05/2026 journal articles
EDITORIAL: IT’S TIME TO ADDRESS THE RECRUITMENT BOTTLENECK
Gregory Cooper
J Prev Alz Dis 2026;5(13)
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CITATION:
Gregory Cooper (2025): Editorial: It’s time to address the recruitment bottleneck. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100571
EVALUATING EVIDENCE-BASED RECRUITMENT STRATEGIES FOR ALZHEIMER’S DISEASE AND RELATED DEMENTIAS CLINICAL TRIAL RESEARCH: A LITERATURE REVIEW
Mireille Jacobson, Christina Deuschle, Desi Peneva, Alice Nuo-Yi Wang, Cooper Roache, Meghan Walsh, Phyllis Barkman Ferrell, Maria-Alice Manetas, Rema Raman, Paul Aisen, Dana Goldman
J Prev Alz Dis 2026;5(13)
Show summaryHide summaryBACKGROUND: With the prevalence of Alzheimer’s disease and related dementias (ADRD) rising, prevention and treatment clinical trials are increasingly important. Yet inadequate participant recruitment to ADRD research—a leading cause of trial delays, suspensions, or discontinuations—continues to hinder innovation and increase costs. This literature review aimed to identify ADRD recruitment strategies that are effective and ineffective, based on quantitative outcomes, with the goal of optimizing recruitment and advancing recruitment science.
METHODS: PubMed, Google Scholar, relevant ADRD websites, and references were searched for studies meeting inclusion criteria—those reporting quantitative outcomes aimed at improving recruitment rates, timely recruitment, or representation. Reference lists from relevant systematic reviews and meta-analyses, including publications from leading researchers, were also examined. The Mixed Methods Appraisal Tool (MMAT) was used to assess evidence quality.
RESULTS: The search yielded 965 publications, of which 50 met inclusion criteria. Few studies reported recruitment methods for pharmacological trials, and many lacked sufficient detail or standardized reporting to assess quality using MMAT criteria, making it difficult to determine effectiveness. Recruitment efforts deemed successful by study authors often relied on multi-pronged approaches integrating community engagement, structured outreach, and digital tools. However, evidence for effective and scalable strategies remains limited.
CONCLUSION: Advancing ADRD recruitment science requires progress in two key areas: embedding recruitment evaluation directly into trial protocols and encouraging broader sharing of recruitment data. Routine practices, such as publishing recruitment outcomes and adopting standardized reporting, can help close the evidence gap. These approaches enable comparison, replication, and generalizability of effective strategies, ultimately accelerating progress in ADRD research.
CITATION:
Mireille Jacobson ; Christina Deuschle ; Desi Peneva ; Alice Nuo-Yi Wang ; Cooper Roache ; Meghan Walsh ; Phyllis Barkman Ferrell ; Maria-Alice Manetas ; Rema Raman ; Paul Aisen ; Dana Goldman (2026): Evaluating evidence-based recruitment strategies for Alzheimer’s disease and related dementias clinical trial research: A literature review. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100532
EDITORIAL: MOVING TOWARD A MORE RIGOROUS SCIENCE OF RECRUITMENT IN CLINICAL RESEARCH. COMMENTARY ON “EVALUATING EVIDENCE-BASED RECRUITMENT STRATEGIES FOR ALZHEIMER’S DISEASE AND RELATED DEMENTIAS CLINICAL TRIAL RESEARCH: A LITERATURE REVIEW”
Jaime Perales-Puchalt, Eric D. Vidoni
J Prev Alz Dis 2026;5(13)
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CITATION:
Jaime Perales-Puchalt ; Eric D. Vidoni (2025): Editorial: Moving toward a more rigorous science of recruitment in clinical research. Commentary on “Evaluating evidence-based recruitment strategies for Alzheimer’s disease and related dementias clinical trial research: a literature review”. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100561
POINT OF VIEW : HEALTHY LONGEVITY, INTRINSIC CAPACITY, GEROSCIENCE AND ALZHEIMER’S DISEASE PREVENTION
Bruno Vellas
J Prev Alz Dis 2026;5(13)
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CITATION:
Bruno Vellas (2025): Point of View: Healthy longevity, intrinsic capacity, geroscience and Alzheimer’s disease prevention. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100570
MEMORY CONSOLIDATION AND ARIA IN INDIVIDUALS RECEIVING ANTI-AMYLOID MONOCLONAL ANTIBODIES
Marc W Haut, Camila Vieira Ligo Teixeira, Patrick D. Worhunsky, Rashi I. Mehta, Joseph E. Malone, Melanie Ward, Cierra M. Keith, Holly E. Phelps, Stephanie Pockl, Nafiisah Rajabalee, Khalid Sharif, Gary Marano, Pierre-Francois D’Haese, Ali R. Rezai
J Prev Alz Dis 2026;5(13)
Show summaryHide summaryAmyloid related imaging abnormalities (ARIA) are the most significant risk associated with the use of anti-amyloid monoclonal antibodies (MAB) for Alzheimer’s disease (AD). Currently, the presence of the APOE ε4 allele is the best predictor for the development of ARIA. However, the degree of baseline memory impairment has not been fully explored as a risk factor for ARIA. Here, we examined MAB outcomes in a memory clinic population and compared patients with AD who developed ARIA to a case-matched group who did not develop ARIA. Participants who developed ARIA had greater numbers of recall intrusions and false positives, both markers for memory consolidation, at baseline than those who did not develop ARIA. We also observed greater baseline hippocampal and supplementary motor cortical atrophy with ARIA. These differences remained when controlling for the APOE ε4 allele and the presence of pretreatment microhemorrhages. Further investigation of memory impairment and associated brain atrophy is warranted to understand ARIA risk and MAB outcomes in AD.
CITATION:
Marc W Haut ; Camila Vieira Ligo Teixeira ; Patrick D. Worhunsky ; Rashi I. Mehta ; Joseph E. Malone ; Melanie Ward ; Cierra M. Keith ; Holly E. Phelps ; Stephanie Pockl ; Nafiisah Rajabalee ; Khalid Sharif ; Gary Marano ; Pierre-Francois D’Haese ; Ali R. Rezai (2026): Memory Consolidation and ARIA in Individuals Receiving Anti-amyloid Monoclonal Antibodies. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100519
AMYLOID SPATIAL EXTENT WITH FLORBETAPIR-PET FOR EARLY DETECTION OF PRECLINICAL ALZHEIMER’S DISEASE
Emma G. Thibault, Grace Del Carmen Montenegro, J?Alex Becker, Julie C? Price, Brian C. Healy, Bernard J. Hanseeuw, Rachel F. Buckley, Heidi I.L. Jacobs, Michael J. Properzi, Reisa A. Sperling, Keith A. Johnson, Michelle E. Farrell
J Prev Alz Dis 2026;5(13)
Show summaryHide summaryBACKGROUND: Prevention of Alzheimer’s disease (AD) requires biomarkers sensitive to the earliest amyloid-β (Aβ) deposits.
OBJECTIVES: To characterize performance of a recently-developed Aβ-PET spatial extent metric (EXT) for early Aβ detection using 18[F]-florbetapir (FBP)-PET, evaluating its sensitivity, reliability, and associations with plasma pTau217, tau-PET, and cognition.
DESIGN: Longitudinal study with up to 5.5 years of PET, plasma and cognitive measures.
SETTING: The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s disease (A4) Study and its companion screen-fail study Longitudinal Evaluation of Amyloid and Neurodegeneration Risk (LEARN) conducted across 67 international sites.
PARTICIPANTS: 1118 cognitively unimpaired older adults from the A4 placebo arm and LEARN.
