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ASSOCIATION OF VASCULAR ENDOTHELIAL GROWTH FACTOR LEVELS WITH RISK OF ALZHEIMER’S DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS

S.S. Zakariaee, N. Naderi, E. Azizi

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BACKGROUND: Alzheimer’s disease (AD) is a progressive neurodegenerative illness that leads to impairment of cognitive functions and memory loss. Even though there is a plethora of research reporting the abnormal regulation of VEGF expression in AD pathogenesis, whether the CSF and serum VEGF are increased in AD is an open question yet. In this study, the association of CSF and serum VEGF concentrations with the risk of Alzheimer’s disease was investigated using systematic review and meta-analysis. METHODS: A systematic literature search was carried out using online specialized biomedical databases of Web of Science, Pubmed, Scopus, Embase, and Google Scholar until Feb 2023 without restriction to the beginning time. The meta-analysis was performed using the random-effects model and only case-control publications describing VEGF concentrations in Alzheimer’s patients were considered for calculating the pooled effect size. RESULTS: In the systematic literature search, 6 and 13 studies met the inclusion criteria to evaluate CSF and serum VEGF concentrations of Alzheimer’s patients, respectively. This meta-analysis retrieved a total number of 2380 Alzheimer’s patients and 5368 healthy controls. Under the random-effects model in the meta-analysis, the pooled SMD for CSF and serum VEGF concentrations of Alzheimer’s patients were -0.13 (95%CI,-0.42–0.16) and 0.23 (95%CI,-0.27–0.73), respectively. Results of meta-regression analysis showed that the quality scores of papers and female sex ratios of participants did not affect the associations of VEGF concentrations with the risk of Alzheimer’s disease. However, the age average of patients significantly affects the associations of CSF VEGF concentrations with the risk of Alzheimer’s disease (P=0.051). There was a statistically significant subgroup effect for the disease severity of Alzheimer’s patients which modifies the associations of serum VEGF concentrations with the risk of Alzheimer’s disease (P<0.01) and subgroup analysis shows that study location modifies the associations of CSF and serum VEGF concentrations with the risk of Alzheimer’s disease (P<0.01). CONCLUSION: The results show that the serum VEGF concentrations increased for Alzheimer’s patients in accordance with the increased expression of VEGF and the VEGF levels of Alzheimer’s patients decreased by increasing their disease severities. Therefore, in addition to detecting AD in the earliest stages of the disease, serum VEGF could be a promising biomarker to follow up on the disease and evaluate the clinical course of the disease.

CITATION:
S.S. Zakariaee ; N. Naderi ; E. Azizi (2024): Association of Vascular Endothelial Growth Factor Levels with Risk of Alzheimer’s Disease: A Systematic Review and Meta-Analysis. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.18

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JPAD Volume 11, N°02 - 2024

 

ANTI-AMYLOID THERAPIES FOR ALZHEIMER’S DISEASE: AN ALZHEIMER EUROPE POSITION PAPER AND CALL TO ACTION

A.C. Bradshaw, J. Georges, on behalf of the Alzheimer Europe Board

J Prev Alz Dis 2024;2(11):265-273

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The growing prevalence and burden of Alzheimer’s disease has catalysed huge investments in research on its causes, diagnosis, treatment and care. After many high-profile failures, recent clinical trials of anti-amyloid drugs have marked a turning point for the field, leading to the approval of the first disease-modifying therapies for Alzheimer’s disease by the FDA. It is now up to European regulators to determine whether there is sufficient evidence to approve these drugs for patients with mild cognitive impairment or mild dementia due to Alzheimer’s disease. Here, we outline Alzheimer Europe’s position on anti-amyloid therapies for Alzheimer’s disease, which was adopted by the Board of Alzheimer Europe following consultations with our member associations and with the European Working Group of People with Dementia. Beyond questions of drug efficacy, safety and cost, we highlight important issues that must be addressed by industry, regulators, payers, healthcare systems and governments, to ensure that patients have timely, appropriate and equitable access to innovative treatments, regardless of their socio-economic background, insurance status, or place of residence. We also call for continued investment in research on treatments that might benefit people with more advanced Alzheimer’s disease – as well as support and care services that can help people live well with dementia at all stages of the disease.

CITATION:
A.C. Bradshaw ; J. Georges ; on behalf of the Alzheimer Europe Board ; (2024): Anti-Amyloid Therapies for Alzheimer’s Disease: An Alzheimer Europe Position Paper and Call to Action. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.37

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ETHICAL CONSIDERATIONS AT THE INTERSECTION OF SOCIAL MEDIA AND DEMENTIA PREVENTION RESEARCH

V. Hrincu, G. Zaleski, J.M. Robillard

J Prev Alz Dis 2024;2(11):274-284

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online engagement for dementia prevention research. Existing social media guidelines are broad and lack empirical justification reflecting the values and priorities of the dementia community and the challenges specific to prevention research. OBJECTIVES: By engaging professional and community experts, we sought to identify the ethical issues, motivators, and barriers pertaining to social media engagement for dementia prevention research. DESIGN: Semi-structured, qualitative interviews conducted online. SETTING: We recruited participants using a combination of accessible online databases, advertisements/posters through organizational newsletters and websites, social media, registries, and from our network of colleagues. PARTICIPANTS: Professional experts working in dementia research (n=15; e.g., researchers, coordinators) and experts with lived experience (n=14). Experts were from Canada, the USA, the UK, and Chile. MEASUREMENTS: Discussions were analyzed using thematic qualitative analysis methods. RESULTS: Professional experts revealed a dearth of social media guidelines for prevention research, relying on informal sources to supplement ethics board approval. They sought methods of strategic communication for public dialogue (e.g., misinformation, criticism). Experts by experience appreciated the educational benefits of social media but raised risks such as diminished online privacy, dementia-related stigma, being targeted for predatory practices, and misinformation. Various digital inequities (e.g., age, socioeconomic status) dampen social media’s reach to diverse publics. Participants acknowledged that younger aging populations have more digital fluency and may benefit more from social media research engagement. CONCLUSIONS: Research professionals and community members identified ethical and contextual factors surrounding the use of social media for dementia prevention, and a need for more guidance. The next project phase will use these data to inform the co-creation of ethical guidelines for brain health research.

CITATION:
V. Hrincu ; G. Zaleski ; J.M. Robillard ; (2024): Ethical Considerations at the Intersection of Social Media and Dementia Prevention Research. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.4

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ALZHEIMER’S DISEASE BIOMARKER DECISION-MAKING AMONG PATIENTS WITH MILD COGNITIVE IMPAIRMENT AND THEIR CARE PARTNERS

C.G. Cox, C.R. Salazar, A.I. Birnbaum, M. Witbracht, S.P. Tam, G.T. Thai, S.A. Sajjadi, D.L. Gillen, J.D. Grill

J Prev Alz Dis 2024;2(11):285-293

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BAKGROUND Alzheimer’s disease (AD) biomarker tests can be ordered as part of the diagnostic workup of patients with mild cognitive impairment (MCI). Little is known about how patients with MCI and their care partners decide whether to pursue testing. OBJECTIVE: To examine factors that influence AD biomarker testing decisions among patients with MCI and their care partners. DESIGN: We performed structured research interviews with patients with MCI and their study partners to assess the importance of eight factors in the decision whether to undergo AD biomarker testing (6-point Likert scale; 1-extremely unimportant to 6-extremely important): cost, fear of testing procedures, learning if AD is the cause of cognitive problems, concern about health insurance, instructing future planning, informing treatment decisions, family members’ opinions, and doctor recommendation. SETTING: Two researchers administered interviews with participants in-person (i.e., participant home, research center) or remotely (i.e., telephone, video-conference). PARTICIPANTS: We completed interviews with 65 patients with a diagnosis of MCI and 57 study partners, referred by dementia specialist clinicians from the University of California, Irvine health system. MEASUREMENTS: We used generalized estimating equations (GEE) to examine the mean importance of each factor among patients and study partners, and the mean difference in importance of each factor within dyads. RESULTS: One third of participants reported the patient had previously undergone AD biomarker testing. Fifty-five percent of patients and 65% of study partners who reported no previous testing indicated a desire for the patient to be tested. GEE analyses found that patients and study partners rated the following factors with highest importance: informing treatment decisions (mean score 5.29, 95% CI: 5.06, 5.52 for patients; mean score 5.56, 95% CI: 5.41, 5.72 for partners); doctor recommendation (4.94, 95% CI: 4.73, 5.15 for patients; 5.16, 95% CI: 4.97, 5.34 for partners); and instructing future planning (4.88, 95% CI: 4.59, 5.16 for patients; 5.11, 95% CI: 4.86, 5.35 for partners). High dyadic agreement was observed for all factors except fear of testing, which patients rated with lower importance than their study partners. CONCLUSIONS Biomarker testing for AD in patients with MCI is a rapidly evolving practice and limited data exist on patient perspectives. In this study, most patients and their care partners were interested in testing to help inform treatment decisions and to plan for the future. Participants placed high importance on clinician recommendations for biomarker testing, highlighting the need for clear communication and education on the options, limitations, risks, and benefits of testing.

