06/2025 journal articles
EDITORIAL: NOT A SLAM DUNK (OR FREE LUNCH): THE COMPLEX FUTURE OF ALZHEIMER\'S COMBINATION THERAPY
Cristina Sampaio
J Prev Alz Dis 2025;6(12)
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CITATION:
Cristina Sampaio (2025): Editorial: Not a slam dunk (or Free Lunch): The complex future of Alzheimer's combination therapy. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100211
EDITORIAL: HERPES ZOSTER AND DEMENTIA : MORE EVIDENCES FOR A CAUSAL LINK
Jean-François Dartigues, Morgane Linard
J Prev Alz Dis 2025;6(12)
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CITATION:
Jean-François Dartigues ; Morgane Linard (2025): Editorial: Herpes zoster and dementia : more evidences for a causal link. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100201
EDITORIAL: PREVENTING ALZHEIMER\'S DISEASE BY CORRECTING LIFESTYLE FACTORS?
Natalio Vita
J Prev Alz Dis 2025;6(12)
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CITATION:
Natalio Vita (2025): Editorial: Preventing Alzheimer's disease by correcting lifestyle factors?. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100212
EDITORIAL: BRAIN HEALTH PRO/SANTE CERVEAU PRO: THE DEVELOPMENT OF A WEB-BASED PROGRAM FOR DEMENTIA LITERACY AND RISK FACTOR REDUCTION
Alex Bahar-Fuchs
J Prev Alz Dis 2025;6(12)
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CITATION:
Alex Bahar-Fuchs (2025): Editorial: Brain health PRO/santé cerveau PRO: The development of a web-based program for dementia literacy and risk factor reduction. The Journal of Prevention of Alzheimer’s Disease (JPAD).
CITATION:
Alex Bahar-Fuchs (2025): Editorial: Brain health PRO/santé cerveau PRO: The development of a web-based program for dementia literacy and risk factor reduction. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2025.8
CHALLENGES AND OPPORTUNITIES FOR NOVEL COMBINATION THERAPIES IN ALZHEIMER\'S DISEASE: A REPORT FROM THE EU/US CTAD TASK FORCE
D. Angioni, L. Middleton, R. Bateman, P. Aisen, A. Boxer, S. Sha, J. Zhou, I. Gerlach, R. Raman, H. Fillit, S. Salloway, R. Sperling, B. Vellas, J. Cummings
J Prev Alz Dis 2025;6(12)
Show summaryHide summaryFollowing the recent approvals of anti-amyloid immunotherapies as “first-in-kind” disease-modifying agents for Alzheimer's disease (AD), there is an emerging emphasis in combination therapies, given the complex and multifactorial etiopathogenesis and pathophysiology of the disease. The EU/US CTAD Task Force met in Madrid in October 2024, to discuss biological rationale and methodological issues and outline potential directions for future research in combination therapies. The Task Force agreed on the necessity and urgency of advancing combination therapies for AD treatment. As of January 1, 2024, in the drug development pipeline, there were 21 combination trials (13 % of all trials). The combination of anti-amyloid and anti-tau therapies could become a central focus of the field. Combinations involving anti-inflammatory and immune mechanisms with anti-amyloid or other therapies also have promise. To facilitate the development and implementation of combination therapies, collaborations between sponsors and public-private partnerships are essential. Optimizing the likelihood of success primarily requires leveraging the use of biomarkers and a clearer understanding of the biological mechanisms underpinning AD and their interactions, especially those involving amyloid, tau, and inflammation, that lead to cognitive decline and progression.
CITATION:
D. Angioni ; L. Middleton ; R. Bateman ; P. Aisen ; A. Boxer ; S. Sha ; J. Zhou ; I. Gerlach ; R. Raman ; H. Fillit ; S. Salloway ; R. Sperling ; B. Vellas ; J. Cummings (2025): Challenges and opportunities for novel combination therapies in Alzheimer's disease: a report from the EU/US CTAD Task Force. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100163
HERPES ZOSTER AS RISK FACTOR FOR DEMENTIA: A MATCHED COHORT STUDY OVER 20 YEARS IN A 10-MILLION POPULATION IN ITALY
Lorenzo Blandi, Paola Bertuccio, Carlo Signorelli, Helmut Brand, Timo Clemens, Cristina Renzi, Anna Odone
J Prev Alz Dis 2025;6(12)
Show summaryHide summaryBACKGROUND: Herpes Zoster is caused by the reactivation of the Varicella-Zoster Virus. Zoster may influence the occurrence of dementia, but contradictory results about this association emerged from recent studies. These findings did not consider the severity of Zoster and observed individuals for limited follow-up time. Our study used a region-wide Italian registry to investigate the association between severe Zoster infection and dementia occurrence over a 23-year period.
METHODS: We included people aged ≥ 50 and hospitalised with Zoster, and two comparison cohorts from both the general population and the hospitalised population without Zoster. By random sampling, the matching 1:5 was based on sex, birth year, and entry date in the cohort. Dementia and Zoster were identified through validated algorithms. A Fine-Gray sub-distribution hazard model was used, accounting for competing risk of death.
RESULTS: We identified 132,968 individuals, of whom 12,088 with severe Zoster, 60,440 matched controls among the general population, and 60,440 matched controls among the hospitalised population. In severe cases of Herpes Zoster, the overall adjusted sub-distributed hazard ratio of dementia was 1.13 (95 % CI 1.07–1.19) compared to the general population, and 1.08 (95 % CI 1.03–1.14) compared to hospitalised population. Hazard ratios were still significant in different strata group, including by sex, age group (including in 50–65 younger adults) and at different follow-up period.
CONCLUSIONS: Our population-based study found an increased risk of developing dementia among severe Zoster cases. Those results support the importance of improving Zoster prevention and extending the vaccination recommendations to younger age groups.
CITATION:
Lorenzo Blandi ; Paola Bertuccio ; Carlo Signorelli ; Helmut Brand ; Timo Clemens ; Cristina Renzi ; Anna Odone (2025): Herpes zoster as risk factor for dementia: a matched cohort study over 20 years in a 10-million population in Italy. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100167
LIFESTYLE FACTORS AND PLASMA BIOMARKERS OF ALZHEIMER\'S DISEASE: A NARRATIVE REVIEW
Claudie Hooper, Nicola Coley, Julien Delrieu, Sophie Guyonnet
J Prev Alz Dis 2025;6(12)
Show summaryHide summaryAlzheimer's disease (AD) is a neurodegenerative disorder characterised by amyloid-β (Aβ), tau hyperphosphorylation and neurodegeneration. Blood-based biomarkers are emerging as a minimally invasive tool for disease detection and monitoring. This review depicts the relationships between modifiable lifestyle factors (nutrition, physical activity (PA), sleep, alcohol consumption, smoking, and social isolation) and plasma biomarkers of AD: Aβ42, Aβ40, Aβ42/40, phosphorylated tau, total tau, neurofilament light chain (NfL) and glial fibrillary acidic protein. Limited evidence suggests that better nutrition is associated with favourable AD plasma biomarker profiles and that PA is associated with less plasma NfL and Aβ, whilst poor sleep is associated with elevated plasma Aβ. However, lack of data and inconsistent findings highlight the need for further investigation to substantiate or refute these trends. Moreover, future research should include the analysis of lifestyle on plasma biomarkers according to gender, metabolic health and APOE status. Considering the growing emphasis on modifiable lifestyle factors for preventing and delaying dementia onset further investigation is justified.
