Ahead of print articles
ASSOCIATIONS OF MODIFIABLE AND NON-MODIFIABLE RISK FACTORS WITH LONGITUDINAL WHITE MATTER HYPERINTENSITIES, AMYLOID-Β AND TAU - A PROSPECTIVE COHORT STUDY
Isabelle Glans, Niklas Mattsson-Carlgren, Olof Strandberg, Erik Stomrud, Rik Ossenkoppele, Danielle van Westen, Nicola Spotorno, Oskar Hansson, Sebastian Palmqvist
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BACKGROUND: The global prevalence of dementia is rapidly expanding and is expected to triple by 2050. Approximately 45 % of dementia cases are estimated to be attributable to potentially modifiable risk factors. Identifying how these factors contribute to specific brain pathologies may improve strategies to reduce dementia incidence.
OBJECTIVES, DESIGN, SETTING: The aim of this study was to identify both non-modifiable and modifiable risk factors associated with longitudinal changes in white matter hyperintensities (WMH), amyloid-beta (Aβ) and tau. Data were acquired in the prospective observational Swedish BioFINDER-2 study between May 2017-January 2025. All participants underwent clinical assessments, questionnaires and at least two magnetic resonance imaging (MRI), Aβ Positron Emission Tomography (PET) and tau PET scans, respectively. Mixed-effects models were used to assess the associations between non-modifiable and modifiable risk factors and WMH (MRI), Aβ (PET) and tau (PET).
PARTICIPANTS: A total of 494 cognitively unimpaired participants were included, of whom 365 were amyloid-negative (CU Aβ−) and 129 were amyloid-positive (CU Aβ+).
MEASUREMENTS AND MAIN OUTCOMES: Non-modifiable (age, apolipoprotein E (APOE) ɛ4 genotype and sex) and modifiable risk factors (co-morbidities at baseline, such as hypertension and cardiovascular disease, BMI, and sleep duration) were analyzed with mixed-effects models, adjusted for age and sex, to predict longitudinal measurements of WMH, Aβ and tau.
RESULTS: Mean age was 64.8 (SD 13.3) years and mean follow-up was 3.9 (SD 1.5) years. Predictors represent baseline data, both predictors and outcomes are on standardized scales. Linear mixed-effects models, adjusted for age and sex, showed that higher blood pressure (β = 0.02, 95 % CI :0.01–0.02), presence of hyperlipidemia (β = 0.03, 0.01–0.05), ischemic heart disease (β = 0.06, 0.03–0.09), smoking (β = 0.02, 0.00–0.03) and lower education (β = -0.01, -0.02– -0.01) were associated with a longitudinal increase in WMH. Presence of the APOE ε4 allele was linked to faster Aβ accumulation (β = 0.03, 0.02–0.04) and tau (β = 0.01, 0.00–0.03), but only to Aβ among Aβ+ positive participants. Higher depression score (β = 0.01, 0.00–0.01) and diabetes (β = 0.02, 0.00–0.04) were associated with faster Aβ accumulation. Lower BMI was associated with faster accumulation of tau (β = -0.01, -0.02– -0.01).
CONCLUSIONS: Modifiable risk factors of future dementia primarily affect accumulation of cerebral vascular pathology, although lower BMI was associated with tau accumulation and diabetes with Aβ accumulation.
CITATION:
Isabelle Glans ; Niklas Mattsson-Carlgren ; Olof Strandberg ; Erik Stomrud ; Rik Ossenkoppele ; Danielle van Westen ; Nicola Spotorno ; Oskar Hansson ; Sebastian Palmqvist (2025): Associations of modifiable and non-modifiable risk factors with longitudinal white matter hyperintensities, amyloid-β and tau - a prospective cohort study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100448
TRAJECTORY OF COGNITIVE DECLINE BEFORE AND AFTER INCIDENT HEART FAILURE AMONG OLDER ADULTS: A 20-YEAR, POPULATION-BASED, PROSPECTIVE COHORT STUDY
Haibin Li, Frank Qian, Wuxiang Xie, Man Wang, Jianian Hua, Jiao Wang, Xinye Zou, Zhiyuan Wu, Xia Li, Deqiang Zheng, Xiuhua Guo, Hongjia Zhang
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BACKGROUND: The magnitude of cognitive change before and after incident heart failure (HF) is unclear. We investigated whether incident HF is associated with changes in cognitive function at the time of diagnosis and accelerated trajectory in cognitive decline in the subsequent years.
METHODS: We used data from the Health and Retirement Study, a nationally representative survey of US adults aged 50 years or older. Participants underwent a cognitive assessment at baseline (wave 5, 2000), and at least 1 other time point (from wave 6 [2002] to wave 15 [2020]). The outcomes were change in global cognition, memory, and executive function. Outcomes were standardized into Z-scores, with higher scores indicating better cognitive performance. Linear mixed-effects models estimated changes in cognition at the time of HF (change in the intercept) and the rate of cognitive change over the years after HF (change in the slope), after adjusting for pre-HF cognitive trajectories and potential confounders.
RESULTS: We included 12 850 adults (mean [SD] age, 66.1 [9.4] years; 61.8 % women). Over a median follow-up of 16 years (interquartile range: 8 to 20 years), 1457 participants had incident HF. The annual rate of cognitive decline before HF diagnosis among individuals with incident HF was similar to that of participants who remained HF-free throughout follow-up. However, incident HF was associated with subsequent decreases in global cognition (−0.073 SD [95 % CI −0.109 to −0.038]), memory (−0.070 SD [95 % CI −0.108 to −0.032]), and executive function (−0.054 SD [95 % CI −0.092 to −0.016]) around the time of the HF diagnosis. Moreover, individuals with incident HF vs those without HF demonstrated faster and long-term declines in global cognition (−0.011 SD/year [95 % CI −0.018 to −0.004]) and executive function (−0.008 SD/year [95 % CI −0.015 to −0.001]), but not in memory (−0.006 SD/year [95 % CI −0.013 to 0.001]) over the years after HF compared with pre-HF slopes.
CONCLUSIONS: Incident HF was associated with subsequent decreases in cognitive function at the time of diagnosis and accelerated cognitive decline over the following years.
CITATION:
Haibin Li ; Frank Qian ; Wuxiang Xie ; Man Wang ; Jianian Hua ; Jiao Wang ; Xinye Zou ; Zhiyuan Wu ; Xia Li ; Deqiang Zheng ; Xiuhua Guo ; Hongjia Zhang (2025): Trajectory of cognitive decline before and after incident heart failure among older adults: A 20-Year, population-based, prospective cohort study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100450
ASSOCIATIONS OF PLASMA BIOMARKERS WITH LONGITUDINAL CO-PATHOLOGIES IN ALZHEIMER’S DISEASE AND CEREBRAL SMALL VESSEL DISEASE COMORBIDITY
Jing Yang, Xinyuan Zhao, Yidan Liu, Yangwei Cai, Yuhua Fan, Alzheimer’s Disease Neuroimaging Initiative
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BACKGROUND: Plasma glial fibrillary acidic protein (GFAP), neurofilament light (NfL), phosphorylated tau217 (p-tau217), and the β-amyloid (Aβ) 42/40 ratio are emerging indicators of neuroinflammation, neurodegeneration, and AD-specific pathology, while their specific roles within Alzheimer’s disease (AD) and cerebral small vessel disease (CSVD) comorbidity are not fully understood.
METHODS: Participants with normal cognition or mild cognitive impairment were drawn from the Alzheimer’s Disease Neuroimaging Initiative database. Multivariable linear regression and linear mixed-effects models were employed to examine associations of baseline plasma biomarkers with neuropathological features and cognition. Furthermore, Cox proportional hazards models assessed the associations of plasma biomarkers with the risk of comorbid AD and CSVD.
RESULTS: In total populations, elevated GFAP and p-tau217 were significantly associated with greater white matter hyperintensity (WMH) burden, hippocampal atrophy, cerebral Aβ burden, and cognitive decline at baseline and with progression over time (|β| = 0.007 to 1.670, p = 0.047 to <0.0001). Within disease-specific subgroups, GFAP, p-tau217, and Aβ42/40 ratio demonstrated associations with hippocampal atrophy or WMH progression in CSVD (|β| = 0.011 to 0.220, p = 0.046 to 0.010), whereas GFAP, NfL, p-tau217, and Aβ42/40 ratio were linked to hippocampal atrophy and/or WMH progression in typical AD (|β| = 0.013 to 0.191, p = 0.044 to 0.0002). For Cox proportional hazards models, p-tau217 demonstrated greater precision in predicting progression to the CSVD phenotype within the AD subgroup (Hazard ratios = 1.267 to 3.811, p = 0.046 to 0.034).
CONCLUSION: These findings underscore the potential role of plasma biomarkers in elucidating the synergistic mechanisms underlying AD and CSVD comorbidity.
