medRxiv - Geriatric Medicine最新文献

{"title":"Association of Cerebral Microbleeds and Risk of Stroke and Mortality in Posterior Circulation Cerebral Infarction","authors":"Xueping zheng, Yajuan Wang, Xiaoyan Sun, Shasha Wu, Jianxiu Sun, Yuyuan Yang, Moxin Luan, Fei Yu, Jing Zhou, Xiaosa Chi","doi":"10.1101/2024.07.25.24311035","DOIUrl":"https://doi.org/10.1101/2024.07.25.24311035","url":null,"abstract":"Objective\u0000This study was investigated to determine whether CMBs were associated with the risk of recurrent stroke or all-cause death in patients with acute posterior circulation cerebral infarction.\u0000Methods\u0000A retrospective analysis was conducted on 323 patients with acute posterior circulation cerebral infarction who aged ≥ 45 years and were hospitalized at Qingdao University Affiliated Hospital from January 1, 2016 to December 31, 2020. Patients were divided into different CMBs groups according to the presence, number and distribution of CMBs. Occurrence of stroke and death was recorded during follow-up. We drew Kaplan Meier survival curves and constructed Cox proportional hazards regression models based on different CMBs groups and clinical outcomes. Results A total of 323 patients were enrolled in our study, and 138 (42.72%) had CMBs. During a median follow-up of 1357 days, 87 (26.94%) experienced recurrent stroke or death. ≥5 CMBs (HR 1.723; 95% CI 1.021-2.907; P=0.041) and lobar CMBs (HR 2.312; 95% CI 1.204-4.441; P=0.012) were independent predictors associated with the composite risk of recurrent stroke and all-cause death. All CMBs statuses were not significantly correlated with the risk of recurrent stroke. The presence of CMBs (HR 3.358; 95% CI 1.259-8.954; P=0.015), ≥ 5 CMBs (HR 5.290; 95% CI 1.599-17.499; P=0.006) and deep CMBs (HR 3.265; 95% CI 1.003-10.628; P=0.049) were all independent factors associated with all-cause death.\u0000Conclusions\u0000In patients with acute posterior circulation cerebral infarction, ≥5 CMBs and lobar CMBs may increase the risk of poor clinical outcome (the composite of recurrent stroke and all-cause death). Furthermore, the presence CMBs, ≥ 5 CMBs and deep CMBs all independently may increase the risk of all-cause death.","PeriodicalId":501025,"journal":{"name":"medRxiv - Geriatric Medicine","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141778396","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":"Uncovering the multivariate genetic architecture of frailty with genomic structural equation modelling","authors":"Isabelle F Foote, Jonny P Flint, Anna E Furtjes, Donncha S Mullin, John D Fisk, Tobias K Karakach, Andrew Rutenberg, Nicholas G Martin, Michelle K Lupton, David J Llewellyn, Janice M Ranson, Simon R Cox, Michelle Luciano, Kenneth Rockwood, Andrew D Grotzinger","doi":"10.1101/2024.07.24.24310923","DOIUrl":"https://doi.org/10.1101/2024.07.24.24310923","url":null,"abstract":"Frailty is a multifaceted clinical state associated with accelerated aging and adverse health outcomes. Informed etiological models of frailty hold promise for producing widespread health improvements across the aging population. Frailty is currently measured using aggregate scores, which obscure etiological pathways that are only relevant to subcomponents of frailty. Therefore, we performed the first multivariate genome-wide association study of the latent genetic architecture between 30 frailty deficits, which identified 408 genomic risk loci. Our model included a general factor of genetic overlap across all deficits, plus six novel factors indexing shared genetic signal across specific groups of deficits. Follow-up analyses demonstrated the added clinical and etiological value of the six factors, including predicting frailty in external datasets, divergent genetic correlations with clinically relevant outcomes, and unique underlying biology linked to aging. This suggests nuanced models of frailty are key to understanding its causes and how it relates to worse health.","PeriodicalId":501025,"journal":{"name":"medRxiv - Geriatric Medicine","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141778397","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":"Impact