05/2024 journal articles
EDITORIAL: AMPLIFYING EFFICIENCY AND ACCURACY IN DEMENTIA DRUG DEVELOPMENT
O. Lerch, S.Z. Levine, S. Sivakumaran, M.W. Lutz, O. Chiba-Falek, N. Mazer, M. Bairu, I.R.J. Hebold Haraldsen, P.M. Rossini, P.J. Snyder, J. Bouteiller, Z.S. Khachaturian, A.S. Khachaturian
J Prev Alz Dis 2024;5(11):1180-1182
Show summaryHide summary
CITATION:
O. Lerch ; S.Z. Levine ; S. Sivakumaran ; M.W. Lutz ; O. Chiba-Falek ; N. Mazer ; M. Bairu ; I.R.J. Hebold Haraldsen ; P.M. Rossini ; P.J. Snyder ; J. Bouteiller ; Z.S. Khachaturian ; A.S. Khachaturian (2024): Amplifying Efficiency and Accuracy in Dementia Drug Development. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.167
PREVALENCE ESTIMATION OF DEMENTIA/ALZHEIMER’S DISEASE USING HEALTH AND RETIREMENT STUDY DATABASE IN THE UNITED STATES
A.A. Tahami Monfared, N. Hummel, A. Chandak, A. Khachatryan, R. Zhang, Q. Zhang
J Prev Alz Dis 2024;5(11):1183-1188
Show summaryHide summaryBACKGROUND: Updated prevalence estimates along the continuum of Alzheimer’s disease (AD) can foster a more nuanced and effective approach to managing AD within the current healthcare landscape.
OBJECTIVES: This study aims to estimate the prevalence and severity distribution of dementia/AD (including mild, moderate, and severe stages) and all-cause mild cognitive impairment (MCI) in the United States using data from the Health and Retirement Study (HRS).
DESIGN: Retrospective study.
SETTING: Data from the bi-annual HRS surveys involving in-depth interviews of a representative sample of Americans aged >50 years.
PARTICIPANTS: Dementia/AD and all-cause MCI patients from the 4 most recent HRS surveys (2014, 2016, 2018 and 2020).
MEASUREMENTS: AD was identified based on diagnosis (self-report). Cognitive performance (modified Telephone Interview of Cognitive Status [TICS-m]) scores in the dementia/AD range were also captured; all-cause MCI was similarly identified using the TICS-m. Dementia/AD and MCI prevalence, as well as the distribution by dementia/AD stage (mild, moderate, or severe), were estimated. Sampling weights developed by HRS were applied to ensure the sample’s representativeness of the target population and unbiased estimates for population parameters.
RESULTS: Across the four HRS surveys, the total number of HRS respondents ranged from 15,000 to 21,000 (unweighted); 7,000 to 14,000 had TICS-m scores. The estimated prevalence of AD (all severity categories combined) in the 2014, 2016, 2018, and 2020 HRS surveys was 1.2%, 1.2%, 1.3% and 1.0%, respectively using the diagnosis-based approach; using the cognitive performance-based approach, 23-27% patients had scores in the dementia/AD ranges across the 4 surveys. The estimated prevalence of all-cause MCI was consistently 23% in each survey. In the 2020 survey, the distribution of mild, moderate, and severe disease stages was 34%, 45%, and 21%, respectively, in patients self-reporting an AD diagnosis, and 55%, 40%, and 5%, respectively in all patients meeting TICS-m threshold for dementia/AD.
CONCLUSION: The prevalence of AD diagnosis based on self-report was approximately 1% across the 4 most recent HRS surveys and may reflect the proportion of patients who have actively sought healthcare for AD. Among HRS survey respondents with cognitive scores available, over 20% were in the dementia/AD range. The distribution of disease by stage differed for self-reported AD diagnosis vs dementia/AD based on cognitive scores. Discordance in estimates of dementia/AD and stage distributions underscores a need for better understanding of clinical practice patterns in AD diagnosis, use of clinical assessment tools, and severity classification in the United States. Accurate patient identification is needed, especially early in the AD disease continuum, to allow for timely and appropriate initiation of new anti-amyloid treatments.
CITATION:
A.A. Tahami Monfared ; N. Hummel ; A. Chandak ; A. Khachatryan ; R. Zhang ; Q. Zhang (2024): Prevalence Estimation of Dementia/Alzheimer’s Disease Using Health and Retirement Study Database in the United States. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.114
PLASMA BIOMARKERS OF ALZHEIMER’S DISEASE AND NEURODEGENERATION ACCORDING TO SOCIODEMOGRAPHIC CHARACTERISTICS AND CHRONIC HEALTH CONDITIONS
H.T. Zheng, Z. Wu, M.M. Mielke, A.M. Murray, J. Ryan
J Prev Alz Dis 2024;5(11):1189-1197
Show summaryHide summaryUltrasensitive assays have been developed which enable biomarkers of Alzheimer’s disease pathology and neurodegeneration to be measured in blood. These biomarkers can aid in diagnosis, and have been used to predict risk of cognitive decline and Alzheimer’s disease. The ease and cost-effectiveness of blood collections means that these biomarkers could be applied more broadly in population-based screening, however it is critical to first understand what other factors could affect blood biomarker levels. The aim of this review was to determine the extent that sociodemographic, lifestyle and health factors have been associated with blood biomarkers of Alzheimer’s disease and neuropathology. Of the 32 studies included in this review, all but one measured biomarker levels in plasma, and age and sex were the most commonly investigated factors. The most consistent significant findings were a positive association between age and neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), and females had higher GFAP than men. Apolipoprotein ε4 allele carriers had lower Aβ42 and Aβ42/40 ratio. Body mass index was negatively associated with GFAP and NfL, and chronic kidney disease with higher levels of all biomarkers. Too few studies have investigated other chronic health conditions and this requires further investigation. Given the potential for plasma biomarkers to enhance Alzheimer’s disease diagnosis in primary care, it is important to understand how to interpret the biomarkers in light of factors that physiologically impact blood biomarker levels. This information will be critical for the establishment of reference ranges and thus the correct interpretation of these biomarkers in clinical screening.
CITATION:
H.T. Zheng ; Z. Wu ; M.M. Mielke ; A.M. Murray ; J. Ryan ; (2024): Plasma Biomarkers of Alzheimer’s Disease and Neurodegeneration According to Sociodemographic Characteristics and Chronic Health Conditions. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.142
PERFORMANCE OF PLASMA BIOMARKERS COMBINED WITH STRUCTURAL MRI TO IDENTIFY CANDIDATE PARTICIPANTS FOR ALZHEIMER’S DISEASE-MODIFYING THERAPY
M. Manjavong, J.M. Kang, A. Diaz, M.T. Ashford, J. Eichenbaum, A. Aaronson, M.J. Miller, S. Mackin, R. Tank, M. Weiner, R. Nosheny, for the Alzheimer’s Disease Neuroimaging Initiative
J Prev Alz Dis 2024;5(11):1198-1205
Show summaryHide summaryBACKGROUND: Recently, two monoclonal antibodies that lower amyloid plaques have shown promising results for the treatment of Mild Cognitive Impairment (MCI) and mild dementia due to Alzheimer’s disease (AD). These treatments require the identification of cognitively impaired older adults with biomarker evidence of AD pathology using CSF biomarkers or amyloid-PET. Previous studies showed plasma biomarkers (plasma Aβ42/Aβ40 and p-tau181) and hippocampal volume from structural MRI correlated with brain amyloid pathology. We hypothesized plasma biomarkers with hippocampal volume would identify patients who are suitable candidates for disease-modifying therapy.
OBJECTIVES: To evaluate the performance of plasma AD biomarkers and hippocampal atrophy to detect MCI or AD with amyloid pathology confirmed by amyloid-PET or CSF biomarkers in ADNI.
DESIGN: A cross-sectional and longitudinal study.
SETTING AND PARTICIPANTS: Data were from the Alzheimer’s Disease Neuroimaging Initiative. Participants were aged 55-90 years old with plasma biomarker and structural MRI brain data.
MEASUREMENTS: The optimum cut-off point for plasma Aβ42/Aβ40, p-tau181, and NFL and the performance of combined biomarkers and hippocampal atrophy for detecting cognitive impairment with brain amyloid pathology were evaluated. The association between baseline plasma biomarkers and clinical progression, defined by CDR-Sum of Boxes (CDR-SB) and diagnostic conversion over two years, was evaluated using a Weibull time-to-event analysis.
RESULTS: A total of 428 participants were included; 167 had normal cognition, 245 had MCI, and 16 had mild AD. Among MCI and AD, 140 participants had elevated amyloid levels by PET or CSF. Plasma Aβ42/Aβ40 provided the best accuracy (sensitivity 79%, specificity 66%, AUC 0.73, 95% CI 0.68-0.77) to detect drug candidate participants at baseline. Combined plasma Aβ42/40, p-tau181, and hippocampal atrophy increased the specificity for diagnosis (96%), but had lower sensitivity (34%), and AUC (0.65). Hippocampal atrophy combined with the abnormal plasma p-tau181 or hippocampal atrophy alone showed high sensitivity to detect clinical progression (by CDR-SB worsening) of the drug-candidate participants within the next 2 years (sensitivity 93% and 89%, respectively).
CONCLUSION: Plasma biomarkers and structural MRI can help identify patients who are currently eligible for anti-amyloid treatment and are likely to progress clinically, in cases where amyloid-PET or CSF biomarkers are not available.
CITATION:
M. Manjavong ; J.M. Kang ; A. Diaz ; M.T. Ashford ; J. Eichenbaum ; A. Aaronson ; M.J. Miller ; S. Mackin ; R. Tank ; M. Weiner ; R. Nosheny ; for the Alzheimer’s Disease Neuroimaging Initiative ; (2024): Performance of Plasma Biomarkers Combined with Structural MRI to Identify Candidate Participants for Alzheimer’s Disease-Modifying Therapy. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.110
VALIDATION OF AN ULTRA-SENSITIVE METHOD FOR QUANTITATION OF PHOSPHO-TAU 217 (PTAU217) IN HUMAN PLASMA, SERUM, AND CSF USING THE ALZPATH PTAU217 ASSAY ON THE QUANTERIX HD-X PLATFORM
H. Zhang, J. Liu, N. Zhang, A. Jeromin, Z.J. Lin
J Prev Alz Dis 2024;5(11):1206-1211
Show summaryHide summaryBACKGROUND: Both blood (plasma and serum) and CSF tau phosphorylated at Threonine 217 (pTau217) have been shown to be able to discriminate early to mild Alzheimer’s disease (AD) from non-AD neurodegenerative disorders and healthy controls with high sensitivity and specificity.
OBJECTIVES: We report the full validation of the ALZpath ultra-sensitive pTau217 research-use only (RUO) assays for human EDTA plasma, serum, and CSF using the Quanterix Simoa HD-X platform, in support of clinical trials and early diagnosis of Alzheimer’s disease.
METHODS: The ALZpath pTau217 Simoa Advantage v2 kit from ALZpath/Quanterix was used for method development and validation of pTau217 in human plasma, serum, and CSF. All three method validations have followed the 2018 FDA BMV and 2022 ICH M10 guidelines.
RESULTS: Validation of pTau217 quantitation in human plasma, serum, and CSF demonstrated that the validated pTau217 assay has an analytical LLOQ of 0.00977 pg/mL. It is one of the most sensitive assays with a minimal required sample volume of 33.3 µl for plasma and serum, and 5 µl for CSF, and is relatively cost-effective, compared to the currently published data. The minimum required dilution (MRD) for plasma, serum, and CSF were determined. The analyte passed short-term stability tests. It was also tolerant of moderate hemolytic, and lipemic interferences in plasma and serum. pTau217 was detected in 100% of tested healthy control plasma, 90.0% of healthy control serum, 92.3% of healthy control CSF samples, and 100% of AD plasma and CSF samples. The validated assay was successfully applied in the analysis of AD samples, with data showing dramatic differences in the pTau217 levels between healthy control subjects and AD patients in both plasma and CSF.
CONCLUSION: Validation of the ALZpath pTau217 Simoa assay in human plasma, serum, and CSF demonstrates ultra sensitivity, high accuracy, and assay robustness. Together with other established and sensitive assays for pTau181, GFAP, and NfL, these assays have immediate utility for application in clinical trials and can play a role in the early diagnosis of neurodegenerative diseases.
