03/2025 journal articles
EDITORIAL: VISION, COURAGE, AND ACADEMIC FREEDOM
Bruno Vellas
J Prev Alz Dis 2025;3(12)
Show summaryHide summary
CITATION:
Bruno Vellas (2025): Vision, courage, and academic freedom. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100095
VALIDATION OF THE MULTI-DAY BOSTON REMOTE ASSESSMENT OF NEUROCOGNITIVE HEALTH (BRANCH) AMONG COGNITIVELY IMPAIRED & UNIMPAIRED OLDER ADULTS
Emma L. Weizenbaum, Stephanie Hsieh, Cassidy Molinare, Daniel Soberanes, Caitlyn Christiano, Andrea??M? Román Viera, Juliana A.U. Anzai, Stephanie Moreno, Emily C. Campbell, Hyun-Sik Yang, Gad A. Marshall, Reisa A. Sperling, Kathryn V. Papp, Rebecca E. Amariglio
J Prev Alz Dis 2025;3(12)
Show summaryHide summaryBACKGROUND: The multi-day Boston Remote Assessment of Neurocognitive Health (BRANCH) is a remote, web-based assessment designed to capture the earliest cognitive changes in the preclinical stage of Alzheimer's disease (AD). It has been validated in unimpaired older adults, but as individuals progress on the AD continuum, assessments need to remain feasible and valid at different clinical stages. The focus of this study was to assess feasibility and validity of multi-day BRANCH in participants with and without cognitive impairment.
METHODS: For seven days participants completed the BRANCH paradigm to capture a muti-day learning curve score. Participants also completed the mini-mental-status-exam (MMSE) and the Quick Dementia Rating Scale (QDRS). The primary cohort included 81 older adults: 38 with cognitive impairment (CI) and 43 cognitively-unimpaired (CU). A complementary replication cohort included 16 participants with consensus-defined mild cognitive impairment (MCI) and 47 demographically-matched cognitively unimpaired participants.
RESULTS: Multi-day BRANCH was feasibile with 92 % or participants completing all seven days of testing. More CI than CU reported nervousness and found tasks slightly less enjoyable on Day 1, but ratings increased at a similar rate in both groups. Convergent validity was confirmed by a positive association between BRANCH and total MMSE and QDRS scores. There was a large effect size of group status on BRANCH (CI vs. CU; Cohen's d = 0.83) and per logistic regression, BRANCH significantly predicted group status (β = -1.49, p < 0.001); even more so between MCI and CU in the replication cohort.
CONCLUSIONS: Findings suggest that a remotely administered web-based assessment of multi-day learning is feasible and valid in participants with and without cognitive impairment.
CITATION:
Emma L. Weizenbaum ; Stephanie Hsieh ; Cassidy Molinare ; Daniel Soberanes ; Caitlyn Christiano ; Andrea M․ Román Viera ; Juliana A.U. Anzai ; Stephanie Moreno ; Emily C. Campbell ; Hyun-Sik Yang ; Gad A. Marshall ; Reisa A. Sperling ; Kathryn V. Papp ; Rebecca E. Amariglio (2025): Validation of the multi-day Boston remote assessment of neurocognitive health (BRANCH) among cognitively impaired & unimpaired older adults. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100057
MEMSCREEN: A SMARTPHONE APPLICATION FOR DETECTION OF MILD COGNITIVE IMPAIRMENT: A VALIDATION STUDY: SMARTPHONE APP FOR MCI DETECTION
Julien Dumurgier, Claire Paquet, Jacques Hugon, Vincent Planche, Sinead Gaubert, Stéphane Epelbaum, Stéphanie Bombois, Marc Teichmann, Richard Levy, Estelle Baudouin, Agathe Vrillon, Claire Hourrègue, Emmanuel Cognat, Séverine Sabia, Archana Singh-Manoux
J Prev Alz Dis 2025;3(12)
Show summaryHide summaryBACKGROUND AND OBJECTIVES: Primary care is often the first point of contact for patients with cognitive complaints, making initial cognitive screening an essential step to avoid delays in diagnosing Alzheimer's disease (AD) at an early stage. We developed MemScreen, a self-administered smartphone application that assesses overall cognition and verbal memory, and evaluated its ability to detect mild cognitive impairment (MCI) in both general and clinical populations.
METHODS: We conducted two validation cohort studies: (1) UK-based Whitehall II cohort study (13th wave, 2018–2022) involving a general population (MCI defined by poor performance on a global cognitive score), and (2) five French memory clinics involving patients without dementia (amnestic MCI defined by the Free and Cued Selective Reminding Test). MemScreen, MMSE, and TMT-A effectiveness was assessed using Area Under the Curve (AUC) values from unadjusted and adjusted logistic regression models.
RESULTS: In Whitehall II (n = 2118, mean age 75.9 years, 23.9 % women, 14.5 % MCI), median MemScreen completion time was 4 min 18 s. MemScreen had the highest AUC (0.87; 95 % CI: 0.82–0.89) for distinguishing MCI, outperforming MMSE (AUC = 0.79; 0.76–0.82; p = 0.018) and TMT-A (AUC = 0.77; 0.74–0.80; p = 0.023). MemScreen sensitivity and specificity were 78.6 % and 78.7 %, respectively. In memory clinics (n = 303, mean age 70.5 years, 53 % women, 46.9 % amnestic MCI), median completion time was 5 min 17 s. MemScreen showed superior performance (AUC = 0.87; 0.83–0.91) compared to MMSE (AUC = 0.72; 0.67–0.78; p < 0.001) and TMT-A (AUC = 0.63; 0.56–0.69; p < 0.001), with 93.0 % sensitivity and 54.0 % specificity for amnestic MCI.
DISCUSSION: MemScreen outperformed traditional tests in identifying MCI in both general and clinical populations. Its self-administration and short completion time suggest potential as an effective screening tool to optimize memory clinic referrals for AD diagnosis and treatment.