CITATION:
C.G. Cox ; C.R. Salazar ; A.I. Birnbaum ; M. Witbracht ; S.P. Tam ; G.T. Thai ; S.A. Sajjadi ; D.L. Gillen ; J.D. Grill ; (2024): Alzheimer’s Disease Biomarker Decision-Making among Patients with Mild Cognitive Impairment and Their Care Partners. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.10

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A PRAGMATIC, INVESTIGATOR-DRIVEN PROCESS FOR DISCLOSURE OF AMYLOID PET SCAN RESULTS TO ADNI-4 RESEARCH PARTICIPANTS

C.M. Erickson, J. Karlawish, J.D. Grill, K. Harkins, S.M. Landau, M.G. Rivera-Mindt, O. Okonkwo, R.C. Petersen, P.S. Aisen, M.W. Weiner, E.A. Largent

J Prev Alz Dis 2024;2(11):294-302

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BACKGROUND: Prior studies of Alzheimer’s disease (AD) biomarker disclosure have answered important questions about individuals’ safety after learning and comprehending their amyloid PET results; however, these studies have typically employed highly structured disclosure protocols and focused on the psychological impact of disclosure (e.g., anxiety, depression, and suicidality) in homogeneous populations. More work is needed to develop flexible disclosure protocols and study outcomes in ethnoculturally representative samples. METHODS: The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is formally incorporating amyloid PET disclosure into the newest protocol (ADNI-4). Participants across the cognitive spectrum who wish to know their amyloid PET results may learn them. The pragmatic disclosure process spans four timepoints: (1) a pre-disclosure visit, (2) the PET scan and its read, (3) a disclosure visit, and (4) a post-disclosure check-in. This process applies to all participants, with slight modifications to account for their cognitive status. In designing this process, special emphasis was placed on utilizing investigator discretion. Participant measures include perceived risk of dementia, purpose in life, and disclosure satisfaction. Investigator assessment of the disclosure visit (e.g., challenges encountered, topics discussed, etc.) is also included. RESULTS: Data collection is ongoing. Results will allow for more robust characterization of the impact of learning amyloid PET results on individuals and describe the perspectives of investigators. CONCLUSION: The pragmatic design of the disclosure process in ADNI-4 coupled with the novel participant and investigator data will inform future disclosure practices. This is especially important as disclosure of biomarker results expands in research and care.

CITATION:
C.M. Erickson ; J. Karlawish ; J.D. Grill ; K. Harkins ; S.M. Landau ; M.G. Rivera-Mindt ; O. Okonkwo ; R.C. Petersen ; P.S. Aisen ; M.W. Weiner ; E.A. Largent ; (2024): A Pragmatic, Investigator-Driven Process for Disclosure of Amyloid PET Scan Results to ADNI-4 Research Participants. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.33

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HEALTH ECONOMIC CONSIDERATIONS IN THE DEPLOYMENT OF AN ALZHEIMER’S PREVENTION THERAPY

S. Mattke, H. Jun, M. Hanson, S. Chu, J.H. Kordower, E.M. Reiman

J Prev Alz Dis 2024;2(11):303-309

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INTRODUCTION: As treatments for secondary prevention of Alzheimer’s disease (AD) are being studied, concerns about their value for money have appeared. We estimate cost-effectiveness of a hypothetical screening and prevention program. METHODS: We use a Markov model to project cost-effectiveness of a treatment that reduces progression to symptomatic AD by 50% with either chronic treatment until progression to mild cognitive impairment or treatment for one year followed by monitoring with AD blood tests and retreatment with one dose in case of amyloid re-accumulation. Diagnoses would be made with an AD blood test with sensitivity and specificity of 80%, and inconclusive results in 20%. Individuals testing negative would be re-tested in five years and those with inconclusive results in one. RESULTS: The program would generate per-person value of $53,721 from a payer (reduction of direct cost and patient QALY gains) and $69,861 from a societal perspective (adding valuation of reduced caregiver burden). With chronic treatment, it would be cost-effective up to annual drug prices of $7,000 and $10,300, respectively. Time-limited treatment would be cost-effective at annual drug prices of $54,257 and $78,458 from a payer and societal perspective, respectively. Higher specificity of the blood test would decrease cost per person with similar value generation DISCUSSION: A hypothetical prevention treatment for AD could be economically viable from a payer and societal perspective.

CITATION:
S. Mattke ; H. Jun ; M. Hanson ; S. Chu ; J.H. Kordower ; E.M. Reiman ; (2024): Health Economic Considerations in the Deployment of an Alzheimer’s Prevention Therapy. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.23

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POTENTIAL IMPLICATIONS OF SLOWING DISEASE PROGRESSION IN AMYLOID-POSITIVE EARLY ALZHEIMER’S DISEASE: ESTIMATES FROM REAL-WORLD DATA

J. Chandler, N. Done, U. Desai, M. Georgieva, A. Gomez-Lievano, W. Ye, A. Zhao, D. Eid, A. Hilts, N. Kirson, T. Schilling, for the Alzheimer’s Disease Neuroimaging Initiative

J Prev Alz Dis 2024;2(11):310-319

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BACKGROUND: Emerging therapies have shown promising results for slowing the progression of Alzheimer’s disease (AD). However, the potential impact of these therapies on real-world outcomes remains to be explored. OBJECTIVE: To examine the impact of slowing AD progression on functional abilities and behavioral symptoms. DESIGN: Retrospective observational study. SETTING: Data from the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) in the United States (06/2005-11/2021, primary analysis) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (09/2005-03/2022, sensitivity analysis) were used. PARTICIPANTS: Individuals with mild cognitive impairment (MCI) or mild dementia, Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score 0.5-9.0 (inclusive; first visit defined as the index date), and confirmed amyloid positivity were identified in NACC. In ADNI, individuals with at least one clinical center visit with a clinical assessment of MCI or mild dementia and confirmed amyloid positivity were identified. MEASUREMENTS: Hypothetical effects of slowing disease progression as assessed by CDR-SB on functional and behavioral outcomes including the Functional Activities Questionnaire (FAQ) score, Neuropsychiatric Inventory Questionnaire (NPI-Q) score, and the probability of complete dependence over five years were evaluated using multivariable regression among NACC participants, separately for the subgroups with MCI and mild dementia at baseline, respectively. For the ADNI sensitivity analysis, the hypothetical effects of slowing disease progression were evaluated for FAQ score using multivariable regression among the MCI participants only. RESULTS: Compared with natural disease progression, slowing progression by 20% over five years for NACC participants with MCI and mild dementia, respectively, would result in 1.7-point (10.8%) and 1.6-point (12.9%) less deterioration based on FAQ; 0.5-point (20.3%) and 0.5-point (19.3%) less deterioration based on NPI-Q; 4.7 percentage-point (22.2%) and 10.1 percentage-point (21.6%) lower probability of complete dependence. Among ADNI participants, delaying disease progression by 20% or 30% over 4 years would avert deterioration based on FAQ of 1.1 points (20.4%) and 1.6 points (29.6%), respectively, compared to natural disease progression. CONCLUSIONS: Slowing early AD progression could result in preservation of functional and behavioral attributes and functional autonomy for longer.

CITATION:
J. Chandler ; N. Done ; U. Desai ; M. Georgieva ; A. Gomez-Lievano ; W. Ye ; A. Zhao ; D. Eid ; A. Hilts ; N. Kirson ; T. Schilling ; for the Alzheimer’s Disease Neuroimaging Initiative ; (2024): Potential Implications of Slowing Disease Progression in Amyloid-Positive Early Alzheimer’s Disease: Estimates from Real-World Data. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.27

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IMPACT OF DIFFERENTIAL RATES OF DISEASE PROGRESSION IN AMYLOID-POSITIVE EARLY ALZHEIMER’S DISEASE: FINDINGS FROM A LONGITUDINAL COHORT ANALYSIS

J. Chandler, M. Georgieva, U. Desai, N. Done, A. Gomez-Lievano, W. Ye, A. Zhao, D. Eid, A. Hilts, N. Kirson, T. Schilling

J Prev Alz Dis 2024;2(11):320-328

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BACKGROUND: There is limited literature regarding the impact of differential rates of disease progression on longitudinal outcomes in individuals with early Alzheimer’s disease (AD) and confirmed brain amyloid pathology. OBJECTIVES: To describe the underlying characteristics and long-term outcomes associated with different rates of disease progression among amyloid-positive individuals with early symptomatic AD. DESIGN: Retrospective observational study. SETTING: Data from the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) in the United States (06/2005-11/2021). PARTICIPANTS: Individuals with a clinical assessment of mild cognitive impairment or dementia and Clinical Dementia Rating® Dementia Staging Instrument Sum of Boxes (CDR-SB) score 0.5-9.0 (inclusive; first visit defined as the index date) and confirmed amyloid positivity. Participants were stratified into No Progression (change ≤0), Slower Progression (0< change <2.0 points), Median Progression (2.0-point change), and Faster Progression (change >2.0 points) cohorts based on the observed distribution of changes in CDR-SB score between the index and first subsequent visit. MEASUREMENTS: For each cohort, the functional and neuropsychiatric outcomes were described at index and each subsequent visit for up to five years, and least-square (LS) mean changes from baseline were estimated using linear mixed-effects models adjusting for baseline demographic and clinical characteristics. RESULTS: Among 1,263 participants included in the analysis, the mean±standard deviation (SD) age at index was 72.7±9.7 years and 55.3% were males. Demographic characteristics and comorbidity profiles at index were similar across cohorts. However, at index, the Faster Progression (N=279) cohort had higher CDR-SB and Functional Assessment Questionnaire (FAQ) scores compared with the No Progression (N=474), Slower Progression (N=297), and Median Progression (N=213) cohorts. Adjusting for baseline characteristics, at year 5 after index the FAQ score increased by 23.6 points for Faster Progression cohort and 10.4, 15.8, and 19.2 points for the No, Slower, and Median Progression cohorts, respectively. The corresponding increases in Neuropsychiatric Inventory Questionnaire (NPI-Q) scores were 6.7 points for the Faster Progression cohort, and by 1.3, 3.1, and 8.3 points, for the No, Slower, and Median Progression cohorts, respectively. CONCLUSIONS: Despite similar demographic and clinical profiles at baseline, amyloid-positive individuals with greater deterioration based on CDR-SB early in the AD trajectory continue to experience worse functional and behavioral outcomes over time than those with more gradual deterioration in this metric.