MEASUREMENTS: EXT (% of neocortex above region-specific thresholds), global Aβ SUVR, plasma pTau217, medial temporal (MTL) and temporal neocortical (nTEMP) tau-PET SUVR, and Preclinical Alzheimer Cognitive Composite (PACC).
RESULTS: EXT showed high cross-sectional reliability and longitudinal stability. Using EXT reclassified 21.4% of SUVR-participants from Aβ− to Aβ+ and predicted who would progress to SUVR+ 5.5 years later with 83% sensitivity and 94% specificity. In SUVR− individuals, higher pTau217 associated with greater SUVR only within EXT+ individuals. Baseline EXT outperformed SUVR in predicting MTL tau proliferation. For neocortical tau SUVR and PACC change, EXT was the better predictor in earlier Aβ stages (while Aβ spread) while SUVR was superior later (after Aβ was widespread).
CONCLUSIONS: EXT is a robust, generalizable PET metric that detects Aβ before global positivity and early Aβ-related changes in tau and cognition, supporting its relevance for trial enrichment and early therapeutic monitoring in AD prevention trials.
CITATION:
Emma G. Thibault ; Grace Del Carmen Montenegro ; J․Alex Becker ; Julie C․ Price ; Brian C. Healy ; Bernard J. Hanseeuw ; Rachel F. Buckley ; Heidi I.L. Jacobs ; Michael J. Properzi ; Reisa A. Sperling ; Keith A. Johnson ; Michelle E. Farrell (2026): Amyloid spatial extent with florbetapir-PET for early detection of preclinical Alzheimer’s disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100529
DISCORDANCE IN AMYLOID POSITIVITY BETWEEN VISUAL READS AND CENTILOIDS: IMPACT OF WHITE MATTER UPTAKE
Arnaud Charil, Todd M. Nelson, Anthonin Reilhac, Viswanath Devanarayan, Shobha Dhadda, Michael C. Irizarry, Lynn D. Kramer, Larisa Reyderman
J Prev Alz Dis 2026;5(13)
Show summaryHide summaryBACKGROUND: The visual interpretation of amyloid PET scans, or visual read (VR), is the most common technique used in clinical practice to identify the presence of cerebral amyloid plaques. Amyloid status (positive or negative) determined by VR or using a Centiloid (CL) cut-off shows high overall concordance. However, discordant cases can occur where the VR is positive, but the CL is below the positivity cut-off, or vice versa.
OBJECTIVES: The objective of this analysis was to evaluate the rate of discordance and explore potential causes, particularly the role of amyloid tracer uptake in the white matter (WM), when determining amyloid status using VR and CL in screening for the elenbecestat phase 3 studies in early Alzheimer's disease (AD).
DESIGN: Amyloid PET scans using either Florbetapir (Amyvid™), Florbetaben (Neuraceq™) or Flutemetamol (Vizamyl™) from 3,232 participants (1507 VR- and 1725 VR+) with cognitive impairment screened for the elenbecestat phase 3 studies in early AD were visually interpreted at screening by trained neuroradiologists and quantified using CL values.
SETTING: Academic and clinical centers.
INTERVENTIONS/MEASUREMENTS: Quantitatively, amyloid positivity was defined as CL > 32.21. The number of positive cortical regions was determined by counting the number of regions with a standardized uptake value ratio (SUVr) that exceeded 1.17. PET SUVr levels in the cerebral WM were measured using an eroded WM region of interest (ROI). Statistical tests were conducted to detect differences among the four concordance groups, defined by the relationship of VR and CL status (positive or negative). Additionally, tests examined the relationship between uptake in the WM and rates and type of discordance. Receiver operating characteristic (ROC) analysis and DeLong’s test were also used to examine the effect of different tracers on the discordant rates.
RESULT: Discordance was observed in 6.53% of cases (n=211), with VR+/CL- in 4.61% (n=149) and VR-/CL+ in 1.92% (n=62). VR+/CL- discordant cases had significantly fewer amyloid-positive cortical regions compared to both VR+/CL+ and VR-/CL+ cases. VR-/CL+ cases had a significantly higher WM uptake than VR-/CL- and VR+/CL- cases. Our findings revealed a relationship between WM uptake and rates and types of discordance. High WM uptake can erroneously lead to CL+, due to gray matter (GM) contamination from the WM, and VR- status, due to reduced contrast between WM and GM, resulting in VR-/CL+ cases. Conversely, low WM uptake can result in an underestimation of CL values, inaccurately classifying a scan as CL-, and at the same time, the increased contrast may result in a VR+, thereby increasing the occurrence of discordant VR+/CL- cases.
CONCLUSION: Variations in WM uptake significantly contribute to discordances by introducing positive or negative bias in CL values and altering the GM to WM contrast, which forms the basis of the VR. Nevertheless, the rates of discordant cases are low and VR represents a robust and validated method to determine the presence of amyloid deposition. VR enables enrolling patients with amyloid beta pathology, as seen on amyloid PET scans, whereas CL scaling was developed to provide standardized units that more consistently characterize longitudinal amyloid‑β change. These findings reflect the complementary roles of VR and CL in amyloid PET evaluation, with implications for refining diagnostic accuracy and disease monitoring in AD clinical trials and practice.
CITATION:
Arnaud Charil ; Todd M. Nelson ; Anthonin Reilhac ; Viswanath Devanarayan ; Shobha Dhadda ; Michael C. Irizarry ; Lynn D. Kramer ; Larisa Reyderman (2026): DISCORDANCE IN AMYLOID POSITIVITY BETWEEN VISUAL READS AND CENTILOIDS: IMPACT OF WHITE MATTER UPTAKE. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100530
INTERIM ANALYSIS OF ALL-CASE POST-MARKETING SURVEILLANCE STUDY IN JAPAN: LECANEMAB IN PATIENTS WITH EARLY ALZHEIMER’S DISEASE
Atsushi Iwata, Yukinori Sakata, Kinuyo Koizumi, Akira Endo, Weijie Kuang, Kenta Sumitomo, Mika Ishii
J Prev Alz Dis 2026;5(13)
Show summaryHide summaryBACKGROUND: Lecanemab is a monoclonal antibody targeting amyloid-beta protofibrils, indicated for patients with mild cognitive impairment (MCI) and mild dementia due to Alzheimer’s disease.
OBJECTIVES: This study reports interim findings of an ongoing, multicenter, prospective, observational post-marketing study for all patients treated with lecanemab in routine clinical practice in Japan, focusing on amyloid-related imaging abnormalities (ARIAs) and infusion-related reactions primarily observed during up to 28 weeks after treatment initiation.
METHODS: Patients treated with lecanemab at any medical institutions across Japan are included in the study. Data are collected using an electronic data capture system via standardized case report forms (CRFs). Study items included the incidence of ARIA, ARIA-edema or effusion (-E), ARIA-hemorrhage (-H: cerebral microhemorrhages, superficial siderosis, and macrohemorrhage), and infusion-related reactions, reported as adverse drug reactions.
RESULTS: As of July 5, 2025, CRFs from 2675 patients were collected, of whom 2672 had data available for the interim analysis. The median age was 76.0 years, and 62.6 % (1672/2672) of patients were diagnosed with MCI. At Week 28, 7.3 % (195/2672) of patients discontinued treatment, with a mean treatment duration of 189.6 ± 34.4 days. Among 2634 patients confirmed to have undergone MRI scans after treatment initiation, ARIA was observed in 7.1 % (188/2634) of patients, ARIA-E in 3.0 % (78/2634), and ARIA-H in 5.2 % (137/2634). Serious ARIA-H (macrohemorrhage) occurred in two patients (0.1 %). Infusion-related reactions were observed in 17.0 % (455/2672), including 0.7 % (18/2672) serious cases. The proportion of patients who experienced ARIA was highest in patients with apolipoprotein E (APOE) ε4 homozygotes.