CITATION:
Jing Yang ; Xinyuan Zhao ; Yidan Liu ; Yangwei Cai ; Yuhua Fan ; Alzheimer’s Disease Neuroimaging Initiative (2025): Associations of plasma biomarkers with longitudinal co-pathologies in Alzheimer’s disease and cerebral small vessel disease comorbidity. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100449
TAU IN ALZHEIMER\'S DISEASE: SHAPING THE FUTURE PATIENT JOURNEY
Catherine J. Mummery, Christopher Chen Li-Hsian, Cristian A. Lasagna-Reeves, Rik Ossenkoppele, Christopher C. Rowe, Douglas W. Scharre, Huali Wang, Simon Kyaga, Jeffrey L. Cummings
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Alzheimer’s disease is a complex and multifactorial disease characterized by two key pathological hallmarks: amyloid-beta plaques and tau neurofibrillary tangles. Recent progress has led to the development and approval of disease-targeted therapies for Alzheimer’s disease in the form of anti-amyloid-beta monoclonal antibodies. However, findings suggest that amelioration of multiple pathological drivers may be required to maximize clinical effect. An increasing body of evidence suggests that tau is a critical player in Alzheimer’s disease pathophysiology, contributing significantly to neurodegeneration and cognitive decline. There are now several tau-targeting drugs in clinical development. In this review, we build on research and advancements in the field of tau to envision how an increasing focus on tau could shape the future Alzheimer’s disease patient journey. We highlight the potential of tau as both a promising therapeutic target and a valuable biomarker, with the potential to inform treatment decisions and provide insight into disease trajectories. We also consider what a greater focus on tau may bring to an already evolving patient care pathway characterized by an increased influx of patients presenting earlier in the disease continuum, changes in workflow and infrastructural requirements, and increased complexity in treatment decision-making, treatment administration, treatment monitoring, and patient tracking. This review underscores the critical changes that may be required and knowledge gaps to be elucidated to ensure healthcare system preparedness for additional classes of disease-targeted therapy to move toward a next-generation, individualized treatment approach to Alzheimer’s disease diagnosis and care.
CITATION:
Catherine J. Mummery ; Christopher Chen Li-Hsian ; Cristian A. Lasagna-Reeves ; Rik Ossenkoppele ; Christopher C. Rowe ; Douglas W. Scharre ; Huali Wang ; Simon Kyaga ; Jeffrey L. Cummings (2025): Tau in Alzheimer's disease: Shaping the future patient journey. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100447
COST-EFFECTIVENESS ANALYSIS OF BLOOD-BASED BIOMARKER TESTING IN THE DIAGNOSIS OF ALZHEIMER’S DISEASE PATHOLOGY
Yonghong Li, Robert J. Lagier, Michael K. Racke, Yuri A. Fesko
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OBJECTIVES: We aimed to evaluate the cost-effectiveness of blood-based biomarker (BBM) testing vs amyloid positron emission tomography (PET) in patients with signs and symptoms of cognitive decline in a neurologist/specialist care setting.
METHODS: We constructed a decision-tree model to compare diagnostic outcomes and costs of two testing strategies: BBM testing with confirmatory PET scan vs PET scan alone. Their cost-effectiveness was evaluated from a payer perspective with test performance taken from a clinical study and costs including testing/imaging and physician fees.
RESULTS: When access to PET scans is unlimited, BBM triage testing would identify 98.2 % of PET+ patients with a lower average cost per diagnosis compared with PET scan alone ($8868 vs 10,345 per PET+ diagnosis). In terms of incremental cost-effectiveness, BBM triage testing would save $93,984 for each loss of PET+ diagnosis (9.1 times the average cost per PET+ diagnosis by PET scan). Under limited capacity of PET scans, more test-positive patients could be identified using BBM testing than PET scan alone. When access to PET scans is limited to 50 % of the patients, BBM testing would identify 90.6 % more test-positive patients (at 93 % sensitivity) at an incremental cost-effectiveness ratio of $3484 per gain of positive diagnosis, lower than the average cost of a PET+ diagnosis by PET scan ($10,938).
CONCLUSION: BBM testing, compared with PET scan alone, is more efficient in the utilization of available amyloid PET scans and is cost-effective for assessment of Alzheimer’s disease pathology in patients with signs and symptoms of cognitive decline.
CITATION:
Yonghong Li ; Robert J. Lagier ; Michael K. Racke ; Yuri A. Fesko (2025): Cost-effectiveness analysis of blood-based biomarker testing in the diagnosis of Alzheimer’s disease pathology. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100474
HEAD INJURY/TRAUMATIC BRAIN INJURY AND THE RISK OF DEMENTIA: AN OBSERVATIONAL AND MENDELIAN RANDOMIZATION STUDY
Ziyu Ouyang, Bin Jiao, Xuewen Xiao, Qijie Yang, Yuan Zhu, Lu Shen, Nan Li
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BACKGROUND: This study aimed to investigate the link between head injury (HI)/traumatic brain injury (TBI) and dementia risk, as it remains unclear.
METHODS: We examined the associations between HI/TBI-related factors, including the frequency of HIs and the severity of TBI, and the risk of dementia (n = 397,581), as well as neuroimaging outcomes (n = 42,380) using prospective data (50 years at baseline) from the UK Biobank. In the observational analyses, Cox proportional-hazards modeling and logistic regression were used to estimate the associations between factors. Mendelian randomization (MR) was conducted to investigate the underlying causality between TBI (n = 392,423, ncases=19,842) and Alzheimer's disease (AD) (n = 41,944, ncases=21,982).
RESULTS: During the 12.5-year follow-up period, 7524 participants developed dementia. HI and TBI conferred an increased dementia risk (hazard ratio (HR)=1.72, 95 % confidence interval (CI): 1.50–1.97; HR=1.86, 95 % CI: 1.46–2.38, respectively). The risk increased in relation to recurrent HIs (HR=4.05, 95 % CI: 2.24–7.32) or severe TBI (HR=4.50, 95 % CI: 3.18–6.37). Dementia risk was highest during the first 30 months following HI occurrence (HR=2.20, 95 % CI: 1.66–2.92), whereas there was no association after 40 years post-HI. Patients with recurrent HIs also exhibited reduced hippocampal volumes and increased white matter hyperintensity. HI was additionally associated with poorer reasoning ability and longer reaction time. Besides, the MR analysis supported a causal association between TBI and AD (odds ratio (OR)=1.17, 95 % CI: 1.01–1.37).
CONCLUSION: These results imply that HI/TBI is associated with increased dementia risk. Strategies are needed to mitigate the impact of subsequent dementia.
CITATION:
Ziyu Ouyang ; Bin Jiao ; Xuewen Xiao ; Qijie Yang ; Yuan Zhu ; Lu Shen ; Nan Li (2025): Head injury/traumatic brain injury and the risk of dementia: An observational and Mendelian randomization study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100468
ASSOCIATION OF NEIGHBORHOOD DISADVANTAGE WITH ALZHEIMER\'S DISEASE PATHOLOGY AND THE STABILITY OF BLOOD-BASED BIOMARKER PERFORMANCE
Alison Myoraku, Isabella Hausle, Marta Mila-Aloma, Pamela Thropp, Laura A. Wang, P. Murali Doraiswamy, Duygu Tosun, Alzheimer’s Disease Neuroimaging Initiative
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BACKGROUND: Neighborhood-level factors, measured by the Area Deprivation Index (ADI), are linked to comorbidities of Alzheimer's disease and related dementias (ADRD). However, their direct association with AD neuropathology is unclear. The accessibility of blood-based biomarkers (BBMs) like p-tau217 and Aβ42/40 offers a scalable way to investigate these relationships.
OBJECTIVES: To examine the relationship between ADI and levels of key BBMs (p-tau217/Aβ42, p-tau217, and Aβ42/40). We also aimed to assess whether the performance of these BBMs in predicting amyloid PET positivity is consistent across different levels of neighborhood disadvantage.
DESIGN: A cross-sectional analysis using data from an observational cohort study of the Alzheimer’s Disease Neuroimaging Initiative (ADNI).
SETTING: Multicenter observational cohort conducted at 55 sites across the United States.
PARTICIPANTS: The study included 755 ADNI participants with ADI and amyloid PET data. A sub-cohort of 438 participants also had BBM data available.
MEASUREMENTS: National ADI scores were used to stratify participants into least, intermediately, and most disadvantaged groups. Amyloid PET positivity was determined using Centiloid values. Plasma levels of p-tau217, Aβ42, and Aβ40 were measured using Fujirebio assays.
RESULTS: ADI groups differed by sex, ethnoracial background, and MMSE scores. The intermediately disadvantaged group had 1.55 times higher odds of being amyloid PET positive compared to the least disadvantaged group. While this group also showed higher levels of plasma p-tau217/Aβ42 and p-tau217, these differences were no longer significant after accounting for the higher prevalence of amyloid positivity. Critically, the predictive accuracy of all three BBMs for amyloid PET status did not differ across the ADI groups. The p-tau217/Aβ42 ratio performed best, yielding the fewest indeterminate cases in a two-cut-point classification model.
CONCLUSIONS: The diagnostic performance of plasma AD biomarkers is robust and is not compromised by neighborhood-level disadvantage. These findings support the generalizability and equitable clinical utility of biomarkers like p-tau217/Aβ42 for AD diagnosis across diverse socioeconomic settings.