CITATION:
Claudie Hooper ; Nicola Coley ; Julien Delrieu ; Sophie Guyonnet (2025): Lifestyle factors and plasma biomarkers of Alzheimer's disease: A narrative review. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100130
BRAIN HEALTH PRO/SANTE CERVEAU PRO: THE DEVELOPMENT OF A WEB-BASED PROGRAM FOR DEMENTIA LITERACY AND RISK FACTOR REDUCTION
Sylvie Belleville, Nicole D. Anderson, Louis Bherer, Richard Camicioli, Julie Carrier, Senny Chan, Marc Cuesta, Thien Thanh Dang-Vu, Emily Dwosh, Alexandra J. Fiocco, Guylaine Ferland, Brigitte Gilbert, Elaine Harris, Inbal Itzhak, Pamela Jarrett, Mohamed Abdelhafid Kadri, Danielle Laurin, Teresa Liu-Ambrose, Chris A. McGibbon, Laura Middleton, Lesley Miller, Haakon B. Nygaard, Manuel Montero-Odasso, Kelly Murphy, Natalie Phillips, M. Kathleen Pichora-Fuller, Julie M. Robillard, Eric E. Smith, Mark Speechley, Amal Trigui, Walter Wittich, Howard Chertkow, Howard H. Feldman
J Prev Alz Dis 2025;6(12)
Show summaryHide summaryBACKGROUND: Online educational programs focused on ways to improve brain health could increase participant literacy, empowerment, and engagement in activities that support personal brain health, potentially reducing dementia risk.
OBJECTIVES: Our goal was to develop an evidence-based online educational program with a focus on risk and protective factors for dementia. Here we present the rationale and features of the program and include results from a pilot study that assessed usability and acceptability.
DESIGN: This project is part of the Can-Thumbs UP (CTU) initiative. An Intervention Mapping Approach framework and co-construction approach was used to develop the online program. A pre-post pilot open label design was used to test the usability and acceptance of this at-home educational program.
SETTING: The program and assessment for the pilot study were delivered fully remotely.
PARTICIPANTS: Twenty community-dwelling older adults (60–83 years of age, 65 % female) living in Canada who were at increased risk of dementia.
PROGRAM: The Brain Health PRO/Santé Cerveau PRO is a web-based 45-week program available in French and English. It provides general information and guidance on seven modifiable risk factors for dementia: physical activity, nutrition, cognitively stimulating activities, sleep, social and psychological health, vascular health, and vision/hearing. After completing a brief intake questionnaire, users are provided with an individualized risk profile to personalize priorities and goals. During the course of the program, users receive feedback on lifestyle changes. For this pilot study, participants completed a 15-week version of the program.
MEASUREMENTS: This pilot study reports measures of usability (System Usability Scale), acceptance (Technology Acceptance Model-2) as well as risk profiles at intake based on self-reported questionnaires.
RESULTS: Two logic models were developed to identify the determinants of risk for dementia and how these could be targeted by the program. A review of dementia risk and protective factors and online educational programs for older adults, as well as co-creation activities with experts, stakeholders, and citizen advisors, were used to identify the determinants, target, format, and content of the program. The pilot study reports excellent usability and acceptance with scores of 80.4/100 and 93.5/120 respectively.
CONCLUSION: Intervention mapping and co-construction approaches facilitated the design of a program that effectively balances the delivery of scientific content with the specific constraints, needs and abilities of older adults.
CITATION:
Sylvie Belleville ; Nicole D. Anderson ; Louis Bherer ; Richard Camicioli ; Julie Carrier ; Senny Chan ; Marc Cuesta ; Thien Thanh Dang-Vu ; Emily Dwosh ; Alexandra J. Fiocco ; Guylaine Ferland ; Brigitte Gilbert ; Elaine Harris ; Inbal Itzhak ; Pamela Jarrett ; Mohamed Abdelhafid Kadri ; Danielle Laurin ; Teresa Liu-Ambrose ; Chris A. McGibbon ; Laura Middleton ; Lesley Miller ; Haakon B. Nygaard ; Manuel Montero-Odasso ; Kelly Murphy ; Natalie Phillips ; M. Kathleen Pichora-Fuller ; Julie M. Robillard ; Eric E. Smith ; Mark Speechley ; Amal Trigui ; Walter Wittich ; Howard Chertkow ; Howard H. Feldman ; the CTU expert group for the Canadian Consortium on Neurodegeneration in Aging (CCNA), CAN-THUMBS UP Study Group (2025): Brain health PRO/Santé cerveau PRO: The development of a web-based program for dementia literacy and risk factor reduction. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100134
SAMPLE SIZE ESTIMATES FOR BIOMARKER-BASED OUTCOME MEASURES IN CLINICAL TRIALS IN AUTOSOMAL DOMINANT ALZHEIMER\'S DISEASE
David M Cash, Katy E Morgan, Antoinette O\'Connor, Thomas D Veale, Ian B Malone, Teresa Poole, Tammie LS Benzinger, Brian A Gordon, Laura Ibanez, Yan Li, Jorge J. Llibre-Guerra, Eric McDade, Guoqiao Wang, Jasmeer P Chhatwal, Gregory S Day, Edward Huey, Mathias Jucker, Johannes Levin, Yoshiki Niimi, James M Noble, Jee Hoon Roh, Racquel Sánchez-Valle, Peter R Schofield, Randall J Bateman, Chris Frost, Nick C Fox, The Dominantly Inherited Alzheimer Network (DIAN)
J Prev Alz Dis 2025;6(12)
Show summaryHide summaryINTRODUCTION: Alzheimer disease (AD)-modifying therapies are approved for treatment of early-symptomatic AD. Autosomal dominant AD (ADAD) provides a unique opportunity to test therapies in presymptomatic individuals.
METHODS: Using data from the Dominantly Inherited Alzheimer Network (DIAN), sample sizes for clinical trials were estimated for various cognitive, imaging, and CSF outcomes. Sample sizes were computed for detecting a reduction of either absolute levels of AD-related pathology (amyloid, tau) or change over time in neurodegeneration (atrophy, hypometabolism, cognitive change).
RESULTS: Biomarkers measuring amyloid and tau pathology had required sample sizes below 200 participants per arm (examples CSF Aβ42/40: 47[95 %CI 25,104], cortical PIB 49[28,99], CSF p-tau181 74[48,125]) for a four-year trial in presymptomatic individuals (CDR=0) to have 80 % power (5 % statistical significance) to detect a 25 % reduction in absolute levels of pathology, allowing 40 % dropout. For cognitive, MRI, and FDG, it was more appropriate to detect a 50 % reduction in rate of change. Sample sizes ranged from 250 to 900 (examples hippocampal volume: 338[131,2096], cognitive composite: 326[157,1074]). MRI, FDG and cognitive outcomes had lower sample sizes when including indivduals with mild impairment (CDR=0.5 and 1) as well as presymptomatic individuals (CDR=0).
DISCUSSION: Despite the rarity of ADAD, presymptomatic clinical trials with feasible sample sizes given the number of cases appear possible.