CONCLUSION: This interim analysis represents one of the largest real-world lecanemab cohorts reported globally to date. Although absolute rates are not directly comparable with those from clinical trials, the trends in ARIA distributions across APOE genotypes and infusion-related reactions were comparable to those observed in clinical trials.
CITATION:
Atsushi Iwata ; Yukinori Sakata ; Kinuyo Koizumi ; Akira Endo ; Weijie Kuang ; Kenta Sumitomo ; Mika Ishii (2026): Interim analysis of all-case post-marketing surveillance study in Japan: lecanemab in patients with early Alzheimer’s disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100541
CHARACTERISTICS OF INFUSION-RELATED REACTIONS TO LECANEMAB IN EARLY ALZHEIMER’S DISEASE: A MULTICENTER REAL-WORLD STUDY IN NORTHWESTERN CHINA
Peijie Liu, Jie Liu, Jin Wang, Ying Du, Zhirong Liu, Hong Zhang, Aiqin Zhu, Gejuan Zhang, Xinling Meng, Chunmei Zhao, Weiping Zhang, Liangjun Dang, Wei Zhang, Qiumin Qu, Yan Qu
J Prev Alz Dis 2026;5(13)
Show summaryHide summaryBACKGROUND: Infusion-related reactions (IRRs) represent the most common adverse events associated with lecanemab. However, real-world data on IRR characteristics and risk factors in Asian populations, particularly Chinese, remain scarce.
METHODS: In a multicenter prospective registry, 139 patients with early Alzheimer’s disease (AD) receiving lecanemab were included. IRRs were physician-confirmed. Multivariable logistic regression identified independent predictors.
RESULTS: The cumulative IRR incidence was 12.36 %, highest at the first infusion (17.3 %) and decreased significantly thereafter (P < 0.001). Fever (54.2 %) and dizziness (16.7 %) were the most common symptoms. 45.8 % of IRRs occurred 2–24 hours after infusion. All IRRs were mild (Grade 1) and self-limited. Hypertension (OR = 5.017, P = 0.007) and higher Fazekas score (OR = 2.734, P = 0.017) were independently associated with IRR.
DISCUSSION: In this Chinese real‑world cohort, lecanemab‑associated IRRs were less frequent, mild, and delayed. Hypertension and white‑matter hyperintensity severity emerged as key risk factors, underscoring the potential role of cerebrovascular health in IRR susceptibility.
CITATION:
Peijie Liu ; Jie Liu ; Jin Wang ; Ying Du ; Zhirong Liu ; Hong Zhang ; Aiqin Zhu ; Gejuan Zhang ; Xinling Meng ; Chunmei Zhao ; Weiping Zhang ; Liangjun Dang ; Wei Zhang ; Qiumin Qu ; Yan Qu (2026): Characteristics of infusion-related reactions to lecanemab in early Alzheimer’s disease: A multicenter real-world study in Northwestern China. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100542
PREVENTION OF DEMENTIA USING MOBILE PHONE APPLICATIONS (PRODEMOS) – A HEALTH-ECONOMIC COST-UTILITY ANALYSIS IN PEOPLE AGED 55–75 YEARS WITH LOW SOCIO-ECONOMIC STATUS
Ron Handels, Marieke Hoevenaar-Blom, Manshu Song, Carol Brayne, Eric Moll van Charante, Fiona E. Matthews, Junfang Xu, Linus Jönsson, Nicola Coley, Rachael Brooks, Xuening Jian, Tingting Qin, Youxin Wang, Wei Wang, Edo Richard, Anders Wimo, PRODEMOS study group
J Prev Alz Dis 2026;5(13)
Show summaryHide summaryINTRODUCTION: We aimed to explore the potential incremental cost-effectiveness of the PRODEMOS coach-supported mobile health intervention for primary prevention of dementia versus standard of care provided to people aged 55–75 years with low socio-economic status (SES) in the United Kingdom (UK), and any SES in China.
METHODS: 12–18-month PRODEMOS trial (ISRCTN15986016) efficacy outcomes on hypertension, obesity, hypercholesterolemia, physical inactivity and smoking were extrapolated to lifetime impact on dementia onset, myocardial infarction, stroke and death using a health-economic open-source simulation model.
RESULTS: Simulated outcomes showed dementia cases were avoided (UK = -206 (-658 to 281), China = -140 (-456 to 205) per 100,000 persons) and disease-free time was gained for dementia, myocardial infarction and stroke (mean months per person UK = 0.4, 0.0 and 0.0; China = 0.2, 0.0 and 0.0 respectively). Assuming a maximum intervention duration of 10 years with a 10 % annual non-adherence rate, the incremental net health benefit in the UK (-0.190) and China (-0.009) indicated a potential lack cost-effectiveness.
LIMITATIONS: Our method was limited by strong assumptions regarding causality and sustained effectiveness, lack of some country-specific input estimates, and the lack of probabilistic analysis.
CONCLUSION: The PRODEMOS coach-supported mobile health intervention for the primary prevention of dementia, aimed at people aged 55 to 75 years with low SES in the UK and those of any SES in China, may potentially lack cost-effectiveness in both countries. However, lack of data required strong assumptions regarding causality and sustained effectiveness, which limited policy recommendations.
CITATION:
Ron Handels ; Marieke Hoevenaar-Blom ; Manshu Song ; Carol Brayne ; Eric Moll van Charante ; Fiona E. Matthews ; Junfang Xu ; Linus Jönsson ; Nicola Coley ; Rachael Brooks ; Xuening Jian ; Tingting Qin ; Youxin Wang ; Wei Wang ; Edo Richard ; Anders Wimo ; PRODEMOS study group (2026): Prevention of dementia using mobile phone applications (PRODEMOS) – a health-economic cost-utility analysis in people aged 55–75 years with low socio-economic status. The Journal of Frailty and Aging (JFA). https://doi.org/10.1016/j.tjpad.2026.100526
NUTRITIONAL SUPPLEMENTS AND COGNITION IN HEALTHY AGING AND MILD COGNITIVE IMPAIRMENT PATIENTS: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS
Xing Liu, Chenyi Yang, Xinyi Wang, Huihui Liao, Huan Liu, Ji Ma, Yi Sun, Haiyun Wang
J Prev Alz Dis 2026;5(13)
Show summaryHide summaryBACKGROUND: Nutritional supplementation is increasingly regarded as a potential strategy to preserve or enhance cognitive function in individuals with healthy aging and mild cognitive impairment (MCI). However, its overall efficacy remains uncertain due to inconsistent findings across clinical trials.
METHODS: In accordance with the guidelines outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Network Meta-Analyses, we conducted a comprehensive systematic search. Our inclusion criteria focused on randomized controlled trials (RCTs) that examined the impact of nutrient supplementation on cognitive function within healthy aging and MCI patients. The primary outcome of interest was the change in cognitive function, while the secondary outcome involved alterations in blood biochemical markers (e.g., homocysteine, vitamin B12, and serum folate levels).
RESULTS: The meta-analysis results indicated that docosahexaenoic acid (DHA)+eicosapentaenoic acid (EPA)+vitamin E+tryptophan+melatonin, as well as melatonin alone, significantly enhanced global cognitive function. Additionally, DHA, folic acid+DHA, and the DHA+EPA+vitamin E+tryptophan+melatonin were all effective in augmenting memory. DHA alone was found to be beneficial in improving processing speed, whereas vitamin D3 was associated with improvements in visuospatial function. Notably, sensitivity analyses revealed that while most domain-specific effects remained stable, the rankings of certain small-sample interventions were sensitive to study duration and sample size. Supplementation with folic acid, vitamin B12, and vitamin B6, whether administered individually or in combination, resulted in varying improvements in blood biomarkers, including homocysteine, vitamin B12, and serum folate levels.
