05/2025 journal articles
EDITORIAL: ARE APPROPRIATE USE RECOMMENDATIONS USEFUL IN CLINICAL PRACTICE?
Serge Gauthier
J Prev Alz Dis 2025;5(12)
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CITATION:
Serge Gauthier (2025): Are Appropriate Use Recommendations useful in clinical practice?. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100165
DONANEMAB: APPROPRIATE USE RECOMMENDATIONS
G.D. Rabinovici, D.J. Selkoe, S.E. Schindler, P. Aisen, L.G. Apostolova, A. Atri, S.M. Greenberg, S.B. Hendrix, R.C. Petersen, M. Weiner, S. Salloway, J. Cummings
J Prev Alz Dis 2025;5(12)
Show summaryHide summaryDonanemab (Kisunla®), an IgG1 monoclonal antibody targeting N-terminal pyroglutamate-modified forms of amyloid-β, is approved in the United States for treatment of early symptomatic Alzheimer's disease (AD). Appropriate Use Recommendations (AUR) were developed to guide the implementation of donanemab in real-world practice, prioritizing safety considerations and opportunity for effectiveness. The AUR were developed by the AD and Related Disorders Therapeutic Workgroup by consensus, integrating available data and expert opinion. Appropriate candidates for donanemab treatment include persons with mild cognitive impairment or mild dementia due to AD (Clinical Stages 3–4, MMSE 20–30) who have biomarker confirmation of AD pathology by PET or CSF. Tau PET is not required for eligibility. Apolipoprotein E (APOE) genotyping should be performed prior to treatment to inform an individual's risk of developing Amyloid-Related Imaging Abnormalities (ARIA). Pre-treatment MRI should be obtained no more than 12 months prior to treatment. Patients with findings of >4 cerebral microbleeds, cortical superficial siderosis or a major vascular contribution to cognitive impairment should be excluded from treatment. The decision to initiate therapy should be grounded in a shared decision-making process that emphasizes the patient's values and goals of care. Donanemab is administered as a monthly intravenous infusion. Surveillance MRIs to evaluate for ARIA should be performed prior to the 2nd, 3rd, 4th and 7th infusions, prior to the 12th dose in higher risk individuals, and at any time ARIA is suspected clinically. Clinicians may consider discontinuing treatment if amyloid clearance is demonstrated by amyloid PET, typically obtained 12–18 months after initiating treatment.
CITATION:
G.D. Rabinovici ; D.J. Selkoe ; S.E. Schindler ; P. Aisen ; L.G. Apostolova ; A. Atri ; S.M. Greenberg ; S.B. Hendrix ; R.C. Petersen ; M. Weiner ; S. Salloway ; J. Cummings (2025): Donanemab: Appropriate use recommendations. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100150
DISTINCT TRAJECTORIES OF SUBJECTIVE COGNITIVE DECLINE BEFORE DIAGNOSIS OF NEUROCOGNITIVE DISORDERS: LONGITUDINAL MODELLING OVER 18 YEARS
Tau Ming Liew, Tau Ming Liew
J Prev Alz Dis 2025;5(12)
Show summaryHide summaryBACKGROUND: Subjective cognitive decline (SCD) is an established predictor of neurocognitive disorders (NCD) (i.e. mild cognitive impairment and dementia). Yet, its construct remains contentious. Many individuals with SCD do not progress to NCD, leading to an alternative term in the literature – ‘functional cognitive disorders’ – to describe the SCD experience in these individuals.
OBJECTIVES: To examine the distinct differences in trajectories of SCD between those who did and did not eventually develop NCD.
DESIGN: Case-control study.
SETTING: Alzheimer's Disease Centers across USA.
PARTICIPANTS: A total of 5,167 participants aged ≥50 years were followed up near-annually to evaluate for SCD and NCD (median follow-up=8.1 years; range=1.0–18.0). Cases were defined as those who developed incident NCD during follow-up; controls completed ≥10 years of follow-up and had normal cognition throughout follow-up period.
MEASUREMENTS: SCD was evaluated with a yes/no question based on “perceived decline in memory relative to previously attained abilities”. The trajectories of SCD were modelled with mixed-effect logistic regression, using a backward timescale.
RESULTS: Those who developed NCD (cases) had new onset of SCD within past 20 years, which became particularly noticeable 13–14 years before diagnosis, and became even more evident in the last 4 years. Those who did not develop NCD (controls) reported SCD since younger age, with the probability of SCD remaining constant over time. The distinctive trajectories were consistent across Alzheimer's and non-Alzheimer's disease, and among those with higher baseline rates of SCD due to psychiatric conditions.
CONCLUSIONS: SCD exhibits distinctive trajectories among those who do and do not progress to NCD. These distinctive trajectories can inform NCD risk for early interventions, and guide public health messaging to distinguish high-risk SCD from normal ageing. Future SCD scales may possibly need to evaluate symptom changes over a longer, 20-year horizon to better capture the new onset of SCD within this longer timeframe.
CITATION:
Tau Ming Liew (2025): Distinct trajectories of subjective cognitive decline before diagnosis of neurocognitive disorders: Longitudinal modelling over 18 years. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100123
CLARITY AD: ASIAN REGIONAL ANALYSIS OF A PHASE III TRIAL OF LECANEMAB IN EARLY ALZHEIMER\'S DISEASE
Christopher Chen, Sadao Katayama, Jae-Hong Lee, Jun-Young Lee, Masaki Nakagawa, Kentaro Torii, Tomoo Ogawa, Amitabh Dash, Michael Irizarry, Shobha Dhadda, Michio Kanekiyo, Steve Hersch, Takeshi Iwatsubo
J Prev Alz Dis 2025;5(12)
Show summaryHide summaryBACKGROUND: Across Asia, Alzheimer's disease prevalence is expected to rise dramatically due to, among other factors, rapidly aging populations. Alzheimer's disease pathology is triggered by the accumulation of soluble and insoluble aggregated Aβ peptides (oligomers, protofibrils, and fibrils). Lecanemab is a recently approved humanized IgG1 monoclonal antibody that preferentially targets soluble aggregated Aβ species (oligomers, protofibrils), with activity at insoluble fibrils. In the recent 18-month phase 3 Clarity AD study, lecanemab demonstrated a consistent slowing of decline in clinical (global, cognitive, functional, and quality of life) outcomes, and reduction in brain amyloid in early Alzheimer's disease. Lecanemab was well tolerated in Clarity AD, with an increase in incidence of infusion related reactions and amyloid-related imaging abnormalities (ARIA) versus placebo.
OBJECTIVES: The objective of this manuscript is to present the results for the Asian region population of Clarity AD.
DESIGN: The core Clarity AD study was an 18-month, multicenter, double-blind, placebo-controlled, parallel-group study.
SETTING: Academic and clinical centers in Asia.
PARTICIPANTS: A total of 294 individuals with early Alzheimer's disease (i.e., mild cognitive impairment or mild Alzheimer's disease).
INTERVENTION: Eligible patients were randomized across 2 treatment groups (placebo and lecanemab 10 mg/kg biweekly) according to a fixed 1:1 schedule.
MEASUREMENTS: The primary efficacy endpoint in the core study was change in the Clinical Dementia Rating-Sum-of-Boxes (CDR-SB) from baseline at 18 months. Key secondary endpoints included change from baseline at 18 months in amyloid PET Centiloids (in patients participating in the amyloid PET sub-study), AD COMposite Score (ADCOMS) and AD Assessment Scale-Cognitive Subscale 14 (ADAS-Cog14). Safety was monitored throughout the study in a blinded manner by the sponsor and in an unblinded manner by an independent data safety monitoring committee.