CITATION:
David M Cash ; Katy E Morgan ; Antoinette O'Connor ; Thomas D Veale ; Ian B Malone ; Teresa Poole ; Tammie LS Benzinger ; Brian A Gordon ; Laura Ibanez ; Yan Li ; Jorge J. Llibre-Guerra ; Eric McDade ; Guoqiao Wang ; Jasmeer P Chhatwal ; Gregory S Day ; Edward Huey ; Mathias Jucker ; Johannes Levin ; Yoshiki Niimi ; James M Noble ; Jee Hoon Roh ; Racquel Sánchez-Valle ; Peter R Schofield ; Randall J Bateman ; Chris Frost ; Nick C Fox ; The Dominantly Inherited Alzheimer Network (DIAN) (2025): Sample size estimates for biomarker-based outcome measures in clinical trials in autosomal dominant Alzheimer's disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100133
A SYSTEMATIC REVIEW OF TARGETED DEMENTIA RISK REDUCTION INTERVENTIONS IN MIDDLE-AGED ADULTS IN PRIMARY CARE
Mary Tullipan, Johnson George, Parker Magin, Kali Godbee, Jane Ferns, Claire Frewin
J Prev Alz Dis 2025;6(12)
Show summaryHide summaryBACKGROUND: Pathological changes of dementia are thought to commence in mid-life, making mid-life an attractive target for dementia risk reduction. This review assessed the current literature on multidomain dementia risk-reduction interventions in mid-life.
METHODS: We systematically searched MEDLINE, CINAHL and EMBASE for eligible studies. Studies were included if (i) participants had a mean age between 45 and 65 years, (ii) the intervention was delivered in a primary care setting and targeted two or more dementia risk factors, and (iii) outcomes were change in cognitive function or change in risk score. Data was extracted and assessed for bias using the revised Cochrane risk-of-bias assessment tool.
RESULTS: Seven studies were included. Participants' mean age ranged from 45.3 to 64.2 years. Interventions ranged from 10 weeks to 9.8 years and targeted between two and six dementia risk factors. There was a large variation in the type of outcome and statistical tests utilised across the included studies, impacting the ability to draw comparisons between the studies and draw conclusions regarding treatment effects. There was a high risk of bias in three of the studies and some concerns of bias in the other four studies. Two studies assessing dementia risk found a reduction in risk scores at their primary endpoint. None of the included studies found a statistically significant change in cognition from their interventions. This may be attributable in part to not assessing cognition prior to the interventions, limited risk factors being addressed, and the short follow-up/duration of the studies.
CONCLUSION: Current evidence for multidomain dementia risk-reduction interventions in mid-life is not definitive; however, given their substantive potential benefits and likely limited harms, they may be considered for implementation in clinical practice after further evaluation. Future trials that have longer follow-ups, target a broader range of dementia risk factors, and that use consistent outcome measures will be valuable. Strategies to maximise implementation of multidomain interventions and long-term effectiveness will enhance the evidence base for dementia prevention in primary care.
CITATION:
Mary Tullipan ; Johnson George ; Parker Magin ; Kali Godbee ; Jane Ferns ; Claire Frewin (2025): A systematic review of targeted dementia risk reduction interventions in middle-aged adults in Primary Care. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100187
DIETARY PATTERNS AND BLOOD-BASED BIOMARKERS OF ALZHEIMER\'S DISEASE IN COGNITIVELY INTACT OLDER ADULTS: FINDINGS FROM A POPULATION-BASED STUDY
Anja Mrhar, Adrián Carballo-Casla, Giulia Grande, Martina Valletta, Claudia Fredolini, Laura Fratiglioni, Milica Gregori? Kramberger, Aleš Kuhar, Bengt Winblad, Amaia Calderón-Larrañaga, Davide Liborio Vetrano
J Prev Alz Dis 2025;6(12)
Show summaryHide summaryBACKGROUND: Diet can impact cognitive aging, but comprehensive data from human studies is lacking and the underlying biological mechanisms are still not fully understood.
OBJECTIVES: To investigate the associations between two dietary patterns consistently linked to inflammation and brain health [the Mediterranean diet (MDS) and inflammatory potential of diet (EDII)] and five blood-based biomarkers of Alzheimer´s disease (AD) in a sample of dementia-free community-dwelling older adults.
DESIGN AND SETTING: We used cross-sectional data from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K).
PARTICIPANTS: Participants who were institutionalized, had dementia or Parkinson's disease, or had missing data on diet and/or biomarkers were excluded. Our study sample consisted of 1907 adults ≥60 years old.
MEASUREMENTS: Adherence to the MDS and EDII was assessed using a validated food frequency questionnaire. T-tau, p-tau181, Aβ 42/40, NfL, and GFAP were measured in serum. Associations were estimated through quantile regression models at the 25th, 50th, and 75th percentiles of the biomarkers’ levels, and were adjusted for potential confounders and stratified by sex, age, and APOE-e4 genotype.
RESULTS: In the whole sample, higher adherence to the MDS was associated with lower levels of p-tau181 at the 50th and 75th percentiles [β (95% CI) per 1-SD increment = -0.028 (-0.053, -0.002) and -0.036 (-0.072, -0.001), respectively], while higher adherence to the EDII was associated with higher levels of NfL at the 75th percentile [β (95% CI) per 1-SD increment =0.031 (0.008, 0.053)]. Associations with other biomarkers were only apparent at lower levels of their distribution. Subgroup analyses showed: 1) a stronger inverse association between the MDS and p-tau181 in APOE-e4 carriers than non-carriers, and 2) an inverse association of the MDS with GFAP only in participants ≥78 years.
CONCLUSIONS: Diet seems to be associated with biomarkers of AD pathology in cognitively intact older adults. Some associations were more apparent in the presence of genetic predisposition for AD or advanced age.
CITATION:
Anja Mrhar ; Adrián Carballo-Casla ; Giulia Grande ; Martina Valletta ; Claudia Fredolini ; Laura Fratiglioni ; Milica Gregorič Kramberger ; Aleš Kuhar ; Bengt Winblad ; Amaia Calderón-Larrañaga ; Davide Liborio Vetrano (2025): Dietary patterns and blood-based biomarkers of Alzheimer's disease in cognitively intact older adults: Findings from a population-based study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100124
BASELINE HABITUAL DIETARY NITRATE INTAKE AND ALZHEIMER\'S DISEASE RELATED NEUROIMAGING BIOMARKERS IN THE AUSTRALIAN IMAGING, BIOMARKERS AND LIFESTYLE STUDY OF AGEING
Anjana Rajendra, Nicola P. Bondonno, Kevin Murray, Liezhou Zhong, Stephanie R. Rainey-Smith, Samantha L. Gardener, Lauren C. Blekkenhorst, Vincent Doré, Victor L. Villemagne, Simon M. Laws, Belinda M. Brown, Kevin Taddei, Colin L. Masters, Christopher C. Rowe, Christopher C. Rowe, Jonathan M. Hodgson, Catherine P. Bondonno, AIBL Research Group
J Prev Alz Dis 2025;6(12)
Show summaryHide summaryBACKGROUND: Dietary nitrate, as a nitric oxide (NO) precursor, may support brain health and protect against dementia.
OBJECTIVE: Our primary aim was to investigate whether dietary nitrate is associated with neuroimaging markers of brain health linked with Alzheimer's disease (AD).
PARTICIPANTS: Study participants were cognitively unimpaired individuals from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL) who had β-amyloid positron emission tomography (PET) scans (n = 554) and magnetic resonance imaging (MRI) scans (n = 335) and had completed a Food Frequency Questionnaire at baseline.
METHODS: Source-specific nitrate intakes were estimated using comprehensive nitrate food composition databases. Rates of cerebral β-amyloid (Aβ) deposition, measured using PET, and rates of brain atrophy, measured using MRI, were assessed between baseline and 126-months follow-up, at intervals of 18 months. Multivariable-adjusted linear mixed effect models were used to examine associations between baseline source-specific nitrate intake and rates of (i) cerebral Aβ deposition and (ii) brain atrophy, over the 126 months of follow-up. Analyses were carried out following stratification of the sample by established dementia Alzheimer's disease (AD) risk factors including sex and presence or absence of the apolipoprotein E (APOE) ε4 allele.