CONCLUSIONS: Nutritional supplementation demonstrates nuanced, domain-specific benefits rather than universal cognitive enhancement. While specific multi-nutrient combinations show potential, their effects are significantly influenced by baseline cognitive status, age, and intervention duration. Our findings suggest that nutritional strategies should be tailored to individual cognitive profiles, emphasizing the need for personalized interventions and further high-quality, longitudinal trials to confirm long-term clinical impact.
CITATION:
Xing Liu ; Chenyi Yang ; Xinyi Wang ; Huihui Liao ; Huan Liu ; Ji Ma ; Yi Sun ; Haiyun Wang (2026): Nutritional supplements and cognition in healthy aging and mild cognitive impairment patients: a systematic review and network meta-analysis. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100518
SOCIODEMOGRAPHIC DIFFERENCES IN DEMENTIA PREVENTION KNOWLEDGE IN GERMANY: IMPLICATIONS FOR TARGETED HEALTH COMMUNICATION
Pauline Albus, Ann-Kristin Folkerts, Josef Kessler, Sebastian Köhler, Elke Kalbe
J Prev Alz Dis 2026;5(13)
Show summaryHide summaryBACKGROUND: Dementia is a leading cause of disability and mortality worldwide. While the disorder is widely recognized, public awareness of modifiable risk and potentially protective factors remains limited. This is despite evidence that a substantial proportion of cases could be prevented or delayed by modifying personal risk factors. To date, the influence of sociodemographic factors on knowledge about dementia prevention has not been sufficiently examined, particularly in Germany, leaving a critical gap for targeted public health strategies.
OBJECTIVES: To assess awareness of the preventability of dementia and to evaluate knowledge of risk and protective factors in the German population, with particular focus on the influence of age, sex, and education.
DESIGN: Online, cross-sectional survey study.
SETTING: German population. A link to the survey was distributed nationwide via e-mail, flyers, and social media.
PARTICIPANTS: Adults aged ≥18 years without diagnosed cognitive impairment. A total of 2610 individuals completed the survey, of whom 2515 (mean age 52.5 years, range 18–95, 69.8% female) were included in the analysis.
MEASUREMENTS: Awareness of dementia, risk factors, and preventability was assessed using two dichotomous and three Likert-scale items. Knowledge of 23 evidence-based risk and protective factors (plus sham items) was measured with Likert-scale items. Composite knowledge scores were derived from these items, including separate subscores for medical and lifestyle-related risk factors. Preferred information dissemination sources were assessed using a multiple-choice item. Analyses included descriptive statistics and regression models with age, sex, and education as predictors.
RESULTS: While almost all respondents (98.2%) affirmed knowing what dementia is, only 73% affirmed awareness of risk-modifying factors, with substantial subgroup differences. Nearly 38% did not agree that dementia can be prevented, including a higher proportion of those aged ≥75 years (52%). Lifestyle factors, such as physical, mental, and social activity and diet, were most frequently recognized (>75%), whereas medical and environmental risks (e.g., cardiovascular disease, kidney disease, air pollution) were consistently underrecognized (<50%). Overall, younger age, female sex, and higher education were predictors of significantly higher knowledge scores, with education showing the strongest effect. Preferred information sources also differed systematically; lower-educated participants and men were more likely to rely on general practitioners, while higher-educated groups preferred digital resources and specialized organizations.
CONCLUSIONS: Compared with findings from previous German surveys, awareness of dementia preventability is higher in the present sample; however, knowledge about specific influencing factors—particularly medical—remains limited. As awareness, knowledge, and preferred information channels differ across age, sex, and education groups, educational efforts should be tailored accordingly.
CITATION:
Pauline Albus ; Ann-Kristin Folkerts ; Josef Kessler ; Sebastian Köhler ; Elke Kalbe (2026): Sociodemographic differences in dementia prevention knowledge in Germany: Implications for targeted health communication. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100517
PLASMA GFAP OUTPERFORMS CSF GFAP IN DETECTING AMYLOID PATHOLOGY AND IS ASSOCIATED WITH INCREASED RISK OF CLINICAL PROGRESSION IN EARLY ALZHEIMER’S DISEASE
Arda C. Cetindag, Carola G. Schipke, Hermann Esselmann, Niels Kruse, Jens Wiltfang, Anja Schneider, Klaus Fliessbach, Carolin Miklitz, Franziska Maier, Katharina Buerger, Daniel Janowitz, Michael Ewers, Sophia Stöcklein, Robert Perneczky, Boris-Stephan Rauchmann, Carolin Kurz, Stefan Teipel, Ingo Kilimann, Doreen Goerss, Christoph Laske, Sebastian Sodenkamp, Elham Najafpour, Michael Wagner, Sandra Roeske, Ingo Frommann, Melina Stark, Frederic Brosseron, Alfredo Ramirez, Luca Kleineidam, Josef Priller, Eike Jakob Spruth, Maria Gemenetzi, Slawek Altenstein, Emrah Düzel, Wenzel Glanz, Enise I. Incesoy, Michaela Butryn, Chris Bauer, Frank Jessen, Oliver Peters
J Prev Alz Dis 2026;5(13)
Show summaryHide summaryBACKGROUND: Early and accurate detection of Alzheimer’s disease (AD) is essential for timely intervention and development of disease-modifying treatments. The DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) provides a deeply phenotyped cohort covering preclinical and early clinical stages, including subjective cognitive decline (SCD) and mild cognitive impairment (MCI). Astrocyte reactivity and its biomarkers, particularly glial fibrillary acidic protein (GFAP), have gained increasing attention in AD research; however, the relationship between GFAP and amyloid in early disease, as well as its potential prognostic value beyond its association with amyloid status, remains insufficiently understood.
OBJECTIVES: To evaluate the performance of CSF and plasma GFAP across early disease stages, compare these measures according to amyloid status, and assess the prognostic value of GFAP for clinical progression across diagnostic stages during longitudinal follow-up.
SETTING: This study used data from the multicenter DELCODE cohort in Germany, including participants with available plasma and/or CSF samples and standardized clinical, cognitive, imaging, and biomarker assessments.
MEASUREMENTS: GFAP concentrations in plasma and CSF were quantified using validated immunoassay platforms. Standard CSF AD biomarkers and ApoE genotype were measured using established assays. Amyloid status was defined by the CSF Aβ42/40 ratio. Longitudinal follow-up occurred annually for up to ∼10 years, with clinical conversion determined according to NIA-AA criteria.
RESULTS: Plasma and CSF GFAP increased across the AD continuum, with higher levels in MCI and AD (p < 0.001). Plasma GFAP showed a stronger association with amyloid status than CSF GFAP across all groups. In MCI, plasma GFAP combined with age and ApoE4 yielded an AUC of 0.87. Elevated plasma GFAP predicted increased risk of conversion to MCI (HR = 2.19, p < 0.001; adjusted HR = 1.70, p = 0.0056) and AD dementia (HR = 3.5; adjusted HR = 2.49 both p < 0.001).
CONCLUSION: Plasma GFAP is a sensitive, minimally invasive biomarker with diagnostic relevance for amyloid detection and prognostic relevance for clinical progression in early AD.