RESULTS: Of the total of 1795 subjects randomized in Clarity AD, 294 subjects were in the Asian region (Japan:152; Korea:129; Singapore:13). The efficacy of lecanemab was consistent with the overall population. For the primary endpoint, there was a slowing of decline with lecanemab in the CDR-SB at 18 months compared to placebo in the Asian region (adjusted mean difference: -0.349; 95 % confidence intervals: -0.773, 0.076; 24 % slowing of decline). Results for the secondary efficacy endpoints also favored lecanemab versus placebo in Asians. Lecanemab was well tolerated in Asian subjects, with a safety profile in Asian subjects similar to the overall Clarity AD population. The most common adverse events of special interest were ARIA-H (lecanemab:14.4 %; placebo:16.2 %), ARIA-E (lecanemab:6.2 %; placebo:1.4 %), and infusion-related reactions (lecanemab:12.3 %; placebo:1.4 %). Incidence of adverse events leading to study drug dose interruption or withdrawal, infusion-related reactions, ARIA-E and ARIA-H was lower for the lecanemab treated group in the Asian region relative to the overall Clarity AD population. Results from quality of life and biomarker assessments in the Asia region were also generally similar to the overall Clarity AD population.
CONCLUSION: In the Clarity AD Asian region cohort, the overall efficacy, biomarker changes and safety profile of lecanemab were consistent with the overall population, with a favorable risk-benefit profile and manageable risks. ARIA events and infusion-related reactions occurred less commonly with lecanemab in the Asian region subgroup than the overall population.
CITATION:
Christopher Chen ; Sadao Katayama ; Jae-Hong Lee ; Jun-Young Lee ; Masaki Nakagawa ; Kentaro Torii ; Tomoo Ogawa ; Amitabh Dash ; Michael Irizarry ; Shobha Dhadda ; Michio Kanekiyo ; Steve Hersch ; Takeshi Iwatsubo (2025): Clarity AD: Asian regional analysis of a phase III trial of lecanemab in early Alzheimer's disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100160
HEALTHY DIETARY PATTERNS IN RELATION TO COGNITIVE PERFORMANCE AND ALZHEIMER\'S DISEASE MORTALITY
Yiying Gong, Hui Chen, Yuxuan Gu, Jie Shen, Ting Shen, Yihong Ding, Mengxi Lu, Liyan Huang, Minqing Yan, Peige Song, Yajie Zhu, Shuang Rong, Changzheng Yuan
J Prev Alz Dis 2025;5(12)
Show summaryHide summaryBACKGROUND: Dietary factors play a major role in cognitive aging, but few studies have assessed and compared the associations between specific dietary patterns and Alzheimer's disease (AD) mortality.
METHODS: We included 27,773 U.S. participants (mean age = 59.8 years, 51.4 % female) from the National Health and Nutrition Examination Survey (NHANES) between 1998 and 2016, with follow-up for AD mortality until December 2019. Five dietary pattern scores were calculated utilizing one (1999–2002) or two repeated (2003–2016) 24hr dietary recalls, including the Healthy Eating Index (HEI-2015), the healthful plant-based diet index (hPDI), the alternate Mediterranean diet (aMED), the Dietary Approach to Stop Hypertension diet (DASH), and the Mediterranean-DASH Intervention for Neurodegeneration Delay diet (MIND) scores. We utilized Cox proportional hazard models to evaluate the associations of these dietary pattern scores with AD mortality.
RESULTS: A total of 260 AD deaths occurred during a median follow-up of 9.8 years. Higher aMED score was associated with a lower risk of AD mortality (HRT3 vs T1: 0.72, 95 % CI, 0.52–1.00, p-trend = 0.041). In a sub-sample of 2,713 participants in NHANES 2011-2014, 432 individuals had prevalent psychometric mild cognitive impairment (p-MCI). Higher aMED, MIND, HEI-2015, and hPDI were associated with lower odds of p-MCI. The potential contributors to these associations included higher intake levels of vegetables and nuts, moderate alcohol consumption, and lower intake level of sweets.
CONCLUSIONS: The Mediterranean dietary pattern was associated with more favorable cognitive outcomes among middle-aged and older adults, underscoring the importance of a healthy diet for long-term benefits in cognitive and brain health.
CITATION:
Yiying Gong ; Hui Chen ; Yuxuan Gu ; Jie Shen ; Ting Shen ; Yihong Ding ; Mengxi Lu ; Liyan Huang ; Minqing Yan ; Peige Song ; Yajie Zhu ; Shuang Rong ; Changzheng Yuan (2025): Healthy dietary patterns in relation to cognitive performance and Alzheimer's disease mortality. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100100
BRAIN HEALTH SERVICES FOR THE SECONDARY PREVENTION OF COGNITIVE IMPAIRMENT AND DEMENTIA: OPPORTUNITIES, CHALLENGES, AND THE BUSINESS CASE FOR EXISTING AND FUTURE FACILITIES
Giovanni B. Frisoni, Federica Ribaldi, Gilles Allali, Théophile Bieth, Andrea Brioschi Guevara, Stefano Cappa, Lisa Cipolotti, Kristian Steen Frederiksen, Jean Georges, Frank Jessen, Giacomo Koch, Hugh Masters, Augusto J. Mendes, Lutz Frölich, Valentina Garibotto, Oriol Grau-Rivera, Federico E. Pozzi, Dorota Religa, Ayda Rostamzadeh, Lenny Shallcross, Susan D. Shenkin, Wiesje M. van der Flier, Meike W. Vernooij, Leonie N.C. Visser, Jeffrey L. Cummings, Philip Scheltens, Bruno Dubois, Elena Moro, Claudio L.A. Bassetti, Miia Kivipelto
J Prev Alz Dis 2025;5(12)
Show summaryHide summaryA European Task Force has recently developed and published the concept and protocols for the setup of the innovative health offer of Brain Health Services for the secondary prevention of dementia and cognitive impairment (dBHS). dBHS are outpatient health care facilities where adult persons can find an assessment of their risk of developing cognitive impairment and dementia, have their risk level and contributing factors communicated using appropriate language supported by adequate communication tools, can decide to participate to programs for personalized risk reduction if at higher risk, and benefit from cognitive enhancement interventions. This health offer is distinct from that of currently active memory clinics. The ultimate aim of dBHS is to extend healthy life, free from cognitive impairment. Here, we (i) discuss the pertinent opportunities and challenges for those persons who want to benefit from dBHS, professionals, and wider society, (ii) describe the concepts, protocols, organizational features, and patient journeys of some currently active dBHS in Europe, and (iii) argue in favor of the business case for dBHS in Europe.
CITATION:
Giovanni B. Frisoni ; Federica Ribaldi ; Gilles Allali ; Théophile Bieth ; Andrea Brioschi Guevara ; Stefano Cappa ; Lisa Cipolotti ; Kristian Steen Frederiksen ; Jean Georges ; Frank Jessen ; Giacomo Koch ; Hugh Masters ; Augusto J. Mendes ; Lutz Frölich ; Valentina Garibotto ; Oriol Grau-Rivera ; Federico E. Pozzi ; Dorota Religa ; Ayda Rostamzadeh ; Lenny Shallcross ; Susan D. Shenkin ; Wiesje M. van der Flier ; Meike W. Vernooij ; Leonie N.C. Visser ; Jeffrey L. Cummings ; Philip Scheltens ; Bruno Dubois ; Elena Moro ; Claudio L.A. Bassetti ; Miia Kivipelto (2025): Brain health services for the secondary prevention of cognitive impairment and dementia: Opportunities, challenges, and the business case for existing and future facilities. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100098
CARDIOVASCULAR-KIDNEY-METABOLIC SYNDROME AND INCIDENCE OF DEMENTIA AMONG OLDER ADULTS
Xiaqing Jiang, Amber L. Bahorik, Christina S. Dintica, Kristine Yaffe
J Prev Alz Dis 2025;5(12)
Show summaryHide summaryBACKGROUND: Cardiovascular-Kidney-Metabolic Syndrome (CKM) has profound impacts on cardiovascular events and mortality, yet its association with dementia risk remains poorly understood.