CITATION:
Julien Dumurgier ; Claire Paquet ; Jacques Hugon ; Vincent Planche ; Sinead Gaubert ; Stéphane Epelbaum ; Stéphanie Bombois ; Marc Teichmann ; Richard Levy ; Estelle Baudouin ; Agathe Vrillon ; Claire Hourrègue ; Emmanuel Cognat ; Séverine Sabia ; Archana Singh-Manoux (2025): MemScreen: A smartphone application for detection of mild cognitive impairment: A validation study: Smartphone App for MCI Detection. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100077
EFFECTIVENESS OF DIGITAL SCREENING TOOLS IN DETECTING COGNITIVE IMPAIRMENT AMONG COMMUNITY-DWELLING ELDERLY IN NORTHERN CHINA: A LARGE COHORT STUDY
Xiaonan Zhang, Feifei Zhang, Sijia Hou, Chenxi Hao, Xiangmin Fan, Yarong Zhao, Wenjing Bao, Junpin An, Shuning Du, Guowen Min, Qiuyan Wang, Wencheng Zhu, Yang Li, Hui Zhang
J Prev Alz Dis 2025;3(12)
Show summaryHide summaryINTRODUCTION: This study assessed the effectiveness of three digital screening tools in detecting cognitive impairment (CI) in a large cohort of community-dwelling elderly individuals and investigated the relationship between key digital features and plasma p-tau217 levels.
METHODS: This community-based cohort study included 1,083 participants aged 65 years or older, with 337 diagnosed with CI and 746 classified as normal controls (NC). We utilized two screening approaches: traditional methods (AD8, MMSE scale, and APOE genotyping) and digital tools (drawing, gait, and eye tracking). LightGBM-based machine learning models were developed for each digital screening tool and their combination, and their performance was evaluated. The correlation between key digital features and plasma p-tau217 levels was analyzed as well.
RESULTS: A total of 21 drawing, 71 gait, and 35 eye-tracking parameters showed significant differences between the two groups (all p < 0.05). The area under the curve (AUC) values for the drawing, gait, and eye-tracking models in distinguishing CI from NC were 0.860, 0.848, and 0.895, respectively. The combination of eye-tracking and drawing achieved the highest classification effectiveness, with an AUC of 0.958, and accuracy, sensitivity, and specificity all exceeded 85%. The fusion model achieved an AUC of 0.928 in distinguishing mild cognitive impairment (MCI) from NC. Additionally, several digital features (including two drawing, ten gait, and one eye-tracking parameters) were significantly correlated with plasma p-tau217 levels (all |r| > 0.3, p < 0.001).
DISCUSSION: Digital screening tools offer objective, accurate, and efficient alternatives for detecting CI in community settings, with the fusion of drawing and eye-tracking providing the best performance (AUC = 0.958).
CITATION:
Xiaonan Zhang ; Feifei Zhang ; Sijia Hou ; Chenxi Hao ; Xiangmin Fan ; Yarong Zhao ; Wenjing Bao ; Junpin An ; Shuning Du ; Guowen Min ; Qiuyan Wang ; Wencheng Zhu ; Yang Li ; Hui Zhang (2025): Effectiveness of digital screening tools in detecting cognitive impairment among community-dwelling elderly in Northern China: A large cohort study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100080
BRAIN HEALTH CLINICS – AN EVOLVING CLINICAL PATHWAY?
Anneka F. Butters, Jonathan Blackman, Hannah Farouk, Saba Meky, Margaret A. Newson, Tomas Lemke, Natalie Rosewell, James A. Selwood, Nicholas L. Turner, Elizabeth J. Coulthard, Hilary A. Archer
J Prev Alz Dis 2025;3(12)
Show summaryHide summaryBACKGROUND: Dementia clinics traditionally focus on diagnosis and post-diagnostic care. Awareness is increasing that attention to risk factors and their prevention also forms a key part of dementia management.
OBJECTIVES: To describe our Bristol Brain Health clinic including 1) Clinical pathway 2) Patient population 3) Patient experience 4) Evaluation in line with published gold standards.
DESIGN/ SETTING: Observational, (longitudinal/retrospective) clinical cohort study of patients attending the North Bristol NHS Trust's Brain Health Service.
PARTICIPANTS: One-hundred and ten patients with mild cognitive disorders attending clinic between 2017- 2023.
MEASUREMENTS: We collected data from medical records including clinical assessments, cerebrospinal fluid (CSF) for biomarkers of Alzheimer's Disease (AD), and a lifestyle questionnaire. Descriptive statistics were performed and a clinic evaluation was carried out using recommendations from The European Task Force for Brain Health Services.
RESULTS: Average age was 63.9 years (SD: 11.2). 74 patients were male (62.8 %). The mean baseline Montreal Cognitive Assessment (MoCA) score was 24.4 (SD: 3.6). 73 patients (66.4 %) received a preventative lifestyle intervention with a review of risk and protective factors for dementia, and development of a bespoke risk reduction plan. Commonly identified risk factors; low mood; n = 61 (55.5 %), hypertension; n = 54 (49.1 %), high cholesterol; n = 42 (47.3 %), and hearing loss; n = 44 (40 %). CSF testing for AD was carried out in 38 individuals and was positive in 17 cases. At last review, one fifth of patients had progressed to dementia. Most common diagnoses; AD; n = 22 (20 %), Functional Cognitive Disorder; n = 16 (14.6 %), Vascular; n = 8 (7.3 %). Patient feedback was good, with all responders recommending the clinic and more than three-quarters of patients being ‘extremely likely” to. Clinic evaluation highlighted ‘Risk Assessment’ and ‘Personalised Intervention’ as brain health pillar strengths. ‘Cognitive Enhancement’ was an area for further development.
CONCLUSIONS: Our patients had access to a range of cutting-edge, diagnostic assessments, in addition to a preventative lifestyle intervention. Our population had a high rate of dementia risk factors and a heterogeneous range of diagnoses. CSF biomarker testing was helpful for differentiating between those with early AD, and others with a multi-factorial presentation. The attendance rates for our preventative intervention suggests patients are receptive to taking a proactive approach to managing risk. This population merits further investigation and continued targeting with preventative measures.