CITATION:
J. Chandler ; M. Georgieva ; U. Desai ; N. Done ; A. Gomez-Lievano ; W. Ye ; A. Zhao ; D. Eid ; A. Hilts ; N. Kirson ; T. Schilling ; (2024): Impact of Differential Rates of Disease Progression in Amyloid-Positive Early Alzheimer’s Disease: Findings from a Longitudinal Cohort Analysis . The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.28

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VALIDATION, DEPLOYMENT, AND REAL-WORLD IMPLEMENTATION OF A MODULAR TOOLBOX FOR ALZHEIMER’S DISEASE DETECTION AND DEMENTIA RISK REDUCTION: THE AD-RIDDLE PROJECT

K. Malzbender, P. Barbarino, P. Barkman Ferrell, A. Bradshaw, A.J. Brookes, C. Díaz, W.M. van der Flier, J. Georges, O. Hansson, M. Hartmanis, L. Jönsson, R. Krishnan, T. MacLeod, F. Mangialasche, P. Mecocci, C. Minguillon, L. Middleton, S. Pla, S.P. Sardi, M. Schöll, M. Suárez-Calvet, W. Weidner, P.J. Visser, H. Zetterber, N. Bose, A. Solomon, M. Kivipelto, on behalf of the AD-RIDDLE Consortium

J Prev Alz Dis 2024;2(11):329-338

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The Real-World Implementation, Deployment, and Validation of Early Detection Tools and Lifestyle Enhancement (AD-RIDDLE) project, recently launched with the support of the EU Innovative Health Initiative (IHI) public-private partnership and UK Research and Innovation (UKRI), aims to develop, test, and deploy a modular toolbox platform that can reduce existing barriers to the timely detection, and therapeutic approaches in Alzheimer’s disease (AD), thus accelerating AD innovation. By focusing on health system and health worker practices, AD-RIDDLE seeks to improve and smooth AD management at and between each key step of the clinical pathway and across the disease continuum, from at-risk asymptomatic stages to early symptomatic ones. This includes innovation and improvement in AD awareness, risk reduction and prevention, detection, diagnosis, and intervention. The 24 partners in the AD-RIDDLE interdisciplinary consortium will develop and test the AD-RIDDLE toolbox platform and its components individually and in combination in six European countries. Expected results from this cross-sectoral research collaboration include tools for earlier detection and accurate diagnosis; validated, novel digital cognitive and blood-based biomarkers; and improved access to individualized preventative interventions (including multimodal interventions and symptomatic/disease-modifying therapies) across diverse populations, within the framework of precision medicine. Overall, AD-RIDDLE toolbox platform will advance management of AD, improving outcomes for patients and their families, and reducing costs.

CITATION:
K. Malzbender ; P. Barbarino ; P. Barkman Ferrell ; A. Bradshaw ; A.J. Brookes ; C. Díaz ; W.M. van der Flier ; J. Georges ; O. Hansson ; M. Hartmanis ; L. Jönsson ; R. Krishnan ; T. MacLeod ; F. Mangialasche ; P. Mecocci ; C. Minguillon ; L. Middleton ; S. Pla ; S.P. Sardi ; M. Schöll ; M. Suárez-Calvet ; W. Weidner ; P.J. Visser ; H. Zetterberg ; N. Bose ; A. Solomon ; M. Kivipelto ; on behalf of the AD-RIDDLE Consortium ; (2024): Validation, Deployment, and Real-World Implementation of a Modular Toolbox for Alzheimer’s Disease Detection and Dementia Risk Reduction: The AD-RIDDLE Project. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.32

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EXPLORING THE ASSOCIATION BETWEEN AMYLOID-Β AND MEMORY MARKERS FOR ALZHEIMER’S DISEASE IN COGNITIVELY UNIMPAIRED OLDER ADULTS

M.A. Parra, Y. Gazes, C. Habeck, Y. Stern

J Prev Alz Dis 2024;2(11):339-347

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BACKGROUND: Memory tests vary in their sensitivity for detection of pre-symptomatic Alzheimer’s disease (AD). The Visual Short-Term Memory Binding Test (VSTMBT) identifies AD-related performance deficits in older adults who are otherwise cognitively unimpaired. OBJECTIVE: We investigated the association of this psychometric measure with brain amyloidosis and atrophy. DESIGN: Cross-sectional mixed and correlational. SETTING: Cognitive Reserve Study from Columbia University. PARTICIPANTS: a sample of 39 cognitively unimpaired older adults (Age: M=65.3, SD=3.07) was obtained from the above study. MEASUREMENTS: Extensive neuropsychological and neuroimaging (MRI and amyloid-β PET) assessments were carried out. RESULTS: Performance on the VSTMBT allowed us to split the sample into Low Binding Cost (LBC, N=21) and High Binding Cost (HBC, N=18). Groups were matched according to age [p=0.702], years of education [0.071], and sex [p=0.291]. HBC’s performance was comparable to that seen in symptomatic AD. Groups only differed in their amyloid-β deposition on PET in regions of the right ventral stream linked to visual cognition and affected early in AD pathogenesis (lateral-occipital cortex, p = 0.008; fusiform gyrus, p = 0.017; and entorhinal cortex, p = 0.046). Other regions known to be linked to low-level visual integration function also revealed increased amyloid-β deposition in HBC. CONCLUSIONS: VSTMB deficits are associated with neuropathogenesis (i.e., amyloid-β deposition) in the earliest affected regions in pre-symptomatic AD. The VSTMB test holds potential for the identification of cognitively unimpaired older adults with very early AD pathogenesis and may thus be a useful tool for early intervention trials or other forms of clinical research.

CITATION:
M.A. Parra ; Y. Gazes ; C. Habeck ; Y. Stern ; (2024): Exploring the Association between Amyloid-β and Memory Markers for Alzheimer’s Disease in Cognitively Unimpaired Older Adults. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.11

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WHO BENEFITED THE MOST? EFFECTIVENESS OF A LIFESTYLE INTERVENTION AGAINST COGNITIVE DECLINE IN OLDER WOMEN AND MEN – SECONDARY ANALYSIS OF THE AGEWELL. DE-TRIAL

F.G. Wittmann, A. Pabst, A. Zülke, M. Luppa, I. Blotenberg, M.I. Cardona, A. Bauer, S. Fuchs, I. Zöllinger, L. Sanftenberg, C. Brettschneider, J. Döhring, L. Lunden, D. Czock, B. Wiese, J.R. Thyrian, W. Hoffmann, T. Frese, J. Gensichen, H.-H. König, H. Kaduszkiewicz, S.G. Riedel-Heller

J Prev Alz Dis 2024;2(11):348-355

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INTRODUCTION: Differences between women and men matter in the prevalence and risk factors of dementia. We aimed to examine potential sex differences regarding the effectiveness by running a secondary analysis of the AgeWell.de trial, a cluster-randomized multicenter multi-domain lifestyle intervention to reduce cognitive decline. METHODS: Intention-to-treat analyses of women (n=433) and men (n=386) aged 60 to 77 years were used for models including interactions between intervention group allocation and sex followed by subgroup analysis stratified by sex on primary and secondary outcomes. Further, the same procedure was repeated for age groups (60-69 vs. 70-77) within sex-specific subgroups to assess the effectiveness in different age groups. Trial registration: German Clinical Trials Register (ref. number: DRKS00013555). RESULTS: No differences were found between women and men in the effectiveness of the intervention on cognitive performance. However, women benefitted from the intervention regarding depressive symptoms while men did not. Health-related quality of life was enhanced for younger intervention participants (60-69 years) in both women and men. CONCLUSION: The AgeWell.de intervention was able to improve depressive symptoms in women and health-related quality of life in younger participants. Female participants between 60 and 69 years benefited the most. Results support the need of better individually targeted lifestyle interventions for older adults.