CITATION:
Alison Myoraku ; Isabella Hausle ; Marta Mila-Aloma ; Pamela Thropp ; Laura A. Wang ; P. Murali Doraiswamy ; Duygu Tosun ; Alzheimer’s Disease Neuroimaging Initiative (2025): Association of neighborhood disadvantage with Alzheimer's disease pathology and the stability of blood-based biomarker performance. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100445
DONANEMAB IN EARLY SYMPTOMATIC ALZHEIMER’S DISEASE: RESULTS FROM THE TRAILBLAZER-ALZ 2 LONG-TERM EXTENSION
Jennifer A. Zimmer, John R. Sims, Cynthia D. Evans, Emel Serap Monkul Nery, Hong Wang, Alette M. Wessels, Giulia Tronchin, Shoichiro Sato, Lars Lau Raket, Lars Lau Raket, Christophe Sapin, Marie-Ange Paget, Ivelina Gueorguieva, Paul Ardayfio, Rashna Khanna, Dawn A. Brooks, Brandy R. Matthews, Mark A. Mintun, Alzheimer’s Disease Neuroimaging Initiative
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BACKGROUND: Donanemab significantly slowed clinical progression in participants with early symptomatic Alzheimer’s disease (AD) during the 76-week placebo-controlled period of TRAILBLAZER-ALZ 2.
METHODS: Participants who completed the placebo-controlled period were eligible for the 78-week, double-blind, long-term extension (LTE). Early-start participants were randomized to donanemab in the placebo-controlled period. Delayed-start participants (randomized to placebo) started donanemab in the LTE. Participants who met amyloid treatment course completion criteria were switched to placebo. An external control cohort comprised participants from the AD Neuroimaging Initiative (ADNI).
RESULTS: At 3 years, donanemab slowed disease progression on the Clinical Dementia Rating Scale (CDR)-Sum of Boxes (CDR-SB) in early-start participants versus a weighted ADNI control (-1.2 points; 95 % confidence interval [CI], -1.7, -0.7). Seventy-six weeks after initiating donanemab, delayed-start participants also demonstrated slower CDR-SB progression versus a weighted ADNI control (-0.8 points; 95 % CI, -1.3, -0.3). Participants who completed treatment by 52 weeks demonstrated similar slowing of CDR-SB progression at 3 years. Compared with delayed-start participants, early-start participants demonstrated a significantly lower risk of disease progression on the CDR-Global over 3 years (hazard ratio=0.73; p < 0.001). In both groups, >75 % of participants assessed by positron emission tomography 76 weeks after starting donanemab achieved amyloid clearance (<24.1 Centiloids). The addition of LTE data to prior modeling predicted a median reaccumulation rate of 2.4 Centiloids/year. No new safety signals were observed compared to the established donanemab safety profile.
CONCLUSIONS: Over 3 years, donanemab-treated participants with early symptomatic AD demonstrated increasing clinical benefits and a consistent safety profile, with limited-duration dosing.
CITATION:
Jennifer A. Zimmer ; John R. Sims ; Cynthia D. Evans ; Emel Serap Monkul Nery ; Hong Wang ; Alette M. Wessels ; Giulia Tronchin ; Shoichiro Sato ; Lars Lau Raket ; Scott W. Andersen ; Christophe Sapin ; Marie-Ange Paget ; Ivelina Gueorguieva ; Paul Ardayfio ; Rashna Khanna ; Dawn A. Brooks ; Brandy R. Matthews ; Mark A. Mintun ; Alzheimer’s Disease Neuroimaging Initiative (2025): Donanemab in early symptomatic Alzheimer’s disease: results from the TRAILBLAZER-ALZ 2 long-term extension. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100446
SYSTEMATIC POST-TRANSLATIONAL MODIFICATION GENOME WIDE IDENTIFIES THERAPEUTIC TARGETS FOR ALZHEIMER’S DISEASE: EVIDENCE FROM MULTI-COHORT ANALYSIS
Xiaoming Wang, Yuancheng Liu, Juncai Fu, Yizhao Li, Mengying Zhao, Qing Tian
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BACKGROUND: The rapid increase in the incidence of Alzheimer’s disease (AD) has raised concerns, given its profound effects on both society and the economy. Despite extensive research efforts in this area, there are no existing treatments that have the ability to change the progression of the disease.
METHODS: To identify the distinct subtypes of AD, consensus clustering was employed. Following this, module genes were identified through the implementation of WGCNA. In addition, the investigation included the identification of hub genes through the application of machine learning. Ultimately, a thorough analysis was performed utilizing a methodical strategy to perform post-translational modification (PTM) genome wide.
RESULTS: GO and KEGG analyses were conducted by examining of 21 different types of PTMs, revealing that the majority of these genes play key roles in the PTM pathways, as well as AD-related pathways. Correlation analysis revealed that these PTM were significantly correlated with gamma secretase activity, beta secretase activity, amyloid-beta 42, clinical dementia rating, Braak stage, plaque, and neurofibrillary tangle. Then, two distinct subtypes of PTM were identified, each characterized by unique clinical characteristic. By utilizing machine learning, we developed an PTM.score, and has shown impressive predictive capabilities for AD when tested against various datasets (brain AUC: 0.859, blood AUC: 0.898), indicating its potential utility in clinical settings for risk stratification and therapeutic decision-making. Moreover, our investigation led to the identification of two genes (TRIM47 and LNX1) that may represent potential drug targets for AD (brain tissues or blood samples). Research further indicated a potential correlation between TRIM47 and concentrations of CSF Aβ (OR 1.068 (1.029–1.108)), CSF p-tau (OR 1.315 (1.136–1.524)), and total hippocampal (OR 1.176 (1.058–1.307)).
CONCLUSIONS: The findings from this study not only enhance our comprehension of the underlying mechanisms of AD but also serve to inform and direct future initiatives in drug discovery. By focusing on TRIM47, the work paves the way for identifying innovative therapeutic strategies.
CITATION:
Xiaoming Wang ; Yuancheng Liu ; Juncai Fu ; Yizhao Li ; Mengying Zhao ; Qing Tian (2025): Systematic post-translational modification genome wide identifies therapeutic targets for Alzheimer’s disease: evidence from multi-cohort analysis. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100422>
JPAD Volume 13, N°01 - 2026
EDITORIAL: WHAT CAN ARTIFICIAL INTELLIGENCE BRING TO ALZHEIMER’S DISEASE CLINICAL TRIALS? A FIRST PERSPECTIVE
Lefkos T Middleton, Sandrine Andrieu
J Prev Alz Dis 2026;1(13)
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CITATION:
Lefkos T Middleton ; Sandrine Andrieu (2025): Editorial: What can artificial intelligence bring to Alzheimer’s disease clinical trials? A first perspective. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100423
EDITORIAL: ARTIFICIAL INTELLIGENCE AND THE ACCELERATION OF ALZHEIMER’S RESEARCH - FROM PROMISE TO PRACTICE
Gregory J. Moore, Niranjan Bose, Husseini K. Manji, Eric M. Reiman, Reisa Sperling
J Prev Alz Dis 2026;1(13)
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CITATION:
Gregory J. Moore ; Niranjan Bose ; Husseini K. Manji ; Eric M. Reiman ; Reisa Sperling (2025): Editorial: Artificial intelligence and the acceleration of Alzheimer’s research - From promise to practice. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100421
A BENCHMARK OF TEXT EMBEDDING MODELS FOR SEMANTIC HARMONIZATION OF ALZHEIMER\'S DISEASE COHORTS
Tim Adams, Yasamin Salimi, Mehmet Can Ay, Diego Valderrama, Marc Jacobs, Holger Fröhlich
J Prev Alz Dis 2026;1(13)
Show summaryHide summaryBACKGROUND: Harmonizing diverse healthcare datasets is a challenging task due to inconsistent naming conventions. Manual harmonization is time- and resource-intensive, limiting scalability for multi-cohort Alzheimer's Disease research. Large Language Models, or specifically text-embedding models, offer a promising solution, but their rapid development necessitates continuous, domain-specific benchmarking, especially since general established benchmarks lack clinical data harmonization use cases.
OBJECTIVES: To evaluate how different text-embedding models perform for the harmonization of clinical variables.
DESIGN AND SETTING: We created a novel benchmark to assess how well different Language Model embeddings can be used to harmonize cohort study metadata with an in-house Common Data Model that includes cohort-to-cohort mappings for a wide range of Alzheimer’s Disease cohorts. We evaluated five different state-of-the-art text embedding models for seven different data sets in the context of Alzheimer’s disease.
PARTICIPANTS: No patient data were utilized for any of the analyses, as the evaluation was based on semantic harmonization of cohort metadata only.
MEASUREMENTS: Text descriptions of variables from different modalities were included for the analyses, namely clinical, lifestyle, demographics, and imaging.
RESULTS: Our benchmark results favored different models compared to general-purpose benchmarks. This suggests that models fine-tuned for generic tasks may not translate well to real-world data harmonization, particularly in Alzheimer’s disease. We propose guidelines to format metadata to facilitate manual or model-assisted data harmonization. We introduce an open-source library (https://github.com/SCAI-BIO/ADHTEB) and an interactive leaderboard (https://adhteb.scai.fraunhofer.de) to aid future model benchmarking.
CONCLUSIONS: Our findings highlight the importance of domain-specific benchmarks for clinical data harmonization in the field of Alzheimer’s disease and motivate standards for naming conventions that may support semi-automated mapping applications in the future.