CITATION:
H. Zhang ; J. Liu ; N. Zhang ; A. Jeromin ; Z.J. Lin ; (2024): Validation of an Ultra-Sensitive Method for Quantitation of Phospho-Tau 217 (pTau217) in Human Plasma, Serum, and CSF using the ALZpath pTau217 Assay on the Quanterix HD-X Platform. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.155
PROGRESS IN THE TREATMENT OF ALZHEIMER’S DISEASE IS NEEDED – POSITION STATEMENT OF EUROPEAN ALZHEIMER’S DISEASE CONSORTIUM (EADC) INVESTIGATORS
F. Jessen, M.G. Kramberger, D. Angioni, D. Aarsland, M. Balasa, K. Bennys, M. Boada, M. Boban, A. Chincarini, L. Exalto, A. Felbecker, K. Fliessbach, G.B. Frisoni, A.J. Garza-Martínez, T. Grimmer, B. Hanseeuw, J. Hort, A. Ivanoiu, S. Klöppel, L. Krajcovicova, B. McGuinness, P. Mecocci, A. de Mendonca, A. Nous, P.-J. Ousset, C. Paquet, R. Perneczky, O. Peters, M. Tabuas-Pereira, F. Piazza, D. Plantone, M. Riverol, A. Ruiz, G. Sacco, I. Santana, N. Scarmeas, E. Solje, E. Stefanova, S. Sutovsky, W. van der Flier, T. Welsh, A. Wimo, B. Winblad, L. Frölich, S. Engelborghs
J Prev Alz Dis 2024;5(11):1212-1218
Show summaryHide summaryβ-amyloid-targeting antibodies represent the first generation of effective causal treatment of Alzheimer’s disease (AD) and can be considered historical research milestones. Their effect sizes, side effects, implementation challenges and costs, however, have stimulated debates about their overall value. In this position statement academic clinicians of the European Alzheimer’s Disease Consortium (EADC) discuss the critical relevance of introducing these new treatments in clinical care now. Given the complexity of AD it is unlikely that molecular single-target treatments will achieve substantially larger effects than those seen with current β-amyloid-targeting antibodies. Larger effects will most likely only be achieved incrementally by continuous optimization of molecular approaches, patient selection and combinations therapies. To be successful in this regard, drug development must be informed by the use of innovative treatments in real world practice, because full understanding of all facets of novel treatments requires experience and data of real-world care beyond those of clinical trials. Regarding the antibodies under discussion we consider their effects meaningful and potential side effects manageable. We assume that the number of eventually treated patient will only be a fraction of all early AD patients due to narrow eligibility criteria and barriers of access. We strongly endorse the use of these new compound in clinical practice in selected patients with treatment documentation in registries. We understand this as a critical step in advancing the field of AD treatment, and in shaping the health care systems for the new area of molecular-targeted treatment of neurodegenerative diseases.
CITATION:
F. Jessen ; M.G. Kramberger ; D. Angioni ; D. Aarsland ; M. Balasa ; K. Bennys ; M. Boada ; M. Boban ; A. Chincarini ; L. Exalto ; A. Felbecker ; K. Fliessbach ; G.B. Frisoni ; A.J. Garza-Martínez ; T. Grimmer ; B. Hanseeuw ; J. Hort ; A. Ivanoiu ; S. Klöppel ; L. Krajcovicova ; B. McGuinness ; P. Mecocci ; A. de Mendonca ; A. Nous ; P.-J. Ousset ; C. Paquet ; R. Perneczky ; O. Peters ; M. Tabuas-Pereira ; F. Piazza ; D. Plantone ; M. Riverol ; A. Ruiz ; G. Sacco ; I. Santana ; N. Scarmeas ; E. Solje ; E. Stefanova ; S. Sutovsky ; W. van der Flier ; T. Welsh ; A. Wimo ; B. Winblad ; L. Frölich ; S. Engelborghs ; ; (2024): Progress in the Treatment of Alzheimer’s Disease Is Needed – Position Statement of European Alzheimer’s Disease Consortium (EADC) Investigators. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.153
CLINICAL MEANINGFULNESS IN ALZHEIMER’S DISEASE CLINICAL TRIALS. A REPORT FROM THE EU-US CTAD TASK FORCE
D. Angioni, J. Cummings, C.J. Lansdall, L. Middleton, C. Sampaio, S. Gauthier, S. Cohen, R.C. Petersen, D.M. Rentz, A.M. Wessels, S.B. Hendrix, F. Jessen, M.C. Carrillo, R.S. Doody, M. Irizarry, J.S. Andrews, B. Vellas, P. Aisen
J Prev Alz Dis 2024;5(11):1219-1227
Show summaryHide summaryRecent positive results of three phase III anti-amyloid monoclonal antibody trials are transforming the landscape of disease-modifying therapeutics for Alzheimer’s disease, following several decades of failures. Indeed, all three trials have met their primary endpoints. However, the absolute size of the benefit measured in these trials has generated a debate on whether the change scores observed on clinical outcome assessments represent a clinically meaningful benefit to patients. An evidence-based conclusion is urgently required to inform decision-making related to the approval, reimbursement, and ultimately, the management of emerging therapies in clinical practice. The EU-US CTAD Task Force met in Boston to address this important question. The current state-of-the-art knowledge for interpreting clinical meaningfulness of AD clinical trial results, including the point of view of patients and study partners on what is clinically meaningful, was discussed and is summarized here. A combination of methodologies to address the challenges emerged. There remain gaps in the understanding of clinical meaningfulness that only long-term longitudinal studies will be able to address.
CITATION:
D. Angioni ; J. Cummings ; C.J. Lansdall ; L. Middleton ; C. Sampaio ; S. Gauthier ; S. Cohen ; R.C. Petersen ; D.M. Rentz ; A.M. Wessels ; S.B. Hendrix ; F. Jessen ; M.C. Carrillo ; R.S. Doody ; M. Irizarry ; J.S. Andrews ; B. Vellas ; P. Aisen (2024): Clinical Meaningfulness in Alzheimer’s Disease Clinical Trials. A Report from the EU-US CTAD Task Force. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.112
A STATISTICAL FRAMEWORK FOR ASSESSING THE RELATIONSHIP BETWEEN BIOMARKERS AND CLINICAL ENDPOINTS IN ALZHEIMER’S DISEASE
T. Chen, R.M. Hutchison, C. Rubel, J. Murphy, J. Xie, P. Montenigro, W. Cheng, K. Fraser, G. Dent, S. Hendrix, O. Hansson, P. Aisen, Y. Tian, J. O’Gorman
J Prev Alz Dis 2024;5(11):1228-1240
Show summaryHide summaryChanges in biomarker levels of Alzheimer’s disease (AD) reflect underlying pathophysiological changes in the brain and can provide evidence of direct and downstream treatment effects linked to disease modification. Recent results from clinical trials of anti–amyloid β (Aβ) treatments have raised the question of how to best characterize the relationship between AD biomarkers and clinical endpoints. Consensus methodology for assessing such relationships is lacking, leading to inconsistent evaluation and reporting. In this review, we provide a statistical framework for reporting treatment effects on early and late accelerating AD biomarkers and assessing their relationship with clinical endpoints at the subject and group levels. Amyloid positron emission tomography (PET), plasma p-tau, and tau PET follow specific trajectories during AD and are used as exemplar cases to contrast biomarkers with early and late progression. Subject-level correlation was assessed using change from baseline in biomarkers versus change from baseline in clinical endpoints, and interpretation of the correlation is dependent on the biomarker and disease stage. Group-level correlation was assessed using the placebo-adjusted treatment effects on biomarkers versus those on clinical endpoints in each trial. This correlation leverages the fundamental advantages of randomized placebo-controlled trials and assesses the predictivity of a treatment effect on a biomarker or clinical benefit. Harmonization in the assessment of treatment effects on biomarkers and their relationship to clinical endpoints will provide a wealth of comparable data across clinical trials and may yield new insights for the treatment of AD.
CITATION:
T. Chen ; R.M. Hutchison ; C. Rubel ; J. Murphy ; J. Xie ; P. Montenigro ; W. Cheng ; K. Fraser ; G. Dent ; S. Hendrix ; O. Hansson ; P. Aisen ; Y. Tian ; J. O’Gorman (2024): A Statistical Framework for Assessing the Relationship between Biomarkers and Clinical Endpoints in Alzheimer’s Disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.126
SEMORINEMAB PHARMACOKINETICS AND THE EFFECT ON PLASMA TOTAL TAU PHARMACODYNAMICS IN CLINICAL STUDIES
V. Ramakrishnan, B. Bender, J. Langenhorst, M.O. Magnusson, M. Dolton, J. Shim, R.N. Fuji, C. Monteiro, E. Teng, N. Kassir, J. Jin
J Prev Alz Dis 2024;5(11):1241-1250
Show summaryHide summaryBACKGROUND: Semorinemab is a monoclonal antibody that targets the N-terminal domain of the tau protein that is in clinical development for the treatment of Alzheimer’s disease.
OBJECTIVES: To perform model-based evaluations of the observed pharmacokinetics in serum and the total plasma tau target-engagement dynamics from clinical studies evaluating semorinemab.
DESIGN: The observed semorinemab pharmacokinetics and plasma tau target engagement from phase 1 and 2 clinical studies were modeled using a non-linear mixed effect target-mediated drug disposition model. The model was simulated to understand target engagement at clinical dose levels.
SETTINGS AND PARTICIPANTS: The clinical studies testing semorinemab were evaluated in healthy volunteers, subjects with prodromal-to-mild Alzheimer’s disease, and subjects with mild-to-moderate Alzheimer’s disease. The data included a total of 8430 semorinemab serum concentrations and 4772 total tau protein plasma concentrations from 463 subjects treated with a range of single and multiple doses of semorinemab.
MEASUREMENTS: Serum concentrations of semorinemab and the total plasma tau concentrations were measured after administration of a range of doses of semorinemab to subjects with Alzheimer’s disease. A sensitivity analysis was performed wherein key target-mediated drug disposition model parameters were estimated separately between healthy volunteers, subjects with prodromal-to-mild Alzheimer’s disease, and subjects with mild-to-moderate Alzheimer’s disease.
RESULTS: Serum concentrations of semorinemab were consistent across studies and showed a dose-proportional increase across the evaluated dose range. The pharmacokinetic profile was comparable between healthy volunteers and subjects with Alzheimer’s disease. Total plasma tau concentrations increased in a dose-dependent non-linear manner upon semorinemab administration. The target-mediated drug disposition model adequately described the serum pharmacokinetics and protein dynamics with an estimated antibody-ligand binding strength, Kss, of 42.7 nM. The estimated values of clearance and central volume of distribution were 0.109 L/day/70 kg and 2.95 L/70 kg, respectively, and were consistent with typical values for IgG mAbs. In the sensitivity analysis, Kss (32 nM) and baseline tau protein (0.30 µM) were estimated to be lower for healthy volunteers compared to subjects with Alzheimer’s disease but were comparable between subjects with Alzheimer’s disease of different severities (Kss: 52-57 nM, baseline tau: 0.44-0.47 µM). The models suggested that peripheral target engagement was over 90% at the clinical doses in each of the diagnostic subgroups.
CONCLUSION: Our target-mediated drug disposition model adequately described the serum pharmacokinetics and the peripheral non-linear increase with dose of the total tau. The model confirmed that these dose-response relationships were consistent across populations of healthy volunteers and subjects with different severities of Alzheimer’s disease.
CITATION:
V. Ramakrishnan ; B. Bender ; J. Langenhorst ; M.O. Magnusson ; M. Dolton ; J. Shim ; R.N. Fuji ; C. Monteiro ; E. Teng ; N. Kassir ; J. Jin (2024): Semorinemab Pharmacokinetics and The Effect on Plasma Total Tau Pharmacodynamics in Clinical Studies. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.146
ALZHEIMER’S DISEASE LINKAGE TO REAL-WORLD EVIDENCE (AD-LINE) STUDY: LINKING CLAIMS DATA TO PHASE 3 GRADUATE STUDY OF GANTENERUMAB
H. Fillit, S. Seleri Assunção, T. Majda, C.D. Ng, T.M. To, I.M. Abbass, K. Raimundo, C. Wallick, O.V. Tcheremissine
J Prev Alz Dis 2024;5(11):1251-1259
Show summaryHide summaryBACKGROUND: Linking data from clinical trials and real-world claims may improve the robustness of trial data and provide information on the health, economic, and societal impacts of a disease.