CITATION:
Arda C. Cetindag ; Carola G. Schipke ; Hermann Esselmann ; Niels Kruse ; Jens Wiltfang ; Anja Schneider ; Klaus Fliessbach ; Carolin Miklitz ; Franziska Maier ; Katharina Buerger ; Daniel Janowitz ; Michael Ewers ; Sophia Stöcklein ; Robert Perneczky ; Boris-Stephan Rauchmann ; Carolin Kurz ; Stefan Teipel ; Ingo Kilimann ; Doreen Goerss ; Christoph Laske ; Sebastian Sodenkamp ; Elham Najafpour ; Michael Wagner ; Sandra Roeske ; Ingo Frommann ; Melina Stark ; Frederic Brosseron ; Alfredo Ramirez ; Luca Kleineidam ; Josef Priller ; Eike Jakob Spruth ; Maria Gemenetzi ; Slawek Altenstein ; Emrah Düzel ; Wenzel Glanz ; Enise I. Incesoy ; Michaela Butryn ; Chris Bauer ; Frank Jessen ; Oliver Peters (2025): Plasma GFAP outperforms CSF GFAP in detecting amyloid pathology and is associated with increased risk of clinical progression in early Alzheimer’s disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100544
PERFORMANCE OF A FULLY AUTO-MATED PLASMA TAU PHOSPHORY-LATED AT THREONINE 217 IMMU-NOASSAY TO REFLECT AMYLOID-BETA BURDEN IN AN UNSELECTED COHORT REPRESENTATIVE OF CLI-NICAL PRACTICE
Sayuri Hortsch, Annunziata Di Domenico, Niels Borlinghaus, David Caley, Laura Kaminioti-Dumont, Sara Bohn Jeppesen, Armand González-Escalante, Craig Ritchie, Kristian Steen Frederiksen, Marc Suárez-Calvet
J Prev Alz Dis 2026;5(13)
Show summaryHide summaryBACKGROUND: With the emergence of disease-modifying anti-amyloid-beta (Aβ) therapies for Alzheimer’s disease (AD), early and accurate quantitative measures of Aβ burden are critical. Blood-based biomarkers are a scalable and minimally invasive diagnostic solution; plasma tau phosphorylated at threonine 217 (pTau217) is a promising marker for Aβ pathology. The clinical performance of the prototype ElecsysⓇ Phospho-Tau (217P) Plasma immunoassay (Roche Diagnostics) to detect Aβ burden was investigated in an unselected cohort reflective of clinical practice.
METHODS: Plasma was prospectively collected from participants aged 55 to 80 years with objective or subjective cognitive decline under evaluation for AD. Participants were recruited at multiple clinical sites spanning primary and secondary care. Plasma pTau217 concentrations measured using the prototype pTau217 plasma immunoassay were compared with amyloid positron emission tomography centiloid-based classification at different cutoffs, with further analyses performed at centiloid cutoff 30.
OUTCOMES: Among 588 participants, plasma pTau217 demonstrated high concordance with centiloid-based classification at selected cutoffs. The discriminative ability of plasma pTau217 to detect Aβ pathology peaked at centiloid cutoff 32 (area under the curve=0.933). Subgroup analyses at centiloid cutoff 30 demonstrated good discrimination of Aβ positivity/negativity by clinical diagnosis, age, and sex. Moderately decreased kidney function to kidney failure was found to influence plasma pTau217 levels.
INTERPRETATION: The prototype pTau217 plasma immunoassay showed high accuracy in reflecting Aβ burden among individuals presenting with cognitive complaints across diverse clinical settings. These findings support its potential implementation into routine clinical practice for early detection of AD, alongside standard clinical and neuropsychologic assessments.
CITATION:
Sayuri Hortsch ; Annunziata Di Domenico ; Niels Borlinghaus ; David Caley ; Laura Kaminioti-Dumont ; Sara Bohn Jeppesen ; Armand González-Escalante ; Craig Ritchie ; Kristian Steen Frederiksen ; Marc Suárez-Calvet (2026): Performance of a fully automated plasma tau phosphorylated at threonine 217 immunoassay to reflect amyloid-beta burden in an unselected cohort representative of clinical practice. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100534
SCREENING FOR ALZHEIMER’S DISEASE IN THE COMMUNITY USING AN AI-DRIVEN SCREENING PLATFORM: DESIGN OF THE PREDICTOM STUDY
Anna-Katharine Brem, Zunera Khan, Jonas Radermacher, Kostas Georgiadis, Ioulietta Lazarou, Margarita Grammatikopoulou, Ellie Pickering, Johanna Mitterreiter, Jon Arild Aakre, Nicholas J. Ashton, Miguel Baquero, Maria Beser-Robles, Claire Braboszcz, Sigurd Brandt, James Brown, Federica Cacciamani, Sarah Campill, Christopher Collins, Pushkar Deshpande, Ana Diaz, Stanley Durrleman, Sebastiaan Engelborghs, Laura Ferré-González, Giovani B. Frisoni, Martha Therese Gjestsen, Dianne Gove, Lee Honigberg, Bin Huang, Anett Hudak, Sandeep Kaushik, Tamas Letoha, Gaby Marquardt, Augusto J. Mendes, Matthias Müllenborn, Lucas Paletta, Nuno Pedrosa de Barros, Martin Pszeida, Audun Osland Vik-Mo, Hossein Rostamipour, Robert Perneczky, Boris-Stephan Rauchmann, Silvia Russegger, Timo Schirmer, Amied Shadmaan, Ana Beatriz Solana, Aureli Soria-Frisch, Paulina Tegethoff, Annemie Ribbens, Sara De Witte, Mark van der Giezen, Spiros Nikolopoulos, Anne Corbett, Holger Fröhlich, Dag Aarsland, the PREDICTOM Consortium
J Prev Alz Dis 2026;5(13)
Show summaryHide summaryBACKGROUND: Recent developments in physiological, imaging and digital biomarkers combined with the approval of new disease-modifying drugs against Alzheimer’s disease (AD) and diagnostic blood tests provide an opportunity to shift the first diagnostic steps to the home-setting. While these novel biomarkers enable scalable screening and earlier detection and treatment of AD, they require an evaluation of their accuracy, feasibility, and safety in primary care and the community setting.
OBJECTIVES: The aim of PREDICTOM is to develop and test the accuracy of an artificial intelligence (AI) driven screening platform for the risk assessment and early detection of AD to extend the clinical pathway to home-based screening using established and novel biomarkers.
DESIGN/SETTING: PREDICTOM is a European (Norway, UK, Belgium, France, Switzerland, Germany, Spain) observational, prospective cohort study using a cloud-based platform that stores a digitalised journey for each participant and provides a collection of artificial-intelligence (AI) algorithms and tools for risk assessment and early diagnosis and prognosis.
PARTICIPANTS: Cohort 1 consists of 4000 adults aged 50 years or older at risk of developing AD. Cohort 2 consists of 615 participants selected from Cohort 1 based on estimates indicating high (N = 415) or low (N = 200) risk of AD. Data from existing cohorts will guide the analytic strategy of the study.
MEASUREMENTS: Cohort 1 will undergo home-based assessments (Level 1), Cohort 2 will undergo in-clinic assessments (Levels 2 and 3). Level 1 includes at-home screening, collecting digital and physiological data (questionnaires, cognition, hearing, eye-tracking) and biofluids (capillary blood via finger-stick and saliva) for biomarker analysis. Level 2 comprises a more complex biomarker collection, most of which can be completed in primary care, including EEG, MRI, venous blood, microbiome from stool, cognition, hearing, and eye-tracking. Level 3 includes a diagnostic evaluation to confirm or rule out AD pathology using established biomarkers (cerebrospinal fluid, or amyloid PET).