CITATION:
Anneka F․ Butters ; Jonathan Blackman ; Hannah Farouk ; Saba Meky ; Margaret․ A Newson ; Tomas Lemke ; Natalie Rosewell ; James․ A․ Selwood ; Nicholas․ L․ Turner ; Elizabeth․ J․ Coulthard ; Hilary․ A․ Archer (2025): Brain health clinics – An evolving clinical pathway?. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100051
TAILORING IMPLEMENTATION STRATEGIES FOR THE HEALTHY ACTIONS AND LIFESTYLES TO AVOID DEMENTIA OR HISPANOS Y EL ALTO A LA DEMENCIA PROGRAM: LESSONS LEARNED FROM A SURVEY STUDY
Sara Moukarzel, Carlos E.E. Araujo-Menendez, Eliza Galang, Zvinka Z. Zlatar, Howard H. Feldman, Sarah J. Banks, HALT-AD Study Group
J Prev Alz Dis 2025;3(12)
Show summaryHide summaryBACKGROUND: Healthy Actions and Lifestyles to Avoid Dementia Program (HALT-AD) or Hispanos y el ALTo a la Demencia is a recently-developed online educational platform to help individuals identify and modify their own dementia modifiable risk factors (MRF). In light of known challenges in recruiting and retaining diverse participants in research studies, there is a need to identify data-informed strategies that will contribute to effective outreach and tailored implementation of HALT-AD among its intended users of Hispanic and non-Hispanic midlife and older adults in the US.
OBJECTIVES: To identify factors (i.e, demographic, medical, psychosocial and environmental) that may facilitate or impede effective program enrollment and participation.
DESIGN: Cross-sectional study.
SETTING: Data from an online and self-administered survey conducted between January and April 2023.
PARTICIPANTS: Residents of California, predominately San Diego, who were 50 to 85 years old, with no dementia or Alzheimer's disease, proficient in English or Spanish and with enough technical ability to complete the survey electronically (n=157; 43% Hispanic).
INTERVENTION (if any): none.
MEASUREMENTS: RedCap was used to capture answers to closed and open-ended survey questions. Mixed-methods analysis was used: For quantitative data, descriptive statistics, comparisons by group (Hispanic/non-Hispanic), and exploratory factor analysis were conducted in SPSS. Thematic analysis with open coding in Excel was used for qualitative responses.
RESULTS: Independent of ethnicity, participants’ most preferred method of reach for recruitment was through a conversation with their doctor or with a family member or friend. Their least preferred method was receiving a Facebook advertisement especially among non-Hispanics. Interest in program participation did not differ by sociodemographic characteristics or self-rated satisfaction with individualized MRFs. Instead, having higher confidence in one's ability to commit to behavior change was significantly associated with higher interest in program participation. While a common theme to motivate both groups to participate was the potential to decrease dementia risk, non-Hispanics were motivated by the premise of supporting research and having a positive user experience. For program implementation, Hispanics were more likely to be interested in participating if live sessions, either online or in-person, were provided to offer support with making lifestyle changes as adjunct to completing online courses independently. In both groups, participation may be further facilitated by offering wearable devices which provide participants with feedback on lifestyle change progress.
CONCLUSIONS: A “one-size-fits-all” approach to recruitment and implementation of HALT-AD may not be effective in enrolling and retaining participants in future studies or for clinical use. Instead, a tailored approach that accounts for personal and ethnically-dependent preferences may be more beneficial.
CITATION:
Sara Moukarzel ; Carlos E.E. Araujo-Menendez ; Eliza Galang ; Zvinka Z. Zlatar ; Howard H. Feldman ; Sarah J. Banks ; HALT-AD Study Group (2025): Tailoring implementation strategies for the healthy actions and lifestyles to Avoid Dementia or Hispanos y el ALTo a la Demencia Program: Lessons learned from a survey study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100053
EFFECT OF A SINGLE NONPHARMACOLOGICAL INTERVENTION ON COGNITIVE FUNCTIONING IN OLDER ADULTS WITH MILD-TO-MODERATE ALZHEIMER\'S DISEASE: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS: NON-DRUG INTERVENTIONS FOR ALZHEIMER\'S DISEASE
Kejin Chen, Xiaoyan Zhao, Jingwen Zhou
J Prev Alz Dis 2025;3(12)
Show summaryHide summaryMost studies of nonpharmacological interventions have used a combination of medications in experimental and control groups to improve cognitive functioning or to control symptoms, but the results have been inconsistent with respect to the effects of single nonpharmacological interventions on cognitive functioning in older patients with Alzheimer's disease. The aim of this study was to assess the effect of a single nonpharmacological intervention on cognitive functioning in older adults with mild-to-moderate Alzheimer's disease. We conducted a systematic review and meta-analysis in the first week of January 2024, searching eight electronic databases for articles that reflect on non-pharmacological interventions in Alzheimer's disease published between January 1, 1986, and December 31, 2023. All included articles had to be randomized controlled trials. The primary measure was the change in cognitive function before and after the intervention. Data were extracted by two authors and quality was assessed using the Cochrane Handbook. With the exception of the Montreal Cognitive Assessment (MoCA) scale [MD=2.99, 95% CI (-0.66,6.63)], the differences between the intervention group and the control group were significant for all the remaining scales, namely, the Mini-Mental State Examination (MMSE) [SMD=0.65, 95% CI (0.15,1.15)], Activity of Daily Living Scale (ADL) [MD=-2.30, 95% CI (-3.63,0.97)], Quality of Life in Alzheimer's Disease Scale (QoL-AD) [MD=5.03, 95% CI (2.27,7.78)], Neuropsychiatric Inventory (NPI) [MD=-2.16, 95% CI (-3.86,0.46)], and Alzheimer's Disease Assessment Scale-cognitive score (ADAS-cog) [MD=-5.21, 95% CI (-7.89,2.54)]. Subgroup analysis revealed that the most effective intervention was exercise therapy, followed by repetitive transcranial magnetic stimulation. On the other hand, music therapy was not found to be effective. Current evidence suggests that nonpharmacological interventions can be used to improve cognitive functioning in older adults with mild-to-moderate Alzheimer's disease. This study was registered in PROSPERO (registration number: CRD42024497247).
CITATION:
Kejin Chen ; Xiaoyan Zhao ; Jingwen Zhou (2025): Effect of a single nonpharmacological intervention on cognitive functioning in older adults with mild-to-moderate Alzheimer's disease: A meta-analysis of randomized controlled trials: non-drug interventions for Alzheimer's disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100050
SOCIAL ISOLATION, LONELINESS, AND THEIR JOINT EFFECTS ON COGNITIVE DECLINE AND INCIDENT ALZHEIMER\'S DISEASE: FINDINGS FROM THE CHICAGO HEALTH AND AGING PROJECT
Ted K.S. Ng, Todd Beck, Kyle R. Dennis, Pankaja Desai, Kristin Krueger, Klodian Dhana, Robert S. Wilson, Denis A. Evans, Kumar B. Rajan
J Prev Alz Dis 2025;3(12)
Show summaryHide summaryBACKGROUND: There has been contradictory evidence on the prospective associations between social isolation/loneliness (SI/L) and cognitive decline (CD). There is also a scarcity of large and diverse population-based cohort studies examining SI/L that have confirmed clinical diagnoses of Alzheimer's Disease (AD). Notably, beyond individual associations, whether the effects of SI/L compound and accelerate CD and incident AD are not known.