CITATION:
F.G. Wittmann ; A. Pabst ; A. Zülke ; M. Luppa ; I. Blotenberg ; M.I. Cardona ; A. Bauer ; S. Fuchs ; I. Zöllinger ; L. Sanftenberg ; C. Brettschneider ; J. Döhring ; L. Lunden ; D. Czock ; B. Wiese ; J.R. Thyrian ; W. Hoffmann ; T. Frese ; J. Gensichen ; H.-H. König ; H. Kaduszkiewicz ; S.G. Riedel-Heller (2024): Who Benefited the Most? Effectiveness of a Lifestyle Intervention Against Cognitive Decline in Older Women and Men – Secondary Analysis of the AgeWell.de-trial. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.13

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ROLES OF BASELINE INTRINSIC CAPACITY AND ITS SUBDOMAINS ON THE OVERALL EFFICACY OF MULTIDOMAIN INTERVENTION IN PROMOTING HEALTHY AGING AMONG COMMUNITYDWELLING OLDER ADULTS: ANALYSIS FROM A NATIONWIDE CLUSTER-RANDOMIZED CONTROLLED TRIAL

C.-K. Liang, W.-J. Lee, M.-Y. Chou, A.-C. Hwang, C.-S. Lin, L.-N. Peng, F.-Y. Hsiao, C.-H. Loh, L.-K. Chen

J Prev Alz Dis 2024;2(11):356-365

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Background: Impaired intrinsic capacity (IC), which affects approximately 90% of older adults, is associated with a significantly heightened risk of frailty and cognitive decline. Existing evidence suggests that multidomain interventions have the potential to enhance cognitive performance and yield positive effects on physical frailty. OBJECTIVE: To examine roles of baseline IC and its subdomains on the efficacy of multidomain interventions in promoting healthy aging in older adults. DESIGN: a cluster-randomized controlled trial. Setting and Participants: 1,054 community-dwelling older adults from 40 community-based clusters across Taiwan. INTERVENTION: A 12-month pragmatic multidomain intervention of exercise, cognitive training, nutritional counseling and chronic condition management. MEASUREMENTS: Baseline IC was measured by 5 subdomains, including cognition (Montreal Cognitive Assessment, MoCA), sensory (visual and hearing impairment), vitality (handgrip strength or Mini-Nutritional Assessment-short form), psychological well-being (Geriatric Depression Scale-5), and locomotion (6m gait speed). Outcomes of interest were cognitive performance (MoCA scores) and physical frailty (CHS frailty score) over a follow-up period of 6 and 12 months. RESULTS: Of all participants (mean age:75.1±6.4 years, 68.6% female), about 90% participants had IC impairment at baseline (2.0±1.2 subdomains). After covariate adjustment using a generalized linear mixed model (GLMM), the multidomain intervention significantly prevented cognitive declines and physical frailty, particularly in those with IC impairment ≥ 3 subdomains (MoCA: coefficient: 1.909, 95% CI: 0.736 ~ 3.083; CHS frailty scores: coefficient = -0.405, 95% CI: -0.715 ~ -0.095). To assess the associations between baseline poor capacity in each IC subdomain and MoCA/CHS frailty scores over follow-up, a 3-way interaction terms (time*intervention*each poorer IC subdomains) were added to GLMM models. Significant improvements in MoCA scores were shown for participants with poorer baseline cognition (coefficient= 1.138, 95% CI: 0.080 ~ 2.195) and vitality domains (coefficient= 1.651, 95% CI: 0.541 ~ 2.760). The poor vitality domain also had a significant modulating effect on the reduction of CHS frailty score after the 6- and 12-month intervention period (6 months: coefficient= -0.311, 95% CI: -0.554 ~ -0.068; 12 months: coefficient= -0.257, 95% CI: -0.513 ~ -0.001). CONCLUSION AND IMPLICATIONS: A multidomain intervention in community-dwelling older adults improves cognitive decline and physical frailty, with its effectiveness influenced by baseline IC, highlighting the importance of personalized strategies for healthy aging.

CITATION:
C.-K. Liang ; W.-J. Lee ; M.-Y. Chou ; A.-C. Hwang ; C.-S. Lin ; L.-N. Peng ; F.-Y. Hsiao ; C.-H. Loh ; L.-K. Chen ; (2024): Roles of Baseline Intrinsic Capacity and its Subdomains on the Overall Efficacy of Multidomain Intervention in Promoting Healthy Aging among Community-Dwelling Older Adults: Analysis from a Nationwide Cluster-Randomized Controlled Trial. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.20

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A PHASE 1 SINGLE-ASCENDING-DOSE TRIAL IN HEALTHY VOLUNTEERS TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND IMMUNOGENICITY OF INTRAVENOUS PNT001, A NOVEL MID-DOMAIN TAU ANTIBODY TARGETING CIS-PT231 TAU

W. Luca, K. Foster, K. McClure, M.K. Ahlijanian, M. Jefson

J Prev Alz Dis 2024;2(11):366-374

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BACKGROUND: PNT001 is a humanized full-length IgG4 S228P monoclonal antibody that binds the cis conformation of the phosphorylated Thr231-Pro232 motif in human full-length (2N4R) tau (cis-pT231 tau) with high selectivity and affinity. It binds selectively to cis-pT231 tau in human tauopathy brain sections, inhibits aggregation of tau, and has shown efficacy in preclinical models of tauopathy. Good Laboratory Practice six-month toxicology studies in cynomolgous monkeys have shown no test article-related findings. OBJECTIVES: To evaluate the safety, tolerability, pharmacokinetics, and immunogenicity of single escalating intravenous doses of PNT001 in healthy volunteers. DESIGN: Phase 1, randomized, double-blind, and placebo-controlled 16-week study. SETTING: Subjects were recruited across three clinical research sites in the United States. PARTICIPANTS: Fifty healthy volunteer subjects enrolled, with 49 receiving the double-blind study drug. INTERVENTION: Six cohorts were administered single escalating doses of PNT001 (33, 100, 300, 900, 2,700, and 4,000 mg). The subjects were randomized 6:2 (PNT001:placebo). MEASUREMENTS: Safety was evaluated by the occurrence of adverse events, electrocardiography, physical examinations, neurological examinations, vital signs, and suicidality. Pharmacokinetics and biomarkers were assessed via serum and cerebrospinal fluid sample analyses. RESULTS: Dose continuation after review of sentinel group data and dose escalation after completion of full cohort data were determined by an external, independent safety board. There were no study pauses or safety concerns identified by the safety board. A total of 49 subjects received the study drugs, with 36 receiving PNT001 and 13 receiving placebo. There were three related non-serious adverse events, each Grade 1, which occurred at the lowest doses and resolved without sequelae. No maximum tolerated dose was identified, and no premature discontinuations, dose reductions, or interruptions due to treatment-related adverse events occurred. One unrelated serious adverse event occurred in a placebo subject with an undisclosed medical condition. No other safety findings were identified. Doses of 900–4,000 mg produced concentrations in the cerebrospinal fluid exceeding the binding affinity constant of PNT001 for cis-pT231 tau (45 ng/mL), indicating that concentrations sufficient for target engagement can be obtained in the cerebrospinal fluid within the tested dose range. The serum pharmacokinetic profile was as expected for a monoclonal antibody. The terminal half-lives ranged from 23.8–33.8 days, and the cerebrospinal fluid exposures were approximately 0.1% of the plasma concentration and dose-proportional. Of the 36 subjects receiving PNT001, one post-baseline positive anti-drug antibody result was observed at Day 112 in a subject who received PNT001 (300 mg). CONCLUSIONS: Single doses of PNT001 were safe and well-tolerated at all dose levels studied, including those doses expected to produce therapeutic benefit. These results support multiple ascending dose trials in patients with neurodegenerative tauopathies for this novel mid-domain tau antibody.

CITATION:
W. Luca ; K. Foster ; K. McClure ; M.K. Ahlijanian ; M. Jefson ; (2024): A Phase 1 Single-Ascending-Dose Trial in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Intravenous PNT001, a Novel Mid-domain Tau Antibody Targeting cis-pT231 Tau. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.25

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VORTIOXETINE TREATMENT FOR DEPRESSION IN PATIENTS WITH PRODROMAL VS MILD ALZHEIMER’S DISEASE: A SIXMONTH, OPEN-LABEL, OBSERVATIONAL STUDY