OBJECTIVE: To report on the feasibility of linking trial data to Medicare claims data in early symptomatic Alzheimer’s disease (AD) in the US.
DESIGN AND SETTING: Alzheimer’s Disease Linkage to Real-World Evidence (AD-LINE) was a noninterventional cohort study that included participants recruited from the GRADUATE program whose trial data were linked to their Medicare claims.
PARTICIPANTS: AD-LINE participants were 66 years and older with early symptomatic AD (ie, mild cognitive impairment [MCI] due to AD or mild AD dementia) and were enrolled in the GRADUATE program and a Medicare fee-for-service or Medicare Advantage plan.
MEASUREMENTS: The Centers for Medicare & Medicaid Services linked participants’ clinical trial identifiers to their Medicare beneficiary identifiers using a deterministic, exact matching process. Demographics and clinical characteristics of the AD-LINE cohort at baseline were collected. Outcomes measured in this study included healthcare resource utilization derived from Medicare claims data.
RESULTS: In total, 147 participants across 21 US sites were invited to participate and 111 provided informed consent. Of those, 61 patients had linkable data (ie, Medicare beneficiary identifier), Medicare Parts A/B enrollment, and no health maintenance organization (HMO) enrollment in the year before trial entry. Of the 61 participants whose data were analyzed in this study, 30 had MCI due to AD and 31 had mild AD dementia. Participants in the MCI due to AD group had more healthcare resource utilization on average in the baseline period than those in the mild AD dementia group (29.9 [SD, 20.9] vs 24.5 claims [SD, 12.3]). In an ad hoc analysis, a relatively high concordance (85.3%) was seen between the rates of clinically confirmed AD diagnosis and evidence of AD diagnosis in claims data.
CONCLUSION: This linkage process may serve as a proof of concept for researchers interested in linking clinical trial and real-world claims data. The lessons learned from AD-LINE and innovation of data linkage approaches may encourage key stakeholders to link data in the future.
CITATION:
H. Fillit ; S. Seleri Assunção ; T. Majda ; C.D. Ng ; T.M. To ; I.M. Abbass ; K. Raimundo ; C. Wallick ; O.V. Tcheremissine (2024): Alzheimer’s Disease Linkage to Real-World Evidence (AD-LINE) Study: Linking Claims Data to Phase 3 GRADUATE Study of Gantenerumab. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.115
JAPANESE SUBGROUP ANALYSES FROM EMERGE AND ENGAGE, PHASE 3 CLINICAL TRIALS OF ADUCANUMAB IN PATIENTS WITH EARLY ALZHEIMER’S DISEASE
Y. Toda, T. Iwatsubo, Y. Nakamura, N. Matsuda, M. Miyata, M. Jin, T. Chen, K. Kuribayashi, Y. Tian, R. Hughes, J. Yamamoto, K.K. Muralidharan, C. Rubel, R.M. Hutchison, S. Budd Haeberlein
J Prev Alz Dis 2024;5(11):1260-1269
Show summaryHide summaryBACKGROUND: Global prevalence and incidence of dementia continue to rise at a rapid rate. There is a need for new Alzheimer’s disease (AD) treatments globally. Aducanumab is a human monoclonal antibody that selectively targets aggregated soluble amyloid beta oligomers and insoluble amyloid beta fibrils. In June 2021, aducanumab was approved by the US Food and Drug Administration for the treatment of AD under the accelerated approval pathway.
OBJECTIVES: We evaluated the efficacy, safety, biomarker and pharmacokinetics (PK) of aducanumab in Japanese subgroups in EMERGE and ENGAGE studies.
DESIGN: EMERGE and ENGAGE were two randomized, double-blind, placebo-controlled, global, phase 3 studies of aducanumab in patients with early AD (mild cognitive impairment due to AD or mild AD dementia).
SETTING: These studies involved 348 sites in 20 countries.
PARTICIPANTS: Participants enrolled in Japan included 121 (7.4% of total 1638 in EMERGE) and 100 (6.1% of total 1647 in ENGAGE) patients (aged 50–85 years with confirmed amyloid pathology) who met clinical criteria for mild cognitive impairment due to AD or mild AD dementia.
INTERVENTION: Participants were randomly assigned 1:1:1 to receive aducanumab low dose (3 or 6 mg/kg target dose), high dose (6 or 10 mg/kg target dose) or placebo via IV infusion once every 4 weeks over 76 weeks.
MEASUREMENTS: The primary outcome measure was change from baseline to Week 78 on the Clinical Dementia Rating Sum of Boxes (CDR-SB), an integrated scale that assesses both function and cognition. Other measures included safety assessments; secondary and tertiary clinical outcomes that assessed cognition, function, and behavior; biomarker endpoints (amyloid PET and plasma p-tau181); serum PK profiles and immunogenicity.
RESULTS: Results from the Japanese subgroup analyses were generally consistent with those of the overall study population across endpoints, while a lower mean body weight (kg) and a smaller proportion of ApoE ε4 carriers were observed in the Japanese subgroup population. A treatment effect was observed in favor of aducanumab on the primary and secondary efficacy endpoints at Week 78 in EMERGE, but not ENGAGE. The incidence and type of adverse events in the Japanese subgroups were generally comparable to those observed in the overall study population; amyloid related imaging abnormalities (ARIA) were common treatment-related adverse events that appeared to be related to the aducanumab dose. ARIA incidence was generally lower in the Japanese subgroup compared with the overall population. Consistent with the overall data set, a robust dose-dependent decrease in amyloid beta levels as assessed with amyloid-PET and plasma p-tau181 was observed. Serum PK profiles and immunogenicity of aducanumab in Japanese population were consistent with the non-Japanese population.
CONCLUSION: Efficacy, safety, biomarker, and PK profiles of aducanumab were consistent between the Japanese subgroup and the overall population. A positive treatment effect of aducanumab on efficacy endpoints was observed in EMERGE, but not in ENGAGE.
CITATION:
Y. Toda ; T. Iwatsubo ; Y. Nakamura ; N. Matsuda ; M. Miyata ; M. Jin ; T. Chen ; K. Kuribayashi ; Y. Tian ; R. Hughes ; J. Yamamoto ; K.K. Muralidharan ; C. Rubel ; R.M. Hutchison ; S. Budd Haeberlein (2024): Japanese Subgroup Analyses from EMERGE and ENGAGE, Phase 3 Clinical Trials of Aducanumab in Patients with Early Alzheimer’s Disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.106
FLAVONOID-RICH FRUIT INTAKE IN MIDLIFE AND LATE-LIFE AND ASSOCIATIONS WITH RISK OF DEMENTIA: THE FRAMINGHAM HEART STUDY
C. Lyu, P.F. Jacques, P.M. Doraiswamy, B. Young, A.S. Gurnani, R. Au, P.H. Hwang
J Prev Alz Dis 2024;5(11):1270-1279
Show summaryHide summaryBACKGROUND: Fruits are an important source of flavonoids, and greater intake of dietary flavonoids in older adults has been shown to be associated with decreased risk of dementia. It is unclear whether this relationship is similar or different between younger adults and older adults.
OBJECTIVES: We examined for associations between midlife and late-life intake of flavonoid-rich fruits and incident dementia. We hypothesized that greater total cumulative intake of flavonoid-rich fruits in midlife and late-life adults would be associated with reduced risk of all-cause dementia.
DESIGN: Longitudinal, cohort study design.
SETTING: Framingham Heart Study, which is a longitudinal, multi-generational community-based cohort based in Framingham, Massachusetts, USA.
PARTICIPANTS: Participants from the Framingham Heart Study Offspring cohort were included (n = 2,790) who attended the fifth core exam between 1991 to 1995, and were dementia-free and at least 45 years of age at that time, as well as had valid food frequency questionnaires from the fifth to ninth core exams.
MEASUREMENTS: Consumption of fruits with high flavonoid content or are important contributors to overall flavonoid intake was collected via food frequency questionnaire. Flavonoid-rich fruits from the food frequency questionnaire included raisins or grapes, prunes, bananas, fresh apples or pears, apple juice or cider, oranges, orange juice, grapefruit, grapefruit juice, strawberries, blueberries, and peaches, apricots, or plums. Dementia ascertainment was based on a multidisciplinary consensus committee, and included all-cause dementia and Alzheimer’s disease dementia diagnoses based on research criteria. Cox models were used to examine associations between cumulative fruit intake and incident dementia, stratified by midlife (45-59 years; n = 1,642) and late-life (60-82 years; n = 1,148).
RESULTS: Greater cumulative total fruit intake in midlife, but not late-life, was significantly associated with a 44% decreased risk of all-cause dementia (HR = 0.56; 95% CI = 0.32 – 0.98; p = 0.044). Decreased risk of all-cause dementia was also associated with higher intake of apples or pears in midlife and late-life, as well as higher intake of raisins or grapes in midlife only, and higher intake of oranges, grapefruit, blueberries, and peaches, apricots, or plums in late-life only.
CONCLUSIONS: Among participants from the Framingham Heart Study, greater overall consumption of flavonoid-rich fruits in midlife was associated with reduced risk of dementia, though intake of specific fruits in midlife and late-life may have a protective role against developing dementia. These findings may help to inform future recommendations on when dietary interventions may be most beneficial to healthy brain aging across the life course.
CITATION:
C. Lyu ; P.F. Jacques ; P.M. Doraiswamy ; B. Young ; A.S. Gurnani ; R. Au ; P.H. Hwang (2024): Flavonoid-Rich Fruit Intake in Midlife and Late-Life and Associations with Risk of Dementia: The Framingham Heart Study. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.116
EVALUATING THE CAUSAL EFFECT OF TYPE 2 DIABETES ON ALZHEIMER’S DISEASE USING LARGE-SCALE GENETIC DATA
D. Liu, A. Baranova, F. Zhang
J Prev Alz Dis 2024;5(11):1280-1282
Show summaryHide summaryBACKGROUND: Alzheimer’s disease (AD) has a high comorbidity with type 2 diabetes (T2D). However, there is still some controversy over whether T2D has a causal impact on AD at present.
OBJECTIVES: We aimed to reveal whether T2D has a causal effect on AD using large-scale genetic data.
METHODS: Firstly, we performed a primary two-sample Mendelian randomization (MR) analysis to assess the potential causal effects of T2D on AD. For this analysis, we used the largest available genome-wide association studies (GWAS) T2D (T2D1, including 80,154 cases and 853,816 controls) and AD (AD1, including 111,326 cases and 677,663 controls) datasets. Additionally, we performed a validation MR analysis using two largely overlapping-sample datasets from FinnGen, including T2D (T2D2, including 57,698 cases and 308,252 controls) and AD (AD2, including 13,393 cases and 363,884 controls). In all MR analyses, the inverse variance-weighted method was used as the primary analysis method, supplemented by the weighted-median and MR-Egger techniques.
RESULTS: In the primary analysis, we found that T2D was not associated with the risk of AD (OR: 0.98, CI: 0.95-1.01, P=0.241). Similarly, no significant association was detected in the validation MR analysis (OR: 0.97, CI: 0.64-1.47, P=0.884).
CONCLUSION: Our findings provide robust evidence that T2D does not have a causal impact on AD. Future studies need to further explore the effect of T2D on the non-AD components of the dementia phenotype.
CITATION:
D. Liu ; A. Baranova ; F. Zhang (2024): Evaluating the Causal Effect of Type 2 Diabetes on Alzheimer’s Disease Using Large-Scale Genetic Data. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.148
METABOLIC SYNDROME STATUS CHANGES AND COGNITIVE FUNCTIONING: INSIGHTS FROM THE LIFELINES COHORT STUDY
I. Frentz, S. Marcolini, C.C.I. Schneider, M.A. Ikram, J. Mondragon, P.P. De Deyn
J Prev Alz Dis 2024;5(11):1283-1290
Show summaryHide summaryBACKGROUND: Metabolic syndrome is associated with increased risk of dementia. Yet, findings on how longitudinal development of metabolic syndrome status affects cognition remain controversial.