OBJECTIVES: We hypothesized that SI and L, independently, would be associated with CD and incident AD to a similar extent, and the association of SI with CD and incident AD would be higher in lonely older adults.
DESIGN: Prospective cohort study.
SETTING: Urban Chicago areas.
PARTICIPANTS: We analyzed data in the Chicago Health and Aging Project (CHAP), which comprised 7,760 biracial community-dwelling older adults [mean age (standard deviation (SD))=72.3 (6.3); 64 % Black & 63 % women; mean (SD) of follow-up=7.9 (4.3) years].
INTERVENTION (if any): NA.
MEASUREMENTS: Linear mixed and logistic regression models were used to regress CD and incident AD separately on the SI index/L.
RESULTS: SI index and L were significantly associated with CD, with one-point increase of beta estimate (SE, p-value) = -0.002 (0.001,0.022) and -0.012 (0.003,<0.001), respectively. Given that the SI index ranges from 0 to 5 and the L from 0 to 1, they had similar effect sizes. Similarly, there were significant associations between SI index and incident AD, odds ratio (95 % CI, p-value) = 1.183 (1.016–1.379,0.029), and between L and incident AD, 2.117 (1.227–3.655,0.006). When stratified by loneliness status, compared to older adults who were not isolated and not lonely, older adults who reported being socially isolated and not lonely experienced accelerated CD, -0.003 (0.001,0.004), despite no significantly increased odds of incident AD.
CONCLUSIONS: SI/L had significant associations with CD and incident AD. Notably, socially isolated older adults who reported not being lonely appeared to be most socially vulnerable to CD. These findings suggest a specific at-risk subgroup of socially vulnerable older adults for future targeted interventions to improve cognitive health.
CITATION:
Ted K.S. Ng ; Todd Beck ; Kyle R. Dennis ; Pankaja Desai ; Kristin Krueger ; Klodian Dhana ; Robert S. Wilson ; Denis A. Evans ; Kumar B. Rajan (2025): Social isolation, loneliness, and their joint effects on cognitive decline and incident Alzheimer's disease: Findings from the Chicago health and aging project. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100046
USE OF LECANEMAB AND DONANEMAB IN THE CANADIAN HEALTHCARE SYSTEM: EVIDENCE, CHALLENGES, AND AREAS FOR FUTURE RESEARCH
Eric E. Smith, Natalie A. Phillips, Howard H. Feldman, Michael Borrie, Aravind Ganesh, Alexandre Henri-Bhargava, Philippe Desmarais, Andrew Frank, AmanPreet Badhwar, Laura Barlow, Robert Bartha, Sarah Best, Jennifer Bethell, Jaspreet Bhangu, Sandra E. Black, Christian Bocti, Susan E. Bronskill, Amer M. Burhan, Frederic Calon, Richard Camicioli, Howard Chertkow
J Prev Alz Dis 2025;3(12)
Show summaryHide summaryLecanemab and donanemab are monoclonal antibody therapies that remove amyloid-beta from the brain. They are the first therapies that alter a fundamental mechanism, amyloid-beta deposition, in Alzheimer disease (AD). To inform Canadian decisions on approval and use of these drugs, the Canadian Consortium on Neurodegeneration in Aging commissioned Work Groups to review evidence on the efficacy and safety of these new therapies, as well as their projected impacts on Canadian dementia systems of care. We included persons with lived experience with Alzheimer disease in the discussion about the benefits and harms. Our review of the trial publications found high quality evidence of statistically significant group differences, but also recognized that there are mixed views on the clinical relevance of the observed differences and the value of therapy for individual patients. The drugs are intended for persons with early AD, at a stage of mild cognitive impairment or mild dementia. If patients are treated, then confirmation of AD by positron emission tomography or cerebrospinal fluid analysis and monitoring for risk of amyloid-related imaging abnormalities was recommended, as done in the clinical trials, although it would strain Canadian resource capacity. More data are needed to determine the size of the potentially eligible treatment population in Canada.
CITATION:
Eric E. Smith ; Natalie A. Phillips ; Howard H. Feldman ; Michael Borrie ; Aravind Ganesh ; Alexandre Henri-Bhargava ; Philippe Desmarais ; Andrew Frank ; AmanPreet Badhwar ; Laura Barlow ; Robert Bartha ; Sarah Best ; Jennifer Bethell ; Jaspreet Bhangu ; Sandra E. Black ; Christian Bocti ; Susan E. Bronskill ; Amer M. Burhan ; Frederic Calon ; Richard Camicioli ; Howard Chertkow (2025): Use of lecanemab and donanemab in the Canadian healthcare system: Evidence, challenges, and areas for future research. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100068
AMERICAN\'S OVERALL AND EQUITY-BASED SOCIETAL VALUATION OF A DISEASE-MODIFYING ALZHEIMER\'S TREATMENT: RESULTS FROM A DISCRETE CHOICE EXPERIMENT
Francisco Perez-Arce, Jeremy Burke, Lila Rabinovich, Quanwu Zhang, Amir Abbas Tahami Monfared, Soeren Mattke
J Prev Alz Dis 2025;3(12)
Show summaryHide summaryOBJECTIVES: To estimate Americans’ willingness-to-pay (WTP) for universal access to a disease-modifying Alzheimer's disease (AD) treatment with a discrete choice experiment in a nationally representative sample. As part of this experiment, we examined whether providing information about the higher disease burden among minorities and persons of lower socioeconomic status (SES) changes WTP.
METHODS: We conducted an information experiment using the nationally representative Understanding America Study (UAS) panel. Participants were provided with general information about AD and a hypothetical treatment that reduces disease progression by 30 %. Two-thirds of the sample were randomized to receive additional information about the higher prevalence of Alzheimer's among either lower SES groups or racial/ethnic minorities. We measured participants' WTP for making the treatment nationally available as a fixed annual fee and income-proportionate fee. Differences in WTP between those exposed to the additional information and those who were not provide the societal valuation of the equity-enhancing effects of the AD treatment.