A. Padovani, S. Caratozzolo, A. Benussi, A. Galli, L. Rozzini, M. Cosseddu, R. Turrone, A. Pilotto

J Prev Alz Dis 2024;2(11):375-381

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BACKGROUND: Depressive symptoms are common in Alzheimer disease (AD) from the prodromal stage. The benefits of antidepressants have been investigated in patients with AD dementia with mixed results. OBJECTIVES: This study aimed to compare the efficacy of vortioxetine in prodromal and mild-to-moderate AD patients with depression, and to assess the comparative effect on secondary measures, including behavioral disturbances, cognitive function, and activities of daily living. PARTICIPANTS: All subjects with AD at a single-center dementia center underwent a standard evaluation with mini-mental state examination (MMSE), basic and instrumental activities of daily living (BADL and IADL), geriatric depression scale (GDS), neuropsychiatric inventory (NPI), and clinical evaluation every six months. MEASUREMENTS: The study specifically assessed patients on vortioxetine with available six-month follow-up data. The changes in GDS, NPI, MMSE, BADL/IADL at six months in the entire AD population and mild-to-moderate AD vs prodromal population were analyzed using repeated measure multivariate analyses. Linear regression analyses were implemented to evaluate baseline demographics and clinical characteristics associated with depressive and cognitive improvements at six months. RESULTS: Out of 680 AD patients, 115 were treated with vortioxetine, and 89 with six-month follow-up data were included in the analyses. A significant improvement at follow-up was observed for GDS, NPI total and sub score items (mood, anxiety, apathy, sleep disturbances, eating abnormalities). Both mild-to-moderate and prodromal AD showed a positive GDS response, whereas mild-to-moderate AD showed a better improvement on total NPI and apathy/nighttime behaviors subitems compared to prodromal AD. Higher baseline GDS score was the only variable associated with higher responses in linear regression analyses. MMSE showed a significant improvement at six months in the entire cohort, with a greater effect in prodromal vs mild-to-moderate AD. Cognitive improvement (i.e., MMSE changes) was associated with cognitive status at baseline but independent of the antidepressant/behavioral changes (i.e., GDS/NPI). CONCLUSIONS: Our results suggest that vortioxetine is highly tolerable and clinically effective in both prodromal and mild-to-moderate AD with depression. Patients with mild-to-moderate AD benefited more from a wide range of behavioral disturbances. The study also showed significant improvement in global cognitive measures, especially in prodromal AD subjects. Further studies are needed to investigate the independent beneficial effect of vortioxetine on depression and cognition in AD.

CITATION:
A. Padovani ; S. Caratozzolo ; A. Benussi ; A. Galli ; L. Rozzini ; M. Cosseddu ; R. Turrone ; A. Pilotto ; (2023): Vortioxetine Treatment for Depression in Patients with Prodromal vs Mild Alzheimer’s Disease: A Six-Month, Open-Label, Observational Study. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2023.132

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A CHOLECYSTOKININ ANALOGUE AMELIORATES COGNITIVE DEFICITS AND REGULATES MITOCHONDRIAL DYNAMICS VIA THE AMPK/DRP1 PATHWAY IN APP/PS1 MICE

L. Hao, M. Shi, J. Ma, S. Shao, Y. Yuan, J. Liu, Z. Yu, Z. Zhang, C. Hölscher, Z. Zhang

J Prev Alz Dis 2024;2(11):382-401

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BACKGROUND: There are no drugs on the market that can reverse or slow Alzheimer’s disease (AD) progression. A protease-resistant Cholecystokinin (CCK) analogue used in this study is based on the basic structure of CCK, which further increases the stability of the peptide fragment and prolongs its half-life in vivo. We observed a neuroprotective effect of CCK-8L in APPswe/PS1dE9 (APP/PS1) AD mice. However, its corresponding mechanisms still need to be elucidated. OBJECTIVE: This study examined CCK-8L’s neuroprotective effects in enhancing cognitive impairment by regulating mitochondrial dynamics through AMPK/Drp1 pathway in the APP/PS1 AD mice. METHODS: Behavioural tests are applied to assess competence in cognitive functions. Transmission electron microscopy (TEM) was performed to observe the ultrastructure of mitochondria of hippocampal neurons, Immunofluorescent staining was employed to assay for Aβ1-42, APP, Adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) and dynamin-related protein1 (Drp1). CRISPR/Cas9 was utilized for targeted knockout of the CCKB receptor (CCKBR) in the mouse APP/PS1 hippocampal CA1 region. A model of lentiviral vector-mediated overexpression of APP in N2a cells was constructed. RESULTS: In vivo, experiments revealed that CCK analogue and liraglutide significantly alleviated cognitive deficits in APP/PS1 mice, reduced Aβ1-42 expression, and ameliorated l damage, which is associated with CCKBR activation in the hippocampal CA1 region of mice. In vitro tests showed that CCK inhibited mitochondrial fission and promoted fusion through AMPK/Drp1 pathway. CONCLUSIONS: CCK analogue ameliorates cognitive deficits and regulates mitochondrial dynamics by activating the CCKB receptor and the AMPK/Drp1 pathway in AD mice.

CITATION:
L. Hao ; M. Shi ; J. Ma ; S. Shao ; Y. Yuan ; J. Liu ; Z. Yu ; Z. Zhang ; C. Hölscher ; Z. Zhang (2024): A Cholecystokinin Analogue Ameliorates Cognitive Deficits and Regulates Mitochondrial Dynamics via the AMPK/Drp1 Pathway in APP/PS1 Mice. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.6

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COST-EFFECTIVENESS OF PREVENTION FOR PEOPLE AT RISK FOR DEMENTIA: A SCOPING REVIEW AND QUALITATIVE SYNTHESIS

A. Braun, M. Höfler, S. Auer

J Prev Alz Dis 2024;2(11):402-413

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Dementia is from an economic perspective a main challenge for economies worldwide because of increasing costs. Since there is no cure in sight, prevention seems the most promising approach for reducing health care cost due to Dementia. On the contrary, approximately 40% of dementias is attributable to modifiable risk factors and first studies showed that multidomain interventions may be effective for preventing dementia. Considering the increasing economic burden, for many health administrations worldwide, cost-effectiveness plays a mayor role. This scoping review wants to bring evidence to the question if prevention for people at risk may be cost-effective. Therefore, the four databases Medline (via Pubmed), CINHAL (via EBSCO), Business Source Complete (via EBSCO), and the Health Economic Evaluation database (HEED) were used to conduct a scoping review using PICO and a systematic search string. 3,629 studies were identified and seven met all inclusion criteria. The included studies showed clear cost-effectiveness for most multidomain interventions. The gained QALYs at mean were 0.08 (SD=0.08) and the intervention average costs 472.20 EUR per Person (SD=74.06 EUR). The Incremental Cost-Effectiveness Ratios varied between –80,427.97 and 104,189.82 EUR per QALY. The three core results are (i) prevention programs focusing on people at risk may be cost-effective and cost-efficient, (ii) multimodal prevention reveal cost saving potential, when the people at risk are defined well, (iii prevention in middle-aged cohorts may be also cost-effective if life-style related risk factors are addressed.

CITATION:
A. Braun ; M. Höfler ; S. Auer ; (2024): Cost-Effectiveness of Prevention for People at Risk for Dementia: A Scoping Review and Qualitative Synthesis. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.12

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CLINICAL CORRELATES OF THE PET-BASED BRAAK STAGING FRAMEWORK IN ALZHEIMER’S DISEASE

A.C. Macedo, D.F.P.A. Durço, C. Tissot, J. Therriault, A.O. Vilela de Faria, É. Aumont, S. Servaes, N. Rahmouni, J. Fernandez-Arias, Y.-T. Wang, F.Z. Lussier, A. Bieger, E.R. Zimmer, T.A. Pascoal, S. Gauthier, P. Rosa-Neto

J Prev Alz Dis 2024;2(11):414-421

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In vivo Alzheimer’s disease diagnosis and staging is traditionally based on clinical features. However, the agreement between clinical and pathological Alzheimer’s disease diagnosis, whose diagnosis assessment includes amyloid and Braak histopathological tau staging, is not completely convergent. The development of positron emission tomography (PET) tracers targeting neurofibrillary tangles offers prospects for advancing the staging of Alzheimer’s disease from both biological and clinical perspectives. Recent advances in radiochemistry made it possible to apply the postmortem Braak staging framework to tau-PET images obtained in vivo. Here, our aim is to provide a narrative review of the current literature on the relationship between Alzheimer’s disease clinical features and the PET-based Braak staging framework. Overall, the available studies support the stepwise increase in disease severity following the advance of PET-based Braak stages, with later stages being associated with worse cognitive and clinical symptoms. In line with this, there is a trend for unimpaired cognition, mild cognitive impairment, and Alzheimer’s disease dementia to be compatible with early, intermediate, and late patterns of tau deposition based on PET-based Braak stages. Moreover, neuropsychiatric symptom severity seems to be linked to the extent of tau-PET signal across Braak areas. In sum, this framework seems to correspond well with the clinical progression of Alzheimer’s disease, which is an indication of its potential utility in research and clinical practice, especially for detecting preclinical tau levels in individuals without symptoms. However, further research is needed to improve the generalizability of these findings and to better understand the applications of this staging framework.

