortality, and CVD mortality. Each standard deviation increase in PhenoAgeAccel (4.63 years) was associated with 7%, 9%, 29%, 14%, and 16% higher risks of these outcomes, respectively, but not with arrhythmias or cerebrovascular disease. Associations with any CVD, IHD, and CVD mortality were stronger in women. Higher PhenoAgeAccel was also associated with adverse cardiac remodeling, including lower left ventricular volume, stroke volume, mass, LVGFI, and ejection fraction. Cardiac remodeling and cardiometabolic diseases partially mediated these associations.</p><p><strong>Conclusions: </strong>Our study examines the association between accelerated aging and cardiac phenotypes and their important independent mediating role in the accelerated aging-cardiovascular outcome relationship. Improving cardiac remodeling and metabolic health may mitigate the effects of biological aging on CVD risk.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Finding the Turning Point in Aging: A Comparison of Physical, Cognitive, and Psychological Trajectories Among Centenarians and Non-Centenarians.","authors":"Erfei Zhao, Jennifer Ailshire, Jung Ki Kim, Eileen M Crimmins","doi":"10.1093/gerona/glag116","DOIUrl":"https://doi.org/10.1093/gerona/glag116","url":null,"abstract":"<p><strong>Background: </strong>Centenarians tend to delay age-related decline until very late life and generally experience slower deterioration across health domains. However, timing and pace of decline across physical, cognitive, and psychological domains among centenarians, compared to other long-lived groups, remain poorly characterized.</p><p><strong>Methods: </strong>Using the nationally representative Health and Retirement Study (1993-2022), we modeled trajectories of disease burden, physical functioning, psychological wellbeing, and cognition among participants born before 1922 (N = 7,237), followed up to 29 years. Participants were categorized by survival groups: centenarians (100+), nonagenarians (90-99), octogenarians (80-89), and septuagenarians (73-79). Joinpoint regression identified ages at which decline accelerated and quantified rates of change.</p><p><strong>Results: </strong>Those who lived to older ages-nonagenarian and centenarian decedents-maintained higher levels of physical/cognitive functioning into later life but showed sharp accelerations thereafter. Across physical functioning and cognition, onset of accelerated decline shifted later among those who survived longer, with centenarians showing the latest age at acceleration. Prior to acceleration, ADL/IADL limitations increased by approximately 0.04-0.05 points per year, rising to 0.20-0.34 points per year thereafter, while prevalence of cognitive impairment accelerated from roughly 1% to 4-6% per year. Individuals who survived longer also maintained lower depressive symptoms and disease burden into advanced ages, although cardiovascular conditions continued to rise.</p><p><strong>Conclusions: </strong>Exceptional longevity is marked by preserved physical and cognitive function followed by rapid late-life declines. Pinpointing when this tipping point occurs offers a quantitative basis for targeting interventions-medical, behavioral, and social-that sustain function and delay deterioration at the population level.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence for an energy conservation model of inflammaging and immunosenescence in the US Health and Retirement Study and UK Biobank.","authors":"Jacob E Aronoff, Maximilien Franck, Alan A Cohen, Benjamin C Trumble","doi":"10.1093/gerona/glag119","DOIUrl":"https://doi.org/10.1093/gerona/glag119","url":null,"abstract":"<p><p>The development of chronic inflammation in later life (inflammaging), alongside changes in immune cell profiles and impaired pathogen defense (immunosenescence), contribute to health risk. However, these processes have been hypothesized as adaptive remodeling of the immune system in response to accumulating somatic damage. Here we consider a recently developed theoretical framework to understand their relationship: the Brain-Body Energy Conservation model of aging. This model views immunosenescence as part of an energy conserving response to the rising energy expenditure of inflammaging. This response promotes short term survival against somatic damage at the expense of future health risk. For example, naïve T cells, which enhance defense against future infections, decline with age, while proteins that suppress the immune response to infection, including IL-10, increase. GDF-15, which is produced in response to chronic inflammation and metabolic stress, and similarly suppresses the immune response to infection, also increases with age. We find evidence consistent with this model in the US Health and Retirement Study (HRS, n = 8,184) and UK Biobank (UKB, n = 40,510). Across both cohorts, the key inflammaging marker TNFR1 partially mediated the age-related increases in IL-10 and GDF-15. In the HRS flow cytometry data, TNFR1 also mediated age-related decreases in naïve T cells. Finally, we assessed vulnerability to a novel future infection using the UKB medical records data on hospitalization or death from COVID-19 (n = 586 hospitalized or died). TNFR1, IL-10, and GDF-15, measured pre-pandemic, all partially mediated the age-related increased risk.