CONCLUSIONS: PREDICTOM will develop AI-driven algorithms for the early detection of AD using biomarkers that can be collected at home or in the community care setting, and evaluate their integration into a well-defined and comprehensive clinical pathway.
CITATION:
Anna-Katharine Brem ; Zunera Khan ; Jonas Radermacher ; Kostas Georgiadis ; Ioulietta Lazarou ; Margarita Grammatikopoulou ; Ellie Pickering ; Johanna Mitterreiter ; Jon Arild Aakre ; Nicholas J. Ashton ; Miguel Baquero ; Maria Beser-Robles ; Claire Braboszcz ; Sigurd Brandt ; James Brown ; Federica Cacciamani ; Sarah Campill ; Christopher Collins ; Pushkar Deshpande ; Ana Diaz ; Stanley Durrleman ; Sebastiaan Engelborghs ; Laura Ferré-González ; Giovani B. Frisoni ; Martha Therese Gjestsen ; Dianne Gove ; Lee Honigberg ; Bin Huang ; Anett Hudak ; Sandeep Kaushik ; Tamas Letoha ; Gaby Marquardt ; Augusto J. Mendes ; Matthias Müllenborn ; Lucas Paletta ; Nuno Pedrosa de Barros ; Martin Pszeida ; Audun Osland Vik-Mo ; Hossein Rostamipour ; Robert Perneczky ; Boris-Stephan Rauchmann ; Silvia Russegger ; Timo Schirmer ; Amied Shadmaan ; Ana Beatriz Solana ; Aureli Soria-Frisch ; Paulina Tegethoff ; Annemie Ribbens ; Sara De Witte ; Mark van der Giezen ; Spiros Nikolopoulos ; Anne Corbett ; Holger Fröhlich ; Dag Aarsland ; the PREDICTOM Consortium (2025): Screening for Alzheimer’s disease in the community using an AI-driven screening platform: design of the PREDICTOM study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100545
RIGHT-LATERALIZED CEREBELLAR CORTICAL THICKENING IS ASSOCIATED WITH MILD BEHAVIORAL IMPAIRMENT IN MILD COGNITIVE IMPAIRMENT
Sohee Kim, Young-Chul Jung, Eosu Kim, Keun You Kim, for the Alzheimer\'s Disease Neuroimaging Initiative
J Prev Alz Dis 2026;5(13)
Show summaryHide summaryBACKGROUND: Mild Behavioral Impairment (MBI) reflects later-life emergence of persistent neuropsychiatric symptoms and is increasingly recognized as an early manifestation of neurodegenerative disease, yet cerebellar correlates remain underexplored. We tested whether cerebellar morphometry is associated with incident MBI in mild cognitive impairment (MCI).
METHODS: Using longitudinal Alzheimer’s Disease Neuroimaging Initiative data, MBI was derived from Neuropsychiatric Inventory/ Neuropsychiatric Inventory-Questionnaire items mapped to five diagnostic domains and defined as new symptoms persisting for ≥2 consecutive visits after a symptom-free baseline. Of 530 MCI participants without baseline symptoms, 181 who developed MBI were matched 1:1 to controls by age, sex, and education. DeepCERES quantified lobular cerebellar cortical thickness and asymmetry from 3T T1-weighted MRI. We used logistic regression with false discovery rate correction and conducted domain-specific analyses (affective dysregulation, impulse dyscontrol, decreased motivation).
RESULTS: MBI cases had lower Mini Mental State Examination scores and higher dementia conversion than controls. Greater thickness in right cerebellar lobules IV (OR 1.215), V (OR 1.122), and VIIIB (OR 1.169), and greater asymmetry in right lobule V (OR 1.035), were associated with incident MBI. Affective dysregulation showed the strongest, largely right-lateralized associations and greater interhemispheric asymmetry. Main results were unchanged after separate sensitivity adjustments for Mini Mental State Examination scores and for index-visit psychiatric medication use.
CONCLUSION: Incident MBI in MCI is linked to right-lateralized cerebellar cortical thickening and asymmetry, most prominently for affective dysregulation. These patterns may reflect early compensatory and/or neuroinflammatory processes within cerebello–cortical circuits relevant to affect regulation.
CITATION:
Sohee Kim ; Young-Chul Jung ; Eosu Kim ; Keun You Kim ; for the Alzheimer's Disease Neuroimaging Initiative (2025): Right-lateralized cerebellar cortical thickening is associated with mild behavioral impairment in mild cognitive impairment. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100540
VISUOSPATIAL MEMORY DEFICIT, PLASMA P-TAU217, AND AΒ42/AΒ40 RATIO ENHANCE SENSITIVITY TO IDENTIFY AΒ PET POSITIVITY IN INDIVIDUALS WITH SCD
Qinjie Li, Lin Huang, Ying Wang, Yihui Guan, Fang Xie, Qihao Guo
J Prev Alz Dis 2026;5(13)
Show summaryHide summaryINTRODUCTION: We hypothesize that specific cognitive assessments and plasma biomarkers may exhibit heightened sensitivity during the stage of subjective cognitive decline (SCD). The integration of these plasma biomarkers and cognitive assessments could enhance the ability to predict beta-amyloid (Aβ) pathology in individuals with SCD.
METHODS: A total of 231 participants, including 74 normal controls (NC) and 157 SCD, underwent Aβ and tau PET scans and blood testing for Aβ40, Aβ42, p-tau181, p-tau217, NfL, and GFAP. Cognitive assessments, plasma biomarkers, tau PET SUVr, and demographics were compared between Aβ+ and Aβ− groups within NC and SCD. The least absolute shrinkage and selection operator (LASSO) and logistic regression were employed to perform variable selection and develop predictive models.
RESULTS: We observed significantly worse global cognition, visuospatial memory performance, executive function, and metamemory, as well as higher tau PET SUVr, elevated levels of p-tau217, p-tau181, and GFAP, and lower Aβ42/Aβ40 ratios in SCD Aβ+ compared to SCD Aβ-. The model incorporating BVMT-LD and p-tau217 achieved a slightly higher AUC than the model using p-tau217 and Aβ42/Aβ40 (0.94 vs. 0.93). Partial correlation analyses indicated that both auditory verbal memory (AVLT-LD) and visuospatial memory (BVMT-LD) were significantly negatively associated with p-tau217, whereas only AVLT-LD demonstrated a significant negative association with tau pathology severity.
CONCLUSION: Visuospatial memory deficit and plasma p-tau217 are powerful biomarkers for identifying Aβ+ in SCD. Auditory verbal memory links to tau pathology severity, while visuospatial memory is more sensitive to Aβ deposition, supporting early intervention to prevent AD progression.