CITATION:
A.C. Macedo ; D.F.P.A. Durço ; C. Tissot ; J. Therriault ; A.O. Vilela de Faria ; É. Aumont ; S. Servaes ; N. Rahmouni ; J. Fernandez-Arias ; Y.-T. Wang ; F.Z. Lussier ; A. Bieger ; E.R. Zimmer ; T.A. Pascoal ; S. Gauthier ; P. Rosa-Neto ; (2024): Clinical Correlates of the PET-based Braak Staging Framework in Alzheimer’s Disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.15

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CYTOMEGALOVIRUS INFECTION AND ALZHEIMER’S DISEASE: A META-ANALYSIS

Q. Ji, W. Lian, Y. Meng, W. Liu, M. Zhuang, N. Zheng, I.K. Karlsson, Y. Zhan

J Prev Alz Dis 2024;2(11):422-427

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Background: Evidence on the association of cytomegalovirus (CMV) infection with Alzheimer’s disease (AD) is scarce and the results are inconsistent. OBJECTIVE: To investigate the association of CMV infection with the risk of AD. METHODS: Observational studies on the relationship between CMV infection and AD were identified from PubMed, Embase, Web of Science, and the Cochrane Library until September 30, 2022. The quality of included studies was assessed using the Newcastle-Ottawa Scale. Random-effect meta-analysis was performed using a generic inverse-variance method, followed by sensitivity analyses and subgroup analyses based on study designs, regions, adjustments, and population types. RESULTS: Our search yielded 870 articles, of which 200 were duplicates and 663 did not meet the inclusion criteria, and finally yielded seven studies with 6,772 participants. No strong evidence was observed in the summary analysis for the association of CMV infection and risk of AD (odds ratio [OR] = 1.33; 95% confidence interval [CI]: 0.88, 2.03, I2 =69.9%). However, subgroup analysis showed that an increased risk of AD was detected in East Asians (OR = 2.39; 95% CI: 1.63, 3.50, I2 = 0.00%), cohort studies (OR = 1.99; 95% CI: 1.35, 2.94, I2 = 28.20%), and studies with confounder adjustment (OR = 2.05; 95% CI: 1.52, 2.77, I2 = 0.00%). CONCLUSIONS: This meta-analysis provides evidence to support the heterogeneity of the associations between CMV infection and AD. Future studies with larger sample sizes and multi-ethnic populations are necessary.

CITATION:
Q. Ji ; W. Lian ; Y. Meng ; W. Liu ; M. Zhuang ; N. Zheng ; I.K. Karlsson ; Y. Zhan ; (2023): Cytomegalovirus Infection and Alzheimer’s Disease: A Meta-Analysis. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2023.126

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NANOLITHIUM, A NEW TREATMENT APPROACH TO ALZHEIMER’S DISEASE: A REVIEW OF EXISTING EVIDENCE AND CLINICAL PERSPECTIVES

S. Guilliot, E.N. Wilson, J. Touchon, M.E. Soto

J Prev Alz Dis 2024;2(11):428-434

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Lithium has been approved and used for several decades in the treatment of psychiatric disorders, and its potential effect in neurodegenerative diseases has been subject to increasing research interest in recent years. Nanolithium is a new experimental product using a novel drug-delivery technology (Aonys®), which optimizes its bioavailability while reducing its toxicity profile. Therapeutic doses of lithium used in Nanolithium are more than 50 times lower than the minimal dose of classical lithium salts. In this review we report data from non-clinical pharmacology studies supporting Nanolithium efficacy and the mechanism of action in Alzheimer’s disease. GSK-3β inhibition is thought to be central to Nanolithium’s mechanism of action, triggering a reduction of the production of toxic amyloid plaques and decrease in tau hyperphosphorylation, which could potentially benefit both neuropsychiatric symptoms and cognitive decline. We then summarize outcomes from non-clinical proof-of-concept studies. These data supported the initiation of a currently ongoing phase II proof-of-concept study to evaluate the safety and efficacy of Nanolithium in patients with mild-to-severe Alzheimer’s disease. We highlight key aspects of the study design. We finish this review with a discussion on the potential place of Nanolithium in the current and future Alzheimer’s disease treatment landscape.

CITATION:
S. Guilliot ; E.N. Wilson ; J. Touchon ; M.E. Soto (2024): Nanolithium, a New Treatment Approach to Alzheimer’s Disease: A Review of Existing Evidence and Clinical Perspectives. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.26

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PERSONALIZED COMPUTATIONAL CAUSAL MODELING OF THE ALZHEIMER DISEASE BIOMARKER CASCADE

J.R. Petrella, J. Jiang, K. Sreeram, S. Dalziel, P.M. Doraiswamy, W. Hao, for the Alzheimer’s Disease Neuroimaging Initiative

J Prev Alz Dis 2024;2(11):435-444

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BACKGROUND: Mathematical models of complex diseases, such as Alzheimer’s disease, have the potential to play a significant role in personalized medicine. Specifically, models can be personalized by fitting parameters with individual data for the purpose of discovering primary underlying disease drivers, predicting natural history, and assessing the effects of theoretical interventions. Previous work in causal/mechanistic modeling of Alzheimer’s Disease progression has modeled the disease at the cellular level and on a short time scale, such as minutes to hours. No previous studies have addressed mechanistic modeling on a personalized level using clinically validated biomarkers in individual subjects. OBJECTIVES: This study aimed to investigate the feasibility of personalizing a causal model of Alzheimer’s Disease progression using longitudinal biomarker data. DESIGN/SETTING/PARTICIPANTS/MEASUREMENTS: We chose the Alzheimer Disease Biomarker Cascade model, a widely-referenced hypothetical model of Alzheimer’s Disease based on the amyloid cascade hypothesis, which we had previously implemented mathematically as a mechanistic model. We used available longitudinal demographic and serial biomarker data in over 800 subjects across the cognitive spectrum from the Alzheimer’s Disease Neuroimaging Initiative. The data included participants that were cognitively normal, had mild cognitive impairment, or were diagnosed with dementia (probable Alzheimer’s Disease). The model consisted of a sparse system of differential equations involving four measurable biomarkers based on cerebrospinal fluid proteins, imaging, and cognitive testing data. RESULTS: Personalization of the Alzheimer Disease Biomarker Cascade model with individual serial biomarker data yielded fourteen personalized parameters in each subject reflecting physiologically meaningful characteristics. These included growth rates, latency values, and carrying capacities of the various biomarkers, most of which demonstrated significant differences across clinical diagnostic groups. The model fits to training data across the entire cohort had a root mean squared error (RMSE) of 0.09 (SD 0.081) on a variable scale between zero and one, and were robust, with over 90% of subjects showing an RMSE of < 0.2. Similarly, in a subset of subjects with data on all four biomarkers in at least one test set, performance was high on the test sets, with a mean RMSE of 0.15 (SD 0.117), with 80% of subjects demonstrating an RMSE < 0.2 in the estimation of future biomarker points. Cluster analysis of parameters revealed two distinct endophenotypic groups, with distinct biomarker profiles and disease trajectories. CONCLUSION: Results support the feasibility of personalizing mechanistic models based on individual biomarker trajectories and suggest that this approach may be useful for reclassifying subjects on the Alzheimer’s clinical spectrum. This computational modeling approach is not limited to the Alzheimer Disease Biomarker Cascade hypothesis, and can be applied to any mechanistic hypothesis of disease progression in the Alzheimer’s field that can be monitored with biomarkers. Thus, it offers a computational platform to compare and validate various disease hypotheses, personalize individual biomarker trajectories and predict individual response to theoretical prevention and therapeutic intervention strategies.

CITATION:
J.R. Petrella ; J. Jiang ; K. Sreeram ; S. Dalziel ; P.M. Doraiswamy ; W. Hao ; for the Alzheimer’s Disease Neuroimaging Initiative (2023): Personalized Computational Causal Modeling of the Alzheimer Disease Biomarker Cascade. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2023.134

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FRUIT INTAKE AND ALZHEIMER’S DISEASE: RESULTS FROM MENDELIAN RANDOMIZATION

W.-Z. Liao, X.-F. Zhu, Q. Xin, Y.-T. Mo, L.-L. Wang, X.-P. He, X.-G. Guo

J Prev Alz Dis 2024;2(11):445-452

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Alzheimer’s disease (AD) is the leading cause of dementia in old age, recognized as a global health priority. To explore causal effects of fresh fruit intake and dried fruit intake on AD liability, this study utilized GWAS from the UK Biobank and FinnGen to conduct Mendelian randomization (MR) analysis, and used inverse variance weighted (IVW), MR-Egger, and weighted median approaches for MR estimates, and visual inspections judged result stability. Results suggested little evidence of a potential causal relationship between fresh fruit intake and AD (OR=0.97, 95%CI=0.50-1.91, P=0.939), while significant, robust causality was indicated between dried fruit intake and AD (OR=4.09, 95%CI=2.07-8.10, P<0.001). Stability evaluations showed no heterogeneity or pleiotropy affecting interpretability and credibility of primary analyses. In conclusion, we strengthened evidence for positive causality from dried fruit intake to AD liability, with causality from fresh fruit intake on AD risk was not demonstrated.