of APOE, Klotho and sex on cognitive decline with aging","authors":"Kengo Shibata, Cheng Chen, Xin You Tai, Sanjay G Manohar, Masud Husain","doi":"10.1101/2024.07.20.24310745","DOIUrl":"https://doi.org/10.1101/2024.07.20.24310745","url":null,"abstract":"The effects of APOE and Klotho genes, both implicated in aging, on human cognition as a function of sex and age are yet to be definitively established. Here we showed in the largest cohort studied to date (N = 320,861) that APOE homozygous ε4 carriers had a greater decline in cognition with aging compared to ε3 carriers (ε4/ε3 & ε3/ε3) as well as smaller hippocampi and amygdala (N = 37,976). Critically, sex and age differentially affected the decline in cognition. Younger (40 - 50 years) female homozygous ε4 carriers showed a cognitive advantage over female ε3 carriers, but this advantage was not present in males. By contrast, Klotho-VS heterozygosity did not affect cognition or brain volume, regardless of APOE genotype, sex or age. These cognitive trajectories with aging demonstrate clear sex-dependent antagonistic pleiotropy effects of APOE ε4, but no effects of Klotho genotype on cognition and brain volume.","PeriodicalId":501025,"journal":{"name":"medRxiv - Geriatric Medicine","volume":"181 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141737415","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 higher benefit of lecanemab in males compared to females in CLARITY AD is probably due to a real sex effect","authors":"Daniel Andrews, Simon Ducharme, Howard Chertkow, Maria Pia Sormani, D. Louis Collins, Alzheimer's Disease Neuroimaging Initiative","doi":"10.1101/2024.07.11.24310278","DOIUrl":"https://doi.org/10.1101/2024.07.11.24310278","url":null,"abstract":"INTRODUCTION: The Phase 3 trial CLARITY AD found that lecanemab slowed cognitive decline by a statistically significant 27% vs. placebo. However, the subgroup analysis indicated a significant sex difference in the effect, and recent work has implied that lecanemab has either no or limited effectiveness in females. To resolve this ambiguity, we used simulations constrained by the trial design to determine whether the difference could be explained by known sex differences in Alzheimer's progression, or as an isolated random event.\u0000METHODS: Simulations were generated using linear mixed models of cognitive decline fit to data from ADNI participants who satisfied CLARITY AD inclusion criteria. RESULTS: The statistically nonsignificant 7.9% sex difference in cognitive decline rate observed in our selected ADNI participants does not explain the trial's 31% sex difference in lecanemab's effect. A 31% difference occurred randomly in only 12 of our 10,000 simulations, signifying a probability of 0.0012. DISCUSSION: Our results are consistent with those from CLARITY AD. Lecanemab likely affects females and males differently, but we cannot conclude that the drug is ineffective in females.","PeriodicalId":501025,"journal":{"name":"medRxiv - Geriatric Medicine","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141611937","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":"Multinational evaluation of anthropometric age (AnthropoAge) as a measure of biological age in the USA, England, Mexico, Costa Rica, and China: a population-based longitudinal study","authors":"Carlos Alberto Fermín-Martínez, Daniel Ramírez-García, Neftali Eduardo Antonio-Villa, Jerónimo Prezalonso-Espinosa, Diego Aguilar-Ramírez, Carmen García-Peña, Luis Miguel Gutierrez-Robledo, Jacqueline A. Seiglie, Omar Yaxmehen Bello-Chavolla","doi":"10.1101/2024.07.09.24310149","DOIUrl":"https://doi.org/10.1101/2024.07.09.24310149","url":null,"abstract":"OBJECTIVE: To validate AnthropoAge, a new metric of biological age (BA), for prediction of all-cause mortality and age-related outcomes and characterize population-specific aging patterns using multinational longitudinal cohorts.