CITATION:
Tim Adams ; Yasamin Salimi ; Mehmet Can Ay ; Diego Valderrama ; Marc Jacobs ; Holger Fröhlich (2025): A benchmark of text embedding models for semantic harmonization of Alzheimer's disease cohorts. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100420
TOWARDS AN AI BIOMEDICAL SCIENTIST: ACCELERATING DISCOVERIES IN NEURODEGENERATIVE DISEASE
Kaleigh F. Roberts, Eric C. Landsness, Justin Reese, Donald Elbert, Gabrielle Strobel, Elizabeth Wu, Yixin Chen, Albert Lai, Zachary B. Abrams, Mingfang Zhu, Justin Melendez, Srinivas Koutarapu, Sihui Song, Yun Chen, Robert Lazar, Payam Barnaghi, John F. Crary, Sergio Pablo Sardi, Marc D. Voss, Rajaraman Krishnan, Joel W. Schwartz, Ron Mallon, Gustavo A. Jimenez-Maggiora, Chenguang Wang, Thomas Sandmann, Niranjan Bose, Mukta Phatak, Gayle Wittenberg, Yannis G. Kevrekidis, Cassie S. Mitchell, Ludovico Mitchener, Cassie S. Mitchell, Ludovico Mitchener, Towfique Raj, Luca Foschini, Gregory J. Moore, Randall J. Bateman
J Prev Alz Dis 2026;1(13)
Show summaryHide summaryDespite major advances in Alzheimer’s disease and related diseases (ADRD) research, the translation of discoveries into impactful clinical interventions remains slow. Overwhelming data complexity, fragmented knowledge, and prolonged research cycles hinder progress in understanding and treating neurodegenerative diseases. Artificial intelligence (AI) offers a promising path forward, particularly when developed as a scientist-in-the-loop system that collaborates with researchers throughout the scientific discovery process. This paper introduces the concept of an AI Biomedical Scientist, an intelligent platform designed to support literature synthesis, hypothesis generation, experimental design, and data interpretation. This platform aims to function as a holistic scientific partner, integrating diverse biomedical data and expert reasoning to accelerate discovery. We review commercial and academic efforts and introduce targeted Minimum Viable Products (MVPs) needed for general biomedical research lab utilization of AI, such as robust and accurate tools for literature and data analysis, negative data models, and virtual peer review, with a longer-term vision of foundation models trained directly on biomedical datasets. In AD and neurodegeneration research, such tools are anticipated to deliver efficiency gains ranging from modest improvements in specific research tasks to potential multi-fold accelerations in discovery workflows as systems mature and scale. This review examines the technical foundations, challenges, and anticipated impacts of AI and aims to inform and engage researchers in utilizing these systems to transform biomedical discovery, starting with AD and extending to other complex conditions.
CITATION:
Kaleigh F. Roberts ; Eric C. Landsness ; Justin Reese ; Donald Elbert ; Gabrielle Strobel ; Elizabeth Wu ; Yixin Chen ; Albert Lai ; Zachary B. Abrams ; Mingfang Zhu ; Justin Melendez ; Srinivas Koutarapu ; Sihui Song ; Yun Chen ; Robert Lazar ; Payam Barnaghi ; John F. Crary ; Sergio Pablo Sardi ; Marc D. Voss ; Rajaraman Krishnan ; Joel W. Schwartz ; Ron Mallon ; Gustavo A. Jimenez-Maggiora ; Chenguang Wang ; Thomas Sandmann ; Niranjan Bose ; Mukta Phatak ; Gayle Wittenberg ; Yannis G. Kevrekidis ; Cassie S. Mitchell ; Ludovico Mitchener ; Towfique Raj ; Luca Foschini ; Gregory J. Moore ; Randall J. Bateman (2025): Towards an AI biomedical scientist: Accelerating discoveries in neurodegenerative disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100398
AI MODELS, BIAS AND DATA SHARING EFFORTS TO TACKLE ALZHEIMER\'S DISEASE AND RELATED DEMENTIAS
Vijaya B. Kolachalama, Vijay Sureshkumar, Rhoda Au
J Prev Alz Dis 2026;1(13)
Show summaryHide summaryArtificial intelligence (AI), often seen as a harbinger of future innovation, also presents a dilemma: it can perpetuate existing human biases. However, this issue is not novel or unique to AI. Humans have long been the progenitors of biases, and AI, as a product of human creation, often mirrors these inherent tendencies. Here, we present a perspective on the development and use of AI, recognizing it as a tool influenced by human input and societal norms, rather than an autonomous entity. Modern efforts to technologically enabled data collection approaches and model development, particularly in the context of Alzheimer’s disease and related dementias, can potentially reduce bias in AI. We also highlight the importance of data sharing from existing legacy cohorts to help accelerate ongoing AI model development efforts for greater scientific good and clinical care.
CITATION:
Vijaya B. Kolachalama ; Vijay Sureshkumar ; Rhoda Au (2025): AI models, bias and data sharing efforts to tackle Alzheimer's disease and related dementias. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100400
MINING THE GAPS: DECIPHERING ALZHEIMER’S BIOLOGY THROUGH AI-DRIVEN RECONCILIATION
Cory C. Funk, Tom Paterson, Alex Bangs, David M. Cannon, George Savage, Eric Ringger, Lee Hood
J Prev Alz Dis 2026;1(13)
Show summaryHide summaryAlzheimer’s disease remains one of the most complex and contested domains in biomedicine, characterized by fragmented findings, competing hypotheses, and limited translational success. We propose that AI can offer not just technical acceleration but a deeper epistemic contribution: reconciliation. Rather than optimizing predictive performance or replicating existing assumptions, the goal is to align disparate data, methods, and mechanistic insights into coherent models that explain how the disease emerges, progresses, and can be treated. This approach centers on digital twins, not as monolithic models, but as flexible, testable architectures grounded in homeostasis, destabilization, and multiscale coherence. Through an iterative, interoperable AI architecture, digital twins integrate evidence, resolve contradictions, and highlight where critical gaps remain. This framework moves beyond incremental progress within the prevailing model to catalyzing a paradigm shift in how Alzheimer’s is understood. Reconciliation, in this sense, is not a method but a guiding principle for transforming both the science and its applications.
CITATION:
Cory C. Funk ; Tom Paterson ; Alex Bangs ; David M. Cannon ; George Savage ; Eric Ringger ; Lee Hood (2025): Mining the gaps: Deciphering Alzheimer’s biology through AI-driven reconciliation. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100402
MULTI-MODAL DATA ANALYSIS FOR EARLY DETECTION OF ALZHEIMER’S DISEASE AND RELATED DEMENTIAS
Liming Wang, Jim Glass, Lampros Kourtis, Rhoda Au
J Prev Alz Dis 2026;1(13)
Show summaryHide summaryUntil recently, accurate early detection of clinical symptoms associated with Alzheimer’s disease (AD) and related dementias (ADRD) has been difficult. Digital technologies have created new opportunities to capture cognitive and other AD/ADRD related behaviors with greater sensitivity and specificity. Speech captured through digital recordings has shown recent promise at feasible levels of scalability because of the widespread penetration of smartphones. One such study is described in detail to illustrate the depth in which artificial intelligence (AI) analytic approaches can be used to amplify the value of audio recordings. Another modality that has also attracted research interest are ocular scans that have near term potential for validation as a digital biomarker and a point of entry for clinical care workflows. Single modality measures, however, are rapidly giving way to multi-modality sensors that are embedded in all smartphones and other internet-of-things connected devices. Artificial intelligence (AI) driven analytic approaches are able to divine clinical signals from these high dimensional digital data streams. These data driven findings are setting the stage for a future state in which AD/ADRD detection will be possible at the earliest possible stage of the neurodegenerative process and enable interventions that would significantly attenuate or alter the trajectory, preventing disease from reaching the clinical diagnosis threshold.
CITATION:
Liming Wang ; Jim Glass ; Lampros Kourtis ; Rhoda Au (2025): Multi-modal data analysis for early detection of alzheimer’s disease and related dementias. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100399
REINVENTING “N” IN THE A/T/N FRAMEWORK: THE CASE FOR DIGITAL
Rhoda Au, Zachary Popp, Spencer Low, Nicholas J. Ashton, Henrik Zetterberg
J Prev Alz Dis 2026;1(13)
Show summaryHide summaryBreakthroughs in biomarkers for amyloid (A), tau (T), and neurodegeneration (N) have advanced the prospects of accurate Alzheimer’s disease (AD) diagnosis. However, presence of pathology does not always translate into clinical expression and there are still clear knowledge gaps as to whether someone with AD biological indicators will lead to clinically apparent disease necessary to warrant drug treatments that carry toxicity risk. Reliance on decades-old assessment tools inhibits detection and monitoring at preclinical and early disease stages when new treatments could prove most effective. Evidence has accumulated that digital measures provide accurate detection of disease at early stages. We call for a re-evaluation of the A/T/N diagnostic framework, with digital evaluation measures complementing non-AD specific neurodegeneration markers, and even potentially replacing those non-specific to AD, to provide a clinically relevant feature critical to clinical trial advances and treatment decisions. Achieving this will only be possible if further research into novel digital evaluation tools is pursued with the same support and consideration as amyloid and tau.