CITATION:
W.-Z. Liao ; X.-F. Zhu ; Q. Xin ; Y.-T. Mo ; L.-L. Wang ; X.-P. He ; X.-G. Guo (2024): Fruit Intake and Alzheimer’s Disease: Results from Mendelian Randomization. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.31

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CARDIOVASCULAR RISK SCALES ASSOCIATION WITH CEREBROSPINAL FLUID ALZHEIMER’S DISEASE BIOMARKERS IN CARDIOVASCULAR LOW CARDIOVASCULAR RISK REGIONS

G. García-Lluch, J. Pardo, L. Moreno, C. Peña-Bautista, M. Baquero, C. Cháfer-Pericás

J Prev Alz Dis 2024;2(11):453-462

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BACKGROUND: Cardiovascular risk factors are associated with Alzheimer’s Disease (AD) development. However, few studies compare the overall cardiovascular risk with AD biomarkers, and when done, they are mainly performed in moderate cardiovascular risk regions. OBJECTIVES: To determine whether cardiovascular risk in older adults is associated with pathological cerebrospinal fluid (CSF) biomarkers of AD in a low cardiovascular risk population. DESIGN: This is a cross-sectional study performed between 2017 and 2020. PARTICIPANTS: The present work included patients between 50 and 75 years old who were negative for CSF AD biomarkers and had minimum cognitive alterations (controls) and patients with positive CSF AD biomarkers and in early stages of AD (cases). MEASUREMENTS: CSF biomarkers included total tau, phosphorylated tau 181 and amyloid ß42 (Aß42). Analytical variables were obtained. ERICE, SCORE2 and Framingham scales were used to calculate the overall patient’s cardiovascular risk. The Aß42/Aß40 ratio and neurofilaments were explored when available. RESULTS: Two hundred and thirty-three patients were included. Nearly 76% of the sample had AD. AD patients had higher cardiovascular risk than controls (p-value < 0.05). ERICE and SCORE2 were associated with AD presence. Framingham was not. A correlation between elevated cardiovascular risk and higher total tau and NfL levels was observed when adjusted by age. CONCLUSION: Cardiovascular risk assessment may be helpful in neurodegenerative disorders detection, as it is associated with CSF total tau and NfL. ERICE and SCORE2 may be useful scales in low cardiovascular risk regions to improve cardiovascular control and prevent neurodegenerative pathologies.

CITATION:
G. García-Lluch ; J. Pardo ; L. Moreno ; C. Peña-Bautista ; M. Baquero ; C. Cháfer-Pericás (2024): Cardiovascular Risk Scales Association with Cerebrospinal Fluid Alzheimer’s Disease Biomarkers in Cardiovascular Low Cardiovascular Risk Regions. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.16

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THE MAPP ROOM MEMORY TEST: EXAMINING CONTEXTUAL MEMORY USING A NOVEL COMPUTERIZED TEST IN COGNITIVELYUNIMPAIRED INDIVIDUALS WITH AUTOSOMAL DOMINANT ALZHEIMER’S DISEASE

A. Giudicessi, P.A. Aduen, J.T. Fox-Fuller, J.E. Martinez, L.A. Gonzalez, C. Vila-Castelar, A. Baena, C. Pluim McDowell, A. Cronin-Golomb, F. Lopera, Y.T. Quiroz

J Prev Alz Dis 2024;2(11):463-468

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Contextual memory, the ability to remember spatial or temporal features related to an event, is affected in Alzheimer’s disease (AD). There is a shortfall of tests that measure contextual memory. To evaluate visuospatial contextual memory, we developed a computerized cognitive test, the MAPP Room Memory Test, which requires participants to identify in which visual scene target items were previously presented. We hypothesized that cognitively-unimpaired carriers of an autosomal dominant AD mutation (Presenilin-1 E280A, n=15) would perform more poorly on this test than non-carrier family members (n=31). Compared to non-carriers, the carriers had significantly worse delayed room recognition. The results indicate that the MAPP Room Memory Test may be sensitive to subtle cognitive changes associated with risk of AD. Future studies with larger samples using the MAPP Room Memory Test and biomarkers are needed to examine whether this test may also be sensitive to the earliest pathological changes in preclinical AD.

CITATION:
A. Giudicessi ; P.A. Aduen ; J.T. Fox-Fuller ; J.E. Martinez ; L.A. Gonzalez ; C. Vila-Castelar ; A. Baena ; C. Pluim McDowell ; A. Cronin-Golomb ; F. Lopera ; Y.T. Quiroz ; (2024): The MAPP Room Memory Test: Examining Contextual Memory Using a Novel Computerized Test in Cognitively-Unimpaired Individuals with Autosomal Dominant Alzheimer’s Disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.7

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BEYOND VISION: A VIEW FROM EYE TO ALZHEIMER’S DISEASE AND DEMENTIA

C. Zheng, R. Zeng, G. Wu, Y. Hu, H. Yu

J Prev Alz Dis 2024;2(11):469-483

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With the aging of the global population, the health care burden of Alzheimer’s disease (AD) and dementia is considered to increase dramatically in the coming decades. Given the insufficiency of effective interventions for AD and dementia, clinical research on identifying potentially modifiable risk factors and early diagnostic biomarkers becomes a public health priority. Currently, extracerebral manifestations with a large proportion of ocular involvement are usually recognized to precede the symptoms of AD and dementia. Growing epidemiologic evidence also suggests that eye disorders, such as cataracts, age-related macular degeneration, glaucoma, diabetic retinopathy, and so on, are closely associated with and even have a higher incidence of AD and dementia. The eye, as an extension of the central nervous system, therefore has the potential to provide a feasible approach to detecting structural and functional abnormalities of the brain. Numerous new imaging modalities are developed and give novel insights into the detection of several neurodegenerative, vascular, neuropathological, and other ocular abnormalities of AD and dementia in scientific research and clinical application. This review provides an overview of the epidemiologic associations between eye disorders and AD or dementia and summarizes the recent advances in ocular examinations and techniques employed for the detection of AD and dementia. With more brain-and-eye interconnections being identified, the eye is becoming a noninvasive and easily accessible window for the early diagnosis and prevention of AD and dementia.

CITATION:
C. Zheng ; R. Zeng ; G. Wu ; Y. Hu ; H. Yu (2023): Beyond Vision: A View from Eye to Alzheimer’s Disease and Dementia. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2023.118

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HIGHER COGNITIVE RESERVE IS BENEFICIAL FOR COGNITIVE PERFORMANCE VIA VARIOUS LOCUS COERULEUS FUNCTIONAL PATHWAYS IN THE PRE-DEMENTIA STAGE OF ALZHEIMER’S DISEASE

L. Gong, K. Chen, H. Zhang, S. Zhang, W. Luo, W. Zhou, B. Zhang, R. Xu, C. Xi, for the Alzheimer’s Disease Neuroimaging Initiative

J Prev Alz Dis 2024;2(11):484-494

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BACKGROUND: Cognitive reserve (CR) shows protective effects on cognitive function in older adult and in Alzheimer’s disease (AD). However, the brain mechanisms underlying the CR effect on the non-dementia AD spectrum (subjective cognitive decline (SCD) and mild cognitive impairment (MCI)) are unknown. The aim of this study was to investigate the potential moderate effect of CR on brain functional networks associated with cognitive performance. METHODS: We selected 200 participants, including 48 cognitively normal (CN) and 56 SCD, and 96 patients with MCI from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Seed-based locus coeruleus functional connectivity (LC FC) was conducted to detect early brain functional changes in the non-dementia AD spectrum. CR was assessed via years of education and intelligence (IQ). The ANDI composite executive function scores (ADNI-EF) and ADNI composite memory scores (ANDI-MEM) at baseline and 24-month follow-up were used to assess cognitive performance. RESULTS: Compared to the CN group, the SCD group showed abnormal LC FC with the executive control network (dorsolateral prefrontal cortex, DLPFC), salience network, sensorimotor network, reward network, and hippocampus, while these alterations were inverted at the MCI stage. The LC-hippocampus FC was correlated with ADNI-MEM at baseline and follow-up, and these relationships were moderated by education. The LC-DLPFC FC was correlated with ADNI-EF at baseline, and this association was moderated by IQ. CONCLUSION: Our results manifested that higher levels of CR would confer protective effects on SCD and MCI. Furthermore, IQ and education could moderate the relationship between LC FC and cognition through different pathways.

CITATION:
L. Gong ; K. Chen ; H. Zhang ; S. Zhang ; W. Luo ; W. Zhou ; B. Zhang ; R. Xu ; C. Xi (2023): Higher Cognitive Reserve Is Beneficial for Cognitive Performance Via Various Locus Coeruleus Functional Pathways in the Pre-Dementia Stage of Alzheimer’s Disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2023.127

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INTEGRATED BIOINFORMATIC ANALYSIS AND VALIDATION IDENTIFIES IMMUNE MICROENVIRONMENT-RELATED POTENTIAL BIOMARKERS IN ALZHEIMER’S DISEASE

F. Yang, N. Zhang, G.-Y. Ou, S.-W. Xu

J Prev Alz Dis 2024;2(11):495-506

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BACKGROUND: Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases, accompanied by cognitive and memory impairment, accounting for about 60% - 80% of dementia types. The pathogenesis of AD has not been clarified, and there is no effective therapy to prevent or treat AD. In this study, we aimed to identify the potential biomarkers involved in the brain immune microenvironment in AD. METHODS: AD datasets from GEO database were obtained to identify the differentially expressed disease-related genes (DEDRGs) in AD through weighted gene co-expression network analysis (WGCNA) and differential expression analysis. Functional Enrichment analysis was performed to explore the potential biological function of DEDRGs. The hub DEDRGs were identified through the protein-protein interaction (PPI) network. Furthermore, the CIBERSORT algorithm was employed to bulk gene expression profiles of AD to depict the immune microenvironment characteristics in AD. Pearson’s correlation analysis was utilized to depict the correlation between each of immune cells and hub DEDRGs. RESULTS: A total of 27 DEDRGs were identified through WGCNA and differential expression analysis. Functional enrichment analysis of 27 DEDRGs indicated that chemokine signaling pathway was the most significantly enriched KEGG pathway, response to biotic stimulus was the most significantly enriched GO term, and most of DEDRGs were enriched into urinary system cancer in DO analysis. 6 hub DEDRGs, ANGPT1, CCL2, CD44, CXCR4, GJA1 and VCAM1, were screened through PPI network and all of them were up-regulated in AD. Immune infiltration analysis revealed that there were higher infiltration levels of T cells CD4 memory activated, T cells gamma delta, NK cells resting and macrophages M0, and lower infiltration level of NK cell activated in AD, and macrophages M2 owned the highest positively association with VCAM1 and CXCR4, but VCAM1 was statistically and negatively correlated to T cells CD8. CONCLUSION: Our study identified 6 hub DEDRGs, ANGPT1, CCL2, CD44, CXCR4, GJA1 and VCAM1, were statistically associated with immune infiltrating cells, and were significantly related to the pathological development of AD, which may provide a theoretical basis for developing potential biomarkers and implementing effective therapies against AD.