OBJECTIVES: To investigate associations between CKM and dementia risk.
DESIGN: The prospective cohort study is within the Health, Aging, and Body Composition study, which enrolled participants from 1997 to 1998, with a 15-year follow-up for incident dementia.
SETTING: The population-based study took place in two US communities in Memphis, Tennessee, and Pittsburgh, Pennsylvania.
PARTICIPANTS: Of the 3,075 participants aged 70 to 79 years initially enrolled, 14 were excluded for lacking baseline cognitive assessment, 308 for baseline cognitive impairment, 4 for missing follow-up, and 108 for missing CKM data, resulting in 2,641 in the analysis.
MEASUREMENTS: CKM staging, as defined recently by the American Heart Association framework, was based on constructs comprising dysfunctional adiposity, metabolic risk factors, chronic kidney disease (CKD), and cardiovascular disease (CVD). Dementia was identified using hospital records, prescriptions for dementia medication, and a test of global cognition. Adjusted Cox and Fine-Gray proportional hazards models were used to estimate dementia risk and account for competing risk of death.
RESULTS: The 2,641 participants had a mean (SD) age of 74 (2.8) years at baseline; 53 % were female, 36 % were of Black race, and had a range of baseline CKM: 3 % Stage 0 (no CKM), 4 % Stage 1 (excess/dysfunctional adiposity), 26 % Stage 2 (metabolic risk factors), 24 % Stage 3 (subclinical CVD and CKD), and 43 % Stage 4 (clinical CVD and CKD). Compared to participants with CKM Stages 0–2, those with CKM Stages 3–4 had a 50 % increase in dementia risk (hazard ratio 1.50, 95 % CI 1.20 to 1.86) in the fully adjusted model. The association remained significant after additional adjustment for metabolic risk factors, CVD, and CKD, both separately and together. Accounting for competing risk of death yielded similar results.
CONCLUSIONS: Among community-dwelling older adults, advanced CKM is associated with an increased risk of dementia. Older adults with CKM may need to be followed closely for adverse cognitive outcomes, and modifiable risk factors should be managed proactively.
CITATION:
Xiaqing Jiang ; Amber L. Bahorik ; Christina S. Dintica ; Kristine Yaffe (2025): Cardiovascular-kidney-metabolic syndrome and incidence of dementia among older adults. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100112
COMPARATIVE EFFICACY AND SAFETY OF ANTIDIABETIC AGENTS IN ALZHEIMER\'S DISEASE: A NETWORK META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Zixin Cai, Jiaxin Zhong, Guanghui Zhu, Jingjing Zhang
J Prev Alz Dis 2025;5(12)
Show summaryHide summaryBACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited treatment options. Emerging evidence suggests that antidiabetic agents may offer neuroprotective effects by targeting shared pathophysiological mechanisms such as insulin resistance and neuroinflammation. However, the comparative efficacy, and safety of these agents in the treatment of AD remain unclear.
OBJECTIVES: This study aimed to systematically evaluate and compare the efficacy and safety of antidiabetic agents for improving cognitive outcomes, reducing amyloid-β (Aβ) deposition, and managing adverse effects in patients with AD, using a network meta-analysis of randomized controlled trials (RCTs).
METHODS: A comprehensive literature search was conducted across multiple databases to identify RCTs examining the effects of antidiabetic agents in patients with AD. The primary outcomes included cognitive performance (e.g., MMSE scores), Aβ deposition (measured via CSF biomarkers), and safety/adverse effects. A network meta-analysis was performed to integrate direct and indirect evidence, ranking interventions using Surface Under the Cumulative Ranking (SUCRA) probabilities. Risk of bias was assessed using the Cochrane risk-of-bias tool.
RESULTS: A total of 26 studies, involving 7,361 participants, were included in the analysis. The interventions evaluated included insulin detemir (both low-dose and high-dose), liraglutide, exenatide, metformin, and pioglitazone. Both low-dose insulin detemir (mean difference: 2.10, 95 % CI: 1.04 to 3.15), high-dose insulin detemir (mean difference: 1.40, 95 % CI: -0.07 to 2.88), exenatide (mean difference: 1.19, 95 % CI: 0.06 to 2.32), and metformin combined with exenatide (mean difference: 1.06, 95 % CI: -1.68 to 3.80) showed cognitive improvements compared to placebo. Among these, low-dose insulin detemir demonstrated the most significant improvement. In terms of reducing Aβ deposition, metformin ranked highest in effectiveness, with the highest SUCRA score (84.6), followed by high-dose insulin detemir (SUCRA: 54.1). Low-dose insulin detemir (SUCRA: 51.1) also demonstrated moderate efficacy. Low-dose insulin detemir showed some reduction in Aβ deposition (mean difference: -0.31, 95 % CI: -2.82 to 2.20), although statistical significance was limited. Liraglutide exhibited the highest rate of study treatment withdrawal (mean difference: 1.97, 95 % CI: -0.07 to 4.00), while pioglitazone demonstrated the lowest withdrawal rates (mean difference: 0.07, 95 % CI: -0.03 to 0.17).
CONCLUSIONS: This network meta-analysis provides valuable insights into the comparative efficacy and safety of antidiabetic agents in AD. Low-dose insulin detemir demonstrated the most significant cognitive improvement and a moderate effect on reducing Aβ deposition. Metformin emerged as the most effective agent for reducing Aβ levels, though its effects on cognitive function were less pronounced. Safety profiles varied, with liraglutide associated with the highest rate of treatment withdrawals, while pioglitazone demonstrated the lowest incidence of treatment-related discontinuations. These findings support the potential use of antidiabetic agents, particularly insulin detemir, as a therapeutic option for AD, although further studies are needed to confirm their long-term benefits and safety.
CITATION:
Zixin Cai ; Jiaxin Zhong ; Guanghui Zhu ; Jingjing Zhang (2025): Comparative efficacy and safety of antidiabetic agents in Alzheimer's disease: A network meta-analysis of randomized controlled trials. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100111
ASSOCIATION OF DIETARY FATTY ACIDS WITH LONGITUDINAL CHANGE IN PLASMA-BASED BIOMARKERS OF ALZHEIMER\'S DISEASE
Serena S. Hoost, Lawrence S. Honig, Min Suk Kang, Aanya Bahl, Annie J. Lee, Danurys Sanchez, Dolly Reyes-Dumeyer, Rafael A. Lantigua, Jeffrey L. Dage, Adam M. Brickman, Jennifer J. Manly, Richard Mayeux, Yian Gu
J Prev Alz Dis 2025;5(12)
Show summaryHide summaryBACKGROUND: Elevated intake of omega-3 polyunsaturated fatty acids is linked to a reduced risk of dementia in some prospective studies. However, few studies have examined the relationship between nutrient intake and plasma biomarkers of Alzheimer's disease.
OBJECTIVES: We explored whether omega-3, omega-6, and monounsaturated fat intakes were associated with changes in plasma biomarkers of Alzheimer's disease over time.
DESIGN: The Washington Heights-Inwood Columbia Aging Project is a prospective cohort study (1994–2021); the data set used here includes a mean follow-up of 7.0 years.
SETTING: Community-based in New York City.
PARTICIPANTS: 599 dementia-free individuals at baseline who completed a 61-item food frequency questionnaire and had biomarkers measured in plasma from at least two different time points.