CITATION:
Rhoda Au ; Zachary Popp ; Spencer Low ; Nicholas J. Ashton ; Henrik Zetterberg (2025): Reinventing “N” in the A/T/N framework: The case for digital. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100395
THE EVOLUTION OF ALZHEIMER’S TARGET IDENTIFICATION: TOWARDS A FUSION OF ARTIFICIAL AND CELLULAR INTELLIGENCE
Gayle Wittenberg, Fiona Elwood, Andrea Houghton, Tommaso Mansi, Bart Smets, Simon Lovestone
J Prev Alz Dis 2026;1(13)
Show summaryHide summaryDecades of advances unfolding in parallel across diverse domains have delivered to science rapid rises in the scale of multiplexing, population-level cohort sizes, global computational capacity, massive-scale artificial intelligence (AI) models, and advanced human cellular modeling capabilities. These have generated unprecedented volumes of data, allowing researchers to explore Alzheimer’s disease (AD) biology at a depth and scale never before possible. The explosion of multi-omics datasets and computational power heralds an era in which the complexity of AD can be meaningfully dissected and reconstructed leveraging AI. These can be applied to advance our understanding of the root causes of disease, fundamentally a forward problem, tracing how dysfunction emergence from interactions across genes, cells and environments over time. On the other hand, therapeutic discovery requires addressing the inverse problem, working back from the diseased state to pinpoint upstream interventions that restore health. Human induced pluripotent stem cells (iPSCs) and other human cell models play a pivotal role in this process, naturally computing the mapping from perturbation to phenotype at scale. By recreating human-relevant biology, this cellular intelligence enables validation of targets predicted by AI and testing of interventions that drive therapeutic progress. We look to the next horizon in Alzheimer’s research as a collaboration, a convergence of three forms of intelligence: human, artificial and cellular. In unison, these complementary forces will shape a new frontier for AD research where scientific innovation and human ingenuity work together bringing hope for meaningful advances and new therapies.
CITATION:
Gayle Wittenberg ; Fiona Elwood ; Andrea Houghton ; Tommaso Mansi ; Bart Smets ; Simon Lovestone (2025): The evolution of Alzheimer’s target identification: Towards a fusion of artificial and cellular intelligence. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100417
SOLVING THE \'GOLDILOCKS PROBLEM\' IN DEMENTIA CLINICAL TRIALS WITH MULTIMODAL AI
Andrew E. Welchman, Zoe Kourtzi
J Prev Alz Dis 2026;1(13)
Show summaryHide summaryThe development of effective therapeutics for Alzheimer’s Disease and related dementias (ADRD) has been hindered by patient heterogeneity and the limitations of current diagnostic tools. New treatments have no chance of working if given to patients who cannot benefit from them. This perspective explores how advances in Artificial Intelligence (AI), particularly multimodal machine learning, can solve the ‘Goldilocks problem’ of identifying patients for inclusion in clinical trials and support precision treatment in real-world healthcare settings. We examine the challenges of patient stratification, grounded by a conceptual framework of identifying each person’s stage and subtype of dementia. We review data from several clinical trials of Alzheimer’s disease therapeutics, to explore how AI-guided patient stratification can improve trial outcomes, reduce costs and improve recruitment. Further, we discuss the integration of AI into clinical workflows, the importance of model interpretability and generalizability, and ethical imperative to address algorithmic bias. By combining AI with scientific insight, clinical expertise, and patient experience, we argue that intelligent analytics can accelerate the discovery and delivery of new diagnostics and therapeutics, ultimately transforming dementia care and improving outcomes for patients around the globe.
CITATION:
Andrew E. Welchman ; Zoe Kourtzi (2025): Solving the 'Goldilocks problem' in dementia clinical trials with multimodal AI. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100397
AI-AUGMENTED FRAMEWORKS FOR ENHANCING ALZHEIMER’S DISEASE CLINICAL TRIALS: A MEMORY CLINIC PERSPECTIVE
Francesco K. Yigamawano, Aubrey R. Odom, Chonghua Xue, Hemant K. Pandey, Vijaya B. Kolachalama
J Prev Alz Dis 2026;1(13)
Show summaryHide summaryAlzheimer’s disease (AD) clinical trials continue to face major hurdles in patient identification, resulting in delayed timelines, underpowered studies, and escalating costs. This perspective explores these challenges through the lens of a memory clinic, where hundreds of cases often translate into only a handful of enrollments. We highlight the potential of artificial intelligence (AI) to address this gap by powering chatbots for awareness and pre-screening, decision support tools for case identification, and algorithms for matching patients to trial-specific criteria, automating and streamlining the recruitment process. We also examine critical considerations in developing such AI-driven tools, including data standardization, privacy protections, and ethical safeguards. With thoughtful implementation, these innovations could accelerate more inclusive and efficient AD trials, ultimately bringing therapies to patients faster.
CITATION:
Francesco K. Yigamawano ; Aubrey R. Odom ; Chonghua Xue ; Hemant K. Pandey ; Vijaya B. Kolachalama (2025): AI-augmented frameworks for enhancing Alzheimer’s disease clinical trials: A memory clinic perspective Author links open overlay panel. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.1003968
EFFECT OF OBICETRAPIB, A POTENT CHOLESTERYL ESTER TRANSFER PROTEIN INHIBITOR, ON P-TAU217 LEVELS IN PATIENTS WITH CARDIOVASCULAR DISEASE
Michael H Davidson, Michael Szarek, Philip Scheltens, Everard Vijverberg, Andrew Hsieh, Marc Ditmarsch, Douglas Kling, Danielle Curcio, Stephen J Nicholls, Kausik K Ray, Jeffrey L. Cummings, John JP Kastelein
J Prev Alz Dis 2026;1(13)
Show summaryHide summaryBACKGROUND: Cholesteryl ester transfer protein (CETP) inhibition reduces low density lipoprotein-cholesterol (LDL-C) while simultaneously increasing high density lipoprotein-cholesterol (HDL-C) levels and improving HDL-particle functionality. These lipoprotein modifications may provide a novel pathway for Alzheimer disease (AD) prevention through effects on lipid modulation, antioxidant activity, and neuro-inflammation. This approach could prove particularly beneficial for APOE4 carriers, who face elevated risks for both AD and atherosclerotic cardiovascular disease (ASCVD).
OBJECTIVES: To examine the effects of obicetrapib, an oral CETP inhibitor, on biomarker changes indicative of AD pathology among patients with ASCVD
DESIGN: This was a pre-specified substudy of the BROADWAY trial, a phase 3, double-blind, placebo-controlled pivotal registration trial to evaluate the LDL-C lowering efficacy of obicetrapib in adult patients with established ASCVD and/or heterozygous familial hypercholesterolemia (HeFH), whose LDL-C was not adequately controlled, despite being on maximally tolerated lipid-lowering therapy.
SETTING: The trial was conducted across 188 sites in China, Europe, Japan, and the United States. Participants were recruited from cardiology clinics and lipid specialty centers from 2021 to 2024.
PARTICIPANTS: Participants with ASCVD in BROADWAY who had known ApoE status and phosphorylated tau-217 (p-tau217) measured at baseline and 12 months.
INTERVENTION: Participants in BROADWAY were randomized 2:1 to receive oral obicetrapib 10 mg daily or placebo for 12 months.
MEASUREMENTS: AD plasma biomarkers were measured at baseline and 12 months using standardized SIMOA assays. The key outcome measure of interest was change in plasma p-tau217 from baseline to 12 months. Other outcome measures included changes in p-tau217/(Aβ42:40), p-tau181, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL).
RESULTS: The analysis population consisted of 1535 (61 %) of the 2530 BROADWAY participants. Median age was 67 years and 67.0 % were male. Baseline p-tau217 levels varied significantly by ApoE subgroups, with ApoE4 carriers generally having higher concentrations and ApoE4/E4 participants exhibiting the highest median concentration (0.56 pg/mL). Obicetrapib significantly attenuated p-tau217 increases compared to placebo (adjusted mean 2.09 % vs 4.94 %; P = 0.025). Treatment differences were most pronounced in ApoE4 carriers, where adjusted mean increases were 1.92 % and 6.91 %, for obicetrapib and placebo, respectively (P = 0.041). Furthermore, among ApoE4/E4 participants, there was a 7.81 % adjusted mean decrease in p-tau217 with obicetrapib compared to a 12.67 % increase with placebo, representing a 20.48 % treatment difference (P = 0.010). Positive trends were observed across secondary biomarkers, with obicetrapib also significantly limiting increases in the p-tau217/Aβ42:40 ratio compared to placebo (2.51 % vs 6.55 %; P = 0.004). In addition, among ApoE4/E4 participants, obicetrapib demonstrated significant effects on GFAP (-6.39 % vs +8.85 %; P = 0.006) and NfL (-10.49 % vs +6.82 %; P = 0.020). Strong correlations were observed between end-of-study obicetrapib plasma concentrations and biomarker improvements (r=-0.64), suggesting CETP inhibition as a potential mechanism, although other drug effects may also contribute to these changes.