CITATION:
F. Yang ; N. Zhang ; G.-Y. Ou ; S.-W. Xu ; (2024): Integrated Bioinformatic Analysis and Validation Identifies Immune Microenvironment-Related Potential Biomarkers in Alzheimer’s Disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.5

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THE IMPACT OF TESTOSTERONE ON ALZHEIMER’S DISEASE ARE MEDIATED BY LIPID METABOLISM AND OBESITY: A MENDELIAN RANDOMIZATION STUDY

L. Zhang, F. Yang, J. Ma, Y. Hu, M. Li, C. Wang, X. Chang, L. Yang

J Prev Alz Dis 2024;2(11):507-513

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BACKGROUND: To investigate the causal relationship between testosterone (BT) levels and Alzheimer’s disease (AD) risk and to quantify the role of obesity and lipid metabolism as potential mediators. METHODS: We used a two-sample, two-step MR to determine:1) the causal effect of BT levels on AD; 2) the causal effect of two lipid metabolites, obesity and LDLc on AD; and 3) the mediating effects of these metabolites. Pooled data for BT levels and lipid metabolism were obtained from the UK Biobank. AD data were obtained from the Alzheimer’s Disease Project International Genomics Consortium, FinnGen Consortium, and UK Biobank study. Effect estimates from external genome-wide association study (GWAS) pooled statistics were obtained using inverse variance-weighted (IVW) MR analysis. RESULTS: Higher levels of BT were associated with a reduced risk of AD (odds ratio [OR] 0.9992, 95% CI 0.9985-0.9998, P = 0.019), and there was a negative correlation with LDLc (OR 0.9208, 95% CI 0.8569-0.9895, P = 0.024) and obesity class 2 (OC2) (OR 0.7445, 95% CI 0.5873-0.9437, P = 0.014). Conversely, there was a positive correlation between LDLc (OR 1.0014, 95% CI 1.0000-1.0029, P = 0.043) and OC2 (OR 1.0005, 95% CI 1.0001-1.0009, P = 0.003) and AD. Mediation analysis showed that the indirect effect of BT levels on AD was achieved through LDLc and OC2, which accounted for 17% and 17% of the total effect, respectively. CONCLUSION: Our study identified a causal role of BT levels in LDLc and OC2. BT levels may affect AD through LDLc and OC2 metabolic processes.

CITATION:
L. Zhang ; F. Yang ; J. Ma ; Y. Hu ; M. Li ; C. Wang ; X. Chang ; L. Yang ; (2023): The Impact of Testosterone on Alzheimer’s Disease Are Mediated by Lipid Metabolism and Obesity: A Mendelian Randomization Study. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2023.116

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UNSUPERVISED ONLINE PAIRED ASSOCIATES LEARNING TASK FROM THE CAMBRIDGE NEUROPSYCHOLOGICAL TEST AUTOMATED BATTERY (CANTAB®) IN THE BRAIN HEALTH REGISTRY

M.T. Ashford, A. Aaronson, W. Kwang, J. Eichenbaum, S. Gummadi, C. Jin, N. Cashdollar, E. Thorp, E. Wragg, K.H. Zavitz, F. Cormack, T. Banh, J.M. Neuhaus, A. Ulbricht, M.R. Camacho, J. Fockler, D. Flenniken, D. Truran, R.S. Mackin, M.W. Weiner, R.L. Nosheny

J Prev Alz Dis 2024;2(11):514-524

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BACKGROUND: Unsupervised online cognitive assessments have demonstrated promise as an efficient and scalable approach for evaluating cognition in aging, and Alzheimer’s disease and related dementias. OBJECTIVES: The aim of this study was to evaluate the feasibility, usability, and construct validity of the Paired Associates Learning task from the Cambridge Neuropsychological Test Automated Battery® in adults enrolled in the Brain Health Registry. DESIGN, SETTING, PARTICIPANTS, MEASUREMENTS: The Paired Associates Learning task was administered to Brain Health Registry participants in a remote, unsupervised, online setting. In this cross-sectional analysis, we 1) evaluated construct validity by analyzing associations between Paired Associates Learning performance and additional participant registry data, including demographics, self- and study partner-reported subjective cognitive change (Everyday Cognition scale), self-reported memory concern, and depressive symptom severity (Patient Health Questionnaire-9) using multivariable linear regression models; 2) determined the predictive value of Paired Associates Learning and other registry variables for identifying participants who self-report Mild Cognitive Impairment by employing multivariable binomial logistic regressions and calculating the area under the receiver operator curve; 3) investigated feasibility by looking at task completion rates and statistically comparing characteristics of task completers and non-completers; and 4) evaluated usability in terms of participant requests for support from BHR related to the assessment. RESULTS: In terms of construct validity, in participants who took the Paired Associates Learning for the first time (N=14,528), worse performance was associated with being older, being male, lower educational attainment, higher levels of self- and study partner-reported decline, more self-reported memory concerns, greater depressive symptom severity, and self-report of Mild Cognitive Impairment. Paired Associates Learning performance and Brain Health Registry variables together identified those with self-reported Mild Cognitive Impairment with moderate accuracy (areas under the curve: 0.66-0.68). In terms of feasibility, in a sub-sample of 29,176 participants who had the opportunity to complete Paired Associates Learning for the first time in the registry, 14,417 started the task. 11,647 (80.9% of those who started) completed the task. Compared to those who did not complete the task at their first opportunity, those who completed were older, had more years of education, more likely to self-identify as White, less likely to self-identify as Latino, less likely to have a subjective memory concern, and more likely to report a family history of Alzheimer’s disease. In terms of usability, out of 8,395 received requests for support from BHR staff via email, 4.4% (n=374) were related to PAL. Of those, 82% were related to technical difficulties. CONCLUSIONS: Our findings support moderate feasibility, good usability, and construct validity of cross-sectional Paired Associates Learning in an unsupervised online registry, but also highlight the need to make the assessment more inclusive and accessible to individuals from ethnoculturally and socioeconomically diverse communities. A future, improved version could be a scalable, efficient method to assess cognition in many different settings, including clinical trials, observational studies, healthcare, and public health.

CITATION:
M.T. Ashford ; A. Aaronson ; W. Kwang ; J. Eichenbaum ; S. Gummadi ; C. Jin ; N. Cashdollar ; E. Thorp ; E. Wragg ; K.H. Zavitz ; F. Cormack ; T. Banh ; J.M. Neuhaus ; A. Ulbricht ; M.R. Camacho ; J. Fockler ; D. Flenniken ; D. Truran ; R.S. Mackin ; M.W. Weiner ; R.L. Nosheny (2023): Unsupervised Online Paired Associates Learning Task from the Cambridge Neuropsychological Test Automated Battery (CANTAB®) in the Brain Health Registry. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2023.117

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LETTER TO THE EDITOR: ALZHEIMER’S DISEASE-ASSOCIATED APOE Ε4 FREQUENCIES IN INDIAN POPULATION GENOMES MAY SUGGEST IMPLICATIONS IN LECANEMAB TREATMENT

B. Jolly, V. Scaria

J Prev Alz Dis 2024;2(11):525-526

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CITATION:
B. Jolly ; V. Scaria (2023): Letter to the Editor: Alzheimer’s Disease-Associated APOE ε4 Frequencies in Indian Population Genomes May Suggest Implications in Lecanemab Treatment. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2023.122

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LETTER TO THE EDITOR: CHRONIC PAIN IN MULTIPLE SITES AND DEMENTIA: A VICIOUS CYCLE?

J. Tian, G. Jones, X. Lin, Y. Zhou, A. King, J. Vickers, F. Pan

J Prev Alz Dis 2024;2(11):527-528

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CITATION:
J. Tian ; G. Jones ; X. Lin ; Y. Zhou ; A. King ; J. Vickers ; F. Pan (2023): Letter to the Editor: Chronic Pain in Multiple Sites and Dementia: A Vicious Cycle?. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2023.120

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