\u0000METHODS: We analyzed harmonized multinational data from the Gateway to Global Aging, including studies from the US, England, Mexico, Costa Rica, and China. We used body mass index and waist-to-height ratio to estimate AnthropoAge and AnthropoAgeAccel in participants aged 50-90 years old as proxies of BA and age acceleration, respectively. We compared the predictive capacity for all-cause mortality of AnthropoAge and chronological age (CA) using Cox models, described aging trends in all countries and explored the utility of longitudinal assessments of AnthropoAgeAccel to predict new-onset functional decline and age-related diseases using generalized estimating equations (GEE). FINDINGS: Using data from 55,628 participants, we found AnthropoAge (c-statistic 0.772) outperformed CA (0.76) for prediction of mortality independently of comorbidities, sex, race/ethnicity, education, and lifestyle; this result was replicated in most countries individually except for Mexico. Individuals with accelerated aging had a ~39% higher risk of death, and AnthropoAge also identified trends of faster biological aging per year. In longitudinal analyses, higher AnthropoAgeAccel values were independently predictive of self-reported health deterioration and new-onset deficits in basic/instrumental activities of daily living (ADL/IADL), diabetes, hypertension, cancer, chronic lung disease, myocardial infarction, and stroke. CONCLUSIONS: AnthropoAge is a robust and reproducible BA metric associated with age-related outcomes. Its implementation could facilitate modeling trends of biological aging acceleration in different populations, although recalibration may enhance its utility in underrepresented populations such as individuals from Latin America.","PeriodicalId":501025,"journal":{"name":"medRxiv - Geriatric Medicine","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141576655","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":"Effect of intranasal insulin on osteocalcin levels and postoperative delirium in elderly patients undergoing joint replacement","authors":"Yang Mi, Zhou Lei, Long Ge, Liu Xing, Ouyang Wen, Xie Chang, He Xi","doi":"10.1101/2024.07.02.24309290","DOIUrl":"https://doi.org/10.1101/2024.07.02.24309290","url":null,"abstract":"Background. Recently, intranasal insulin has shown great promise in preventing perioperative neurocognitive disorders through ameliorating insulin sensitivity and cognitive function. Whether osteocalcin, as a bone-derived hormone that can directly regulate insulin sensitivity and cognitive function, is linked to the mechanism of intranasal insulin remains ill-defined. Aims. To explore the effect of intranasal insulin on osteocalcin levels and the incidence and severity of postoperative delirium (POD) in elderly patients undergoing joint replacement. Methods. The study is designed as a randomized, double-blind, placebo-controlled clinical study. 212 elderly patients (≥65) were randomly assigned to receive either twice 40 IU insulin (n=106) or placebo (n=106). The incidence and severity of POD were estimated by the Confusion Assessment Method (CAM) and the Delirium Rating Scale (DRS)-98. The levels of total osteocalcin (tOC), uncarboxylated osteocalcin (ucOC), insulin and glucose in venous blood and cerebrospinal fluid were detected by Enzyme-linked immunosorbent assay (ELISA). Insulin sensitivity was assessed by Homeostasis model Assessment of Insulin Resistance (HOMA-IR). The primary objective was to compare the difference of osteocalcin levels and insulin sensitivity between two groups, with the secondary objective to compare the difference of POD incidence and severity. Main Results. It showed that 8 patients (8.33%) occurred POD in insulin group within 5 days after surgery, significantly fewer than 23 patients (23.23%) in placebo group (P=0.004). Mean peak DRS in insulin group was significantly lower than that in placebo group (P<0.001). After intranasal insulin intervention of 3 days, levels of tOC and ucOC in cerebrospinal fluid were significantly elevated in insulin group at D0 (all P<0.001). Levels of tOC in plasma were significantly higher in insulin group than that in placebo group on D0, D1 and D3 (all P<0.001). Plasma ucOC level in insulin group was higher on D0, but lower on D1 and D3 than placebo group (all P<0.001). HOMA-IR was significantly