RESULTS: Average valuations were $252, $260 and $247 per year, and 0.59 %, 0.59 % and 0.61 % of earned income, for the control, race/ethnicity and SES frames, respectively—all statistically indistinguishable. These average results imply that Americans would be willing to pay $33.7 billion based on the fixed fee and $51.4 billion based on the income-related charge for universal access to an AD treatment annually, but their valuation does not further increase when informed about equity considerations.
CONCLUSIONS: While Americans value universal access to an AD treatment highly, health equity considerations did not significantly alter respondents’ WTP.
CITATION:
Francisco Perez-Arce ; Jeremy Burke ; Lila Rabinovich ; Quanwu Zhang ; Amir Abbas Tahami Monfared ; Soeren Mattke (2025): American's overall and equity-based societal valuation of a disease-modifying Alzheimer's treatment: Results from a discrete choice experiment. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100036
EFFECTS OF THE DAVOS ALZHEIMER\'S COLLABORATIVE EARLY DETECTION OF COGNITIVE IMPAIRMENT PROGRAM ON CLINICIAN ATTITUDES, ENGAGEMENT, AND CONFIDENCE
Tabasa Ozawa, Katherine J. Selzler, Daniel E. Ball, Amy Deckert, Tim MacLeod, Otelo Corrêa dos Santos Filho, Ishtar Govia, Janelle N. Robinson, Hisatomo Kowa, Mariana Lopez-Ortega, Alison McKean, Wendy Chambers, Steven R. Smith, Magda Baksh, Deanna R. Willis, Nicole R. Fowler, Soeren Mattke, The DAC Consortium
J Prev Alz Dis 2025;3(12)
Show summaryHide summaryBACKGROUND: The number of people with dementia is expected to grow substantially across the world due to population aging, but cognitive impairment remains undetected and undiagnosed, especially in early stages. Newly available diagnostic tools such as digital cognitive assessments and blood biomarker tests may be well suited to increase the rates of early detection of dementia in primary care.
OBJECTIVES: The objective of the Davos Alzheimer's Collaborative Healthcare System Preparedness (DAC-SP) Early Detection Flagship Program was to improve the rate of early detection of cognitive impairment in primary care and non-specialty settings. We aimed to understand the program's impact on clinician attitudes, engagement, and confidence in diagnosing and managing cognitive impairment.
DESIGN: Survey of participating healthcare professionals before and after the intervention.
SETTING: The DAC Healthcare System Preparedness Early Detection Flagship Program was implemented in seven sites across six countries: Brazil, Jamaica, Japan, Mexico, Scotland, and the United States (2 sites).
PARTICIPANTS: 110 healthcare professionals, including, primary care physicians, specialists (neurologists and psychologists), nurses, nurse practitioners, physician assistants, social workers, and healthcare support workers completed the pre-intervention survey. 68 healthcare professionals completed the post-intervention survey.
INTERVENTION: Participating sites implemented a digital cognitive assessment tool and a blood biomarker test for the Alzheimer's pathology and were trained in the administration of the digital cognitive assessment tool. The intervention was adapted to each site for cultural relevance and operational feasibility.
MEASUREMENTS: Participants completed the General Practitioners Attitude and Confidence Scale for Dementia (GPACS-D), a 15-item scale with three subscales: Attitude to Care (six items), Confidence in Clinical Abilities (six items), and Engagement (three items). In addition to the subscale scores, the total GPACS-D score was reported.
RESULTS: Across all sites, there was a significant increase in the Confidence in Clinical Abilities score from 2.98 (SD = 0.77) pre-intervention to 3.27 (SD = 0.72) post-intervention (p = 0.01), and in the total GPACS-D score from 3.48 (SD = 0.48) to 3.65 (SD = 0.39) (p = 0.01). There were non-significant increases in the Attitude to Care and Engagement scores across all sites.
CONCLUSIONS: The implementation of digital cognitive assessment tools and a blood biomarker test was associated with an increase in healthcare professionals’ confidence in diagnosing and managing patients with cognitive impairment in primary care and non-specialty settings. Digital cognitive assessments and blood biomarker tests are promising tools that could be utilized in primary care to increase clinicians’ confidence in detecting dementia and lead to timely clinical evaluation, treatment, and referral to supportive resources.
CITATION:
Tabasa Ozawa ; Katherine J. Selzler ; Daniel E. Ball ; Amy Deckert ; Tim MacLeod ; Otelo Corrêa dos Santos Filho ; Ishtar Govia ; Janelle N. Robinson ; Hisatomo Kowa ; Mariana Lopez-Ortega ; Alison McKean ; Wendy Chambers ; Steven R. Smith ; Magda Baksh ; Deanna R. Willis ; Nicole R. Fowler ; Soeren Mattke ; The DAC Consortium (2025): Effects of the Davos Alzheimer's Collaborative early detection of cognitive impairment program on clinician attitudes, engagement, and confidence. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100038
MODIFIABLE RISK FACTORS FOR EARLY- AND LATE-ONSET DEMENTIA USING THE KOREAN NATIONAL HEALTH INSURANCE SERVICE DATABASE
Dougho Park, Myeonghwan Bang, Hyoung Seop Kim, Jong Hun Kim
J Prev Alz Dis 2025;3(12)
Show summaryHide summaryBACKGROUND: Early-onset dementia (EOD) and late-onset dementia (LOD) may have distinct modifiable risk-factor profiles.
OBJECTIVE: To identify and compare factors associated with EOD and LOD using a nationwide cohort database.
DESIGN: Nationwide two nested case-control studies.
SETTING: We used the National Health Insurance Service-National Sample Cohort database (2004–2019).
PARTICIPANTS: The initial sample size was 514,866; 5157 EOD and 39,326 LOD cases were matched 1:1 with controls based on age, sex, and the Charlson Comorbidity Index.
MEASUREMENTS: Socioeconomic status, residential area, body mass index, alcohol consumption, smoking status, physical activity, blood pressure, and laboratory findings were analyzed. Multivariable logistic regression models were used to identify the risk factors.
RESULTS: Higher socioeconomic status and increased frequency of physical activity were associated with a lower risk of both EOD and LOD. Rural residence, heavy alcohol consumption, and higher fasting blood sugar levels were associated with an increased risk of LOD, although there was no significant association with EOD. Overall, these factors impacted LOD more strongly than EOD. Demographic and lifestyle factors had a greater effect on LOD than blood pressure and relevant laboratory findings.