CONCLUSIONS: Obicetrapib significantly slowed AD biomarker progression over 12 months in participants with ASCVD, with the greatest effects in ApoE4 carriers. Among ApoE4/E4 participants, obicetrapib reduced p-tau217 levels by a placebo-adjusted 20.48 % and demonstrated consistent effects across multiple AD biomarkers. These findings represent the first demonstration of an oral intervention capable of reducing both beta-amyloid and tau pathology biomarkers in ApoE4 carriers, offering a potential preventive strategy for this high-risk population who currently have no effective prevention options. Future research will need to establish whether these biomarker changes translate to clinical benefits in dedicated AD prevention trials.
CITATION:
Michael H Davidson ; Michael Szarek ; Philip Scheltens ; Everard Vijverberg ; Andrew Hsieh ; Marc Ditmarsch ; Douglas Kling ; Danielle Curcio ; Stephen J Nicholls ; Kausik K Ray ; Jeffrey L. Cummings ; John JP Kastelein (2025): Effect of obicetrapib, a potent cholesteryl ester transfer protein inhibitor, on p-tau217 levels in patients with cardiovascular disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100394
DIETARY INDEX FOR GUT MICROBIOTA (DI-GM) AND COGNITIVE FUNCTION: NHANES FINDINGS AND VALIDATION IN A HONG KONG COHORT WITH METAGENOMIC DATA
Hui Jiang, Jiashuo Zhang, Shuyi Li, Timothy Kwok, Siew C Ng, Allen Ting Chun Lee, Zhilu Xu
J Prev Alz Dis 2026;1(13)
Show summaryHide summaryBACKGROUND: The diet-gut-microbiota-brain axis is critical for maintaining brain health. The Dietary Index for Gut Microbiota (DI-GM), comprising beneficial and unfavorable components, may serve as a proxy for this connection, yet its association with cognition remains underexplored.
METHODS: This study examined the relationship between DI-GM, its components, and cognitive function in older adults using data from the National Health and Nutrition Examination Survey (NHANES). Findings were validated in an independent Hong Kong osteoporosis cohort (OS cohort) with gut metagenomic data to assess of microbiota’s mediating role in diet-cognition relationship. Cognitive assessment in NHANES utilized the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST), while the OS cohort employed the Hong Kong version of the Montreal Cognitive Assessment (HK-MoCA). DI-GM was calculated from 24-hour dietary recalls. The diet-cognition associations were assessed by weighted multivariate regressions, supplemented by restricted cubic spline (RCS), subgroup, correlation network, and mediation analyses.
RESULTS: Higher DI-GM was significantly associated with better performance on DSST (OR=0.90; 95 % CI: 0.82, 0.99; p = 0.033). The beneficial-to-gut-microbiota score (BGMS) associated with lower psychometric mild cognitive impairment (p-MCI) risk (OR=0.88; 95 % CI: 0.80, 0.98; p = 0.022) and better CERAD immediate and delayed recall and DSST (all p < 0.05). The beneficial-to-gut-microbiota components like dietary fiber demonstrated protective effects across cognitive domains, while refined grains was associated with poorer cognition. In the OS cohort, higher dietary fiber intake correlated with higher HK-MoCA score (p < 0.05) and increased abundance of fermenting bacteria. Among these species, Eubacterium ventriosum mediated the beneficial effect of dietary fiber intake on dementia risk reduction, with an indirect effect of -0.014 (95 % CrI: -0.040, -0.001), accounting for approximately 12.7 % of the total effect.
CONCLUSION: Higher adherence to beneficial-to-gut-microbiota dietary patterns, as reflected by DI-GM, was associated with better cognitive function in older adults. These findings highlight the importance of a gut-microbiota-targeted diet in maintaining cognitive health.
CITATION:
Hui Jiang ; Jiashuo Zhang ; Shuyi Li ; Timothy Kwok ; Siew C Ng ; Allen Ting Chun Lee ; Zhilu Xu (2025): Dietary index for gut microbiota (DI-GM) and cognitive function: NHANES findings and validation in a Hong Kong cohort with metagenomic data. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100319
CARDIOVASCULAR-KIDNEY-METABOLIC HEALTH, GENETIC SUSCEPTIBILITY, AND THE RISK OF DEMENTIA: A PROSPECTIVE COHORT STUDY
Yi-Peng Zhang, Jing-Wei Gao, Guang-Hong Liao, Qing-Yuan Gao, Ze-Gui Huang, Chuan-Rui Zeng, Yang-Wei Cai, Yong-Xiang Ruan, Zhi-Teng Chen, Yang-Xin Chen, Jing-Feng Wang
J Prev Alz Dis 2026;1(13)
Show summaryHide summaryBACKGROUND: The joint effect of cardiovascular-kidney-metabolic (CKM) health and genetic susceptibility on dementia remains unclear.
METHODS: This prospective cohort study utilized data from the UK Biobank. CKM syndrome was characterized by the presence of metabolic risk factors, cardiovascular disease, and chronic kidney disease. We employed Cox proportional hazards models to examine the association between CKM syndrome and dementia incidence, while also investigating the influence of genetic risk via polygenic risk score (PRS) and apolipoprotein E (APOE) ε4 status. We also examined the association between CKM syndrome and cognitive function via linear regression model.
RESULTS: Among 331,731 participants (mean ± SD age, 56.53 ± 8.1 years; 156,762 [47.26 %] male), 4413 (1.33 %) developed dementia during a mean follow-up of 12.8 years. Advanced CKM syndrome correlated with higher risk of dementia; compared to stage 0, HRs for dementia were 1.19 (95 % CI 1.01–1.39, P = 0.036), 1.26 (95 % CI 1.09–1.45, P = 0.002), and 2.06 (95 % CI 1.77–2.39, P < 0.001) for stages 1, 2, and 3–4, respectively. Genetic susceptibility further strengthened this association, and the synergistic effect of CKM syndrome, dementia PRS, and APOE ε4 status surpasses the individual contributions of any single factor. These findings remained robust in a series of subgroups and sensitivity analyses. Individuals in the later stages of CKM syndrome demonstrated poorer performance on cognitive function tests.
CONCLUSIONS: Poor CKM health was independently associated with cognitive impairment and an increased risk of dementia. The association between CKM syndrome and risk of dementia could be further strengthened by genetic susceptibility.
CITATION:
Yi-Peng Zhang ; Jing-Wei Gao ; Guang-Hong Liao ; Qing-Yuan Gao ; Ze-Gui Huang ; Chuan-Rui Zeng ; Yang-Wei Cai ; Yong-Xiang Ruan ; Zhi-Teng Chen ; Yang-Xin Chen ; Jing-Feng Wang (2025): Cardiovascular-kidney-metabolic health, genetic susceptibility, and the risk of dementia: A prospective cohort study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100325
PLASMA AND NEUROSTRUCTURAL BIOMARKERS IN THE CLINICAL-BIOLOGICAL CHARACTERIZATION OF EARLY STAGES OF THE ALZHEIMER\'S DISEASE CONTINUUM: FINDINGS FROM THE COMPOSTELA AGING STUDY
Montserrat Zurrón, Arturo Xosé Pereiro, Ana Isabel Rodriguez-Perez, Santiago Galdo-Álvarez, Juan José Ansede, Cristina Lojo-Seoane, Mónica Lindín, David Facal, Miguel Ángel Rivas-Fernández, María Campos-Magdaleno, Ángel Carracedo, José Luis Labandeira-Garcia, Fernando Díaz
J Prev Alz Dis 2026;1(13)
Show summaryHide summaryRecent technical advances in peripheral blood analysis have enabled precise quantification of Alzheimer´s Disease (AD) biomarkers in the early stages of the AD continuum, in an economical, non-invasive and safe manner. The main objective of this study was to contribute to the clinical-biological characterization of the initial stages of cognitive impairment by measurement of blood and neurostructural AD biomarkers in groups of participants classified according to their cognitive clinical phenotype.
Plasma concentrations of p-tau217, p-tau181, total tau, neurofilament light chain and amyloid-β 42/40 ratio biomarkers were measured along with APOE gene variants, hippocampal volume and cortical thickness of the AD signature regions. The cohort of 329 participants included Cognitively Unimpaired (CU), Subjective Cognitive Decline (SCD), single-domain amnestic Mild Cognitive Impairment (sd-aMCI), multidomain aMCI (md-aMCI), and single-domain non-amnestic MCI (sd-naMCI) groups.
P-tau217 concentrations were significantly higher in the md-aMCI and sd-aMCI groups than in the CU, SCD and sd-naMCI groups. P-tau181 concentrations were significantly higher in md-aMCI group than in CU, SCD and sd-naMCI groups. Hippocampal volume and AD signature cortical thickness were significantly lower in the md-aMCI group than in the CU, SCD and sd-naMCI groups. No across group differences were found in the distribution of carriers/non-carriers of APOE-ε4. Mediation analysis revealed that hippocampal volume and AD signature cortical thickness mediated the relationship between p-tau217 and p-tau181 levels and cognitive performance.
Sd-aMCI and md-aMCI represent two distinct and sequential clinical-biological stages of the AD continuum. Conversely, sd-naMCI does not appear to be associated with AD pathology. Finally, the SCD group does not seem to display a higher risk of progression along the AD continuum than the CU group.