OBJECTIVES: This study examines whether individuals with different changes in metabolic syndrome status differ in cognitive functioning. Additionally, the prevalence of metabolic syndrome within the Lifelines population-based study is investigated.
DESIGN: 14609 Lifelines participants (mean age 60.8, 56.4% women) were divided into four groups based on their metabolic syndrome status changes between 2007-2013 (1) and between 2014-2017 (2): without metabolic syndrome (N=10863; absent at 1 and 2), de novo metabolic syndrome (N=1340; absent at 1 and present at 2), remitting metabolic syndrome (N=825; present at 1 and absent at 2), and persistent metabolic syndrome (N=1581; present at 1 and 2). ANCOVA models were employed to assess group differences in psychomotor function, visual attention, visual learning, and working memory assessed using the Cogstate Brief Battery.
RESULTS: Accounting for education, age, sex, and time between examinations, groups did not statistically differ in any of the four cognitive outcomes. The prevalence of metabolic syndrome within the Lifelines population increased with age and differed among men and women.
CONCLUSION: Performance in psychomotor function, visual attention, visual learning, and working memory measured by the Cogstate Brief Battery did not differ between individuals with different changes in metabolic syndrome. The length of metabolic syndrome exposure was unknown, making our results exploratory and calling for future studies addressing this gap.
CITATION:
I. Frentz ; S. Marcolin ; C.C.I. Schneider ; M.A. Ikram ; J. Mondragon ; P.P. De Deyn (2024): Metabolic Syndrome Status Changes and Cognitive Functioning: Insights from the Lifelines Cohort Study. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.90
MULTIDOMAIN INTERVENTION FOR THE REVERSAL OF COGNITIVE FRAILTY USING A PERSONALIZED APPROACH (AGELESS TRIAL): RECRUITMENT AND BASELINE CHARACTERISTICS OF PARTICIPANTS
A.M. Ibrahim, D.K.A. Singh, A.F.M. Ludin, P. Subramaniam, C. Ai -Vyrn, N. Ibrahim, H. Haron, A.M. Safien, N.M. Khalid, P. Ponvel, N.H.M. Fadzil, J.M. Hanipah, F. Mangialasche, M. Kivipelto, S. Shahar
J Prev Alz Dis 2024;5(11):1291-1306
Show summaryHide summaryBACKGROUND: Reversal of cognitive frailty through a multidomain intervention is desirable to prevent dementia. AGELESS Trial was conducted to determine the effectiveness of a comprehensive, multidomain intervention on older adults with cognitive frailty in Malaysia. However, conducting a clinical trial, particularly during and after Covid-19, posed unique challenges.
OBJECTIVE: We aimed to investigate the recruitment process and baseline characteristics of the AGELESS Trial participants to better understand an at-risk population and those who agree to participate in an intervention.
DESIGN/SETTING: 24-month, randomized controlled trial.
PARTICIPANTS: Community-dwelling older adults with independent mobility, aged ≥ 60 years, with a mini mental state examination score of 19-25, a clinical dementia rating of 0.5 ≥ 1 Fried’s physical frailty criteria, and < 22 Beck depression inventory.
INTERVENTION: Participants were randomized 1:1 to a structured multidomain intervention consisting of vascular management, diet, exercise, cognitive and psychosocial stimulation, or to the arm, including routine care and general health consultation.
MEASUREMENT: We analyzed the group differences between (1) cognitive frailty and non- cognitive frailty screened subjects, (2) recruited and non-recruited participants, (3) baseline characteristics of participants by arm, (4) adherence to AGELESS intervention at 12 months, and (5) preliminary findings on the effectiveness of the intervention at 12 months.
RESULTS: A total of 957 older adults from two locations, i.e., urban (n = 764) and rural (n = 193) areas, were screened, of whom 38.9% had cognitive frailty and were eligible to participate. Those with cognitive frailty had fewer years of education (B = -0.08; 95%CI = 0.88-0.97; p = 0.002), and lower functioning cognition (B = -0.24; 95%CI = 0.74-0.84; p < 0.001). Among those from urban areas, only 33.1% (n = 106) agreed to participate, particularly those with multimorbidity (B = 0.86; 95%CI = 1.31-4.30; p = 0.01), higher physical activity (B = -1.02; 95%CI = 0.19-0.69; p = 0.002), slower walking speed (B = 1.26; 95%CI = 1.62-7.61; p = 0.001), and higher systolic blood pressure (B = 0.02; 95%CI = 1.00-1.03; p = 0.03). At baseline, participants’ mean age was 68.1±5.6, years of education was 8.3±3.9, body mass index was 27.5±5.3 kg/m2, and mini mental state examination score was 22.7±4.0. Generally, there were no significant differences between the intervention and control groups for the main outcomes, except those in the intervention group had higher body mass index, mid-upper-arm circumference, and waist circumference (p < 0.05 for all parameters). Overall intervention adherence at 12 months was 52.8%, ranging from 52.8%-90.6% for each of the modules. Preliminary analysis of the effectiveness of the intervention at 12 months was positive on most of the cognitive domains, some of the nutrient intake and food groups, physical function, and vascular outcomes (p < 0.05 for all parameters).
CONCLUSION: Despite the challenges posed by the pandemic, screening, recruitment, and 12-month intervention delivery were achieved in a Malaysian multidomain preventive randomized controlled trial in older adults at risk of dementia, with a satisfactory adherence rate and cognitive benefits at 12 months.
CITATION:
A.M. Ibrahim ; D.K.A. Singh ; A.F.M. Ludin ; P. Subramaniam ; C. Ai -Vyrn ; N. Ibrahim ; H. Haron ; A.M. Safien ; N.M. Khalid ; P. Ponvel ; N.H.M. Fadzil ; J.M. Hanipah ; F. Mangialasche ; M. Kivipelto ; S. Shahar (2024): Multidomain Intervention for the Reversal of Cognitive Frailty Using a Personalized Approach (AGELESS Trial): Recruitment and Baseline Characteristics of Participants. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.111
META ANALYSIS OF THE CORRELATION BETWEEN PERIODONTAL HEALTH AND COGNITIVE IMPAIRMENT IN THE OLDER POPULATION
Y.-D. Fu, C.-L. Li, C.-L. Hu, M.-D. Pei, W.-Y. Cai, Y.-Q. Li, L. Xu, Y. Zeng
J Prev Alz Dis 2024;5(11):1307-1315
Show summaryHide summaryOBJECTIVE: To explore the correlation between periodontal health and cognitive impairment in the older population to provide the evidence for preventing cognitive impairment from the perspective of oral health care in older adults.
METHODS: A comprehensive search was conducted in PubMed, Embase, the Cochrane Library, the Web of Science, the China National Knowledge Infrastructure, Wanfang Data, the China Science and Technology Journal Database, and the China Biomedical Literature Database, to include both cross-sectional and longitudinal cohort studies on the association between periodontal health and cognitive impairment in older adults. The search was completed in April 2023. Following quality assessment and data organization of the included studies, meta-analysis was performed using Review Manager 5.4.
RESULTS: Twenty-two studies involving a total of 4,246,608 patients were included to comprehensively assess periodontal health from four dimensions (periodontitis, tooth loss, occlusal support, and masticatory ability), with the outcome variable of cognitive impairment (including mild cognitive impairment, Alzheimer’s disease and all-cause dementia). Meta-analysis showed that, compared to those of periodontally healthy older adults, the risk of cognitive impairment in older adults with poor periodontal health, after adjusting for confounders, was significantly greater for those with periodontitis (OR=1.45, 95% CI: 1.20-1.76, P<0.001), tooth loss (OR=1.80, 95% CI: 1.50-2.15, P<0.001), compromised occlusal support (OR=1.87, 95% CI: 1.29-2.70, P=0.001), and reduced masticatory ability (OR=1.39, 95% CI: 1.11-1.75, P=0.005). The risk of cognitive impairment was higher in older adults with low-dentition than in those with high-dentition. Subgroup analysis revealed older individuals with fewer remaining teeth were at a higher risk of developing cognitive impairment compared to those with more remaining teeth, as shown by the comparison of number of teeth lost (7-17 teeth compared to 0-6 teeth) (OR=1.64, 95% CI: 1.13-2.39, P=0.01), (9-28 teeth compared to 0-8 teeth) (OR=1.13, 95% CI: 1.06-1.20, P<0.001), (19-28 teeth compared to 0-18 teeth) (OR=2.52, 95% CI: 1.32-4.80, P=0.005), and (28 teeth compared to 0-27 teeth) (OR=2.07, 95% CI: 1.54-2.77, P<0.001). In addition, tooth loss in older adults led to a significantly increased risk of mild cognitive impairment (OR=1.66, 95% CI: 1.43-1.91, P<0.001) and all-cause dementia (OR=1.35, 95% CI: 1.11-1.65, P=0.003), although the correlation between tooth loss and the risk of Alzheimer’s disease was not significant (OR=3.89, 95% CI: 0.68-22.31, P=0.13).
CONCLUSION: Poor periodontal health, assessed across four dimensions (periodontitis, tooth loss, occlusal support, and masticatory ability), represents a significant risk factor for cognitive impairment in older adults. The more missing teeth in older adults, the higher risk of developing cognitive impairment, with edentulous individuals particularly susceptible to cognitive impairment. While a certain degree of increased risk of Alzheimer’s disease was observed, no significant association was found between tooth loss and the risk of developing Alzheimer’s disease. Enhancing periodontal health management and delivering high-quality oral health care services to older adults can help prevent cognitive impairment.
CITATION:
Y.-D. Fu ; C.-L. Li ; C.-L. Hu ; M.-D. Pei ; W.-Y. Cai ; Y.-Q. Li ; L. Xu ; Y. Zeng (2024): Meta Analysis of the Correlation between Periodontal Health and Cognitive Impairment in the Older Population. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.87
EVALUATING THE PERFORMANCE OF DIFFERENT CRITERIA IN DIAGNOSING AD AND PRECLINICAL AD WITH THE BAYESIAN LATENT CLASS MODEL
X. Wang, G. Niu, J. Zhao, H. Zhu, F. Li, J. Tian, Z. Zhang, G. Chen, Y. He, Q. Gao
J Prev Alz Dis 2024;5(11):1316-1324
Show summaryHide summaryBACKGROUND: The diagnostic criteria for Alzheimer’s disease (AD) should be highly sensitive and specific. Clinicians have varying opinions on the different criteria, including the International Working Group-1 (IWG-1), International Working Group-2 (IWG-2), and AT(N) criteria. Few studies had evaluated the performance of these criteria in diagnosing AD and preclinical AD when the gold standard was absent.
METHODS: We estimated and compared the performance of these criteria in diagnosing AD using data from 908 subjects in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Additionally, 622 subjects were selected to evaluate and compare the performance of IWG-2 and AT(N) criteria in diagnosing preclinical AD. A novel approach, Bayesian latent class models with fixed effect dependent, was utilized to estimate the diagnostic accuracy of these criteria in detecting different AD statuses simultaneously.
RESULTS: The sensitivity of the IWG-1, IWG-2, and AT(N) criteria in diagnosing AD was 0.850, 0.836, and 0.665. The specificity of these criteria was 0.788, 0.746, and 0.747. The IWG-1 criteria had the highest Youden Index in detecting AD. When diagnosing preclinical AD, the sensitivity of the IWG-2 and AT(N) criteria was 0.797 and 0.955. The specificity of these criteria was 0.922 and 0.720. The IWG-2 criteria had the highest Youden Index.
CONCLUSION: IWG-1 was more suitable than the IWG-2 and AT(N) criteria in detecting AD. IWG-2 criteria was more suitable than AT(N) criteria in detecting preclinical AD.