lower on D3 in insulin group than placebo group (P=0.002). Conclusions. Intranasal insulin notably reduced the incidence and severity of POD in elderly patients undergoing joint replacement, and alco significantly improved central and peripheral osteocalcin levels and peripheral insulin sensitivity. Though these preliminary results needed further confirmation, it suggested that osteocalcin was promisingly involved in the mechanism of intranasal insulin in improving insulin sensitivity and POD. Trial registry numbers. Chinese Clinical Trial Registry (ChiCTR2300068073)","PeriodicalId":501025,"journal":{"name":"medRxiv - Geriatric Medicine","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141576556","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 reliability and validity of a non-wearable indoor positioning system to assess mobility in older adults: A cross-sectional study","authors":"Isabel B. Rodrigues, Patricia Hewston, Jonathan Adachi, Sayem Borhan, George Ioannidis, Alexa Kouroukis, Carolyn Leckie, Andrea Lee, Alexander Rabinovich, Parthipan Siva, Rachel Swance, Suleman Tariq, Lehana Thabane, Alexandra Papaioannou","doi":"10.1101/2024.07.04.24309984","DOIUrl":"https://doi.org/10.1101/2024.07.04.24309984","url":null,"abstract":"Background: Chirp is a privacy-preserving radar sensor developed to continuously monitor older adults' safety and mobility without the need for cameras or wearable devices. Our study purpose was to evaluate the inter-sensor reliability, intrasession test-retest reliability, and concurrent validity of Chirp in a clinical setting. Methods: We recruited 35 community-dwelling older adults (mean age 75.5 (standard deviation: 6.6) years, 86% female). All participants lived alone in an urban city in southwestern Ontario and had access to a smart device with wireless internet. Data were collected with a 4-meter ProtoKinetics ZenoTM Walkway (pressure sensors) with the Chirp sensor (radar positioning) at the end of the walkway. Participants walked during normal and adaptive locomotion experimental conditions (walking-while-talking, obstacle, narrow walking, fast walking). Each of the experimental conditions was conducted twice in a randomized order, with fast walking trials performed last. For intra-session reliability testing, we conducted two blocks of walks within a participant session separated by approximately 30 minutes. Intraclass Correlation Coefficient(A,1) (ICC(A,1)) was used to assess the reliability and validity. Linear regression, adjusted for gender, was used to investigate the association between Chirp and cognition and health-related quality of life scores. Results: The Chirp inter-sensor reliability ICC(A,1)=0.999[95% Confidence Interval [CI]: 0.997 to 0.999] and intrasession test-retest reliability [ICC(A,1) =0.921, 95% CI: 0.725 to 0.969] were excellent across all experimental conditions. Chirp concurrent validity compared to the ProtoKinetics ZenoTM Walkway was excellent across experimental conditions [ICC(A,1)= 0.993, 95% CI: 0.985 to 0.997]. We found a weak association between Chirp and cognition scores using the Montreal Cognitive Assessment across experimental conditions (estimated β-value= 7.79, 95% CI: 2.79 to 12.80) and no association between the Chirp and health-related quality of life using the 12-item Short Form Survey across experimental conditions (estimated β-value=6.12, 95% CI: -7.12 to 19.36). Conclusion: Our results demonstrate that Chirp is a reliable and valid measure to assess gait parameters in clinics among older adults.","PeriodicalId":501025,"journal":{"name":"medRxiv - Geriatric Medicine","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141576653","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":"MitoFit: Evaluation of a Mitochondrial Fitness Science Communication Intervention for Aging Adults","authors":"Cathy A Maxwell, Maulik R Patel, Jeffrey T Boon, Brandon Grubbs, Mary S Dietrich, John Dunavan, Kelly Knickerbocker","doi":"10.1101/2024.07.04.24309859","DOIUrl":"https://doi.org/10.1101/2024.07.04.24309859","url":null,"abstract":"A key driver that leads to age-associated decline and chronic