CONCLUSION: Modifiable risk factors were associated with LOD and EOD. The influence of some modifiable risk factors was more pronounced in the LOD group than in the EOD group. Identifying modifiable risk factors associated with dementia can aid in the development of preventive strategies, underscoring the clinical importance of our findings.
CITATION:
Dougho Park ; Myeonghwan Bang ; Hyoung Seop Kim ; Jong Hun Kim (2025): Modifiable risk factors for early- and late-onset dementia using the Korean national health insurance service database. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100032
PROTOCOL FOR AN INTERGENERATIONAL RANDOMIZED CONTROLLED TRIAL TO ENHANCE PHYSICAL ACTIVITY IN OLDER ADULTS AT RISK FOR ALZHEIMER\'S DISEASE
Caitlin S. Walker, Adrián E. Noriega de la Colina, Linda Li, Carolynn Boulanger, Nagashree Thovinakere, Alix Noly-Gandon, Garance Barnoin, Mitchell Bennett, Jillian Caplan, Laurence Côté, Sarah Elbaz, Shania Fock Ka Bao, Ryan Kara, Nicolas Lavoie, Maggie Nguyen, Franciska Otaner, Helen Pallett-Wiesel, Johanie Victoria Piché, Andreanne Powers, Sofia Ricciardelli, Maiya R. Geddes
J Prev Alz Dis 2025;3(12)
Show summaryHide summaryBACKGROUND: Physical inactivity is one of the most important modifiable risk factors for Alzheimer's disease in North America. Despite this, most older adults are physically inactive. It is currently unknown how to successfully motivate physical activity behavior in older adults at risk for Alzheimer's disease, and this knowledge is crucial for early and effective disease prevention. Prior research has shown that intergenerational social engagement and prosocial behaviours can enhance the health and well-being of older adults.
OBJECTIVES: This manuscript describes the design of a randomized controlled trial that will test the efficacy of a behavioral intervention to enhance physical activity in older adults at risk for Alzheimer's disease.
DESIGN/SETTING: This is a single-blinded, two-arm stratified randomized controlled trial that incorporates a hybrid efficacy and implementation design. Participants are randomized to an intervention or control condition in a 1:1 ratio and are stratified by a multimodal Alzheimer's disease risk score. All study visits are conducted remotely through videoconferencing.
PARTICIPANTS: The study aims to recruit 60 older adults with a first-degree family history of Alzheimer's disease from the PREVENT-AD cohort and 30 younger adults who are paired with older adults in the intervention condition.
INTERVENTION: Older participants in the intervention group will be paired with younger study partners and receive positive, daily messages over four weeks using a novel technology platform. The daily messages combine intergenerational social engagement (growing a virtual garden with a younger study partner) and prosocial goals (donations to charity after reaching step count goals).
MEASUREMENTS: The primary outcome is change in step count compared to baseline measured using a wrist-worn triaxial accelerometer. Secondary outcomes include time spent physically active, mood, generativity, loneliness, and cognition. Target mechanisms (social support and generativity) of physical activity engagement will be examined. Ease of use, acceptability, and feasibility of the technology as well as barriers and facilitators of participation will be assessed.
CONCLUSIONS: This research will advance our understanding of mechanisms and individual differences underlying successful physical activity engagement in older adults who are at risk for Alzheimer's disease. This knowledge will contribute to strategies for promoting health behaviours that can prevent the risk of Alzheimer's disease.
CITATION:
Caitlin S. Walker ; Adrián E. Noriega de la Colina ; Linda Li ; Carolynn Boulanger ; Nagashree Thovinakere ; Alix Noly-Gandon ; Garance Barnoin ; Mitchell Bennett ; Jillian Caplan ; Laurence Côté ; Sarah Elbaz ; Shania Fock Ka Bao ; Ryan Kara ; Nicolas Lavoie ; Maggie Nguyen ; Franciska Otaner ; Helen Pallett-Wiesel ; Johanie Victoria Piché ; Andreanne Powers ; Sofia Ricciardelli ; Maiya R. Geddes (2025): Protocol for an intergenerational randomized controlled trial to enhance physical activity in older adults at risk for Alzheimer's disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100039
ASSOCIATIONS OF ISCHEMIC HEART DISEASE WITH BRAIN GLYMPHATIC MRI INDICES AND RISK OF ALZHEIMER\'S DISEASE
Ming-Liang Wang, Meng-Meng Yu, Zheng Sun, Jun-Jie Zhang, Jing-Kun Zhang, Xue Wu, Xiao-Er Wei, Yue-Hua Li, Alzheimer\'s Disease Neuroimaging Initiative
J Prev Alz Dis 2025;3(12)
Show summaryHide summaryBACKGROUND: The impact of ischemic heart disease (IHD) on the brain glymphatic MRI indices and risk of Alzheimer's disease (AD) remains largely unclear. This study aimed to investigate the associations between IHD, brain glymphatic MRI indices and risk of AD.
METHODS: A total of 1385 non-dementia subjects (55.2 % male, mean age 73.53) were included. Diffusivity along the perivascular space (DTI-ALPS), free water (FW) and choroid plexus volume were used to reflect glymphatic function. The associations of IHD with MRI derived glymphatic indices, PET amyloid, tau and cognitive performance were explored by multiple regression analysis. IHD were tested as predictors of clinical progression using cox proportional hazards modeling. The mediation effect of MRI derived glymphatic indices on the relationship between IHD and cognitive changes was investigated.
RESULTS: Individuals with IHD exhibited glymphatic dysfunction revealed by lower DTI-ALPS (p = 0.035), higher FW (p < 0.001), and higher choroid plexus volume (p = 0.019). IHD had poorer cognitive performance in MMSE (p = 0.022), ADNI-MEM (p = 0.001) and ADNI-MF (p = 0.006), and more amyloid deposition (p = 0.007). IHD had a higher diagnostic conversion risk (HR = 1.321, 95 % CI = 1.003–1.741). IHD was associated with longitudinal cognitive decline in all cognitive tests (p < 0.05 for all) and FW (β = 0.012, 95 % CI 0.001, 0.023, p = 0.038). FW demonstrated an indirect effect (β = -0.0009, 95 % CI: -0.0034, -0.0001) and mediated 13.85 % effect for the relationship between IHD and ADNI-EF decline.
CONCLUSION: IHD is independently associated with AD risk, and brain glymphatic dysfunction may partially mediate this relationship.