MEASUREMENTS: Fatty acid intake tertiles were computed from participant-completed 61-item Willett semi-quantitative food frequency questionnaires (Channing Laboratory, Cambridge, Massachusetts) obtained once at their baseline visit. Plasma-based biomarker assays were performed, using the single molecule array technology Quanterix Simoa HD-X platform, at baseline and follow-up visits. Generalized Estimating Equations (GEE) models were used to evaluate the association between baseline nutrient intake tertile and changes in biomarkers including phospho-tau181, amyloid-beta 42/40 ratio, phospho-tau181/amyloid-beta42 ratio, glial fibrillary acidic protein, neurofilament light chain, and two biomarker patterns derived from Principal Component Analysis (PCA1 and PCA2), with higher scores indicating a high level of neurodegeneration and low level of Alzheimer's disease burden, respectively). Models were adjusted for age, sex, race/ethnicity, education, and calculated total energy intake initially, and additionally for cerebrovascular risk factors.
RESULTS: Higher baseline omega-3 intake tertile was associated with lesser decline in PCA2 (β = 0.221, p < 0.001) and amyloid-beta 42/40 ratio (β = 0.022, p = 0.003), and a lesser rise in phospho-tau181 (β = -0.037, p = 0.001). Higher omega-6 intake tertile was linked to a lesser rise in phospho-tau181 (β = -0.050, p < 0.001) and glial fibrillary acidic protein (β = -0.028, p = 0.002). Most associations persisted after adjusting for cardiovascular risk factors.
CONCLUSIONS: Higher relative baseline intake of omega-3 and omega-6 fatty acids is associated with lesser progression of blood-based biomarkers of Alzheimer's disease. Consuming healthy fatty acids may help prevent accumulation of Alzheimer's disease-related pathological changes.
CITATION:
Serena S. Hoost ; Lawrence S. Honig ; Min Suk Kang ; Aanya Bahl ; Annie J. Lee ; Danurys Sanchez ; Dolly Reyes-Dumeyer ; Rafael A. Lantigua ; Jeffrey L. Dage ; Adam M. Brickman ; Jennifer J. Manly ; Richard Mayeux ; Yian Gu (2025): Association of dietary fatty acids with longitudinal change in plasma-based biomarkers of Alzheimer's disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100117
FEASIBILITY AND ACCEPTABILITY OF REMOTE APOE-GENOTYPING AMONG RESEARCH VOLUNTEERS OF AN ONLINE RECRUITMENT REGISTRY (THE DUTCH BRAIN RESEARCH REGISTRY)
L. Waterink, S.J. van der Lee, D. Nijland, F.I. van der Zee, L.N.C. Visser, Y.A.L. Pijnenburg, S.A.M. Sikkes, W.M. van der Flier, M.D. Zwan
J Prev Alz Dis 2025;5(12)
Show summaryHide summaryBACKGROUND: Participant recruitment for preclinical Alzheimer's disease (AD) prevention studies is challenging. Online registries facilitate large scale prescreening of individuals at risk for AD to accelerate recruitment. APOE-prescreening has the potential to better identify at-risk individuals. This study investigated the feasibility and acceptability of at-home APOE-genotyping in cognitively-normal registrants of an online registry.
METHODS: We invited 9,287 cognitively-normal registrants of Dutch Brain Research Registry (DBRR) aged 50 to 75 for at-home APOE-genotype testing, without receiving the results. Feasibility was measured by participation ratio (participation/interested), swab-return ratio (returned-swabs/participation), and genotyping-success ratio (analyzed swabs/returned swabs). Acceptability was measured with online questions about information provision and project scope. We explored prescreening questions potentially reducing screen-failures.
RESULTS: Feasibility was high with an 0.89 participation ratio (2,886/3,251), 0.90 swab-return ratio (2,886/2,597), 0.99 genotyping-success ratio (2,558/2,597). Acceptability was high, as participants were content with the information provision (87 %-97 %, n = 1,709–1,894), which was also well understood (91 %-93 %, n = 1,772–1,802). Among successful-analyzed swabs (n = 2,558), 27 % participants were APOE-ε4 heterozygote (n = 703), and 2 % homozygote (n = 60). Prescreening on a positive family history leads to a third reduction in the number of invitations needed to identify one APOE-ε4 carrier.
CONCLUSION: Our results suggest that APOE-ɛ4 genotyping in participants of an online research registry is feasible, well received and could be used to prescreen individuals at risk for AD for prevention studies. Adding a positive family history before invitation for APOE-genotyping, would further improve the prescreening process and reduce screen failures when identifying carriers.
CITATION:
L. Waterink ; S.J. van der Lee ; D. Nijland ; F.I. van der Zee ; L.N.C. Visser ; Y.A.L. Pijnenburg ; S.A.M. Sikkes ; W.M. van der Flier ; M.D. Zwan ; (2025): Feasibility and acceptability of remote APOE-genotyping among research volunteers of an online recruitment registry (The Dutch Brain Research Registry). The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100099
MACHINE LEARNING TO DETECT ALZHEIMER\'S DISEASE WITH DATA ON DRUGS AND DIAGNOSES
Johanna Wallensten, Caroline Wachtler, Nenad Bogdanovic, Anna Olofsson, Miia Kivipelto, Linus Jönsson, Predrag Petrovic, Axel C. Carlsson
J Prev Alz Dis 2025;5(12)
Show summaryHide summaryBACKGROUND: Integrating machine learning with medical records offers potential for early detection of Alzheimer's disease (AD), enabling timely interventions.
OBJECTIVES: This study aimed to evaluate the effectiveness of machine learning in constructing a predictive model for AD, designed to predict AD with data up to three years before diagnosis. Using clinical data, including prior diagnoses and medical treatments, we sought to enhance sensitivity and specificity in diagnostic procedures. A second aim was to identify the most important factors in the machine learning models, as these may be important predictors of AD.
DESIGN: The study employed Stochastic Gradient Boosting, a machine learning method, to identify diagnoses predictive of AD using primary healthcare data. The analyses were stratified by sex and age groups.
SETTING: The study included individuals within Region Stockholm, Sweden, using medical records from 2010 to 2022.
PARTICIPANTS: The study analyzed clinical data for individuals over the age of 40. Patients with an AD diagnosis (ICD-10-SE codes F00 or G30) during 2010–2012 were excluded to ensure prospective modeling. In total, AD was identified in 3,407 patients aged 41–69 years and 25,796 patients aged over 69.
MEASUREMENTS: The machine learning model ranked predictive diagnoses, with performance assessed by the area under the receiver operating characteristic curve (AUC). Known and novel predictors were evaluated for their contribution to AD risk.
RESULTS: AUC values ranged from 0.748 (women aged 41–69) to 0.816 (women over 69), with men across age groups falling within this range.
Sensitivity and specificity ranged from 0.73 to 0.79 and 0.66 to 0.79, respectively, across age and gender groups. Negative predictive values were consistently high (≥0.954), while positive predictive values were lower (0.199–0.351).
Additionally, we confirmed known risk factors as predictors and identified novel predictors that warrant further investigation. Key predictors included medical observations, cognitive symptoms, antidepressant treatment, visit frequency, and vitamin B12/folic acid treatment.
CONCLUSIONS: Machine learning applied to clinical data shows promise in predicting AD, with robust model performance across age and sex groups. The findings confirmed known risk factors, such as depression and vitamin B12 deficiency, while also identifying novel predictors that may guide future research. Clinically, this approach could enhance early detection and risk stratification, facilitating timely interventions and improving patient outcomes.