disease is mitochondrial dysfunction. Our prior work revealed strong community interest in the concept of mitochondrial fitness that led to development of a video based science communication intervention to prompt behavior change in adults aged 50+. Aim: To conduct formative and summative evaluations of MitoFit, an instructional, biologically based communication intervention aimed at improving physical activity (PA) in older adults, aged 50+. Methods: Phase 1 formative evaluation- Community-dwelling older adults (N=101), rated the acceptability, appropriateness and helpfulness of our MitoFit video series, titled, How to Slow Down Aging Through Mitochondrial Fitness. (4 out of five on a Likert-scale survey). Phase II summative evaluation- A subgroup of phase I participants (N=19) participated in a 1-month MitoFit intervention prototype to evaluate intervention and data collection feasibility (70% completion). Results: Phase I: Participants (mean age: 67.8 [SD 8.9]; 75% female) rated the MitoFit videos as acceptable (agree: 97%-100%), appropriate (agree: 100%) and helpful (agree: 95%-100%) to support adaptation and continued work on our novel approach. Phase II: Participants (mean age: 71.4 [SD 7.9]; 72% female) demonstrated MitoFit competencies (obtaining pulse, calculating maximum and zone 2 heart rate, demonstration of exercises). At one-month post-instruction, 13 participants (68.4%) had completed a self-initiated daily walking/exercise plan and submitted a daily activity log. Feasibility scores ranged from 89.4% to 94.7%. Fifteen participants (78.9%) stated an intention to continue the MitoFit intervention. Conclusion: MitoFit was enthusiastically embraced, and is a cost-effective, scalable, and efficacious intervention to advance with community-dwelling older adults.","PeriodicalId":501025,"journal":{"name":"medRxiv - Geriatric Medicine","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141576463","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":"Is Australia ready for the rollout of amyloid-targeting therapies for Alzheimer's disease? Results from a national survey characterising current infrastructure capability, workforce and training needs of memory and cognition clinics","authors":"Johannes C Michaelian, Christopher C Rowe, Susan E Kurrle, Constance Dimity Pond, Michael Woodward, Sharon L Naismith","doi":"10.1101/2024.07.05.24309974","DOIUrl":"https://doi.org/10.1101/2024.07.05.24309974","url":null,"abstract":"Background: New amyloid-targeting monoclonal antibody (mAb) therapies for Alzheimer's disease (AD) are currently under review by the Therapeutic Goods Administration for use in Australia.\u0000Aims: To determine the infrastructure, workforce and training needs of Australian memory and cognition clinics to characterise health system preparedness for amyloid-targeting mAb therapies for AD.\u0000Methods: A national, cross-sectional online survey of medical specialists was conducted.\u0000Results: Thirty medical specialists (Geriatricians, n=23; Psychiatrists, n=4; Neurologists, n=3) from 30 different clinics participated (public, 76.7%; private, 23.3%), including metropolitan (73.3%), regional (20.0%) and rural (6.7%) areas. On average, clinics reported assessing 5.4 (SD=3.2) new patients per week, of which 2.4 (range: 0-5) were considered to have Mild Cognitive Impairment (MCI). Only 40% of clinics use biomarkers to assess whether patients with MCI have AD, and 55% have intravenous infusion capability. While the majority of clinicians were confident in their knowledge of mAbs, only 33% felt confident in using these. Identified impediments to clinical implementation included a) lack of real-world experience; b) lack of current Models of Care and appropriate use guidelines; c) current clinic set-up; and d) information about safety.