CITATION:
Qinjie Li ; Lin Huang ; Ying Wang ; Yihui Guan ; Fang Xie ; Qihao Guo (2026): Visuospatial memory deficit, plasma p-tau217, and Aβ42/Aβ40 ratio enhance sensitivity to identify Aβ PET positivity in individuals with SCD. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100525
NEURONAL AUTOANTIBODIES IN NEURODEGENERATIVE DEMENTIA: FROM EVIDENCE TO CLINICAL FRAMEWORK
Heya Luan, Xiaodong Han, Chang Xu, Aidi Shan, Xin Wang, Shaoqi Li, Qi Yao, Tong Cui, Jinxuan Guo, Boye Wen, Yao Sun, Chuqiao Li, Qingyuan Sun, Cuibai Wei
J Prev Alz Dis 2026;5(13)
Show summaryHide summaryNeuronal autoantibodies, including against neuronal surface receptors or intracellular antigens, are established pathogenic mediators and therapeutic targets in autoimmune encephalitis (AIE) and paraneoplastic neurological syndromes (PNS). These antibodies are now increasingly reported in patients with clinically diagnosed neurodegenerative dementia, prompting re-evaluation of a neurodegenerative etiology. Within neurodegenerative trajectories, whether such antibodies act as pathogenic drivers, non-causal markers, or immune modulators remains unresolved, and heterogeneous cohorts, assays, and endpoints limit inference and clinical translation. This review integrates current research at the intersection of autoimmunity and neurodegeneration and highlights accumulating evidence for a biological continuum. This model suggests that antibody-mediated mechanisms may extend beyond acute inflammation, with sustained exposure contributing to time-dependent neurodegeneration. To facilitate clinical translation, we advance a standardized diagnostic workflow comprising three sequential stages: (i) a pretest-probability triage that defines high-risk constellations prompting antibody testing, stratifies patients accordingly; (ii) a specimen-and-assay pathway for standardized testing workflow and structured interpretation of results; and (iii) post-test integrated analysis to adjudicate pathogenic relevance based on phenotype-antibody concordance. By bridging observational research to clinical decision-making, the framework supports identification of an immunologically modulated neurodegenerative subtype with potential for therapeutic intervention, while reducing false positives and avoiding non-essential immunotherapy in low-probability contexts.
CITATION:
Heya Luan ; Xiaodong Han ; Chang Xu ; Aidi Shan ; Xin Wang ; Shaoqi Li ; Qi Yao ; Tong Cui ; Jinxuan Guo ; Boye Wen ; Yao Sun ; Chuqiao Li ; Qingyuan Sun ; Cuibai Wei (2026): Neuronal autoantibodies in neurodegenerative dementia: From evidence to clinical framework. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100515
INTEGRATIVE SMR PRIORITIZES OXIDATIVE STRESS–RELATED REGULATORY GENES FOR ALZHEIMER’S DISEASE WITH BRAIN-TISSUE VALIDATION
Liu Wu, Yu-Ting Dong, Xin Mu, Xiao Luo, Ze-Jun Chen
J Prev Alz Dis 2026;5(13)
Show summaryHide summaryOxidative stress (OS) plays a critical role in the pathogenesis of Alzheimer’s disease (AD), yet its genetic and epigenetic regulatory mechanisms remain unclear. In this study, we applied a three-step summary-based Mendelian randomization (SMR) framework to integrate Alzheimer’s disease (AD) GWAS summary statistics with peripheral-blood eQTL and mQTL datasets, and further evaluated brain-tissue relevance using GTEx v8 and AMP-AD resources. Across the three-step SMR analyses, we prioritized multiple OS-related candidate genes (e.g., CRLS1, PRKAA1, CYP2E1, GPX1, and APP) associated with AD risk, and brain-tissue analyses further highlighted KEAP1, SIRT1, and PRDX5 as region-relevant signals. Functional enrichment analyses highlighted critical pathways such as "Nrf2-mediated antioxidant response" and "PI3K-AKT signaling," emphasizing the roles of oxidative stress, mitochondrial function, and neuroinflammation in AD. Novel regulatory mechanisms were uncovered at methylation sites (e.g., cg20211653 associated with ABCA1), linking epigenetic regulation to transcriptional mechanisms and providing candidates for brain-tissue follow-up. This study provides new insights into the molecular underpinnings of AD, bridging genetic variation, epigenetic regulation, and transcription, and identifies potential therapeutic targets for mitigating oxidative damage and neurodegeneration.
CITATION:
Liu Wu ; Yu-Ting Dong ; Xin Mu ; Xiao Luo ; Ze-Jun Chen (2026): Integrative SMR prioritizes oxidative stress–related regulatory genes for Alzheimer’s disease with brain-tissue validation. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100535
LIVING ARRANGEMENTS AND COGNITIVE RESILIENCE IN AGING: UNRAVELING DISTINCT PATHWAYS THROUGH PLASMA BIOMARKERS
Yuanyuan Peng, Heqianxi Dong, Yu Luo, Wen Zhou, Lu Liu, Ming Chen, Na Liu, Jiwen Che, Feifei Hu, Yifeng Cheng, Xinyan Xie, Yan Zeng
J Prev Alz Dis 2026;5(13)
Show summaryHide summaryBACKGROUND: Global aging and changing family structures necessitate identifying modifiable factors for cognitive health. While social isolation is a known risk, the protective role of specific living arrangements and their interplay with neurobiology is unclear.
OBJECTIVES: This study aimed to: (1) examine the longitudinal association between living arrangements and cognitive function in older adults, and (2) investigate the potential moderating roles of plasma Alzheimer’s disease (AD) biomarkers in this relationship.
METHODS: Using data from the Hubei Memory and Aging Cohort Study, we followed 3403 older adults aged 65 years and above with different living arrangements. Participants underwent standardized cognitive assessments and plasma biomarker measurements, including amyloid-beta (Abeta) 40, Abeta 42, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau (p-tau) 181, and p-tau 217. Linear mixed-effects models were employed to analyze cognitive trajectories.
RESULTS: Compared to older adults living separately from their families, those in two specific living arrangements, living with a spouse only or in multigenerational living, demonstrated significantly better cognitive performance across multiple domains. These protective associations proved robust even after comprehensive adjustment for plasma AD biomarkers. Importantly, we found that higher plasma GFAP levels significantly attenuated the cognitive benefits conferred by favorable living arrangements. In a separate, distinct pathway, higher plasma Abeta40 levels were independently associated with better-preserved language function over time.
CONCLUSIONS: Favorable living arrangements may benefit cognitive health through pathways independent of typical AD pathology. Incorporating living arrangements and plasma biomarkers, particularly GFAP, could enhance risk assessment and targeted interventions for cognitive decline in older adults.
CITATION:
Yuanyuan Peng ; Heqianxi Dong ; Yu Luo ; Wen Zhou ; Lu Liu ; Ming Chen ; Na Liu ; Jiwen Che ; Feifei Hu ; Yifeng Cheng ; Xinyan Xie ; Yan Zeng (2026): Living arrangements and cognitive resilience in aging: unraveling distinct pathways through plasma biomarkers. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100536
MODIFIABLE LIFESTYLE FACTORS FOR DEMENTIA RISK IN AN ONLINE COHORT ASSESSED BY THE MOCA COGNITIVE HEALTH ASSESSMENT INDEX (MOCA-CHAI)
Laura Klaming, Hans-Aloys Wischmann, Murray Gillies, Ziad Nasreddine
J Prev Alz Dis 2026;5(13)
Show summaryHide summaryBACKGROUND: The growing prevalence of dementia highlights the need for a risk assessment tool that is accessible, facilitates the identification of at-risk individuals, and provides evidence-based guidance on how to reduce dementia risk.
OBJECTIVES: We developed, deployed, and evaluated the MoCA-CHAI, a self-administered, online dementia risk assessment for the general public. We provide a brief overview of its development, the self-enrolled population that has completed it, and a preliminary evaluation of its predictive performance.
METHODS: Drawing on the 2024 Lancet report, we developed the MoCA-CHAI translating the 14 identified risk factors into a questionnaire. We used the MoCA XpressO as a measure of cognitive impairment and a proxy measure for the probability of having or developing dementia.
FINDINGS: The MoCA-CHAI was completed by 3886 people. Based on their XpressO score, 11.3% showed a high probability of cognitive impairment. Using a logistic regression analysis, we found that each 1-point increase in MoCA-CHAI score decreases the odds of having cognitive impairment by 1%. Physical inactivity and exposure to air pollution are the most prevalent risk factors across the lifespan. Depression is more prevalent in young adults, while high cholesterol, hypertension, diabetes, and excessive alcohol consumption are more prevalent in middle-aged and older adults.