CITATION:
X. Wang ; G. Niu ; J. Zhao ; H. Zhu ; F. Li ; J. Tian ; Z. Zhang ; G. Chen ; Y. He ; Q. Gao (2024): Evaluating the Performance of Different Criteria in Diagnosing AD and Preclinical AD with the Bayesian Latent Class Model. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.71
VISUAL EVENT-RELATED POTENTIALS UNDER EXTERNAL EMOTIONAL STIMULI AS EARLY SIGNS FOR MILD COGNITIVE IMPAIRMENT
C. Wang, W. Yu, T. Xu, H. Zeng, A. González-Cuello, E. Fernández-Villalba, F. Xu, F. Chu, M.T. Herrero, M. Tao
J Prev Alz Dis 2024;5(11):1325-1338
Show summaryHide summaryBACKGROUND: Alzheimer’s disease (AD) is a neurodegenerative disorder featured by progressive cognitive decline, which manifests in severe impairment of memory, attention, emotional processing and daily activities, leading to significant disability and social burden. Investigation on Mild Cognitive Impairment (MCI), the prodromal and transitional stage between normal aging and AD, serves as a key in diagnosing and slowing down the progression of AD. Numerous effects have been made up to date, however, the attentional mechanisms under different external emotion stimuli in MCI and AD are still unexplored in deep.
OBJECTIVE: To further explore the attentional mechanisms under different external emotion stimuli in both MCI and AD patients.
DESIGN/SETTING/PARTICIPANTS/MEASUREMENTS: In 51 healthy volunteers (Controls, 24 males and 27 females), 52 MCI (19 males and 33 females), and 47 AD (15 males and 32 females) patients, we administered the visual oddball event-related potentials (ERPs) under three types of external emotional stimuli: Neutral, Happiness and Sadness, in which the components N1, P2, N2 and P3 as well as the abnormal cortical activations corresponding to the significant ERP differences in the three groups were observed.
RESULTS: Under all three external emotions, in AD patients, N2 and P3 latencies were significantly prolonged compared to both Controls and MCI. In addition, under Happiness, in MCI, P3 latencies were significantly delayed compared to Controls. Meanwhile, under both Happiness and Sadness, in AD patients, P3 amplitudes were significantly decreased compared to Controls and MCI, respectively. During N2 time window, under Neutral emotion, significant hypoactivation in the right superior temporal gyrus was found in AD patients compared to Controls, and under Happiness, the activation of the right inferior frontal gyrus was significantly attenuated in MCI compared to Controls. Under Sadness, in AD patients, the activation of the right superior frontal gyrus was significantly decreased compared to MCI. During P3 time window, under both Happiness and Sadness, when AD patients compared to MCI, the significantly attenuated activations were located in the right fusiform gyrus and the right middle occipital gyrus, respectively.
CONCLUSION: Our results demonstrated visual attentional deficits under external emotional stimuli in both MCI and AD patients, highlighting the function of Happiness for early detecting MCI, in which the P3 latency and the hypoactivation of right inferior frontal gyrus during N2 time window can be early signs. The current study sheds further light of attentional mechanisms in MCI and AD patients, and indicates the value of emotional processing in the early detection of cognitive dysfunction.
CITATION:
C. Wang ; W. Yu ; T. Xu ; H. Zeng ; A. González-Cuello ; E. Fernández-Villalba ; F. Xu ; F. Chu ; M.T. Herrero ; M. Tao ; (2024): Visual Event-Related Potentials under External Emotional Stimuli as Early Signs for Mild Cognitive Impairment. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.72
DISEASE-MODIFYING ANTIRHEUMATIC DRUGS AND DEMENTIA PREVENTION: A SYSTEMATIC REVIEW OF OBSERVATIONAL EVIDENCE IN RHEUMATOID ARTHRITIS
C.-Y. Wu, L.Y. Xiong, Y.Y. Wong, S. Noor, G. Bradley-Ridout, W. Swardfager
J Prev Alz Dis 2024;5(11):1339-1347
Show summaryHide summaryBACKGROUND: Many observational studies have examined the association of disease-modifying antirheumatic drugs (DMARDs) with dementia risk, but the evidence has been mixed, possibly due to methodological reasons. This systematic review (PROSPERO: CRD42023432122) aims to assess existing observational evidence and to suggest if repurposing DMARDs for dementia prevention merits further investigation.
METHODS: Four electronic databases up to October 26, 2023, were searched. Cohort or case-control studies that examined dementia risk associated with DMARDs in people with rheumatoid arthritis were included. Risk of bias was evaluated using the Cochrane Collaboration’s Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) criteria. Findings were summarized by individual drug classes and by risk of bias.
RESULTS: Of 12,180 unique records, 14 studies (4 case-control studies, 10 cohort studies) were included. According to the ROBINS-I criteria, there were 2 studies with low risk of bias, 1 study with moderate risk, and 11 studies with serious or critical risk. Among studies with low risk of bias, one study suggested that hydroxychloroquine versus methotrexate was associated with lower incident dementia, and the other study showed no associations of tumor necrosis factor (TNF) inhibitors, tocilizumab, and tofacitinib, compared to abatacept, with incident dementia.
CONCLUSION: Studies that adequately addressed important biases were limited. Studies with low risk of bias did not support repurposing TNF inhibitors, tocilizumab, abatacept or tofacitinib for dementia prevention, but hydroxychloroquine may be a potential candidate. Further studies that carefully mitigate important sources of biases are warranted, and long-term evidence will be preferred.
CITATION:
C.-Y. Wu ; L.Y. Xiong ; Y.Y. Wong ; S. Noor ; G. Bradley-Ridout ; W. Swardfager ; (2024): Disease-Modifying Antirheumatic Drugs and Dementia Prevention: A Systematic Review of Observational Evidence in Rheumatoid Arthritis. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.78
THE RELATIONSHIP BETWEEN HISTORY OF TRAUMATIC BRAIN INJURY AND LONGITUDINAL CHANGES IN CORTICAL THICKNESS AMONG PATIENTS WITH ALZHEIMER’S DISEASE
G.M. D’Souza, N.W. Churchill, D.X. Guan, M.A. Khoury, S.J. Graham, S. Kumar, C.E. Fischer, T.A. Schweizer
J Prev Alz Dis 2024;5(11):1348-1354
Show summaryHide summaryBACKGROUND: There has been little direct examination of how traumatic brain injury (TBI) affects the rate of neurodegeneration for individuals with Alzheimer’s disease (AD).
METHODS: The study examined 89 cognitively normal adults (65 with and 24 without prior TBI) and 65 with AD (16 with and 49 without prior TBI). Cortical thickness was quantified from T1-weighted MRI scans at baseline and follow-up (mean interval 33.4 months). Partial least squares analysis was used to evaluate the effects of AD and TBI history on the longitudinal change in cortical thickness.
RESULTS: Significant group effects were identified throughout the frontal and temporal cortices. Comparison of the AD groups to their control cohorts showed greater relative atrophy for the AD cohort with prior TBI.
CONCLUSION: These results indicate that a history of TBI exacerbates longitudinal declines in cortical thickness among AD patients, providing new insights into the shared pathomechanisms between these neurological conditions.
CITATION:
G.M. D’Souza ; N.W. Churchill ; D.X. Guan ; M.A. Khoury ; S.J. Graham ; S. Kumar ; C.E. Fischer ; T.A. Schweizer (2024): The Relationship between History of Traumatic Brain Injury and Longitudinal Changes in Cortical Thickness among Patients with Alzheimer’s Disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.86
BACILLUS CALMETTE-GUERIN (BCG) VACCINE IMPACT ON DEMENTIA RISK IN BLADDER CANCER PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS
M. Ibrahim, P. Kim, R. Marawar, K.I. Avgerinos
J Prev Alz Dis 2024;5(11):1355-1362
Show summaryHide summaryBACKGROUND: The BCG vaccine has been traditionally administered to prevent TB. It has been additionally used in bladder cancer patients as a therapy with success. Some observational studies found that bladder cancer patients receiving BCG may have reduced dementia risk, however, the evidence is not conclusive.
OBJECTIVE: To investigate the impact of BCG vaccine on dementia risk in bladder cancer patients.
METHODS: Six databases were searched from inception to January 13, 2024, for published and unpublished studies that examine the association between BCG and dementia risk in bladder cancer patients. We conducted meta-analyses using a random-effects model.
RESULTS: Eight retrospective cohort studies were included in the systematic review and seven in the meta-analyses. Because there were studies with overlapping populations, two separate main analyses were performed reassuring the avoidance of overlap. The first analysis showed that compared to controls, BCG did not reduce dementia risk [5 studies pooled, n=88,852, HR = 0.65, 95% CI (0.40, 1.06), I2 = 85%] whereas there was a marginally significant risk reduction in the second analysis [6 studies pooled, n=70,025, HR = 0.63, 95% CI (0.40, 0.97), I2 = 83%]. Sensitivity analysis excluding the unpublished studies did not affect the outcome importantly. Additional meta-analysis showed that BCG did not reduce the risk of Alzheimer’s disease.
CONCLUSION: This meta-analysis of observational studies found that BCG administration in bladder cancer patients has likely a minimally positive impact on dementia risk if any. To better understand the effect of BCG on dementia, randomized controlled trials are needed.
CITATION:
M. Ibrahim ; P. Kim ; R. Marawar ; K.I. Avgerinos ; (2024): Bacillus Calmette-Guerin (BCG) Vaccine Impact on Dementia Risk in Bladder Cancer Patients: A Systematic Review and Meta-Analysis. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.94
DOES PLAYING MAHJONG BENEFIT OLDER INDIVIDUALS? A SCOPING REVIEW
Z.C.K. Tse, Y. Cao, B.K.H. Chau, M.K. Yeung, C. Leung, D.H.K. Shum
J Prev Alz Dis 2024;5(11):1363-1377
Show summaryHide summaryPlaying mahjong is a popular intellectual and social leisure activity in Asian countries. It is culturally believed that this activity is beneficial to cognitive and psychological functioning in older adults. However, empirical evidence of the benefits of playing mahjong is scant and scattered across the Western and Asian literature. This scoping review comprehensively examined previous studies of the relationships between playing mahjong and cognitive, psychological, and functional abilities in older adults, highlighted gaps in the literature, and identified directions for future research. A systematic search of the literature was conducted across thirteen Western and Asian databases. Fifty-three studies, including forty-seven observational and six intervention studies, were identified. Overall, the results of the observational studies suggested that more mahjong-playing experience was associated with better cognitive, psychological, and functional abilities. As an intervention, playing mahjong was found to enhance general cognitive abilities and short-term memory and relieve depressive symptoms. However, because most of the reviewed studies adopted a correlational methodology, the neural mechanism underlying the benefits of playing mahjong awaits further elucidation. The findings of this review suggest that more randomized controlled trials should be conducted to explore the effects of playing mahjong on higher-level cognitive functioning in older populations.
CITATION:
Z.C.K. Tse ; Y. Cao ; B.K.H. Chau ; M.K. Yeung ; C. Leung ; D.H.K. Shum ; (2024): Does Playing Mahjong Benefit Older Individuals? A Scoping Review. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.102
RISK OF DEMENTIA IN KOREAN VIETNAM WAR VETERANS
W. Lee, S. Lee, S.-K. Kang, W.-J. Choi
J Prev Alz Dis 2024;5(11):1378-1383
Show summaryHide summaryBACKGROUND: The number of cases of all types of dementia is increasing, and a significant increase in prevalence has been noted among veterans. Evidence of an association between dementia and exposure to chemicals such as Agent Orange from the Vietnam War is still limited, and there is a reported lack of awareness.
OBJECTIVE: This study aimed to investigate the risk of dementia among Vietnam War veterans in Korea.
DESIGN: This retrospective longitudinal study compared the incidence of dementia between Vietnam War veterans and the general population.
SETTING: This study used data from the nationally representative Korean Vietnam War Veterans’ Health Study Cohort, a combined dataset sourced from the Ministry of Patriots and Veterans Affairs in Korea and the National Health Insurance Sharing Service database.
PARTICIPANTS: There were 191,272 Vietnam War veterans and 1,000,320 people of different ages, sexes, and residences. matched control in 2002. The total number of person-years were 18,543,181.
MEASUREMENTS: The dementia group included participants who had visited a medical facility with any of the following ICD-10 codes in the follow-up periods: “F00 Dementia in Alzheimer’s disease,” “F01 Vascular dementia,” “F02 Dementia in other diseases classified elsewhere,” or “F03 Unspecified dementia.”