CITATION:
Ming-Liang Wang ; Meng-Meng Yu ; Zheng Sun ; Jun-Jie Zhang ; Jing-Kun Zhang ; Xue Wu ; Xiao-Er Wei ; Yue-Hua Li ; Alzheimer's Disease Neuroimaging Initiative (2025): Associations of ischemic heart disease with brain glymphatic MRI indices and risk of Alzheimer's disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100045
ASSOCIATIONS OF GLYCEMIC STATUS WITH DYNAMIC DISEASE TRAJECTORIES OF ATRIAL FIBRILLATION AND DEMENTIA
Chenglong Li, Daijun He, Yufan Liu, Chao Yang, Luxia Zhang, Rodica Pop-Busui
J Prev Alz Dis 2025;3(12)
Show summaryHide summaryBACKGROUND: Atrial fibrillation (AF) has been associated with elevated dementia risk, while few studies have examined the role of the optimal glycemic status in disease trajectories of AF and dementia.
OBJECTIVES: We aim to evaluate associations between glycemic status with disease trajectories of AF and dementia, as well as major dementia subtypes, including Alzheimer's disease and vascular dementia.
DESIGN: Population-based cohort study.
SETTING: UK Biobank.
PARTICIPANTS: A total of 458 368 participants who were free of prevalent dementia and AF at baseline, with complete glycemic status assessment.
MEASUREMENTS: Based on clinical recommendations, we categorized glycemic status as low-normal (glycated hemoglobin [HbA1c] <5.5 %), normal (HbA1c 5.5 to 5.9 %), pre-diabetes (HbA1c 6.0 to 6.4 %), diabetes with HbA1c<7 %, and diabetes with HbA1c≥7 %. Outcomes including AF, dementia (all-cause and sub-type dementia), and death were ascertained via linkage to external registry databases. A multi-state survival analysis was conducted to evaluate disease trajectories of AF and dementia.
RESULTS: Better glycemic status was consistently associated with decreased hazards of trajectories of AF and dementia, including progression from AF to the comorbidity of AF and dementia. Among people with diabetes, those with HbA1c<7 % had a 31 % lower hazard (hazard ratio [HR], 0.69; 95 % confidence intervals [CI], 0.51–0.93) of progression from incident AF to dementia comorbidity, compared to those with HbA1c≥7 %. Similar risk reductions were found in individuals with pre-diabetes, normal HbA1c, and low-normal HbA1c, respectively. Strong dose-response associations were observed, with each 1 % increment in HbA1c related to a 28 % higher hazard of progression from AF to dementia comorbidity (HR,1.28; 95 % CI, 1.19–1.37). The glycemic status was most relevant for associations with disease trajectories of AF and vascular dementia, compared to trajectories of AF and Alzheimer's disease.
CONCLUSIONS: The better glycemic status was consistently associated with lower hazards of disease trajectories of AF and dementia, including the reduced risk of progression from incident AF to comorbidity of AF and dementia. These findings support the significance of reaching optimal glycemic status to alleviate the huge disease burden of both AF and dementia simultaneously.
CITATION:
Chenglong Li ; Daijun He ; Yufan Liu ; Chao Yang ; Luxia Zhang ; Rodica Pop-Busui (2025): Associations of glycemic status with dynamic disease trajectories of atrial fibrillation and dementia. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100047
HEARING LOSS, DIET, AND COGNITIVE DECLINE: INTERCONNECTIONS FOR DEMENTIA PREVENTION
Xiaoran Liu, Uzma S. Akhtar, Todd Beck, Kyle Dennis, Denis A Evans, Kumar B Rajan
J Prev Alz Dis 2025;3(12)
Show summaryHide summaryBACKGROUND: Hearing loss poses a significant global public health concern associated with cognitive decline. Among the many risk factors associated with Alzheimer's disease and related dementia (ADRD), hearing loss is the most prevalent sensory impairment in older adults and has emerged as a significant, yet often overlooked, modifiable risk factor for dementia.
OBJECTIVES: To access 1) the association between diet and risk of hearing loss in older adults and 2) the modifying effect of diet on the impact of hearing loss on cognitive decline in an aging population.
DESIGN: Prospective cohort study.
SETTING: The Chicago Health and Aging Project, a community-based cohort study
PARTICIPANTS: A total of 5,145 older adults (62 % non-Hispanic Black, 63 % female).
MEASUREMENTS: Self-reported hearing ability was assessed during each cycle of data collection. Diet was assessed by a 144-item Food Frequency Questionnaire. Diet quality was evaluated using a 144-item Food Frequency Questionnaire, focusing on adherence to dietary patterns such as Dietary Approaches to Stop Hypertension (DASH), Mediterranean, and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND). Cognitive function assessment was conducted during the in-home visits at each cycle. Four cognitive tests, including the East Boston tests of immediate and delayed recall, the mini-mental State Examination, and the Symbol Digit Modalities test, were included. We used linear mixed effect models to examine 1) the association of hearing loss and cognitive decline and 2) the association of diet on cognitive decline through modifying risk hearing loss. Discrete-time survival analysis examined the association between dietary patterns and the time to hearing impairment.
RESULTS: Among 5,145 participants included in the analyses, 747 (14.5 %) reported hearing loss, including 207 Black adults and 199 White adults. Each unit increase in the DASH, MedDiet, and MIND scores was associated with 19 % (95 % CI: 0.79, 0.94, P < 0.001), 11 % (95 % CI: 0.79, 1.00, P = 0.05), and 13 % (95 % CI: 0.87, 0.99, P < 0.05) lower risk for hearing loss, respectively. High adherence to the Western diet was associated with an earlier onset of hearing loss up to 14 months (P < 0.05). Participants had an increased rate of cognitive decline after reporting hearing loss. During follow-up, participants in the highest tertile of the DASH diet score who reported hearing loss experienced a 17 % faster cognitive decline (β = -0.07 ± 0.01) compared to those without hearing loss (β = -0.06 ± 0.003). However, this decline was significantly slower than that of participants observed in the lowest tertile of the DASH diet, who exhibited a 67 % faster cognitive decline (β = -0.10 ± 0.012, P = 0.05).
DISCUSSION: Healthy dietary patterns, particularly the DASH diet, was associated with a reduced risk of hearing loss and slower cognitive decline following hearing loss. Clinically, these findings underscore the importance of dietary quality in preserving cognitive health by potentially mitigating risk of hearing loss or delaying the onset of hearing loss in older adults.