RESULTS: In women carriers of the APOE ε4 allele, higher plant sourced nitrate intake (median intake 121 mg/day), was associated with a slower rate of cerebral Aβ deposition [β: 4.47 versus 8.99 Centiloid (CL) /18 months, p < 0.05] and right hippocampal atrophy [-0.01 versus -0.03 mm3 /18 months, p < 0.01], after multivariable adjustments. Moderate intake showed protective associations in men carriers and in both men and women non-carriers of APOE ε4.
CONCLUSIONS: Associations were observed between plant-derived nitrate intake and cerebral Aβ deposition, particularly in high-risk populations (women and APOE ε4 carriers). Associations were also observed for brain volume atrophy, however these exhibited subgroup variability without clear patterns relative to sex and APOE ε4 allele carriage. These findings suggest a potential link between plant-sourced nitrate and AD related neuroimaging markers of brain health improved brain health, but further validation in larger studies is required.
CITATION:
Anjana Rajendra ; Nicola P. Bondonno ; Kevin Murray ; Liezhou Zhong ; Stephanie R. Rainey-Smith ; Samantha L. Gardener ; Lauren C. Blekkenhorst ; Vincent Doré ; Victor L. Villemagne ; Simon M. Laws ; Belinda M. Brown ; Kevin Taddei ; Colin L. Masters ; Christopher C. Rowe ; Ralph N Martins ; Jonathan M. Hodgson ; Catherine P. Bondonno ; AIBL Research Group (2025): Baseline habitual dietary nitrate intake and Alzheimer's Disease related neuroimaging biomarkers in the Australian Imaging, Biomarkers and Lifestyle study of ageing. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100161
LIFESTYLE AND COGNITION: SEPARATING THE EFFECTS OF AVERAGE LIFESTYLE AND LIFESTYLE CHANGES BASED ON THE LIBRA SCORE
KEJ Wesenhagen, K Deckers, HSJ Picavet, ML Rietman, AAL Kok, S Köhler, MA Ikram, FJ Wolters, M Huisman, WMM Verschuren
J Prev Alz Dis 2025;6(12)
Show summaryHide summaryBACKGROUND: The LIfestyle for BRAin Health (LIBRA) score, consisting of twelve factors, highlights individuals’ potential for dementia risk reduction through lifestyle. The LIBRA score includes modifiable protective factors such as low to moderate alcohol consumption, and risk factors such as hypertension.
OBJECTIVE: We studied whether LIBRA scores are longitudinally associated with cognition, and to what extent this is due to between-person differences or within-person changes in LIBRA scores.
METHODS: Individuals were included from four Dutch community-based cohorts: Doetinchem Cohort Study (DCS; n = 4770), Maastricht Aging Study (MAAS; n = 1295), Longitudinal Aging Study Amsterdam (LASA; n = 2391) and the Rotterdam Study (RS; n = 5205). The number of available LIBRA components (range 7–11) and timepoints (range 3–9) differed per cohort. Outcomes were standardized processing speed (LDST), memory (15-word delayed recall of the verbal learning test (VLT)) and verbal fluency. Hybrid mixed models were fit for the association of 1) mean LIBRA score and 2) change in LIBRA between subsequent timepoints. Models were adjusted for age, sex, education and learning effects. Interactions of the mean LIBRA score with age, and change in LIBRA score with age were tested in two separate models.
RESULTS: Higher (i.e., unhealthier) mean LIBRA scores were associated with worse cognitive speed (lower LDST z-score per 1-point higher LIBRA, range between cohorts: 0.039 – 0.0587), memory (VLT, 0.026 – 0.035), and fluency (0.020 – 0.033). Associations of mean LIBRA scores with cognitive function were stronger with older age (LDST: significant age-interaction, 2 out of 4 cohorts; VLT and fluency: 1 out of 4 cohorts). Relative to 65-year-old individuals with a mean LIBRA score at the 50th percentile, individuals at the 90th percentile of the LIBRA score showed an estimated 1.9–3.2 years more advanced cognitive ageing for LDST, 1.9 – 5.3 years for VLT and 1.4 – 1.7 years for fluency. Within-person change in LIBRA showed no consistent associations with cognitive decline.
CONCLUSIONS: An individual's mean LIBRA score, but not their change in LIBRA score over time, was longitudinally associated with cognitive functioning. In the general population, the investigated version of the LIBRA score is possibly not suitable to capture how cognition (as a proxy for dementia risk) changes with improvements in lifestyle.
CITATION:
KEJ Wesenhagen ; K Deckers ; HSJ Picavet ; ML Rietman ; AAL Kok ; S Köhler ; MA Ikram ; FJ Wolters ; M Huisman ; WMM Verschuren (2025): Lifestyle and cognition: Separating the effects of average lifestyle and lifestyle changes based on the LIBRA score. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100159
ASSOCIATIONS BETWEEN THE EAT-LANCET PLANETARY HEALTH DIET AND INCIDENT DEMENTIA
Jessica Samuelsson, Isabelle Glans, Anna Stubbendorff, Ulrika Ericson, Sebastian Palmqvist, Oskar Hansson, Emily Sonestedt
J Prev Alz Dis 2025;6(12)
Show summaryHide summaryBACKGROUND: The impact of the environmentally sustainable EAT-Lancet diet on dementia risk remains poorly understood. The aim was to investigate associations between the EAT-Lancet diet and incident dementia.
METHODS: Associations of the EAT-Lancet diet with all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD) were investigated among 25,898 participants from the Malmö Diet and Cancer study, Sweden. Participants aged 45–73 years were recruited for the baseline examination between 1991 and 1996, and the mean follow-up time was 18 years. To assess robustness of estimations, we used seven previously constructed EAT-Lancet diet scores. Multi-adjusted Cox proportional hazard analyses were performed, with results presented per 10 % in increment scores. Additionally, we explored the potentially modifying effect of APOE ε4 status in this context.
RESULTS: With one of the scores, higher adherence to the EAT-Lancet diet was associated with a reduced risk of AD and all-cause dementia. Moreover, the results suggest an interplay between the EAT-Lancet diet and APOE ε4 status. A risk-reducing effect was observed among APOE ε4 non-carriers with three of the scores in relation to AD, and with five of the scores in relation to all-cause dementia. No associations were observed among APOE ε4 carriers, or in relation to VaD.
CONCLUSION: The results indicate a risk reducing effect of adhering to the EAT-Lancet diet among APOE ε4 non-carriers, and no negative effects on dementia risk were detected. Future studies should consider the potentially modifying effect of APOE ε4 status, and the implications of methodological differences in measuring adherence to the EAT-Lancet diet.
CITATION:
Jessica Samuelsson ; Isabelle Glans ; Anna Stubbendorff ; Ulrika Ericson ; Sebastian Palmqvist ; Oskar Hansson ; Emily Sonestedt (2025): Associations between the EAT-Lancet planetary health diet and incident dementia. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100166
THE ROLE OF SERUM VITAMINS IN MEDIATING THE EFFECT OF NEURODEGENERATIVE DISEASES ON SUBCORTICAL BRAIN VOLUME
Haonan Li, Meng Cheng, Nannan Zhang, Siqi Wang, Caihua Ye, Haodong Li, Shengnan Wang, Zirui Wang, Xuan Yang, Zhixuan Liu, Xingyu Zhang, Jiayuan Xu, Qiang Xu, Junping Wang
J Prev Alz Dis 2025;6(12)
Show summaryHide summaryBACKGROUND: Neurodegenerative diseases (NDs) lead to a progressive loss of neuronal cells and link to atrophy of subcortical brain structures, but the causal intermediates are not known. To test whether major NDs (Alzheimer's disease (AD), Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis) causally affects subcortical atrophy, and whether serum vitamin level play a mediating role in this process.