RESULTS: The incidence rate ratio for all types of dementia was 1.16, with higher ratios observed for vascular and unspecified dementia, particularly in the younger age groups. There was a significant increase in the risk of dementia, Alzheimer’s disease, vascular dementia, and unspecified dementia.
CONCLUSION: Vietnam War veterans showed an increased risk for all types of dementia. These findings are hypothesized to be due to the effects of the chemicals used during the Vietnam War, which can cause a variety of neurodegenerative diseases. Further studies are warranted to investigate the potential health determinants related to the Vietnam War, focusing on the neurodegenerative effects.
CITATION:
W. Lee ; S. Lee ; S.-K. Kang ; W.-J. Choi ; (2024): Risk of Dementia in Korean Vietnam War Veterans. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.84
MEDICAL COSTS AND CAREGIVER BURDEN OF DELIVERING DISEASE-MODIFYING ALZHEIMER’S TREATMENTS WITH DIFFERENT DURATION AND ROUTE OF ADMINISTRATION
T. Ozawa, G. Franguridi, S. Mattke
J Prev Alz Dis 2024;5(11):1384-1389
Show summaryHide summaryBACKGROUND: Multiple disease modifying treatment for Alzheimer’s disease are currently in clinical development or have been recently approved for use. They have vastly different treatment properties but so far, little work has been done to quantify the impact of treatment properties on the treatment’s value in terms of medical and social care costs and caregiver burden.
OBJECTIVES: This study aims to analyze how the mode of treatment administration, treatment frequency and duration, and monitoring requirements affect the value of disease modifying treatments. In order to isolate these effects, we compare five hypothetical disease modifying treatments with equal efficacy and safety: (1) chronic bi-weekly intravenous infusion, (2) chronic four-weekly intravenous infusion, (3) 52 weeks fixed duration four-weekly intravenous infusion, (4) chronic subcutaneous injections, and (5) chronic oral prescription on their direct medical costs, caregiver burden, and preservation of treatment value.
DESIGN: Survey of Alzheimer’s disease treatment clinics and retrospective data analysis.
SETTING: United States.
MEASUREMENTS: Direct medical cost and caregiver burden of treatment administration and monitoring compared to gross treatment benefit.
RESULTS: Chronic bi-weekly infusion treatment had the highest direct medical cost ($45,208) and caregiver burden ($6,095), reducing the treatment value by 44%, while oral treatment with the lowest direct medical cost ($1,983) and caregiver burden ($457) reduced the treatment value by only 2%. Substantial caregiver burden was reported from the survey, with a reported average of 2.3 hours for an office visit and infusion, 44 minutes of round-trip travel time, and 78% of patients being accompanied by a caregiver for treatment.
CONCLUSION: Burden of chronic intravenous treatments exceed the gross medical and social care cost savings and value of caregiver benefit. The results suggest the need for less complex treatments that require fewer clinic visits to preserve the economic value of disease modifying treatments.
CITATION:
T. Ozawa ; G. Franguridi ; S. Mattke (2024): Medical Costs and Caregiver Burden of Delivering Disease-Modifying Alzheimer’s Treatments with Different Duration and Route of Administration. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.81
MENDELIAN RANDOMIZATION ANALYSIS TO ASSESS WHETHER MAGNETIC RESONANCE IMAGING SIGNS OF CEREBRAL SMALL VESSEL DISEASE CAN CAUSE COGNITIVE DECLINE AND DEMENTIA
L. Liu, Q. Shen, D. Zhang, Y. Bao, F. Xu, H. Huang, Y. Xu
J Prev Alz Dis 2024;5(11):1390-1396
Show summaryHide summaryOBJECTIVE: Cognitive decline and dementia have been linked to cerebral small vessel disease, so we explored using Mendelian randomization whether cerebral small vessel disease visible as 10 neuroimaging signs may cause cognitive decline and dementia.
METHODS: We analyzed publicly available data from genome-wide association studies using two-sample Mendelian randomization involving inverse variance weighting, weighted median, MR-Egger, and MR-PRESSO approaches.
RESULTS: Mendelian randomization suggested that cognitive decline can be caused by lacunar stroke (inverse variance weighting, β = -0.012, 95% CI -0.024 to -0.001, P = 0.033). Furthermore, an elevated burden of white matter hyperintensities was associated with an increased risk of Dementia due to Parkinson’s disease (inverse variance weighting, OR 2.035, 95% CI 1.105 to 3.745, P = 0.023). Notably, no significant associations were observed between neuroimaging markers of Cerebral Small Vessel Disease and other types of dementia.
CONCLUSION: This Mendelian randomization study provides evidence that lacunar stroke and white matter lesions can cause cognitive decline, and that white matter hyperintensity may increase risk of dementia due to Parkinson’s disease. These results underscore the need for further investigations into the neurocognitive effects of cerebral small vessel disease.
CITATION:
L. Liu ; Q. Shen ; D. Zhang ; Y. Bao ; F. Xu ; H. Huang ; Y. Xu (2024): Mendelian Randomization Analysis to Assess Whether Magnetic Resonance Imaging Signs of Cerebral Small Vessel Disease Can Cause Cognitive Decline and Dementia. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.95
LOWER INCIDENCE OF DEMENTIA FOLLOWING CANCER DIAGNOSES: EVIDENCE FROM A LARGE COHORT AND MENDELIAN RANDOMIZATION STUDY
D.T. Bassil, B. Zheng, B. Su, D. Kafetsouli, C. Udeh-Momoh, I. Tzoulaki, S. Ahmadi-Abhari, D.C. Muller, E. Riboli, L.T. Middleton
J Prev Alz Dis 2024;5(11):1397-1405
Show summaryHide summaryBACKGROUND: The reported inverse association between cancer and subsequent Alzheimer’s disease and related dementias (ADRD) remains uncertain.
OBJECTIVES: To investigate the association between these common conditions of old age and explore possible causal factors.
DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: We conducted a large population-based cohort analysis using data from 3,021,508 individuals aged 60 and over in the UK Clinical Practice Research Datalink (CPRD), over a period up to 30 years (1988-2018). Cox proportional hazards models were fitted to estimate hazard ratios (HR) for risk of dementia associated with previous cancer diagnosis. Competing risk models were employed to account for competing risk of death. Two-sample Mendelian Randomization analysis based on meta-analysis data from large-scale GWAS studies was also conducted.
RESULTS: In the CPRD cohort, 412,903 participants had cancer diagnosis and 230,558 were subsequently diagnosed with dementia over a median follow-up period of 7.9 years. Cancer survivors had a 25% lower risk of developing dementia (HR=0.75, 95% CI:0.74-0.76) after adjustment for potential confounders. Accounting for competing risk of death provided a sub-distribution HR of 0.56 (95% CI:0.55-0.56). Results were consistent for prevalent and incident cancer and different common cancer types. Two-sample Mendelian Randomization analysis, using 357 cancer-related instrumental single-nucleotide polymorphisms (SNPs) revealed evidence of vertical pleiotropy between genetically predicted cancer and reduced risk of Alzheimer’s disease (OR=0.97,95% CI:0.95-0.99).
CONCLUSION: Our results provide strong epidemiological evidence of the inverse association between cancer and risk of ADRD and support the potential causal nature of this association via genetic instruments. Further investigations into the precise underlying biological mechanisms may reveal valuable information for new therapeutic approaches.
CITATION:
D.T. Bassil ; B. Zheng ; B. Su ; D. Kafetsouli ; C. Udeh-Momoh ; I. Tzoulaki ; S. Ahmadi-Abhari ; D.C. Muller ; E. Riboli ; L.T. Middleton (2024): Lower Incidence of Dementia Following Cancer Diagnoses: Evidence from a Large Cohort and Mendelian Randomization Study. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.135
ASSOCIATION BETWEEN FAMILY HOUSEHOLD INCOME AND COGNITIVE RESILIENCE AMONG OLDER US ADULTS: A CROSSSECTIONAL STUDY
M. Iskandar, J. Martindale, J.P.W. Bynum, M.A. Davis
J Prev Alz Dis 2024;5(11):1406-1409
Show summaryHide summaryCognitive resilience has emerged as a mechanism that may help explain individual differences in cognitive function associated with aging and/or pathology. It is unknown whether an association exists between family income level and cognitive resilience. We performed a cross-sectional study to estimate the relationship between family income level and high cognitive resilience using the National Health and Nutrition Examination Survey (NHANES) among older adults (age≥60). Logistic regression was used to estimate the association between income level and high cognitive resilience adjusted for other factors. Accounting for differences in education, occupation, and health status, older adults in the highest income category were twice as likely compared to those with very low income to have high cognitive resilience (OR: 1.90, 95% CI: 1.05,3.43). A doseresponse was apparent between income category and high cognitive resilience. The finding that income, above and beyond that of known factors, affects cognitive function is important for future public health strategies that aim to prevent or delay cognitive impairment.
CITATION:
M. Iskandar ; J. Martindale ; J.P.W. Bynum ; M.A. Davis (2024): Association between Family Household Income and Cognitive Resilience among Older US Adults: A Cross-Sectional Study. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.97
LATER-LIFE COGNITIVE TRAJECTORIES AND RISK OF DEATH: RESULTS FROM A 6-YEAR LONGITUDINAL STUDY OF 7082 CHINESE
Y. Zhao, W. Zhou, M. Xing, L. Zhang, Y. Tong, X. Lv, Y. Ma, W. Li
J Prev Alz Dis 2024;5(11):1410-1417
Show summaryHide summaryBACKGROUND AND OBJECTIVES: To identify cognitive decline trajectories in a Chinese elderly population, explore the associations between these trajectories and mortality, and further identify risk factors related to certain trajectories of cognitive decline.
DESIGN: Prospective cohort study.
SETTING: The group-based trajectory modeling and Cox proportional hazards models were conducted to explore the association between cognitive trajectory groups and mortality, while multinomial logistic regression models were constructed to estimate potential risk factors.
PARTICIPANTS: We included 7082 participants aged 65 years or above in three consecutive but non-overlapping cohorts of the Chinese Longitudinal Healthy Longevity Survey with the Chinese version of the Mini-Mental State Examination up to 6 years. Participants were subsequently followed for a median (IQR) of 2.89 (1.38-3.12) years to obtain their survival status and date of death.
MEASUREMENTS: Chinese version of the Mini-Mental State Examination was used to measure participants’ cognitive function.
RESULTS: Through use of group-based trajectory modeling, we determined three cognitive trajectory groups. Then, after adjusting for confounding factors, we found a monotonic and positive association between cognitive decline and mortality risk. Meanwhile, the association varied among elderly populations in different age groups and BMI categories, but did not differ by sex, smoking, drinking and exercising. Older seniors, females and those with poorer baseline cognitive function and less social participation tended to be more likely to be in the unfavorable trajectory groups.
CONCLUSION: We found that the faster the cognitive decline, the higher the mortality, especially among those aged 65-79 years and those overweight. Our findings suggested the importance of implement better monitoring of the cognitive function of the elderly population.
CITATION:
Y. Zhao ; W. Zhou ; M. Xing ; L. Zhang ; Y. Tong ; X. Lv ; Y. Ma ; W. Li ; (2024): Later-Life Cognitive Trajectories and Risk of Death: Results from a 6-Year Longitudinal Study of 7082 Chinese. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.96
ESTIMATING SOCIO-ECONOMIC STATUS FOR ALZHEIMER’S DISEASE TRIALS
D.M. Rentz, J.D. Grill, D.P. Molina-Henry, G.A. Jicha, M.S. Rafii, A. Liu, R.A. Sperling, P.S. Aisen, R. Raman
J Prev Alz Dis 2024;5(11):1418-1425
Show summaryHide summaryINTRODUCTION: Metrics of a participant’s socioeconomic status (SES) are not routinely collected or standardized in clinical trials. This omission limits the ability to evaluate the generalizability of trial results and restricts clinicians from confidently interpreting the efficacy of new treatments across important sub-populations.
METHODS: We adapted an SES measure of social disparity; the Hollingshead Two Factor Index of Social Position, which combines education and occupation into a single metric. We modernized the 1965 occupations to reflect the 2017 careers tabulated by the US Bureau of Labor Statistics. We currently use this adapted measure in Alzheimer’s Clinical Trials Consortium studies.