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing and Internally Validating AI-Based Aging Resilience Biomarkers in Non-Human Primates.","authors":"Robert F Bennett, Jaime L Speiser, John D Olson, George W Schaaf, Thomas C Register, Laura A Cox, J Mark Cline, Ellen E Quillen","doi":"10.1093/gerona/glag112","DOIUrl":"https://doi.org/10.1093/gerona/glag112","url":null,"abstract":"<p><p>Quantifying biological aging is crucial for understanding functional decline before the onset of morbidity. While many accelerated aging and frailty measures based on clinical data exist for humans and several for rodent models of aging, there are few options for non-human primates (NHPs). NHP clinical data has several unique features including a lack of clinically delineated normative values for features and variability in data collection over long lifespans. There are also wide discrepancies in the number of available clinical measures and number of animals across data sets. To address these challenges, we developed and validated \"Aging Resilience\" (AR) metrics using longitudinal, routine clinical data from two distinct non-human primate cohorts: 4,328 baboons and 281 rhesus macaques. We trained five computational models-including Linear Mixed-Effects Models, Random Forest, and Recurrent Neural Networks (RNN)-to predict chronological age, subsequently deriving AR metrics that represent the velocity (Rate of Aging) and cumulative burden (Normalized Cumulative Aging) of physiological deviation. While linear models achieved high precision in predicting chronological age (test R2 up to 0.99), they correlated poorly with actual lifespan. In contrast, AR metrics derived from non-linear models (RNN and Random Forest) displayed strong predictive validity for mortality (Pearson's r > 0.8). These findings highlight a critical paradox: models that best predict chronological age do not necessarily capture the biological resilience determining healthspan. This study establishes a scalable framework for monitoring biological aging in translational models using standard veterinary records.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of high intensity interval training vs. Continuous moderate intensity exercise on body composition among older adults with HIV.","authors":"Grace L Kulik, Vitor H F Oliveira, Melissa P Wilson, Vincent Khuu, Catherine M Jankowski, Stephanie Dillon, Paul Cook, Samantha MaWhinney, Debashis Ghosh, Allison R Webel, Kristine M Erlandson","doi":"10.1093/gerona/glag113","DOIUrl":"https://doi.org/10.1093/gerona/glag113","url":null,"abstract":"<p><p>We compared two exercise intensities on lean and fat mass among older people with HIV (PWH). The High Intensity Exercise to Attenuate Limitations and Train Habits (HEALTH) randomized sedentary PWH ≥50 years to 16 weeks of high-intensity interval training (HIIT) or continuous moderate-intensity exercise (CME), both with resistance exercise. Body composition was measured using dual-energy x-ray absorptiometry (DXA) at baseline and week 16. Primary outcome was percent change in body fat percentage (ratio of fat mass to total mass). Secondary outcomes included percent change in lean, fat, appendicular lean (ALM), and total mass. Linear regression models examined between- and within-group changes from baseline to week 16. Of the 95 participants with pre- and post-DXA scans, the median (interquartile range [IQR]) age was 58 [54-61] years, 14% female, 14% Black, and 14% Hispanic. Fat percentage decreased by -3.3% (95% confidence interval [CI]: -5.2, -1.6) in HIIT and -3.3% (95% CI: -5.3, -1.6) in CME. Fat mass decreased by -3.5% (95% CI: -5.9, -1.0) in HIIT and -3.8% (95% CI: -6.3, -1.3) in CME. Lean mass increased by 1.7% (95% CI: 0.7, 2.7) and ALM by 3.3% (95% CI: 1.3, 5.3) in HIIT and 1.2% (95% CI: 0.2, 2.2) and ALM by 2.6% (95% CI: 0.6, 4.6) in CME. Although both arms had significant improvements compared to baseline, no between arm comparisons were statistically significant. Supervised HIIT or CME combined with resistance training for 16 weeks is an effective strategy for improving body composition in previously sedentary older PWH.