CITATION:
Xiaoran Liu ; Uzma S. Akhtar ; Todd Beck ; Kyle Dennis ; Denis A Evans ; Kumar B Rajan (2025): Hearing loss, diet, and cognitive decline: interconnections for dementia prevention. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100052
PREVENTING DEMENTIA IN ITALY: ESTIMATIONS OF MODIFIABLE RISK FACTORS AND PUBLIC HEALTH IMPLICATIONS
Federica Asta, Guido Bellomo, Benedetta Contoli, Flavia L Lombardo, Valentina Minardi, Simone Salemme, Nicola Vanacore, Maria Masocco
J Prev Alz Dis 2025;3(12)
Show summaryHide summaryBACKGROUND: Dementia is a major global public health challenge, with over 50 million cases in 2020, projected to reach 152 million by 2050. Effective prevention strategies are needed to reduce the impact of modifiable risk factors associated with dementia, particularly in countries with ageing populations like Italy. The Population Attributable Fraction (PAF) and Potential Impact Fraction (PIF) are key metrics for understanding and reducing dementia cases through targeted interventions.
OBJECTIVES: This study aimed to revise and expand PAF estimates for dementia in Italy, integrate them with PIF calculations, and assess the alignment of regional health policies with these risk factors. Additionally, the study explored regional variations in PAFs and evaluated the potential for reducing dementia incidence through feasible public health interventions.
DESIGN: A cross-sectional analysis was conducted using data from two national public health surveillance systems, PASSI and PASSI d'Argento (PdA), to estimate PAFs and PIFs for dementia at both national and regional levels. The study used data collected between 2017 and 2019.
SETTING: Data were drawn from 19 Italian regions and two autonomous provinces, providing national and subnational estimates of modifiable risk factors for dementia.
PARTICIPANTS: The study population included a nationally representative sample of 86,494 individuals aged 18–64 (PASSI) and 48,516 individuals aged 65 and older (PdA).
MEASUREMENTS: PAFs were calculated for 11 of the 12 modifiable risk factors identified by the Lancet Commission in 2021, with data from the PASSI and PdA systems. PIFs were calculated to estimate the potential reduction in dementia cases under different intervention scenarios. Regional variations in PAFs were assessed and aligned with health policies outlined in the Regional Prevention Plans.
RESULTS: The national combined PAF for 11 modifiable risk factors was 39.6 % (95 % CI: 20.8–55.9). Midlife hypertension and physical inactivity were the most significant contributors, accounting for 12.3 % of the total PAF. Cardiovascular risk factors collectively explained over 50 % of preventable dementia cases. Regional PAFs ranged from 31.7 % to 47.5 %, with a clear north-south gradient; southern regions exhibited higher PAFs due to cardiovascular factors. Despite broad consistency between national and regional PAFs, significant variability was found in how regions addressed risk factors, particularly air pollution. At the national level, a 10 % reduction in risk factors would prevent 54,495 dementia cases, with subnational PIFs ranging from 3.7 % to 6.0 %.
CONCLUSIONS: This study highlights the substantial potential for dementia prevention in Italy through targeted public health interventions. However, significant regional disparities in PAFs and the alignment of health policies underscore the need for a more nuanced, regionally tailored approach. Future strategies should integrate both PAF and PIF to maximize the impact of interventions, particularly in addressing cardiovascular risk factors. These findings can guide the development of evidence-based policies to reduce dementia incidence across Italy.
CITATION:
Federica Asta ; Guido Bellomo ; Benedetta Contoli ; Flavia L Lombardo ; Valentina Minardi ; Simone Salemme ; Nicola Vanacore ; Maria Masocco (2025): Preventing dementia in Italy: Estimations of modifiable risk factors and public health implications. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100055
PLASMA NEUROFILAMENT LIGHT MEDIATES THE EFFECTS OF APOLIPOPROTEIN E ON BRAIN ATROPHY AND COGNITIVE DECLINE IN THE COMORBID ALZHEIMER\'S DISEASE AND CEREBRAL SMALL VESSEL DISEASE
Chunhua Zhang, Bingyu Li, Kok Pin Ng, Yaojun Tai, Yuanming Tai, Xicheng Song, Min Kong, Maowen Ba, for Alzheimer\'s Disease Neuroimaging Initiative
J Prev Alz Dis 2025;3(12)
Show summaryHide summaryBACKGROUND: Alzheimer's disease (AD) and cerebral small vessel disease (CSVD) often coexist in older adults and contribute to cognitive impairment. The Apolipoprotein E (APOE) ε4 allele and neuroaxonal injury, measured by plasma neurofilament light chain (NfL), are associated with an increased risk for both AD and CSVD. However, the relationship between APOE ε4, plasma NfL, and their association with the comorbidity of AD and CSVD remains unclear.
OBJECTIVE: To investigate the longitudinal relationship among APOE ε4, elevated plasma NfL, brain atrophy, and cognitive decline in individuals with comorbid AD and CSVD.
METHODS: We included 570 non-demented participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study, categorizing them into four groups based on amyloid-β positivity and CSVD burden. Linear mixed-effects models examined the association among APOE ε4, plasma NfL, brain volume measured by magnetic resonance imaging, and cognition over 2 years. Mediation analyses assessed the role of elevated plasma NfL in the relationship between APOE ε4, brain atrophy, and cognitive decline.
RESULTS: APOE ε4 carriers showed elevated plasma NfL levels, brain atrophy, and cognitive decline. Plasma NfL mediated the effects of APOE ε4 on brain atrophy and cognitive decline in participants with comorbid AD and CSVD.
CONCLUSION: Our findings suggest that neuroaxonal injury as a potential mechanism in the effects of APOE ε4 on brain atrophy and cognitive decline, highlighting the clinical utility of plasma NfL as a potential biomarker for disease progression and response to therapeutic intervention in comorbid AD and CSVD.
CITATION:
Chunhua Zhan ; Bingyu Li ; Kok Pin Ng ; Yaojun Tai ; Yuanming Tai ; Xicheng Song ; Min Kong ; Maowen Ba ; for Alzheimer's Disease Neuroimaging Initiative (2025): Plasma neurofilament light mediates the effects of Apolipoprotein E on brain atrophy and cognitive decline in the comorbid Alzheimer's disease and cerebral small vessel disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100054