METHODS: Using large-scale genome-wide association study (GWAS) summary data, we performed two-sample Mendelian randomization (MR) to assess the causal effect of NDs on the volume of seven subcortical structures, and then adopted two-step multivariable MR approach to quantify the proportion of the effect of NDs on the volume of subcortical regions mediated by serum vitamin level. Finally, we utilized animal experiments to validate results and explored the potential molecular mechanisms.
RESULTS: Genetically predicted AD was associated with atrophy of the nucleus accumbens (NAc) (β = -0.09; p = 5.13 × 10–5), amygdala (β = -0.07; p = 8.44 × 10–4), and hippocampus (β = -0.07; p = 0.001), as well as with low serum vitamin D level (β = -0.02; p = 6.84 × 10–6). Specifically, decreased serum vitamin D level mediated 3.99 % (95 % CI: -0.006 to -5.82 × 10–5) and 3.97 % (95 % CI: -0.007 to -2.94 × 10–4) of the total effect of AD on hippocampal and NAc atrophy, respectively. Animal experiments further confirmed significant delays in hippocampal and NAc atrophy, a significant reduction of β-amyloid deposits and an increase of vitamin D receptor expression in hippocampus in AD mice with high-dose vitamin D diet.
CONCLUSIONS: These findings provide important insights into the effect sizes of vitamin D-mediated roles in AD and atrophy of subcortical structures. Interventions to increase serum vitamin D levels at a population level might attenuate damage to hippocampus in patients with AD.
CITATION:
Haonan Li ; Meng Cheng ; Nannan Zhang ; Siqi Wang ; Caihua Ye ; Haodong Li ; Shengnan Wang ; Zirui Wang ; Xuan Yang ; Zhixuan Liu ; Xingyu Zhang ; Jiayuan Xu ; Qiang Xu ; Junping Wang (2025): The role of serum vitamins in mediating the effect of neurodegenerative diseases on subcortical brain volume. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100155
OPPOSITE CAUSAL EFFECTS OF TYPE 2 DIABETES AND METFORMIN ON ALZHEIMER\'S DISEASE
Dongming Liu, Hongbao Cao, Ancha Baranova, Chenxin Xu, Fuquan Zhang
J Prev Alz Dis 2025;6(12)
Show summaryHide summaryBACKGROUND: Type 2 diabetes (T2D) is commonly co-morbid with Alzheimer's disease (AD). However, it remains unclear whether T2D itself or the antidiabetic drug metformin contributes to the progression of AD.
OBJECTIVE: This study aimed to investigate the overall and independent effects of T2D and metformin use on the risk of AD.
METHODS: Summary genome-wide association study datasets were utilized for the Mendelian randomization (MR) and multivariable MR (MVMR) analyses, including ones for T2D (N = 455,017), metformin (N = 456,276), and AD (N = 453,733). Additionally, using the proportional imbalance method, we analyzed AD-related adverse drug events in the FDA Adverse Event Reporting System (FAERS) database (covering Q1 2004 to Q2 2024).
RESULTS: Our two-sample MR analysis indicated that T2D is not associated with the risk of AD (OR: 1.03, CI: 0.99–1.08, P = 0.128). However, while not statistically significant, genetic signature for metformin exposure demonstrated a trend toward an increased risk of AD (OR: 1.05, CI: 1.00–1.09, P = 0.053). Interestingly, in MVMR analysis, which evaluates independent effects of T2D and metformin exposure on T2D, we found a robust association of T2D with a decrease in the risk of AD (OR: 0.82, CI: 0.68–0.98, P = 0.031), while the use of metformin was associated with a higher risk of AD (OR: 1.26, CI: 1.06–1.50, P = 9.45E-3). In the FAERS database, a total of 228,283 metformin-related adverse event reports from 67,742 cases were found. For metformin as the target drug and AD as the target adverse event, signal analysis reported 29 cases of AD (ROR: 0.83, 95 % CI: 0.58–1.19, P = 0.3126).
CONCLUSIONS: Our study reveals the opposite independent causal effects of T2D and metformin exposure on AD. These findings highlight the importance of assessing AD risk when prescribing metformin to patients with T2D.
CITATION:
Dongming Liu ; Hongbao Cao ; Ancha Baranova ; Chenxin Xu ; Fuquan Zhang (2025): Opposite causal effects of type 2 diabetes and metformin on Alzheimer's disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100129
LATENT COGNITIVE PROFILES AND THEIR ASSOCIATIONS WITH INSTRUMENTAL ACTIVITIES OF DAILY LIVING AMONG OLDER ADULTS WITHOUT DEMENTIA: A UNITED STATES NATIONAL CROSS-SECTIONAL STUDY
Jiaying Li, Sarah L. Szanton, Junxin Li
J Prev Alz Dis 2025;6(12)
Show summaryHide summaryBACKGROUND: Conventional dichotomous classifications of cognitive status in older adults (normal vs impaired) may obscure distinct domain-specific deficits. Identifying nuanced cognitive profiles could enable personalized interventions, particularly when tailored to instrumental activities of daily living (IADLs).
OBJECTIVES: To identify distinct cognitive profiles in older adults without dementia and assess their associations with overall and domain-specific IADL performance.
DESIGN/SETTING/PARTICIPANTS: Cross-sectional data from 2219 adults aged ≥65 years without dementia in the nationally representative National Health and Aging Trends Study.
MEASUREMENTS: Latent profile analysis classified participants across six cognitive domains: episodic memory, executive function, orientation, psychomotor function, visual attention, and working memory. Logistic and linear regression models with Holm-Bonferroni corrections evaluated relationships between cognitive profiles and IADL performance.
RESULTS: Five profiles emerged: Profile 1: Overall intact (50.5 % of participants); Profile 2: Isolated moderate orientation impairment (15.6 %); Profile 3: Mild global impairment with preserved orientation (22.0 %); Profile 4: Mild global impairment with significant orientation impairment (5.5 %); Profile 5: Moderate global impairment (6.2 %). Compared with Profile 1, all other profiles exhibited significantly higher overall IADL difficulty and were more likely to experience challenges with shopping, medication management, meal preparation, and banking (all adjusted p < 0.05). Profile 4 had the highest odds for difficulties with shopping (OR, 2.19; 95 % CI, 1.41–3.38; adjusted p = 0.005) and banking (OR, 3.98; 95 % CI, 2.62–6.04; adjusted p < 0.001), whereas Profile 5 showed the greatest risk for medication management (OR, 2.55; 95 % CI, 1.66–3.90; adjusted p < 0.001) and meal preparation (OR, 2.22; 95 % CI, 1.49–3.31; adjusted p = 0.001).
CONCLUSION: Nearly half of older adults without dementia exhibit distinct cognitive profiles warranting tailored interventions. Profile 5 requires comprehensive strategies, whereas Profiles 2, 3, and 4 may benefit from orientation-targeted and intensity-varied training in other cognition domain. Incorporating specific IADL tasks (e.g., meal preparation, medication management for Profile 5 and shopping, banking for Profile 4) into cognitive interventions may concurrently enhance cognitive health and functional independence.