CITATION:
Johanna Wallensten ; Caroline Wachtler ; Nenad Bogdanovic ; Anna Olofsson ; Miia Kivipelto ; Linus Jönsson ; Predrag Petrovic ; Axel C. Carlsson (2025): Machine learning to detect Alzheimer's disease with data on drugs and diagnoses. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100115
THE ASSOCIATIONS BETWEEN FRESH VEGETABLE AND FRUIT CONSUMPTION AND PLASMA AND PET BIOMARKERS IN PRECLINICAL ALZHEIMER\'S DISEASE: A CROSS-SECTIONAL AND LONGITUDINAL STUDY OF CHINESE POPULATION
Heling Chu, Chuyi Huang, Fang Xie, Qihao Guo
J Prev Alz Dis 2025;5(12)
Show summaryHide summaryBACKGROUND: The identification of the modifiable lifestyle factors including dietary habits in older adults of preclinical Alzheimer's disease (AD) and early effective interventions are of great importance.
OBJECTIVES: We studied whether the consumption of fresh vegetables and fruits was different between cognitively unimpaired (CU) and cognitively impaired (CI) population and mainly investigated the associations between vegetable and fruit consumption and PET and plasma AD biomarkers in older CU adults with higher β-amyloid (Aβ) burden.
DESIGN, SETTING, AND PARTICIPANTS: Older adults with the age of 50–85 years were enrolled for a cross-sectional and longitudinal study. The groups depended on whether the participants were CU or CI. Partial participants whose habits remained unchanged were followed up.
MEASUREMENTS: The consumption data of vegetables and fruits were collected using a validated self-reported questionnaire. We mainly investigated the associations between vegetable and fruit consumption and various biomarkers in CU participants with positive 18F-florbetapir PET scan (Aβ-PET), part of whom also underwent plasma AD biomarkers tests and 18F-MK6240 PET scan (tau-PET). Correlation and multiple linear regression analyses were used to investigate the associations between vegetable and fruit consumption and AD biomarkers.
RESULTS: A total of 1433 participants were enrolled, of which CU accounted for 49.4 %. Most of the intake habits of vegetables and fruits was different between CU and CI participants. 177 CU participants with Aβ-PET positive were selected for the following study. Multiple linear regression analysis showed higher consumption of fresh vegetables (>200 g/d), dark vegetables (>100 g/d, ≥2d/week), fruits (>100 g/d), berries (>100 g/d) and grapes (>100 g/d) more or less had associations with the plasma biomarkers including Aβ40, t-Tau, p-Tau-181 and neurofilament light chain as well as amyloid and Tau PET biomarkers. Most of the habits were associated with the change of cognitive function after an approximately two-year follow-up. Especially, higher intakes of fruits and grapes correlated with both lower Aβ and Tau burden and inversely with cognitive decline after follow-up.
CONCLUSION: Our data indicates that higher consumption of vegetables, dark vegetables, fruits, berries and grapes is associated with amyloid and Tau PET and plasma biomarkers in preclinical AD participants and the changes of cognitive function after follow-up. Higher intakes of fruits (>100 g/d) and grapes (>100 g/d) may be more helpful for reducing the risk of AD development.
CITATION:
Heling Chu ; Chuyi Huang ; Fang Xie ; Qihao Guo (2025): The associations between fresh vegetable and fruit consumption and plasma and PET biomarkers in preclinical Alzheimer's disease: A cross-sectional and longitudinal study of Chinese population. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100076
PREDICTING COGNITIVE DECLINE: DEEP-LEARNING REVEALS SUBTLE BRAIN CHANGES IN PRE-MCI STAGE
Ling Yue, Yongsheng Pan, Wei Li, Junyan Mao, Bo Hong, Zhen Gu, Mingxia Liu, Dinggang Shen, Shifu Xiao
J Prev Alz Dis 2025;5(12)
Show summaryHide summaryBACKGROUND: Mild cognitive impairment (MCI) and preclinical MCI (e.g., subjective cognitive decline, SCD) are considered risk states of dementia, such as Alzheimer's Disease (AD). However, it is challenging to accurately predict conversion from normal cognition (NC) to MCI, which is important for early detection and intervention. Since neuropathological changes may have occurred in the brain many years before clinical AD, we sought to detect the subtle brain changes in the pre-MCI stage using a deep-learning method based on structural Magnetic Resonance Imaging (MRI).
OBJECTIVES: To discover early structural neuroimaging changes that differentiate between stable and progressive cognitive status, and to establish a predictive model for MCI conversion.
DESIGN, SETTING AND PARTICIPANTS: We first created a unique deep-learning framework for pre-AD conversion prediction through the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1) database (n = 845). Then, we tested the model on ADNI-2 (n = 321, followed 3 years) and our private study (n = 109), the China Longitudinal Aging Study (CLAS), to validate the rationality for pre-MCI conversion prediction. The CLAS is a 7-year community-based cohort study in Shanghai. Our framework consisted of two steps: 1) a single-ROI-based network (SRNet) for identifying informative regions in the brain, and 2) a multi-ROI-based network (MRNet) for pre-AD conversion prediction. We then utilized these "ROI-based deep learning" neural networks to create a composite score using advanced algorithm-building. We coined this score as the Progressive Index (PI), which serves as a metric for assessing the propensity of AD conversion. Ultimately, we employed the PI to gauge its predictive capability for MCI conversion in both ADNI-2 and CLAS datasets.
MEASUREMENTS: We primarily utilized baseline T1-weighted MRI scans to identify the most discriminative brain regions and subsequently developed the PI in both training and validation datasets. We compared the PI across different cognitive groups and conducted logistic regression models along with their AUCs, adjusting for education level, gender, neuropsychological test scores, and the presence of comorbid conditions.
RESULTS: We trained the SRNet and MRNet using 845 subjects from ADNI-1 with baseline MRI data, in which AD and progressive MCI (converting to AD within 3 years) patients were considered as positive samples, while NC and stable MCI (remaining stable for 3 years) subjects were considered as negative samples. The convolutional neural networks identified the top 10 regions of interest (ROIs) for distinguishing progressive from stable cases. These key brain regions included the hippocampus, amygdala, temporal lobe, insula, and anterior cerebellum. A total of 321 subjects from ADNI-2, including 209 NC (18 progressive NC (pNC), 113 stable NC (sNC), and 78 remaining NC (rNC)) and 112 SCD (11 pSCD, 5 sSCD, and 96 rSCD), as well as 109 subjects from CLAS, including 17 sNC, 16 pNC, 52 sSCD and 24 pSCD participated in the test set, separately. We found that the PI score effectively sorted all subjects by their stages (stable vs progressive). Furthermore, the PI score demonstrated excellent discrimination between the two outcomes in the CLAS data(p<0.001), even after controlling for age, gender, education level, depression symptoms, anxiety symptoms, somatic diseases, and baseline MoCA score. Better performance for prediction progression to MCI in CLAS was obtained when the PI score was combined with clinical measures (AUC=0.812; 95 %CI: 0.725–0.900).
CONCLUSIONS: This study effectively predicted the progression to MCI among order individuals at normal cognition state by deep learning algorithm with MRI scans. Exploring the key brain alterations during the very early stages, specifically the transition from NC to MCI, based on deep learning methods holds significant potential for further research and contributes to a deeper understanding of disease mechanisms.
CITATION:
Ling Yue ; Yongsheng Pan ; Wei Li ; Junyan Mao ; Bo Hong ; Zhen Gu ; Mingxia Liu ; Dinggang Shen ; Shifu Xiao (2025): Predicting cognitive decline: Deep-learning reveals subtle brain changes in pre-MCI stage. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100079
INTERACTIONS OF PHYSICAL ACTIVITY AND LUNG FUNCTION ON COGNITIVE HEALTH IN OLDER ADULTS: JOINT ASSOCIATION AND MEDIATION ANALYSIS
Peng Hu, Dan Song, Tian Heng, Ling-Ling Yang, Chuan-Chuan Bai, Rui He, Tao Liu, Ya-Xi Luo, Xiu-Qing Yao
J Prev Alz Dis 2025;5(12)
Show summaryHide summaryBACKGROUND: Maintaining cognitive health in old adults has become a significant public health challenge, with lung function and physical activity (PA) as essential modifiable factors. However, the joint and mediation effects of these two factors with cognition remain unclear.