RESULTS: We present the revised table of occupations. We found that the collection of SES data using the modified Hollingshead was feasible in a multi-site clinical trial and scores were distributed across all SES strata.
DISCUSSION: The modified Hollingshead provides a standardized method for collecting SES information, enabling data aggregation, monitoring, and reporting.
CITATION:
D.M. Rentz ; J.D. Grill ; D.P. Molina-Henry ; G.A. Jicha ; M.S. Rafii ; A. Liu ; R.A. Sperling ; P.S. Aisen ; R. Raman (2024): Estimating Socio-Economic Status for Alzheimer’s Disease Trials. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.88
ASSOCIATIONS OF BLOOD PRESSURE TRAJECTORIES WITH SUBSEQUENT COGNITIVE DECLINE, DEMENTIA AND MORTALITY
Y. Zhu, C. Li, D. Gao, X. Huang, Y. Zhang, M. Ji, F. Zheng, W. Xie
J Prev Alz Dis 2024;5(11):1426-1434
Show summaryHide summaryBACKGROUND: Hypertension may harm cognitive performance, but the potential correlates of longitudinal patterns of blood pressure (BP), especially diastolic BP (DBP), to cognition have been unclear.
OBJECTIVES: To examine long-term BP trajectories in relation to subsequent cognitive decline, incident dementia and all-cause mortality in the general population.
DESIGN: Population-based cohort study.
SETTING: Communities in England.
PARTICIPANTS: The study included 7566 participants from the English Longitudinal Study of Ageing (ELSA).
MEASUREMENTS: BP were measured in 1998, 2004, 2008. Group-based trajectory modeling was used to identify long-term patterns of systolic BP (SBP) and DBP. Outcomes including cognitive function, incident dementia, and all-cause mortality were followed up to 10 years.
RESULTS: Five distinct trajectories were identified for SBP and DBP, respectively. The normal-stable trajectory was used as the reference. For cognitive decline, both SBP and DBP trajectories were independently associated with subsequent cognitive decline, with the fastest decline appeared in the high-stable SBP group of 180 mmHg and the low-stable DBP group of 60 mmHg (both P<0.005). For incident dementia, the multivariable adjusted hazard ratio (HR) was also greatest in high-stable group (4.79, 95% confidence interval: 2.84 to 8.07) across all SBP trajectories. Conversely, low (HR: 1.58) and moderate-low stable (HR: 1.56) DBP trajectories increased dementia risk (both P<0.005). Similar patterns were found in BP trajectories in relation to all-cause mortality.
CONCLUSION: Our study evaluates the potential health impact from different BP trajectories and suggests that controlling long-term SBP and maintaining adequate DBP may be relevant for the current practice to promote cognitive health and extend lifespan.
CITATION:
Y. Zhu ; C. Li ; D. Gao ; X. Huang ; Y. Zhang ; M. Ji ; F. Zheng ; W. Xie ; (2024): Associations of Blood Pressure Trajectories with Subsequent Cognitive Decline, Dementia and Mortality. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.91
THE ALZMATCH PILOT STUDY - FEASIBILITY OF REMOTE BLOOD COLLECTION OF PLASMA BIOMARKERS FOR PRECLINICAL ALZHEIMER’S DISEASE TRIALS
S. Walter, O. Langford, G.A. Jimenez-Maggiora, S. Abdel-Latif, R.A. Rissman, J.D. Grill, J. Karlawish, A. Atri, S. Bruschi, K. Hussen, M.C. Donohue, G.A. Marshall, G. Jicha, M. Racke, R.S. Turner, C.H. van Dyck, V. Venkatesh, K.E. Yarasheski, R. Sperling, J. Cummings, P.S. Aisen, R. Raman
J Prev Alz Dis 2024;5(11):1435-1444
Show summaryHide summaryBACKGROUND: Advances in plasma biomarkers to detect Alzheimer’s disease (AD) biology allows researchers to improve the efficiency of participant recruitment into preclinical trials. Recently, protein levels of plasma amyloid-beta and tau proteins have been shown to be predictive of elevated amyloid in brain. Online registries, such as the Alzheimer’s Prevention Trials (APT) Webstudy, include and follow participants using remote assessments to facilitate efficient screening and enrollment of large numbers of individuals who may be at higher risk for AD.
OBJECTIVES: The AlzMatch Pilot Study investigated the feasibility of recruiting individuals from an online registry for blood sample collection at community-based phlebotomy centers and plasma biomarker quantification to assess an individual’s eligibility for AD preclinical trials.
DESIGN: Pilot feasibility study with co-primary outcomes.
SETTING: This pilot feasibility study included participants from the APT Webstudy, the remote assessment arm of the Trial-ready cohort for Preclinical and Prodromal AD (TRC-PAD) Platform. Novel design included collection of electronic consent, use of community laboratories for plasma collection, mass spectrometry-based biomarker assay, and telephone communication of plasma biomarker screening eligibility.
PARTICIPANTS: Participants invited to the AlzMatch pilot feasibility study were active in the APT Webstudy, 50 years of age or older, resided within 50 miles of both a Quest Diagnostics Patient Services Center (a national diagnostic laboratory with convenient locations for sample collection and processing) and one of six TRC-PAD vanguard clinical trial sites, had no self-reported dementia diagnosis, were able to communicate in English and engaged with the APT Webstudy within the prior 6 months.
MEASUREMENTS: Primary feasibility outcomes were completion of electronic consent (e-consent) for invited participants and collection of usable blood samples. Additional feasibility outcomes included invitation response rate, plasma biomarker eligibility status (based on amyloid beta-42/40 [Aβ42/40] concentration ratio), ApoE proteotype, and trial inclusion criterion), and completion of telephone contact to learn eligibility to screen for a study.
RESULTS: 300 APT Webstudy participants were invited to consent to the AlzMatch study. The AlzMatch e-consent rate was 39% (n=117) (95% CI of 33.5%-44.5%) overall, which was higher than the expected rate of 25%. Similar consent rates were observed across participants based on self-defined sex (41% Female (n=75), 37% Male (n=42)) and race and ethnicity (37% from underrepresented groups (URG) (n=36), 40% not from URG (n=79)). Among those that consented (n=117), plasma was successfully collected from 74% (n=87) (95% CI of 66%-82%), with similar rates across sex (76% Female (n=57), 71% Male (n=30)) and race and ethnicity (75% URG (n=27) and 75% not from URG (n=59)). 60% (n=51) of participants with plasma biomarker results were eligible to screen for future preclinical AD trials.
CONCLUSION: Electronic consent of participants through an online registry, blood sample collection at community-based centers, plasma biomarker quantification and reporting, and biomarker assessments for study eligibility were all feasible with similar engagement rates across demographic groups. Although this pilot was a small and selective sample, participants engaged and consented at higher than expected rates. We conclude that collecting blood at community laboratories for biomarker analyses may improve accessibility beyond research, and may facilitate broader access for clinical use of AD plasma biomarkers. Based on our results, an expanded version of the AlzMatch study is underway, which involves expanding invitations to additional APT Webstudy participants and clinical trial sites.
CITATION:
S. Walter ; O. Langford ; G.A. Jimenez-Maggiora ; S. Abdel-Latif ; R.A. Rissman ; J.D. Grill ; J. Karlawish ; A. Atri ; S. Bruschi ; K. Hussen ; M.C. Donohue ; G.A. Marshall ; G. Jicha ; M. Racke ; R.S. Turner ; C.H. van Dyck ; V. Venkatesh ; K.E. Yarasheski ; R. Sperling ; J. Cummings ; P.S. Aisen ; R. Raman (2024): The AlzMatch Pilot Study - Feasibility of Remote Blood Collection of Plasma Biomarkers for Preclinical Alzheimer’s Disease Trials. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.101
HEIGHTENED PREVALENCE OF COMMON HOSPITAL-TREATED INFECTIONS PRECEDING DEMENTIA DIAGNOSIS WITH ACCELERATED DEMENTIA ONSET AFTER INFLUENZA
H. Untersteiner, R. Wurm, B. Reichardt, S. Goeschl, E. Berger-Sieczkowski, T. König, T. Parvizi, S. Silvaieh, E. Stögmann
J Prev Alz Dis 2024;5(11):1445-1454
Show summaryHide summaryBACKGROUND: Since the beginning of Alzheimer’s disease research, the hypothesis that infections are to some extent associated with neurodegenerative processes has been tested repeatedly. Epidemiological studies on the associations between infections and dementia have reported conflicting results.
OBJECTIVES: This study analyses common hospital-treated infections (herpes, influenza, intestinal infections, pneumonia, sepsis, urinary tract infections) and their association with subsequent dementia and time until dementia onset.
DESIGN, SETTING, AND PARTICIPANTS: For this nationwide population-based case-control study, the dataset of the Austrian National Health Insurance Association was used, including dementia patients (dementia cohort) and age- and gender-matched non-demented individuals (control cohort). Only subjects with data availability of at least 10 years prior to the index date (date of dementia diagnosis or date of censoring) were included.
MEASUREMENTS: The incidence of six common infections in older adults (herpes, influenza, intestinal infections, pneumonia, sepsis, and urinary tract infections) was analyzed over a period of 10 years before the censoring date.
RESULTS: The study population consists of 58208 subjects (29104 per study cohort), mean age: 81 years, 54% females. Patients of the dementia cohort had suffered from infections significantly more often than patients of the control cohort (6002, 20.6% vs. 4826, 16.6%; p < 0.001). Influenza, urinary tract infections, intestinal infections, and sepsis showed independent positive associations with subsequent dementia diagnosis, irrespective of other comorbidities (odds ratios: 1.26 (95% CI: 1.06-1.49), 1.23 (95% CI: 1.16-1.30), 1.16 (95% CI: 1.07-1.27), 1.17 (95% CI: 1.01-1.37), respectively). Time from infection to dementia diagnosis was shorter after influenza compared to all other infections (median: 3.4 years (95% CI: 3.1-3.7) vs. 6.6 years (95% CI: 6.4-6.8); p < 0.001).
CONCLUSION: This is the first study to assess the association between infections and dementia over such a long minimum reporting period. These results, supported by consistent data from other epidemiological studies, emphasize the critical importance of infection prevention measures, especially for older adults. Further research is crucial to better understand the nature of the relationship between infections and dementia.
CITATION:
H. Untersteiner ; R. Wurm ; B. Reichardt ; S. Goeschl ; E. Berger-Sieczkowski ; T. König ; T. Parvizi ; S. Silvaieh ; E. Stögmann (2024): Heightened Prevalence of Common Hospital-Treated Infections Preceding Dementia Diagnosis with Accelerated Dementia Onset after Influenza. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.92
VALIDATION OF A COMMUNITY-BASED APPROACH TOWARD PERSONALIZED DEMENTIA RISK REDUCTION: THE KIMEL FAMILY CENTRE FOR BRAIN HEALTH AND WELLNESS
N.D. Anderson, D. D’Amico, S. Rotenberg, D.R. Addis, J. Gillen, D. Moore, J.A. Furlano, B. Tan, M. Binns, M. Santarossa, H. Chertkow, for the Canadian Consortium on Neurodegeneration in Aging (CCNA) CAN-THUMBS UP Study Group
J Prev Alz Dis 2024;5(11):1455-1466
Show summaryHide summaryBACKGROUND/OBJECTIVES: The Kimel Family Centre for Brain Health and Wellness is a research-driven community centre testing the efficacy of personalized dementia risk reduction programming on dementia risk and cognition. The objective of this protocol is to validate this approach by following people for two years.
DESIGN/SETTING: Participants will receive a comprehensive dementia risk assessment, including nonmodifiable and modifiable risk factors, from which they will receive a Personalized Dementia Risk Report and Program Strategy, indicating their health conditions increasing and their risk level in five modifiable risk domains: physical activity, brain-healthy eating, cognitive engagement, social connections, and mental wellbeing. Equipped with this information, participants will enroll in programs within the Centre to address their risk factors. Changes to their dementia risk, cognition, and Personalized Program Strategy will be communicated through re-assessments of risk factors every six months (risk and cognition) and every year (comprehensive assessment).