CITATION:
Jiaying Li ; Sarah L. Szanton ; Junxin Li (2025): Latent cognitive profiles and their associations with instrumental activities of daily living among older adults without dementia: A United States national cross-sectional study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100162
THE COST-EFFECTIVENESS OF AN ONLINE INTERVENTION TO PREVENT DEMENTIA: RESULTS FROM THE MAINTAIN YOUR BRAIN (MYB) RANDOMISED CONTROLLED TRIAL
Heidi J Welberry, Li-Jung Elizabeth Ku, Sophy TF Shih, Louisa R Jorm, Maria Fiatarone Singh, Michael Valenzuela, Jeewani Anupama Ginige, Kaarin J. Anstey, Perminder S. Sachdev, John J McNeil, Nicola T Lautenschlager, Megan Heffernan, Tiffany Chau, Henry Brodaty
J Prev Alz Dis 2025;6(12)
Show summaryHide summaryBACKGROUND: The Maintain Your Brain (MYB) randomised controlled trial (RCT) examined the effect of a multi-domain internet-based dementia prevention program against a control group (information only).
OBJECTIVES: A cost-effective analysis (CEA) quantified the differences in costs (direct healthcare and program costs) and effectiveness outcomes between the intervention and control groups from a healthcare sector perspective.
DESIGN: An economic evaluation was conducted alongside the MYB RCT over three years.
SETTING: Australians aged 55–77 years with at least 2 identified remediable risk factors for cognitive decline/dementia recruited from communities in New South Wales.
PARTICIPANTS: There were 3,025 participants in the intervention group and 3,033 in the control group with available linked healthcare data via the Sax Institute's 45 and Up Study out of the 6104 enrolled in the trial (99.2% of total cohort).
INTERVENTION: The MYB trial comprised a personalised schedule of online coaching in physical activity, nutrition, cognitive activity, and depression or anxiety management.
MEASUREMENTS: The two effectiveness outcomes were global cognition composite (GCC) scores and the Australian National University-Alzheimer's Disease Risk Index –short form (ANU-ADRI-SF) questionnaire scores. Costs included MYB program costs and the direct healthcare costs incurred by the MYB participants. All costs were reported in Australian dollars (AUD$) during the trial period. The time horizon of this analysis was 3 years after randomisation (2018-2021). Incremental cost-effectiveness ratio (ICERs) between the intervention and the control groups were calculated by comparing the average difference in costs to a mean difference in z score for GCC and ANU-ADRI-SF score using the bootstrapped means and 95% Confidence Intervals.
RESULTS: The total unadjusted program and healthcare costs over three years were similar between groups (AUD$16,521 per person in the control group and AUD$16,473 in the intervention group). After adjusting for baseline characteristics, the average difference between groups in total cost per person at three years was not statistically different: AUD$467 favouring the control group (95%CI: -$552 - $1585). This was compared to a significant mean difference (improvement) in GCC z score at three years of 0.18 (95%CI: 0.13, 0.23) and -0.57 (95%CI: -0.95, -0.24) point difference in ANU-ADRI-SF for the intervention versus control. The base case ICERs were AUD$2,568 per 1 standard deviation in z score and $823 per reduction of 1 ANU-ADRI-SF point. With 1000 bootstrapped replications, the scatterplots of ICER ellipses suggest that the MYB intervention was more effective than the control group and with no significant difference in overall healthcare costs.
CONCLUSION: The MYB trial showed cost-effectiveness for preventing cognitive decline and reducing dementia risk. Longer-term follow-up and dissemination to other cohorts is needed to confirm the impact on preventing future cases of dementia and relevance to other socio-economic and cultural/ethnic groups than those enrolled in the original trial.
CITATION:
Heidi J Welberry ; Li-Jung Elizabeth Ku ; Sophy TF Shih ; Louisa R Jorm ; Maria Fiatarone Singh ; Michael Valenzuela ; Jeewani Anupama Ginige ; Kaarin J. Anstey ; Perminder S. Sachdev ; John J McNeil ; Nicola T Lautenschlager ; Megan Heffernan ; Tiffany Chau ; Henry Brodaty (2025): The cost-effectiveness of an online intervention to prevent dementia: Results from the Maintain Your Brain (MYB) randomised controlled trial. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100151
PATIENT MANAGEMENT PATHWAYS IN DEMENTIA – RESOURCE UTILISATION, DIAGNOSIS AND DRUG TREATMENT IN THE STOCKHOLM REGION, SWEDEN
Emil Aho, Dorota Religa, Mozhu Ding, Bengt Winblad, Linus Jönsson, Karin Modig
J Prev Alz Dis 2025;6(12)
Show summaryHide summaryBACKGROUND: New diagnostic and therapeutic options for Alzheimer's disease are beginning to be introduced and expected igto become more widely available in the coming years. Improved understanding of current pathways in diagnosis and initial care of patients with dementia can help inform choices around how best to integrate new technologies in existing care structures.
OBJECTIVES: The aim of this study is to describe the care management pathways defined by the involvement of specialist and primary care for individuals with newly diagnosed dementia. It also seeks to characterise individuals in different management pathways based on resource use prior to diagnosis, the type of dementia diagnosis received, and the proportion who receive symptomatic anti-dementia drug treatment.
DESIGN: Observational cohort study.
SETTING: Stockholm region, Sweden.
PARTICIPANTS: All newly diagnosed dementia cases between 1st January 2018 to 30th June 2020 (n = 9,781). Dementia diagnoses in primary care were based on Regional Stockholm health care database and diagnoses in specialist care were based on the National Patient Register in Sweden.
MEASUREMENTS: Care management pathways were categorized into three groups: primary care only (diagnosed and followed up in primary care), specialist, no follow-up (diagnosed in specialist care but not followed up in specialist care), and specialist with follow-up (diagnosed and followed up in specialist care). These classifications were based on patients’ care episodes from the date of diagnosis and the subsequent 18 months. age at diagnosis, resource utilisation one-year prior diagnosis and diagnosis given and symptomatic anti-dementia treatment 18 months after initial diagnosis.
RESULTS: A total of 9,781 newly diagnosed dementia cases were identified. In the 18 months following diagnosis, 63 % of patients were diagnosed either partly or fully in specialist care, while 37 % were diagnosed solely in primary care. Patients diagnosed and managed only in primary care were older, spent more days in hospital, and received more social care in the year preceding their diagnosis. Their total care costs were also the highest. Alzheimer's disease was the most common diagnosis (48 %), while 27 % had an unspecified dementia diagnosis, varying by care setting (61 % for patients managed in primary care only and 6 % for patients diagnosed and followed up in specialist care). Overall, 47 % of patients received symptomatic anti-dementia treatment, with the highest share for patients diagnosed and followed up in specialist care (73 %) and the lowest in primary care only (19 %). Diagnosis varied by age and care setting Alzheimer's was most common in settings involving specialist care, whereas unspecified dementia was more common in primary care only regardless of age.
CONCLUSION: The findings that patients managed exclusively in primary care were older, had higher pre-diagnosis resource utilisation, and were less likely to receive specific diagnoses or anti-dementia treatments highlight the crucial role of primary care in diagnosing and managing dementia among older individuals with complex needs. Further research is needed to explore primary care's role in diagnosis and treatment across diverse healthcare systems.
Future research is needed to explore whether and how new diagnostic tools and treatment for AD could facilitate timely diagnosis and care for older individuals with dementia in primary care.