CONCLUSIONS: These findings demonstrate that the MoCA-CHAI provides insight into modifiable lifestyle factors and dementia risk. Differences in prevalences of risk factors indicate that prevention strategies need to be tailored to age-specific risk profiles. The MoCA-CHAI may help identify at-risk individuals who could benefit from targeted prevention and monitoring.
CITATION:
Laura Klaming ; Hans-Aloys Wischmann ; Murray Gillies ; Ziad Nasreddine (2025): Modifiable lifestyle factors for dementia risk in an online cohort assessed by the MoCA Cognitive Health Assessment Index (MoCA-CHAI). The Journal of Prevention of Alzheimer’s Disease (JPAD). Laura Klaming
LATE-LIFE BODY MASS INDEX AND AMYLOID INTERACTION ON COGNITIVE DECLINE IN UNIMPAIRED OLDER ADULTS
Wai-Ying Wendy Yau, Rema Raman, Jasmeer Chhatwal, Jeremy J. Pruzin, Zahra Shirzadi, Neelum Aggarwal, Adam M. Brickman, Petrice M. Cogswell, Jonathan Graff-Radford, Jay J. Pillai, Prashanthi Vemuri, Michael S. Rafii, Roy Yaari, Paul Aisen, Reisa Sperling, The A4 and LEARN Study Teams
J Prev Alz Dis 2026;5(13)
Show summaryHide summaryBACKGROUND: The late-life “obesity paradox” of reduced Alzheimer’s disease (AD) risk is postulated to be driven by underlying preclinical/prodromal pathology. However, few studies have directly examined the joint associations of BMI and amyloid pathology with cognitive decline, especially in individuals with preclinical AD targeted in prevention trials.
OBJECTIVE: To determine whether late-life BMI and amyloid pathology have independent or interactive associations with cognition in clinically unimpaired older adults.
DESIGN: Secondary analyses of A4 randomized clinical trial and the companion observational LEARN Study (median follow-up 4.7 years).
SETTING: Multicenter across 67 sites in US, Canada, Australia, and Japan.
PARTICIPANTS: We included 1663 participants (Placebo n = 582, Solanezumab n = 563, LEARN n = 518) who were baseline cognitively unimpaired and medically stable, mean age 71.5 ± 4.7 years, 60% women.
MEASUREMENTS: BMI and global amyloid burden [Florbetapir PET] were measured at baseline. Cognition was measured longitudinally using Preclinical Alzheimer Cognitive Composite.
RESULTS: Higher BMI and amyloid burden were independently associated with worse baseline cognition. Longitudinally, a BMI*Amyloid*Time interaction emerged: lower/normal BMI was associated with more favorable cognitive trajectory at low amyloid levels, but with faster cognitive decline when amyloid was substantially elevated.
CONCLUSIONS: Our cross-sectional findings support a negative association between obesity and cognitive aging up to late-life. Longitudinally, we observed an “obesity paradox”, where higher/obese BMI was associated with more favorable cognitive trajectories in the presence of advanced amyloid pathology. Together, our findings suggest that future trials targeting obesity to slow late-life cognitive decline may benefit from preferentially enrolling younger individuals or those without substantial amyloid accumulation.
CITATION:
Wai-Ying Wendy Yau ; Rema Raman ; Jasmeer Chhatwal ; Jeremy J. Pruzin ; Zahra Shirzadi ; Neelum Aggarwal ; Adam M. Brickman ; Petrice M. Cogswell ; Jonathan Graff-Radford ; Jay J. Pillai ; Prashanthi Vemuri ; Michael S. Rafii ; Roy Yaari ; Paul Aisen ; Reisa Sperling ; The A4 and LEARN Study Teams (2025): Late-life body mass index and amyloid interaction on cognitive decline in unimpaired older adults. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100543
VALIDATION OF A NOVEL COGNITIVE-FUNCTIONAL OUTCOME MEASURE OPTIMIZED FOR EARLY ALZHEIMER’S DISEASE: EVIDENCE FROM THE VIVA-MIND TRIAL
Jasmin A. Duehring, Diane M. Jacobs, David P. Salmon, Andrew J. MacKelfresh, Carolyn Revta, Antje Meyer, Michael Schaeffer, Sylvia Schell-Mader, Tanja Wassmann, Christine Wenzkowski, Howard H. Feldman, Steven D. Edland, ADCS VIVA-MIND Study Group
J Prev Alz Dis 2026;5(13)
Show summaryHide summaryBACKGROUND: Cognitive-functional composite measures are increasingly used as primary efficacy endpoints in early Alzheimer’s disease (AD) trials, where greater sensitivity to decline can improve trial efficiency and reduce sample size requirements.
OBJECTIVES: To compare sensitivity to decline of the Cognitive Functional Component 2 (CFC2), a novel cognitive-functional composite measure described by Raghavan et al. (2013), against the Clinical Dementia Rating - Sum of Boxes (CDR-SB) and other standard cognitive and functional outcomes including MMSE, FAQ, ADAS Cog 13 and ADCOMS using prospective randomized clinical trial data.
DESIGN: The VIVA-MIND trial was a phase 2A/2B randomized controlled trial investigating the safety and efficacy of varoglutamstat in patients with mild cognitive impairment and mild dementia due to AD.
SETTING: The VIVA-MIND trial was conducted between 2021–2024. It was prematurely terminated in mid-2024 by the study sponsor.
PARTICIPANTS: This secondary analysis uses data from 98 participants in the modified intention-to-treat population from the VIVA-MIND trial with complete neuropsychological test data.
MEASUREMENTS: Standard power calculations informed by parameters estimated from linear mixed-effects models were used to determine the relative efficiency of outcome measures.
RESULTS: The CFC2 was more sensitive to decline than the CDR-SB in this population. Use of the CFC2 would yield a 15% reduction in required sample size relative to the CDR-SB. Application of an optimal weighting scheme further improved the sensitivity of the CFC2.
CONCLUSIONS: Practically significant differences in the efficiency of clinical trials in early AD may be realized by the choice of clinical outcome measure and weighting scheme. Although further verification is needed, we replicate a previous finding that the CFC2 may outperform the CDR-SB in the early AD population.
CITATION:
Jasmin A. Duehring ; Diane M. Jacobs ; David P. Salmon ; Andrew J. MacKelfresh ; Carolyn Revta ; Antje Meyer ; Michael Schaeffer ; Sylvia Schell-Mader ; Tanja Wassmann ; Christine Wenzkowski ; Howard H. Feldman ; Steven D. Edland ; ADCS VIVA-MIND Study Group (2026): Validation of a novel cognitive-functional outcome measure optimized for early Alzheimer’s Disease: Evidence from the VIVA-MIND trial. The Journal of Prevention of Alzheimer’s Disease (JPAD).https://doi.org/10.1016/j.tjpad.2026.100531
LETTER TO THE EDITOR: DONANEMAB THERAPY IN ALZHEIMER’S DISEASE WITH MILD COGNITIVE IMPAIRMENT: CONVERGENT AMYLOID, TAU, AND PLASMA BIOMARKER NORMALIZATION WITH COGNITIVE IMPROVEMENT
Limoran Tang, Yun Xu, Hui Zhao
J Prev Alz Dis 2026;5(13)
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CITATION:
Limoran Tang ; Yun Xu ; Hui Zhao (): Letter to the Editor: Donanemab therapy in Alzheimer’s disease with mild cognitive impairment: Convergent amyloid, tau, and plasma biomarker normalization with cognitive improvement. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100533