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147825321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of a Short-Term Multicomponent Functional Exercise Program on the Serum Proteome: An Exploratory Study in Hospitalized Older Adults.","authors":"Maite Izco-Cubero, Mercedes Lachén-Montes, Chenhui Chenhuichen, Ba Cedeño Veloz, Icíar Echeverría-Beistegui, Fabricio Zambom-Ferraresi, Fabiola Zambom-Ferraresi, María Luisa Fernández-González de la Riva, Patricia Álvarez-Rodríguez, Enrique Santamaría, Nicolás Martínez-Velilla","doi":"10.1093/gerona/glag111","DOIUrl":"https://doi.org/10.1093/gerona/glag111","url":null,"abstract":"<p><p>Hospitalization in older adults often leads to disability in daily living activities, thereby increasing the risk of functional and cognitive impairments. This randomized controlled trial analyzed the serum protein profile of patients admitted to an acute geriatric unit who engaged in supervised multicomponent functional exercises compared with a control group. Potential protein biomarkers were assessed using Olink® serum proteomics platform employing two predefined panels: Cardiometabolic and Inflammation. Notably, short-term exercise intervention was associated with moderate but consistent changes in the serum proteome. Nominal differences (p < 0.05, unadjusted) were observed for amyloid beta precursor-like protein 1 (APLP1), complement C1q tumor necrosis factor-related protein 1 (C1QTNF1), interleukin-8 (CXCL8), interleukin-7 (IL-7), M-phase phosphoprotein 8 (MPHOSPH8), neurotrophin 3 (NTF3), tissue-type plasminogen activator (PLAT), SFRS1-interacting protein (PSIP1), pleiotrophin (PTN), cardiac-type troponin I (TNNI3), von Willebrand factor (vWF), and while levels of CD40 ligand (CD40LG) were reduced. These findings suggest that short-term multicomponent functional exercises during acute hospitalization can induce changes in the serum proteome. These molecular alterations provide exploratory insight into the biological processes associated with the functional benefits observed following the intervention in hospitalized older adult patients.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147825372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: A genome-wide association study identified 10 novel genomic loci associated with intrinsic capacity.","authors":"","doi":"10.1093/gerona/glag092","DOIUrl":"10.1093/gerona/glag092","url":null,"abstract":"","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":"81 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13125877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Substituting blood-based biomarkers for imaging measures in Alzheimer's disease studies: implications for sample size and bias.","authors":"Sarah F Ackley, Renaud La Joie, Michelle Caunca, Shubhabrata Mukherjee, Seo-Eun Choi, Emily H Trittschuh, Paul K Crane, Eleanor Hayes-Larson","doi":"10.1093/gerona/glag068","DOIUrl":"10.1093/gerona/glag068","url":null,"abstract":"<p><strong>Background: </strong>Blood-based biomarkers for Alzheimer's disease (AD) pathology are appealing options in large population-based studies due to their low cost, minimal invasiveness, and feasibility of collection in non-clinical settings. Despite these benefits, blood-based biomarkers have lower test-retest reliability than neuroimaging measures like amyloid positron emission tomography (amyloid-PET) Centiloids; trade-offs in power and bias remain unexplored.</p><p><strong>Methods: </strong>We use data from Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) studies, which include both amyloid-PET and blood-based measures, to assess differences in statistical power, required sample size, and bias when replacing a neuroimaging measure with a blood-based measure. We use simulations parameterized based on these studies to show potential implications of using plasma p-tau 181 or p-tau 217, blood-based AD biomarkers, in place of Centiloids from amyloid-PET, when the biomarker is either the exposure or the outcome in an analysis of interest.</p><p><strong>Results: </strong>We demonstrated that substituting amyloid-PET Centiloids with a blood-based measure of p-tau can substantially reduce power, requiring 1.5-6.5 times the sample size to achieve 80% power compared to amyloid-PET. In addition, using a blood-based biomarker as the exposure can introduce significant regression dilution bias, attenuating estimated associations.</p><p><strong>Conclusions: </strong>While blood-based biomarkers are lower cost and easier to collect than neuroimaging measures, their use as proxies for AD pathology may introduce substantial methodological challenges, depending on the p-tau isoform. Consideration of the sample sizes they necessitate and their potential for bias is critical for the design and interpretation of studies employing these biomarkers.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147470705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}