CITATION:
Emil Aho ; Dorota Religa ; Mozhu Ding ; Bengt Winblad ; Linus Jönsson ; Karin Modig (2025): Patient management pathways in dementia – Resource utilisation, diagnosis and drug treatment in the Stockholm region, Sweden. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100132
ASSOCIATION BETWEEN THE USE OF INFORMATION AND COMMUNICATION TECHNOLOGY AND COGNITIVE DECLINE STRATIFIED BY SOCIAL ISOLATION: THE OTASSHA STUDY
Keigo Imamura, Hisashi Kawai, Manami Ejiri, Hiroyuki Sasai, Kazushige Ihara, Harumi Nakada, Atsushi Araki, Hirohiko Hirano, Yoshinori Fujiwara, Takao Suzuki, Shuichi Obuchi
J Prev Alz Dis 2025;6(12)
Show summaryHide summaryBACKGROUND: Prevention of dementia is crucial for reducing its social burden. Social isolation is a known risk factor for dementia. The use of information and communication technology is associated with reduced cognitive decline. However, longitudinal associations of the use of information and communication technology with cognitive function remain unknown, especially for older adults who are socially isolated and at a high risk of cognitive decline.
OBJECTIVES: To investigate the association between the use of information and communication technology and changes in cognitive function among older adults with and without social isolation.
DESIGN: Longitudinal observational study.
SETTING: Data was obtained for two cohorts of community-dwelling older adults aged 65 years with no cognitive impairment (Mini-Mental State Examination score ≥24) at baseline.
PARTICIPANTS: Participants were defined as those who completed baseline assessments of the use of information and communication technology, social isolation, and cognitive function and underwent at least one follow-up assessment of cognitive function in a follow-up survey conducted annually through 2023.
MEASUREMENTS: The use of information and communication technology was measured using the technology usage sub-items of the Japan Science and Technology Agency Index of Competence. Cognitive function and social isolation were assessed using the Mini-Mental State Examination and the six-item Lubben Social Network Scale, respectively. Data from the two cohorts were combined to examine the association between the use of information and communication technology and changes in cognitive function, as well as the association between the use of information and communication technology and the incidence of cognitive decline (Mini-Mental State Examination <24), using mixed effects models and Cox proportional hazards models, respectively. These analyses were conducted separately based on social isolation.
RESULTS: A total of 1,322 participants (mean age: 72.3 years, 39 % male) were included in the final analysis. The median follow-up period was 3.9 years. Individuals who used information and communication technology experienced a slower rate of cognitive decline than non-users (-0.09, 95 % confidence interval: -0.11 to -0.07 vs. -0.18, 95 % confidence interval: -0.21 to -0.15). In addition, information and communication technology use was associated with a significantly lower risk of cognitive decline (hazard ratio: 0.73, 95 % confidence interval: 0.70–0.76). This association remained consistent among older adults with social isolation (hazard ratio: 0.91, 95 % confidence interval: 0.85–0.97).
CONCLUSIONS: The use of information and communication technology was associated with a reduced risk of cognitive decline, even among socially isolated older adults. Creating an environment that enables effective ICT use with appropriate support may help preserve cognitive function in aging populations.
CITATION:
Keigo Imamura ; Hisashi Kawai ; Manami Ejiri ; Hiroyuki Sasai ; Kazushige Ihara ; Harumi Nakada ; Atsushi Araki ; Hirohiko Hirano ; Yoshinori Fujiwara ; Takao Suzuki ; Shuichi Obuchi (2025): Association between the use of information and communication technology and cognitive decline stratified by social isolation: The Otassha study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100138
LONGITUDINAL ASSOCIATIONS OF CAROTID ARTERY STIFFNESS WITH PROGRESSION OF CEREBROVASCULAR DISEASE, INCIDENT DEMENTIA AND COGNITIVE DECLINE IN OLDER ADULTS
Caroline Robert, Lieng-Hsi Ling, Eugene S.J. Tan, Narayanaswamy Venketasubramanian, Shir Lynn Lim, Lingli Gong, Josephine Lunaria Berboso, Arthur Mark Richards, Christopher Chen, Saima Hilal, Josephine Lunaria Berboso, Arthur Mark Richards, Christopher Chen, Saima Hilal
J Prev Alz Dis 2025;6(12)
Show summaryHide summaryBACKGROUND: Carotid artery stiffness is associated with cerebrovascular disease (CeVD) and cognitive impairment, but evidence for its longitudinal effects on progression of CeVD and cognitive decline are limited.
OBJECTIVES: To evaluate the longitudinal associations of carotid artery stiffness with CeVD progression, incident dementia, and cognitive decline.
DESIGN: Longitudinal analyses from a memory-clinic cohort with a follow-up of 2 years.
SETTING: A memory-clinic study.
PARTICIPANTS: 194 participants (mean age=80, 63 % female) with or without cognitive impairments provided consent to take part in the study.
MEASUREMENTS: Participants underwent carotid ultrasonography, brain MRI, and neuropsychological assessments were at baseline and follow-up. Carotid stiffness measures included ß-index, elastic modulus (Ep), and pulse wave velocity-ß (PWV-ß). CeVD markers included white matter hyperintensities (WMH), lacunes, cerebral microbleeds (CMBs) and cortical infarcts. Cognition was assessed with a neuropsychological battery.
RESULTS: After 2 years, incident CeVD cases included lacunes (15.7 %), CMBs (23.8 %), and cortical infarcts (7.6 %). ß-index (ß=0.78, p < 0.001), Ep (ß=0.94, p < 0.001), and PWV-ß (ß=0.15, p = 0.003) were independently associated with WMH progression. Ep (ß=-0.15, p = 0.007) and PWV-ß (ß=-3.68, p = 0.007) were independently associated with visuomotor speed decline. No association was found with incident lacunes, CMBs or dementia.
CONCLUSION: Carotid stiffness progression is associated with WMH progression and visuomotor speed decline.
CITATION:
Caroline Robert ; Lieng-Hsi Ling ; Eugene S.J. Tan ; Narayanaswamy Venketasubramanian ; Shir Lynn Lim ; Lingli Gong ; Josephine Lunaria Berboso ; Arthur Mark Richards ; Christopher Chen ; Saima Hilal (2025): Longitudinal associations of carotid artery stiffness with progression of cerebrovascular disease, incident dementia and cognitive decline in older adults. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100127
MULTI-OMICS ANALYSIS OF DRUGGABLE GENES TO FACILITATE ALZHEIMER\'S DISEASE THERAPY: A MULTI-COHORT MACHINE LEARNING STUDY
Jichang Hu, Yong Luo, Xiaochuan Wang
J Prev Alz Dis 2025;6(12)
Show summaryHide summaryBACKGROUND: The swift rise in the prevalence of Alzheimer's disease (AD) alongside its significant societal and economic impact has created a pressing demand for effective interventions and treatments. However, there are no available treatments that can modify the progression of the disease.
METHODS: Eight AD brain tissues datasets and three blood datasets were obtained. Consensus clustering was utilized as a method to discern the various subtypes of AD. Then, module genes were screened using weighted correlation network analysis (WGCNA). Furthermore, screening hub genes was conducted through machine-learning analyses. Finally, A comprehensive analysis using a systematic approach to druggable genome-wide Mendelian randomization (MR) was conducted.
RESULTS: Two AD subclasses were identified, namely cluster.A and cluster.B. The levels of gamma secretase activity, beta secretase activity, and amyloid-beta 42 were found to be significantly elevated in patients classified within cluster A when compared to those in cluster B. Furthermore, by utilizing the differentially expressed genes shared among these clusters, along with identifying druggable genes and applying WGCNA to these subtypes, we were able to develop a scoring system referred to as DG.score. This scoring system has demonstrated remarkable predictive capability for AD when evaluated against multiple datasets. Besides, A total of 30 distinct genes that may serve as potential drug targets for AD were identified across at least one of the datasets investigated, whether derived from brain samples or blood analyses. Among the identified genes, three specific candidates that are considered druggable (LIMK2, MAPK8, and NDUFV2) demonstrated significant expression levels in both blood and brain tissues. Furthermore, our research also revealed a potential association between the levels of LIMK2 and concentrations of CSF Aβ (OR 1.526 (1.155–2.018)), CSF p-tau (OR 1.106 (1.024–01.196)), and hippocampal size (OR 0.831 (0.702–0.948)).