OBJECTIVES: This study assesses the joint association and mediation effects of lung function and PA with cognition.
DESIGN, SETTING, AND PARTICIPANTS: We utilized cross-sectional data from the 2011–2012 U.S. National Health and Nutrition Examination Survey, including adults aged 60–79 assessed for lung function, PA, and cognition.
MAIN OUTCOMES AND MEASURES: Lung function included forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF) and FEV1/FVC. PA was assessed using the Global Physical Activity Questionnaire, covering occupational PA (OPA), transportation-related PA (TPA), and leisure-time PA (LTPA). Cognition was evaluated using the Digit Symbol Substitution Test, Animal Fluency Test, Delayed Recall Test and Immediate Recall Test. Weighted multiple linear regression models were used to analyze the separate and joint associations of lung function and PA with cognition, while also exploring potential mediation effects between these factors.
RESULTS: A total of 927 participants, representing 35,525,782 U.S. residents, were included, with a weighted median age of 65 (IQR, 63 -71) years, and 53.6 % were female. The results showed a significant positive association between lung function and cognitive function, with FEV1, FVC, and PEF all positively correlated, while the FEV1/FVC showed no notable link. Further analysis revealed the best cognitive performance observed in participants with active LTPA and the highest quartile of lung function, indicating a joint association of LTPA and lung function with cognition. Mediation analysis indicated that lung function mediated 24.1 % (95 %CI: 6.3 % - 47.0 %, P = 0.03) of the relationship between LTPA and cognition, while cognition mediated 10.2 % (95 %CI: 0.5 % - 27.0 %, P = 0.04) of the relationship between LTPA and lung function.
CONCLUSION: Lung function and cognition may have a bidirectional relationship. The combination of active LTPA and better lung function was strongly associated with higher cognition, highlighting the need to strengthen exercise focused on lung function to maintain cognitive health in older adults.
CITATION:
Peng Hu ; Dan Song ; Tian Heng ; Ling-Ling Yang ; Chuan-Chuan Bai ; Rui He ; Tao Liu ; Ya-Xi Luo ; Xiu-Qing Yao (2025): Interactions of physical activity and lung function on cognitive health in older adults: Joint association and mediation analysis. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100090
LMTK2 AND CRB1 ARE TWO NOVEL RISK GENES FOR ALZHEIMER\'S DISEASE IN HAN CHINESE
Xuewen Xiao, Hui Liu, Rui Yao, Yunni Li, Xinxin Liao, Yingzi Liu, Yafang Zhou, Junling Wang, Beisha Tang, Bin Jiao, Jinchen Li, Lu Shen, Shilin Luo
J Prev Alz Dis 2025;5(12)
Show summaryHide summaryBACKGROUND: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease with a substantial genetic background. However, its underlying genetic architecture remains to be elucidated.
METHODS: In this study, we performed whole-exome sequencing in 282 familial and/or early-onset AD patients and 1086 cognitively normal controls in the Han Chinse populations. According to minor allele frequency, variants were divided into common variants (MAF ≥ 0.01) and rare variants (MAF < 0.01). Common variant-based association analysis and gene-based association test aggregating rare variants were performed by PLINK 1.9 and Sequence Kernel Association Test-Optimal, respectively. We replicated the significant results by using the same AD samples and controls from whole genome sequencing (n = 1879). Furthermore, we determined the functions of the novel AD risk genes in vitro.
RESULTS: Common variants association analysis revealed that APOE rs429358 reached statistical whole-exome significance. Gene-level aggregation testing identified that rare damaging variants in LMTK2 and CRB1 conferred risk to AD. All variants are located in highly conserved amino acid regions and are predicted to be damaging. Furthermore, functional studies showed that LMTK2 rare damaging variants (R234P and S974G) enhanced tau phosphorylation levels, tau aggregates formation, and Aβ generation. Meanwhile, the CRB1 Y556X variant caused incomplete translation of CRB1 protein and increased the Aβ42 level and Aβ42/Aβ40 ratio.
CONCLUSION: Our findings indicated that LMTK2 and CRB1 are two novel AD risk genes in Han Chinese, which may provide promising targets for diagnosis and intervention.
CITATION:
Xuewen Xiao ; Hui Liu ; Rui Yao ; Yunni Li ; Xinxin Liao ; Yingzi Liu ; Yafang Zhou ; Junling Wang ; Beisha Tang ; Bin Jiao ; Jinchen Li ; Lu Shen ; Shilin Luo (2025): LMTK2 and CRB1 are two novel risk genes for Alzheimer's disease in Han Chinese. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100087
THE INTERACTION BETWEEN CIRCADIAN SYNDROME AND GENETIC SUSCEPTIBILITY IN THE RISK OF INCIDENT DEMENTIA: A LONGITUDINAL COHORT STUDY
Linling Yu, Wei Liu, Chenqi Liao, Na Shen, Anding Liu, Liming Cheng, Xiong Wang
J Prev Alz Dis 2025;5(12)
Show summaryHide summaryBACKGROUND: Despite growing interest in circadian disturbances as potential triggers for dementia, the specific impact of circadian syndrome (CircS) on dementia incidence remains poorly understood. Moreover, the role of genetic susceptibility modulating these effects remains to be explored.
METHODS: Dementia-free participants from the UK Biobank cohort were included in the analysis. To evaluate the association between CircS and the incidence of dementia, as well as the modifying influence of genetic susceptibility on this relationship, Cox proportional hazards models were utilized.
RESULTS: During a median follow-up period of 14.55 years, 3,965 incident dementia cases were documented. CircS was found to significantly increased the risk of incident dementia, with a hazard ratio (HR) of 1.401 (95 % confidence interval [CI]: 1.296, 1.516). Compared to a CircS score of ≤3, mild CircS (HR: 1.259, 95 % CI: 1.146–1.383), moderate CircS (HR: 1.667, 95 % CI: 1.461–1.903), and severe CircS (HR: 2.028, 95 % CI: 1.397–2.944) were all significantly associated with an elevated risk of dementia. There were significant multiplicative interactions between CircS and genetic susceptibility (Pinteraction<0.001). Participants with both a high polygenic risk score (PRS) and CircS had the highest risk of incident dementia (HR: 2.551, 95 % CI: 2.169, 3.001), compared to those with a low PRS and no CircS.
CONCLUSIONS: CircS was associated with an increased risk of dementia, which might be aggravated by genetic susceptibility.
CITATION:
Linling Yu ; Wei Liu ; Chenqi Liao ; Na Shen ; Anding Liu ; Liming Cheng ; Xiong Wang (2025): The interaction between circadian syndrome and genetic susceptibility in the risk of incident dementia: A longitudinal cohort study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100089
DIAGNOSTIC AND DISCRIMINATIVE ACCURACY OF PLASMA PHOSPHORYLATED TAU 217 FOR SYMPTOMATIC ALZHEIMERʼS DISEASE IN A CHINESE COHORT
Li-Min Li, Ping Che, Dequan Liu, Yu Wang, Jia Li, Dian He, Tao Liu, Nan Zhang
J Prev Alz Dis 2025;5(12)
Show summaryHide summaryBACKGROUND: Plasma phosphorylated tau at threonine 217 (p-tau217) measured with an ultrasensitive immunoassay method has been demonstrated to be an optimal biomarker for Alzheimer's disease (AD).
OBJECTIVES: The aim of this study was to establish the reference interval for plasma p-tau217 in Chinese individuals and evaluate its diagnostic value in symptomatic AD.
DESIGN, SETTING, PARTICIPANTS: We recruited 150 cognitively unimpaired (CU) individuals, 60 patients with AD dementia, 30 patients with mild cognitive impairment (MCI) due to AD, 40 patients with frontotemporal lobar degeneration (FTLD), and 70 patients with subcortical ischaemic vascular dementia (SIVD).