CITATION:
Montserrat Zurrón ; Arturo Xosé Pereiro ; Ana Isabel Rodriguez-Perez ; Santiago Galdo-Álvarez ; Juan José Ansede ; Cristina Lojo-Seoane ; Mónica Lindín ; David Facal ; Miguel Ángel Rivas-Fernández ; María Campos-Magdaleno ; Ángel Carracedo ; José Luis Labandeira-Garcia ; Fernando Díaz (2025): Plasma and neurostructural biomarkers in the clinical-biological characterization of early stages of the Alzheimer's disease continuum: findings from the Compostela Aging Study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100331
BRAIN LYMPHATIC DRAINAGE PATHWAYS, DEEP CERVICAL LYMPHATIC SURGERY, AND CURRENT INSIGHTS: A SYSTEMATIC REVIEW
Theodore Lahmar, Francois Thuau, Gaelle Pinard, Claire Boutoleau-Bretonniere, Pierre Perrot, Ugo Lancien
J Prev Alz Dis 2026;1(13)
Show summaryHide summaryThe discovery of the glymphatic system and the later rediscovery of the meningeal lymphatic network have significantly changed our understanding of central nervous system (CNS) waste clearance. Aging is linked to a gradual decline in these clearance pathways, resulting in waste buildup. As a result, therapeutic strategies targeting cerebral lymphatic function have garnered growing interest, with lymphatic surgery emerging as a promising option.
We conducted a review until July 2025, providing an overview of the potential of lymphatic surgical techniques to enhance CNS metabolic waste clearance pathways as a therapeutic approach for brain lymphatic system disorders.
Currently available data are limited, nine publications addressing this approach. These studies explore an innovative technique involving lymphatico-venous anastomoses (LVA) targeting deep cervical lymphatic vessels to promote clearance for the treatment of Alzheimer’s or Parkinson’s diseases.
Cerebral lymphatic drainage is critical for effective brain waste elimination such as amyloid-β, phosphorylated tau, and α-synuclein, which are linked to neurodegenerative diseases. Viewing these lymphatic dysfunctions as a form of “cerebral lymphedema,” LVA, already used in treating peripheral lymphedema, shows potential as a therapeutic approach. Although clinical evidence is still limited, lymphatic supermicrosurgery presents promising therapeutic possibilities for neurodegenerative diseases and other conditions related to impaired CNS lymphatic outflow.
CITATION:
Theodore Lahmar ; Francois Thuau ; Gaelle Pinard ; Claire Boutoleau-Bretonniere ; Pierre Perrot ; Ugo Lancien (2025): Brain lymphatic drainage pathways, deep cervical lymphatic surgery, and current insights: A systematic review. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100335
ASSOCIATIONS BETWEEN TRAUMATIC BRAIN INJURY AND THE PREVALENCE OF ALZHEIMER’S DISEASE DEMENTIA AND BEHAVIORAL AND PSYCHOLOGICAL SYMPTOMS OF DEMENTIA: A RETROSPECTIVE COHORT STUDY
Han-Kyeol Kim, Sojeong Park, Sung-Woo Kim, Yeonju Jin, Hokyung Lee, Jin Yong Hong, Ickpyo Hong, Min Seok Baek
J Prev Alz Dis 2026;1(13)
Show summaryHide summaryBACKGROUND: Traumatic brain injury is an environmental risk factor that may accelerate the progression of Alzheimer’s disease and behavioral and psychological symptoms of dementia in patients with mild cognitive impairment.
OBJECTIVES: To investigate whether traumatic brain injury in patients with mild cognitive impairment is associated with an increased risk of progression to Alzheimer’s disease dementia and behavioral and psychological symptoms of dementia.
DESIGN: A retrospective cohort study using the Korean National Health Insurance Service database.
SETTING: National-level health data covering healthcare utilization, diagnoses, prescriptions, and procedures in South Korea from January 2012 to December 2021.
PARTICIPANTS: Patients diagnosed with mild cognitive impairment between January 1, 2013, and December 31, 2016, were followed until Alzheimer’s disease dementia diagnosis, behavioral and psychological symptoms of dementia occurrence, death, or December 31, 2021. These patients were classified into two groups according to the presence of traumatic brain injury during the follow-up period.
MEASUREMENTS: Age at the time of mild cognitive impairment diagnosis, sex, income level, the presence of several chronic conditions, presence of traumatic brain injury, progression of Alzheimer’s disease dementia, and behavioral and psychological symptoms of dementia
RESULTS: We assessed 452,718 patients (mean age: 67.16 years). Traumatic brain injury was significantly associated with an increased risk of Alzheimer’s disease dementia progression (hazard ratio = 1.252, 95 % confidence interval: 1.206–1.301), particularly among patients aged <65 years (hazard ratio = 1.560, 95 % confidence interval: 1.391–1.749), and was linked to a higher risk of behavioral and psychological symptoms of dementia following Alzheimer’s disease dementia diagnosis (hazard ratio = 1.300, 95 % confidence interval: 1.181–1.431).
CONCLUSIONS: Our results underscore the importance of traumatic brain injury prevention in patients with mild cognitive impairment for mitigating the progression and neuropsychiatric complications of Alzheimer’s disease.
CITATION:
Han-Kyeol Kim ; Sojeong Park ; Sung-Woo Kim ; Yeonju Jin ; Hokyung Lee ; Jin Yong Hong ; Ickpyo Hong ; Min Seok Baek (2025): Associations between traumatic brain injury and the prevalence of Alzheimer’s disease dementia and behavioral and psychological symptoms of dementia: A retrospective cohort study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100360
ALZHEIMER’S DISEASE PREVENTION BY FLAVONOLS AND THEIR ANALOGS
George Uhl, Balaji Kannan, Joungil Choi, Ian Henderson
J Prev Alz Dis 2026;1(13)
Show summaryHide summaryFour studies now document reduced incidence of Alzheimer’s disease (AD) or dementia diagnoses in aging individuals who report higher dietary intake of flavonols (or their glycosides) years prior to diagnosis vs those with lower intake. These effects are large, almost 50 %, for individuals at higher genetic risk for AD, providing a robust gene x environment interaction. They display a specific structure-activity relationship. These benefits are driven by modest-to-moderate differences in the quantity of flavonol (glycoside) consumed. These data contrast with the failure of late life supplementation with flavonol-rich ginko extract to alter progression to AD in groups of individuals who are not selected for genotype or dietary pattern. Studies of mouse AD models support benefits of the flavonol quercetin. In vitro and in vivo results add the receptor type protein tyrosine phosphatase PTPRD to the list of oxidative and other targets or mechanisms to which flavonol benefits are attributed. The magnitude of flavonol protection for individuals who would otherwise be especially vulnerable to AD, the ease of supplementation strategies with currently-available nutraceuticals and the opportunities for development of improved flavonol analogs all support further exploration of flavonol-based strategies for reducing the incidence of AD with aging.
CITATION:
George Uhl ; Balaji Kannan ; Joungil Choi ; Ian Henderson (2025): Alzheimer’s disease prevention by flavonols and their analogs. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100361
FOLIC ACID SUPPLEMENTATION IMPROVES COGNITION FUNCTION IN PARTICIPANTS WITH CEREBRAL SMALL VASCULAR DISEASE-RELATED COGNITIVE IMPAIRMENT: A RANDOMIZED CONTROLLED TRIAL
Yinyue Liu, Yinyue Liu, Zhengjun Cai, Li Zhao, Yu Wang, Yajie Guo, Xiaonan Su, Yuli Miao, Bin Yi, Yanhong Wang, Xumei Zhang
J Prev Alz Dis 2026;1(13)
Show summaryHide summaryBACKGROUND: The potential improvement of cognitive function through folic acid (FA) supplementation in patients with vascular cognitive impairment (VCI) remains unclear, and no randomized controlled trials (RCTs) have been conducted specifically in populations with cerebral small vessel disease-related cognitive impairment (CSVD-CI).
OBJECTIVE: This study aimed to explore the effects of FA supplementation on cognitive function and angiogenesis-related indicators in patients with CSVD-CI.
DESIGN: Double-blinded, parallel group, randomized controlled trial, with a six-month follow-up period.
SETTING: Department of neurology and neurosurgery in Shanxi, China.
PARTICIPANTS: 220 CSVD-CI patients.
INTERVENTIONS: The intervention consisted of FA tablets (0.4 mg/tablet) administered orally at a dose of two tablets daily for six months, while the placebo tablets were identical in appearance and administration but lacked FA.
MEASUREMENTS: The primary outcome was the Montreal Cognitive Assessment (MoCA) score at six months assessed in the intention-to-treat (ITT) population. Secondary outcomes included Mini-Mental State Examination (MMSE) score, Trail Making Test (TMT), Tinetti Performance Oriented Mobility Assessment (POMA), and five-level EuroQol five-dimensional questionnaire (EQ-5D-5 L).
RESULTS: MoCA and MMSE scores improved significantly in the FA group compared to placebo (both P < 0.05). Additionally, the FA group had statistically significant increases in serum folate and decreases in serum homocysteine (Hcy) (both P < 0.001). Matrix metalloproteinase-9 (MMP-9) expression decreased significantly in the FA group compared with placebo (P < 0.05).
CONCLUSIONS: FA improved cognitive outcomes in CSVD-CI, accompanied by a reduction in serum Hcy levels and MMP-9 expression. Early FA supplementation could help prevent vascular-related cognitive decline in CSVD-CI patients.