\u0000Conclusions: Australia's health system preparedness for amyloid-targeting mAb therapies will require further investment in infrastructure, equity of access, clinician training and support. Long wait-times already impact access to clinics, and with the forecast rise in MCI and dementia cases, services will need to be expanded; while appropriate models of care and clear and efficient inter-sector health pathways will be needed to prepare for the use of mAbs.","PeriodicalId":501025,"journal":{"name":"medRxiv - Geriatric Medicine","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141576660","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 Comprehensive Head-to-Head Comparison of Key Plasma Phosphorylated Tau 217 Biomarker Tests","authors":"Noelle Warmenhoven, Gemma Salvado, Shorena Janelidze, Niklas Mattsson-Carlgren, Divya Bali, Anna Orduna Dolado, Hartmut Kolb, Gallen Triana-Baltzer, Nicolas R. Barthelemy, Suzanne E. Schindler, Andrew J. Aschenbrenner, Cyrus A. Raji, Tammie L.S. Benzinger, John C. Morris, Laura Ibanez, Jigyasha Timsina, Carlos Cruchaga, Randall J Bateman, Nicholas J Ashton, Burak Arslan, Henrik Zetterberg, Kaj Blennow, Alexa Pichet Binette, Oskar Hansson","doi":"10.1101/2024.07.02.24309629","DOIUrl":"https://doi.org/10.1101/2024.07.02.24309629","url":null,"abstract":"Plasma phosphorylated-tau 217 (p-tau217) is currently the most promising biomarkers for reliable detection of Alzheimer′s disease (AD) pathology. Various p-tau217 assays have been developed, but their relative performance is unclear. We compared leading plasma p-tau217 tests using cross-sectional and longitudinal measures of amyloid-β (Aβ)-PET, tau-PET, and cognition as outcomes, and benchmarked them against cerebrospinal fluid (CSF) biomarker tests. Samples from 998 individuals (mean[range] age 68.5[20.0-92.5], 53% female) from the Swedish BioFINDER-2 cohort were analyzed. Plasma p-tau217 was measured with mass spectrometry (MS) assays (the ratio between phosphorylated and non-phosphorylated [%p-tau217WashU]and p-tau217WashU) as well as with immunoassays (p-tau217Lilly, p-tau217Janssen, p-tau217ALZpath). CSF biomarkers included p-tau217Lilly, and the FDA-approved p-tau181/Aβ42Elecsys and p-tau181Elecsys. All plasma p-tau217 tests exhibited high ability to detect abnormal Aβ-PET (AUC range: 0.91-0.96) and tau-PET (AUC range: 0.94-0.97). Plasma %p-tau217WashU had the highest performance, with significantly higher AUCs than all the immunoassays (Pdiff<0.007). For detecting Aβ-PET status, %p-tau217WashU had an accuracy of 0.93 (immunoassays: 0.83-0.88), sensitivity of 91% (immunoassays: 84-87%), and a specificity of 94% (immunoassays: 85-89%). Among immunoassays, p-tau217Lilly and plasma p-tau217ALZpath had higher AUCs than plasma p-tau217Janssen for Aβ-PET status (Pdiff<0.006), and p-tau217Lilly outperformed plasma p-tau217ALZpath for tau-PET status (Pdiff=0.025). Plasma %p-tau217WashU exhibited higher associations with all PET load outcomes compared to immunoassays; baseline Aβ-PET load (R2: 0.72; immunoassays: 0.47-0.58; Pdiff<0.001), baseline tau-PET load (R2: 0.51; immunoassays: 0.38-0.45; Pdiff<0.001), longitudinal Aβ-PET load (R2: 0.53; immunoassays: 0.31-0.38; Pdiff<0.001) and longitudinal tau-PET load (R2: 0.50; immunoassays: 0.35-0.43; Pdiff<0.014). Among immunoassays, plasma p-tau217Lilly was more strongly associated with Aβ-PET load than plasma p-tau217Janssen (Pdiff<0.020) and with tau-PET load than both plasma p-tau217Janssen and plasma p-tau217ALZpath (all Pdiff<0.010). Plasma %p-tau217 also correlated more strongly with baseline cognition (Mini-Mental State Examination [MMSE]) than all immunoassays (R2 %p-tau217WashU: 0.33; immunoassays: 0.27-0.30, Pdiff<0.024). The main results were replicated in an external cohort from Washington University in St Louis (n =219). Finally, p-tau217Nulisa showed similar performance to other immunoassays in subsets of both cohorts.\u0000In summary, both MS- and immunoassay-based p-tau217 tests generally perform well in identifying Aβ-PET, tau-PET, and cognitive abnormalities, but %p-tau217WashU performed significantly better than all the examined immunoassays. Plasma %p-tau217 may be considered as a stand-alone confirmatory test for AD pathology, while some immunoassays might be b","PeriodicalId":501025,"journal":{"name":"medRxiv - Geriatric Medicine","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141576654","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}