CONCLUSIONS: This study provides a notable advancement to the existing literature by offering genetic evidence that underscores the potential therapeutic advantages of focusing on the druggable gene LIMK2 in the treatment of AD. This insight not only contributes to our understanding of AD but also guides future drug discovery efforts.
CITATION:
Jichang Hu ; Yong Luo ; Xiaochuan Wang (2025): Multi-omics analysis of druggable genes to facilitate Alzheimer's disease therapy: A multi-cohort machine learning study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100128
CHRONOTYPE AS A POTENTIAL RISK FACTOR FOR COGNITIVE DECLINE: THE MEDIATING ROLE OF SLEEP QUALITY AND HEALTH BEHAVIOURS IN A 10-YEAR FOLLOW-UP STUDY
A.N. Wenzler, A.C. Liefbroer, R.C. Oude Voshaar, N. Smidt
J Prev Alz Dis 2025;6(12)
Show summaryHide summaryBACKGROUND: – With rising life expectancies and ageing populations worldwide, preserving cognitive health is an urgent global priority. Chronotype could be a potential risk factor for cognitive decline, potentially through mediators sleep quality, alcohol intake, physical activity, and smoking.
METHODS: – This study used data from participants aged 40 years and older from the Lifelines cohort study (n = 23,798). Chronotype, assessed with the Munich ChronoType Questionnaire, was included as a continuous score of mid-point sleep corrected for sleep debt on workdays. Multiple linear regression examined the association between chronotype and cognitive decline, including moderation by age, educational attainment, and sex. The KHB-method was applied to test mediation by sleep quality, alcohol intake, physical activity, and smoking.
OUTCOMES: – Cognition was assessed with the Ruff Figural Fluency Test (RFFT), measuring non-verbal fluency and executive functioning. Cognitive decline was calculated by subtracting the RFFT sum score at baseline from the 10-year follow-up score.
RESULTS: – Chronotype was associated with cognitive decline. Educational attainment, but not age or sex, moderated the relationship. No significant associations were observed in the low- (0.07, 95 % CI: -0.44, 0.57) or middle- (-0.41, 95 % CI: -0.88, 0.06) educational groups. In the high-educational group each one-hour increase in chronotype corresponded to a 0.80-point decline in cognition per decade (95 % CI: -1.34, -0.26). In this group, sleep quality and current smoking mediated 13.52 % and 18.64 % of the association, respectively.
INTERPRETATION: – Chronotype was associated with greater decline in non-verbal fluency and executive functioning among higher educated participants, highlighting the importance of targeted prevention strategies.
CITATION:
A.N. Wenzler ; A.C. Liefbroer ; R.C. Oude Voshaar ; N. Smidt (2025): Chronotype as a potential risk factor for cognitive decline: The mediating role of sleep quality and health behaviours in a 10-year follow-up study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100168
LONG-TERM CUMULATIVE PHYSICAL ACTIVITY ASSOCIATED WITH LESS COGNITIVE DECLINE: EVIDENCE FROM A 16-YEAR COHORT STUDY
Suhang Song, Meng Hsuan Sung, Diana Diaz, Zhuofan Lin, Allan D. Tate, Zhuo Chen, Janani Rajbhandari-Thapa, Grace Bagwell Adams, M. Mahmud Khan, Ye Shen, Lisa M. Renzi-Hammond, Yinzi Jin
J Prev Alz Dis 2025;6(12)
Show summaryHide summaryINTRODUCTION: Physical activity (PA) has been reported to delay cognitive decline. However, the role of long-term, cumulative PA (cPA) in cognitive decline remains unclear.
METHODS: This longitudinal study obtained data from Health and Retirement Study, 2004-2020. Global cognition was operationalized as the sum of memory and executive function scores on a battery of cognitive tests. cPA was operationalized as the area under the curve of the metabolic equivalent of tasks (MET) adjusted PA. Generalized linear mixed models were fitted to examine the associations between cPA and cognitive change.
RESULTS: This study included 13,450 cognitively healthy participants, with a mean follow-up duration of 11.06 (SD=4.91) years. Higher cPA was associated with delayed declines in global cognition (p<.001), memory (p<.001) and executive function (p<.001), and such protective benefits grew over the 16-year study period. Longer PA engagement was associated with progressively delayed cognitive decline.
CONCLUSION: PA engagement over long timeframes may better maintain cognitive performance.
CITATION:
Suhang Song ; Meng Hsuan Sung ; Diana Diaz ; Zhuofan Lin ; Allan D. Tate ; Zhuo Chen ; Janani Rajbhandari-Thapa ; Grace Bagwell Adams ; M. Mahmud Khan ; Ye Shen ; Lisa M. Renzi-Hammond ; Yinzi Jin (2025): Long-term cumulative physical activity associated with less cognitive decline: Evidence from a 16-year cohort study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100194
LETTER TO THE EDITOR: DISPARITIES IN OUT-OF-POCKET COSTS FOR DISEASE-MODIFYING THERAPY UNDER JAPAN\'S UNIVERSAL HEALTH INSURANCE SYSTEM
Kenichiro Sato, Ryoko Ihara, Yoshiki Niimi, Saki Nakashima, Atsushi Iwata, Takeshi Iwatsubo
J Prev Alz Dis 2025;6(12)
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CITATION:
Kenichiro Sato ; Ryoko Ihara ; Yoshiki Niimi ; Saki Nakashima ; Atsushi Iwata ; Takeshi Iwatsubo (2025): Letter to the Editor: Disparities in out-of-pocket costs for disease-modifying therapy under Japan's universal health insurance system. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100170
LETTER TO THE EDITOR: HERPES ZOSTER AND DEMENTIA RISK
Shih-Wei Lai, Kuan-Fu Liao
J Prev Alz Dis 2025;6(12)
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CITATION:
Shih-Wei Lai ; Kuan-Fu Liao (2025): Letter to the Editor: Herpes zoster and dementia risk. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100198
REPLY TO THE LETTER TO THE EDITOR: HERPES ZOSTER AND DEMENTIA RISK
Lorenzo Blandi, Paola Bertuccio, Carlo Signorelli, Helmut Brand, Timo Clemens, Cristina Renzi, Anna Odone
J Prev Alz Dis 2025;6(12)
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CITATION:
Lorenzo Blandi ; Paola Bertuccio ; Carlo Signorelli ; Helmut Brand ; Timo Clemens ; Cristina Renzi ; Anna Odone (2025): Reply to the Letter to the Editor: Herpes Zoster and Dementia Risk. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100197
RESPONSE TO “MULTI-OMICS ANALYSIS OF DRUGGABLE GENES TO FACILITATE ALZHEIMER\'S DISEASE THERAPY: A MULTI-COHORT MACHINE LEARNING STUDY”
Jichang Hu
J Prev Alz Dis 2025;6(12)
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CITATION:
Jichang Hu (2025): Response to “Multi-omics analysis of druggable genes to facilitate Alzheimer's disease therapy: A multi-cohort machine learning study”. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100250
COMMENT ON “MULTI-OMICS ANALYSIS OF DRUGGABLE GENES TO FACILITATE ALZHEIMER\'S DISEASE THERAPY: A MULTI-COHORT MACHINE LEARNING STUDY”
Jihao Xue, Yitian Chen, Ligang Chen, Qijia Yin
J Prev Alz Dis 2025;6(12)
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