CITATION:
Yinyue Liu ; Zili Yu ; Zhengjun Cai ; Li Zhao ; Yu Wang ; Yajie Guo ; Xiaonan Su ; Yuli Miao ; Bin Yi ; Yanhong Wang ; Xumei Zhang (2025): Folic acid supplementation improves cognition function in participants with cerebral small vascular disease-related cognitive impairment: a randomized controlled trial. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100369
ASSOCIATIONS OF CIRCULATING C-REACTIVE PROTEIN LEVELS WITH CENTRAL ALZHEIMER’S DISEASE BIOMARKERS
Hye Ji Choi, Min Soo Byun, Dahyun Yi, Hyejin Ahn, Gijung Jung, Sangyong Park, Joon Hyung Jung, Musung Keum, Bo Kyung Sohn, Yu Kyeong Kim, Hongyoon Choi, Yun-Sang Lee, Jun-Young Lee, Koung Mi Kang, Chul-Ho Sohn, Yen-Ning Huang, Andrew J. Saykin, Kwangsik Nho, Dong Young Lee, KBASE Research Group
J Prev Alz Dis 2026;1(13)
Show summaryHide summaryBACKGROUND: C-reactive protein (CRP) is well-known marker of inflammation and immune response. Its potential role in Alzheimer’s disease (AD) pathophysiology remains unclear, particularly in relation to central AD biomarkers, including beta-amyloid (Aβ), tau, and neurodegeneration.
OBJECTIVES: To investigate the associations between circulating CRP levels and central AD biomarkers-including Aβ deposition, tau, and AD-signature neurodegeneration-in nondemented older adults.
DESIGN, SETTING, PARTICIPANTS: This cross-sectional observational study analyzed data from a Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer Disease conducted from 2014 to 2020. A total of 417 nondemented older adults underwent comprehensive evaluations, including blood sampling and multimodal neuroimaging for measuring of Aβ and AD-signature neurodegeneration. A subset of participants (N = 123) also underwent tau positron emission tomography (PET) scan.
MEASUREMENTS: The primary outcomes were A/T/N biomarkers of AD, including brain Aβ and tau deposition measured via amyloid and tau PET, as well as AD-signature neurodegeneration measured by fluorodeoxyglucose (FDG)-PET. Associations between CRP levels and these biomarkers were analyzed while adjusting for CRP-decreasing allele scores, as well as other confounders, including age, sex, vascular risk score, body mass index, nonsteroidal anti-inflammatory drug (NSAID) usage, smoking status, and APOE ε4 carrier status.
RESULTS: The mean (SD) age of participants was 70.57 (8.00) years, with 179 (42.9 %) females. Circulating CRP levels showed non-linear associations with A/T/N biomarkers of AD, showing a U-shaped relationship with Aβ and tau deposition and an inverted U-shaped association with neurodegeneration. Threshold effect analyses revealed that CRP was inversely associated with Aβ deposition (B = -0.081; 95 % CI, -0.153 to -0.007; p = 0.031) below 0.63 mg/L, after adjusting for all confounding variables. In contrast, higher CRP levels were associated with lower cerebral glucose metabolism in AD-signature regions, indicative of greater AD-related neurodegeneration, when above 2.15 mg/L (B = -0.056; 95 % CI, -0.112 to -0.001; p = 0.042).
CONCLUSIONS: Our study revealed differential associations between circulating CRP levels and central AD biomarkers that varied according to the CRP concentration. Further studies are necessary to elucidate the mechanisms underlying the inverse relationship between circulating CRP and brain Aβ within the clinically normal range, as well as potential aggravating effects of elevated CRP on Aβ-independent neurodegeneration.
CITATION:
Hye Ji Choi ; Min Soo Byun ; Dahyun Yi ; Hyejin Ahn ; Gijung Jung ; Sangyong Park ; Joon Hyung Jung ; Musung Keum ; Bo Kyung Sohn ; Yu Kyeong Kim ; Hongyoon Choi ; Yun-Sang Lee ; Jun-Young Lee ; Koung Mi Kang ; Chul-Ho Sohn ; Yen-Ning Huang ; Andrew J. Saykin ; Kwangsik Nho ; Dong Young Lee ; KBASE Research Group (2025): Associations of circulating c-reactive protein levels with central Alzheimer’s disease biomarkers. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100368
TRENDS IN COGNITIVE IMPAIRMENT AMONG OLDER ADULTS IN CHINA FROM 2002 TO 2022: EVALUATING THE IMPACT OF THE COVID-19 PANDEMIC
Lei Feng, Kaisy Xinhong Ye, Qiushi Feng, Yan Mo, Zuqi Cai, Chunbo Li, Jintai Yu, Bin Li, Andrea B. Maier, Yi Zeng, Zhenglian Wang
J Prev Alz Dis 2026;1(13)
Show summaryHide summaryBACKGROUND: Cognitive impairment is a growing public health concern, particularly in aging populations. While trends in CI prevalence in China were studied up to 2018, no previous research has explored how the COVID-19 pandemic has affected these trends.
OBJECTIVES: This study aims to extend the analysis to 2022, examining the impact of the pandemic on cognitive impairment prevalence.
PARTICIPANTS: The Chinese Longitudinal Healthy Longevity Survey (CLHLS) data across multiple waves (2002 to 2022) was used (n=64,872).
MEASUREMENTS: Cognitive impairment was assessed using a Chinese version of the Mini-Mental State Examination (MMSE). The rural/urban-sex-single age-specific prevalence of cognitive impairment across different waves were estimated using the DemoRates R package. Cognitive impairment trends before and after the onset of the COVID-19 pandemic were compared to identify any significant changes.
RESULTS: In 2018 and previous waves, an average of 16,191 participants per wave were surveyed (four waves), with a cognitive impairment prevalence of 4.3%. In 2022, post–COVID-19, the survey included 14,022 participants and showed a significant increase in CI prevalence to 6.8%. The observed trends were independent of gender, age group, and residential environment (P-trend < 0.001). However, a significant decrease in mean calf circumference, increase in proportion of overweight participants, and increases in daily fruit and vegetable intake and regular physical activity were notable after the pandemic.
CONCLUSION: The study suggests that the COVID-19 pandemic may have contributed to the observed increase in cognitive impairment prevalence in China, underscoring the importance of further research into the long-term cognitive effects of global health crises. These findings highlight the need to strengthen healthcare systems to support cognitive health in an aging population, while considering both pandemic-related and ongoing factors in the management of cognitive impairment.
CITATION:
Lei Feng ; Kaisy Xinhong Ye ; Qiushi Feng ; Yan Mo ; Zuqi Cai ; Chunbo Li ; Jintai Yu ; Bin Li ; Andrea B. Maier ; Yi Zeng ; Zhenglian Wang (2025): Trends in cognitive impairment among older adults in China from 2002 to 2022: Evaluating the impact of the COVID-19 pandemic. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100370
LETTER TO THE EDITOR : COGNITIVE DECLINE AMONG CHINESE OLDER ADULTS: FINDINGS FROM THE CHINESE LONGITUDINAL HEALTHY LONGEVITY SURVEY (CLHLS)
Kaisy Xinhong Ye, Lei Feng, Tih-Shih Lee, Yi Zeng, Zhengliang Wang
J Prev Alz Dis 2026;1(13)
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CITATION:
Kaisy Xinhong Ye ; Lei Feng ; Tih-Shih Lee ; Yi Zeng ; Zhengliang Wang (2025): Letter to the Editor: Cognitive decline among Chinese older adults: Findings from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100393
ERRATUM TO “RESULTS OF THE FIRST-IN-HUMAN, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, SINGLE- AND MULTIPLE-ASCENDING DOSE STUDY OF BIIB113 IN HEALTHY VOLUNTEERS” [THE JOURNAL OF PREVENTION OF ALZHEIMER\'S DISEASE VOLUME 12 (2025) 100302]
Flavia C. Nery, Maciej Kaliszczak, Ben Suttle, Lori Jones, Shuang Wu, Jing Xie, Gioacchino Curiale, Esin Yesilalan, Beth Hirschhorn, Denisa Wilkes, Dave Singh, Martin Bolin, Sangram Nag, Andrea Varrone, Per Stenkrona, Anton Forsberg Morén, Christer Halldin, Jeffrey Yachnin, H. Moore Arnold, Szofia Bullain, Jaren Landen, Diana Gallagher, Heike Hering
J Prev Alz Dis 2026;1(13)
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CITATION:
Flavia C. Nery ; Maciej Kaliszczak ; Ben Suttle ; Lori Jones ; Shuang Wu ; Jing Xie ; Gioacchino Curiale ; Esin Yesilalan ; Beth Hirschhorn ; Denisa Wilkes ; Dave Singh ; Martin Bolin ; Sangram Nag ; Andrea Varrone ; Per Stenkrona ; Anton Forsberg Morén ; Christer Halldin ; Jeffrey Yachnin ; H. Moore Arnold ; Szofia Bullain ; Jaren Landen ; Diana Gallagher ; Heike Hering (2025): Erratum to “Results of the first-in-human, randomized, double-blind, placebo-controlled, single- and multiple-ascending dose study of BIIB113 in healthy volunteers” [The Journal of Prevention of Alzheimer's Disease volume 12 (2025) 100302]. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100425