MEASUREMENTS: The concentrations of plasma p-tau217, total tau, amyloid-beta (Aβ)42 and Aβ40 were measured with a single-molecule array.
RESULTS: Plasma p-tau217 outperformed other biomarkers in discriminating AD patients from CU controls, FTLD patients, and SIVD patients (AUC = 0.983, 0.936, 0.892) and discriminating MCI patients from CU controls (AUC = 0.943). The plasma p-tau217 level was negatively correlated with memory in patients with symptomatic AD.
CONCLUSION: The diagnostic accuracy of plasma p-tau217 was exceptional for AD, even at early stages, in the Chinese population.
CITATION:
Li-Min Li ; Ping Che ; Dequan Liu ; Yu Wang ; Jia Li ; Dian He ; Tao Liu ; Nan Zhang (2025): Diagnostic and discriminative accuracy of plasma phosphorylated tau 217 for symptomatic Alzheimerʼs disease in a Chinese cohort. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100092
MULTISENSORY STIMULATION REDUCES NEUROPSYCHIATRIC SYMPTOMS AND ENHANCES COGNITIVE FUNCTION IN OLDER ADULTS WITH DEMENTIA: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Tiara Octary, Melati Fajarini, Hidayat Arifin, Ruey Chen, Chien-Mei Sung, Li-Fang Chang, Chia-Hui Wang, Kondwani Joseph Banda, Kuei-Ru Chou
J Prev Alz Dis 2025;5(12)
Show summaryHide summaryOBJECTIVE: Multisensory stimulation defined as engaging multiple senses (visual, olfactory, auditory, gustatory, and tactile), has been demonstrated to improve older adults’ general health. However, its effectiveness in mitigating neuropsychiatric symptoms (NPSs) and cognitive deficits in older adults with dementia remains unclear. This meta-analysis evaluated the efficacy of multisensory stimulation in ameliorating NPSs and improving overall cognitive function in older adults with dementia.
METHODS: We searched eight databases to September 2024 without restriction. Older adults with all stages of dementia aged 65 years and above were included. To estimate the pooled effect size, Hedge's g (g) values were calculated using a random-effects model. Heterogeneity was assessed using the Q, I², and τ² statistics. Subgroup and meta-regression analyses were performed to identify moderators. Publication bias was assessed using Begg and Mazumdar's rank correlation and Egger's linear regression tests.
RESULTS: This review included 16 studies (974 patients). Multisensory stimulation significantly reduced agitation (g= −0.96; 95 %CI= −1.44, −0.48), apathy (g= −1.27; 95 %CI= −2.08, −0.46), and depression (g= −0.28; 95 %CI= −0.48, −0.07). Moreover, the intervention significantly improved overall cognitive function (g= 0.30; 95 %CI= 0.09, 0.52). However, multisensory stimulation had no significant effect on anxiety (g= −0.81; 95 %CI= −1.79, 0.17). Significant heterogeneity was observed in agitation, apathy, and anxiety. Moreover, meta-regression analyses by educational level (junior high school and above) revealed significant moderators in agitation.
CONCLUSIONS: Multisensory stimulation shows promise as a non-pharmacological intervention for older adults with dementia. It may effectively mitigate NPSs and improve cognitive function into clinical practice as an alternative therapeutic.
CITATION:
Tiara Octary ; Melati Fajarini ; Hidayat Arifin ; Ruey Chen ; Chien-Mei Sung ; Li-Fang Chang ; Chia-Hui Wang ; Kondwani Joseph Banda ; Kuei-Ru Chou (2025): Multisensory stimulation reduces neuropsychiatric symptoms and enhances cognitive function in older adults with dementia: A meta-analysis of randomized controlled trials. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100091
INTEGRATIVE SINGLE-CELL RNA SEQUENCING AND MENDELIAN RANDOMIZATION ANALYSIS REVEAL THE POTENTIAL ROLE OF SYNAPTIC VESICLE CYCLING-RELATED GENES IN ALZHEIMER\'S DISEASE
Junfeng Zeng, Ruihua Zhang, Huihua Xu, Chengwu Zhang, Li Lu
J Prev Alz Dis 2025;5(12)
Show summaryHide summaryBACKGROUND: Alzheimer's disease (AD) involves alterations in synaptic vesicle cycling (SVC), which significantly affect neuronal communication and function. Therefore, a thorough investigation into the potential roles of SVC-related genes (SVCRGs) in AD can enhance the identification of critical biomarkers that may influence disease progression and treatment responses.
METHODS: The datasets used in this study were sourced exclusively from public databases. By integrating differential expression analysis with Mendelian randomization (MR), we identified SVCRGs as biomarkers for AD. Functional characterization of these biomarkers was performed, followed by integration into a nomogram. Further investigation of immune infiltration in AD patients and healthy individuals was carried out. Ultimately, the potential cellular mechanisms of AD were explored through single-cell RNA sequencing (scRNA-seq) analysis.
RESULTS: ATP6V1D, ATP6V1G2, CLTB, and NSF were identified as biomarkers, exhibiting a positive correlation with each other and a downregulated expression in AD. These markers were pinpointed as protective factors for AD [odds ratio (OR) < 1, P < 0.05], with potential to reduce the risk of the disease. Integrated into a nomogram, they demonstrated satisfactory diagnostic performance and clinical utility, surpassing the use of single gene. They were collectively enriched in pathways related to "interferon gamma response", "inflammatory response", and "TNFα signaling via NFκB". Additionally, an increase in infiltration of 17 immune cell types in AD was noted, particularly cells associated with neuroinflammation such as activated CD8 T cells and various dendritic cells (DCs), suggesting an inflammatory milieu in AD while also displaying a negative correlation with the biomarkers. The cell types were further annotated, revealing specific expressions of biomarkers and uncovering the heterogeneity of excitatory neurons. A significant reduction in the overall number of excitatory neurons under AD conditions was observed, alongside consistent expression of biomarkers during the developmental stages of excitatory neurons.
CONCLUSION: By using MR, we firstly identified four SVCRGs as protective factors for AD, functioning through pathways associated with mitochondrial dysfunction, chronic inflammation, immune dysregulation, and neuronal damage. These genes had the potential to modulate immune cell infiltration activated in AD patients and exhibited cell-type-specific expression profiles within AD-related cellular contexts. Their findings provide novel insights and valuable references for future research on AD pathogenesis and therapeutic strategies.
CITATION:
Junfeng Zeng ; Ruihua Zhang ; Huihua Xu ; Chengwu Zhang ; Li Lu (2025): Integrative single-cell RNA sequencing and mendelian randomization analysis reveal the potential role of synaptic vesicle cycling-related genes in Alzheimer's disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100097
CURRENT STATUS AND FUTURE DIRECTIONS FOR THE DIAGNOSIS AND MANAGEMENT OF MILD COGNITIVE IMPAIRMENT IN SOUTHEAST ASIA: A SEACURE CONSENSUS PAPER
Gursimar Bhalla, Pricilia Tanoto, Ashwati Vipin, Xiao Yuan James Chen, Yi Jin Leow, Christopher Chen, Philip Lin Kiat Yap, Reshma A Merchant, Saima Hilal, Anam Paulus Ong, Encarnita Raya Ampil, Mohamad Imran Idris, Irene Looi, Jacqueline Dominguez, Suraya Yusoff, Maw Pin Tan, Cong Thang Tran, Mai Trang Tong, Vorapun Senanarong, Yuda Turana, Nagaendran Kandiah
J Prev Alz Dis 2025;5(12)
Show summaryHide summaryGlobal aging populations are facing increased prevalence of mild cognitive impairment (MCI) – the preclinical stage of dementia characterized by single/multi-domain neurocognitive decline that does not impair an individual's normal daily functioning. Asian populations are at increased risk of developing MCI and dementia, and many cases go undetected in Southeast Asia (SEA), resulting in increased burden on patients, caregivers and national healthcare systems. There is an urgent need for efficient and scalable diagnostic and management strategies across SEA. Our findings illustrate that current strategies are limited by insufficient resources and a lack of awareness, particularly in developing SEA nations. Strategies for improving the MCI landscape in SEA include increasing widespread community awareness and cognitive health screenings for individuals with a history of vascular risk factors, validation of traditional cognitive screening tests in the respective countries, greater access to blood-biomarker testing, and the development and validation of novel digitized diagnostics.
CITATION:
Gursimar Bhalla ; Pricilia Tanoto ; Ashwati Vipin ; Xiao Yuan James Chen ; Yi Jin Leow ; Christopher Chen ; Philip Lin Kiat Yap ; Reshma A Merchant ; Saima Hilal ; Anam Paulus Ong ; Encarnita Raya Ampil ; Mohamad Imran Idris ; Irene Looi ; Jacqueline Dominguez ; Suraya Yusoff ; Maw Pin Tan ; Cong Thang Tran ; Mai Trang Tong ; Vorapun Senanarong ; Yuda Turana ; Nagaendran Kandiah (2025): Current status and future directions for the diagnosis and management of mild cognitive impairment in Southeast Asia: A SEACURE consensus paper. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100110
THE DISEASE BURDEN, RISK FACTORS AND FUTURE PREDICTIONS OF ALZHEIMER\'S DISEASE AND OTHER TYPES OF DEMENTIA IN ASIA FROM 1990 TO 2021
Jinxuan Guo, Pin Wang, Jin Gong, Wenxian Sun, Xiaodong Han, Chang Xu, Aidi Shan, Xin Wang, Heya Luan, Shaoqi Li, Ruina Li, Boye Wen, Runqi Chen, Sirong Lv, Cuibai Wei
J Prev Alz Dis 2025;5(12)
Show summaryHide summaryBACKGROUND: There is a lack of analysis and prediction of the disease burden of Alzheimer's disease and other dementias (ADOD) in Asia.
OBJECTIVES: This study aims to explore the impact of ADOD on the Asian region during the period from 1990 to 2021.
DESIGN: Data on ADOD in Asia from 1990 to 2021 were collected from the Global Burden of Disease (GBD) Study 2021. We analyzed the number and age-standardized rates (ASRs) of incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) of ADOD from 1990 to 2021. Joinpoint regression analysis was performed, and the average annual percent changes (AAPCs) were calculated to evaluate the trends during this period. Subsequently, an auto - regressive integrated moving average (ARIMA) prediction model analysis was conducted to assess the trends in the next 30 years, aiming to report the epidemiology and disease burden of ADOD in Asia.
RESULTS: According to the analysis of the GBD database in 2021, the deaths, DALYs, incidence, and prevalence of ADOD increased by 297.34 %, 249.54 %, 244.73 %, and 250.44 % in Asia from 1990 to 2021. The ASRs of incidence, prevalence, death, and DALYs in both males and females, which consistently increased over the study period, showed that the ASRs of all females were consistently higher than those of males in Asia from 1990 to 2021. During the period from 1990 to 2021, Qatar and the United Arab Emirates witnessed the greatest changes in the number of DALYs, incidence, and prevalence. Afghanistan and China had the highest age-standardized mortality rate (ASMR) in 2021. It is worth noting that high fasting blood glucose is the top risk factor for the onset of ADOD. Females are more susceptible to the risk factor of high body-mass index (BMI), while males are more likely to be affected by smoking. According to the analysis of the ARIMA prediction model, the disease burden of ADOD in Asia will continue to show an upward trend in the next 30 years.
CONCLUSIONS: We should pay attention to the issue of population aging, attach importance to the intervention measures targeting the risk factors of ADOD, and formulate action plans to address the rising incidence of ADOD.
CITATION:
Jinxuan Guo ; Pin Wang ; Jin Gong ; Wenxian Sun ; Xiaodong Han ; Chang Xu ; Aidi Shan ; Xin Wang ; Heya Luan ; Shaoqi Li ; Ruina Li ; Boye Wen ; Runqi Chen ; Sirong Lv ; Cuibai Wei (2025): The disease burden, risk factors and future predictions of Alzheimer's disease and other types of dementia in Asia from 1990 to 2021. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100122
LETTER TO THE EDITOR: ENHANCING STATIN RESEARCH FOR ALZHEIMER\'S PREVENTION: SUGGESTIONS FOR FUTURE STUDIES AND POLICY IMPLICATIONS
Yumei Zhong, Shanshan Liu, Xiaofeng Lv
J Prev Alz Dis 2025;5(12)
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CITATION:
Yumei Zhong ; Shanshan Liu ; Xiaofeng Lv (2025): Letter to the Editor: Enhancing statin research for Alzheimer's prevention: Suggestions for future studies and policy implications. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100118
REPLY TO THE LETTER TO THE EDITOR: ENHANCING STATIN RESEARCH FOR ALZHEIMER\'S PREVENTION: SUGGESTIONS FOR FUTURE STUDIES AND POLICY IMPLICATIONS
Zirong Ye, Jiahe Deng, Xiuxia Wu, Jingwen Cai, Sicheng Li, Xiaochun Chen, Jiawei Xin
J Prev Alz Dis 2025;5(12)
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CITATION:
Zirong Ye ; Jiahe Deng ; Xiuxia Wu ; Jingwen Cai ; Sicheng Li ; Xiaochun Chen ; Jiawei Xin (2025): Reply to the letter to the Editor: Enhancing Statin Research for Alzheimer's Prevention: Suggestions for Future Studies and Policy Implications. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100119
LETTER TO THE EDITOR: CONCERNS ABOUT ANAVEX\'S CLINICAL TRIAL OF BLARCAMESINE
Jesse Brodkin
J Prev Alz Dis 2025;5(12)
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CITATION:
Jesse Brodkin (2025): Letter to the Editor: Concerns about Anavex's clinical trial of Blarcamesine. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100137
LETTER TO THE EDITOR: REBUTTAL LETTER ON BEHALF OF ALL AUTHORS IN RESPONSE TO THE LETTER TO THE EDITOR
Marwan Noel Sabbagh
J Prev Alz Dis 2025;5(12)
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CITATION:
Marwan Noel Sabbagh (2025): Letter to the Editor: Rebuttal letter on behalf of all authors in response to the Letter to the Editor. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100136
CORRIGENDUM TO “ENHANCING DEMENTIA PREDICTION: A 19-YEAR VALIDATION OF THE CAIDE RISK SCORE WITH INSULIN RESISTANCE AND APOE ε4 INTEGRATION IN A POPULATION-BASED COHORT” [THE JOURNAL OF PREVENTION OF ALZHEIMER\'S DISEASE (2024) 100034]
Elina Pietilä, Eliisa Löyttyniemi, Seppo Koskinen, Jenni Lehtisalo, Matti Viitanen, Juha O. Rinne, Antti Jula, Laura L. Ekblad
J Prev Alz Dis 2025;5(12)
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CITATION:
Elina Pietilä ; Eliisa Löyttyniemi ; Seppo Koskinen ; Jenni Lehtisalo ; Matti Viitanen ; Juha O. Rinne ; Antti Jula ; Laura L. Ekblad (2025): Corrigendum to “Enhancing Dementia Prediction: A 19-Year Validation of the CAIDE Risk Score with Insulin Resistance and APOE ε4 Integration in a Population-Based Cohort” [The Journal of Prevention of Alzheimer's Disease (2024) 100034]. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100158