PARTICIPANTS: Participants (n = 450) will be 50 years of age or older, without a diagnosis of dementia, and sufficiently fluent in English to complete the assessments and understand program instructors. One goal is that our participant sample will include people of low income (with fundraising providing free community centre membership), and from various ethno-racial backgrounds.
INTERVENTION: Participants will select programs to meet their Personalized Program Strategy. For physical activity, they will gradually work toward the Canadian Society for Exercise Physiology guidelines. For brain-healthy eating, they will learn about the Brain Health Food Guide and food label reading, and then take additional programs. For cognitive engagement and mental wellbeing, they will take at least one hour of relevant programming per week. Social connections will be reinforced throughout all programs. All participants will also have access to the Canadian Consortium on Neurodegeneration’s CAN-THUMBS Up online, educational program on modifiable dementia risk factors, called Brain Health PRO.
MEASUREMENTS: The comprehensive assessment includes numerous dementia risk factors, but the primary measures are risk in the five domains, health conditions proximal to those five risk domains, and cognition, and how these are affected by adherence and quality of goal-directed future simulation. We hypothesize a reduced risk in the five domains within six months, improvements in health biomarkers within a year, and maintenance of cognition within two years, with these benefits accruing with greater adherence, but only up to a point, at which benefits will plateau, and greater benefits among participants whose goal-directed simulations are more vivid, personally-relevant, achievable, and positive.
CONCLUSIONS: This innovative approach overcomes a number of limitations present in prior multidomain dementia prevention trials. Adapting a preference clinical trial that is embedded in a community centre, where participants have autonomy to choose programs to address their modifiable dementia risk factors, has real-world applicability in the global effort to reduce dementia risk.
CITATION:
N.D. Anderson ; D. D’Amico ; S. Rotenberg ; D.R. Addis ; J. Gillen ; D. Moore ; J.A. Furlano ; B. Tan ; M. Binns ; M. Santarossa ; H. Chertkow ; for the Canadian Consortium on Neurodegeneration in Aging (CCNA) CAN-THUMBS UP Study Group (2024): Validation of a Community-Based Approach Toward Personalized Dementia Risk Reduction: The Kimel Family Centre for Brain Health and Wellness. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.98
CONTINUOUS ASSOCIATIONS BETWEEN REMOTE SELFADMINISTERED COGNITIVE MEASURES AND IMAGING BIOMARKERS OF ALZHEIMER’S DISEASE
E.A. Boots, R.D. Frank, W.Z. Fan, T.J. Christianson, W.K. Kremers, J.L. Stricker, M.M. Machulda, J.A. Fields, J. Hassenstab, J. Graff-Radford, P. Vemuri, C.R. Jack, D.S. Knopman, R.C. Petersen, N.H. Stricker
J Prev Alz Dis 2024;5(11):1467-1479
Show summaryHide summaryBACKGROUND: Easily accessible and self-administered cognitive assessments that can aid early detection for Alzheimer’s disease (AD) dementia risk are critical for timely intervention.
OBJECTIVES/DESIGN: This cross-sectional study investigated continuous associations between Mayo Test Drive (MTD) – a remote, self-administered, multi-device compatible, web-based cognitive assessment – and AD-related imaging biomarkers.
PARTICIPANTS/SETTING: 684 adults from the Mayo Clinic Study of Aging and Mayo Clinic Alzheimer’s Disease Research Center participated (age=70.4±11.2, 49.7% female). Participants were predominantly cognitively unimpaired (CU; 94.0%).
MEASUREMENTS: Participants completed (1) brain amyloid and tau PET scans and MRI scans for hippocampal volume (HV) and white matter hyperintensities (WMH); (2) MTD remotely, consisting of the Stricker Learning Span and Symbols Test which combine into an MTD composite; and (3) in-person neuropsychological assessment including measures to obtain Mayo Preclinical Alzheimer’s disease Cognitive Composite (Mayo-PACC) and Global-z. Multiple regressions adjusted for age, sex, and education queried associations between imaging biomarkers and scores from remote and in-person cognitive measures.
RESULTS: Lower performances on MTD were associated with greater amyloid, entorhinal tau, and global tau PET burden, lower HV, and higher WMH. Mayo-PACC and Global-z were associated with all imaging biomarkers except global tau PET burden. MCI/Dementia participants showed lower performance on all MTD measures compared to CU with large effect sizes (Hedge’s g’s=1.65-2.02), with similar findings for CU versus MCI only (Hedge’s g’s=1.46-1.83).
CONCLUSION: MTD is associated with continuous measures of AD-related imaging biomarkers, demonstrating ability to detect subtle cognitive change using a brief, remote assessment in predominantly CU individuals and criterion validity for MTD.
CITATION:
E.A. Boots ; R.D. Frank ; W.Z. Fan ; T.J. Christianson ; W.K. Kremers ; J.L. Stricker ; M.M. Machulda ; J.A. Fields ; J. Hassenstab ; J. Graff-Radford ; P. Vemuri ; C.R. Jack ; D.S. Knopman ; R.C. Petersen ; N.H. Stricker (2024): Continuous Associations between Remote Self-Administered Cognitive Measures and Imaging Biomarkers of Alzheimer’s Disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.99
DIGITAL HEALTH TECHNOLOGIES FOR ALZHEIMER’S DISEASE AND RELATED DEMENTIAS: INITIAL RESULTS FROM A LANDSCAPE ANALYSIS AND COMMUNITY COLLABORATIVE EFFORT
S.A. Lott, E. Streel, S.L. Bachman, K. Bode, J. Dyer, C. Fitzer-Attas, J.C. Goldsack, A. Hake, A. Jannati, R.S. Fuertes, P. Fromy
J Prev Alz Dis 2024;5(11):1480-1489
Show summaryHide summaryDigital health technologies offer valuable advantages to dementia researchers and clinicians as screening tools, diagnostic aids, and monitoring instruments. To support the use and advancement of these resources, a comprehensive overview of the current technological landscape is essential. A multi-stakeholder working group, convened by the Digital Medicine Society (DiMe), conducted a landscape review to identify digital health technologies for Alzheimer’s disease and related dementia populations. We searched studies indexed in PubMed, Embase, and APA PsycInfo to identify manuscripts published between May 2003 to May 2023 reporting analytical validation, clinical validation, or usability/feasibility results for relevant digital health technologies. Additional technologies were identified through community outreach. We collated peer-reviewed manuscripts, poster presentations, or regulatory documents for 106 different technologies for Alzheimer’s disease and related dementia assessment covering diverse populations such as Lewy Body, vascular dementias, frontotemporal dementias, and all severities of Alzheimer’s disease. Wearable sensors represent 32% of included technologies, non-wearables 61%, and technologies with components of both account for the remaining 7%. Neurocognition is the most prevalent concept of interest, followed by physical activity and sleep. Clinical validation is reported in 69% of evidence, analytical validation in 34%, and usability/feasibility in 20% (not mutually exclusive). These findings provide clinicians and researchers a landscape overview describing the range of technologies for assessing Alzheimer’s disease and related dementias. A living library of technologies is presented for the clinical and research communities which will keep findings up-to-date as the field develops.
CITATION:
S.A. Lott ; E. Streel ; S.L. Bachman ; K. Bode ; J. Dyer ; C. Fitzer-Attas ; J.C. Goldsack ; A. Hake ; A. Jannati ; R.S. Fuertes ; P. Fromy (2024): Digital Health Technologies for Alzheimer’s Disease and Related Dementias: Initial Results from a Landscape Analysis and Community Collaborative Effort. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.103
POTENTIALLY MODIFIABLE DEMENTIA RISK FACTORS IN CANADA: AN ANALYSIS OF CANADIAN LONGITUDINAL STUDY ON AGING WITH A MULTI-COUNTRY COMPARISON
S. Son, M. Speechley, G.Y. Zou, M. Kivipelto, F. Mangialasche, H.H. Feldman, H. Chertkow, S. Belleville, H. Nygaard, V. Hachinski, F. Pieruccini-Faria, M. Montero-Odasso
J Prev Alz Dis 2024;5(11):1490-1499
Show summaryHide summaryBACKGROUND: It has been suggested that up to 40% of dementia cases worldwide are associated with modifiable risk factors; however, these estimates are not known in Canada. Furthermore, sleep disturbances, an emerging factor, has not been incorporated into the life-course model of dementia prevention.
OBJECTIVE: To estimate the population impact of 12 modifiable risk factors in Canadian adults including sleep disturbances, by sex and age groups, and to compare with other countries.
DESIGN: Cross-sectional analysis of Canadian Longitudinal Study on Aging baseline data.
SETTING: Community.
PARTICIPANTS: 30,097 adults aged 45 years and older.
MEASUREMMENTS: Prevalence and Population Attributable Fractions (PAFs) associated with less education, hearing loss, traumatic brain injury, hypertension, excessive alcohol, obesity, smoking, depression, social isolation, physical inactivity, diabetes, and sleep disturbances.
RESULTS: The risk factors with the largest PAF were later life physical inactivity (10.2%; 95% CI, 6.8% to 13%), midlife hearing loss (6.5%; 3.7% to 9.3%), midlife obesity (6.4%; 4.1% to 7.7%), and midlife hypertension (6.2%; 2.7% to 9.3%). The PAF of later life sleep disturbances was 3.0% (95% CI, 1.8% to 3.8%). The 12 risk factors accounted for 51.9% (32.2% to 68.0%) of dementia among men and 52.4% (32.5% to 68.7%) among women. Overall, the combined PAF of all risk factors was 49.2% (31.1% to 64.9%), and it increased with age.
CONCLUSION: Nearly up to 50% of dementia cases in Canada are attributable to 12 modifiable risk factors across the lifespan. Canadian risk reduction strategies should prioritize targeting physical inactivity, hearing loss, obesity, and hypertension.
CITATION:
S. Son ; M. Speechley ; G.Y. Zou ; M. Kivipelto ; F. Mangialasche ; H.H. Feldman ; H. Chertkow ; S. Belleville ; H. Nygaard ; V. Hachinski ; F. Pieruccini-Faria ; M. Montero-Odasso (2024): Potentially Modifiable Dementia Risk Factors in Canada: An Analysis of Canadian Longitudinal Study on Aging with a Multi-Country Comparison. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.105
A PILOT STUDY OF BRAIN BOOTCAMP, A LOW-INTENSITY INTERVENTION ON DIET, EXERCISE, COGNITIVE ACTIVITY, AND SOCIAL INTERACTION TO IMPROVE OLDER ADULTS’ DEMENTIA RISK SCORES
J. Siette, L. Dodds, K. Deckers, S. Köhler, I. Heger, P. Strutt, C. Johnco, V. Wuthrich, C.J. Armitage
J Prev Alz Dis 2024;5(11):1500-1512
Show summaryHide summaryBACKGROUND: Little is known about the impact of short, low-intensity multidomain dementia risk reduction interventions in older adults.
OBJECTIVES: To examine the effectiveness and feasibility of a low-intensity multidomain lifestyle intervention on dementia risk and dementia literacy in Australian older adults.
DESIGN: Single-group pre-post design.
SETTING: Community-dwelling.
PARTICIPANTS: A total of 853 older Australians (Mean age=73.3 years, SD=6.1) recruited from the community.
INTERVENTION: A 3-month dementia risk reduction program, BRAIN BOOTCAMP, including education, personalised risk information, physical cues for healthier choices and goal setting and planning to target four modifiable risk factors of diet, exercise, cognitive activity and social interaction in older adults.
MEASUREMENTS: The ‘LIfestyle for BRAin health’ (LIBRA) index was used to assess participants’ modifiable dementia risk based on 12 factors, with higher scores indicating greater risk. Dementia literacy was measured using a modified questionnaire derived from Dutch and British surveys, encompassing knowledge, risk reduction, and awareness aspects. Paired t-tests were used to compare dementia risk scores and dementia literacy before and after the program. Multivariate regressions were performed to identify sociodemographic and psychological factors associated with change in the LIBRA index.
RESULTS: Program attrition was high (58.3%). Participants who completed the program had decreased dementia risk scores (Cohen’s d=0.59, p<0.001), increased dementia literacy and awareness (Cohen’s d=0.64, p<0.001) and increased motivation to change lifestyle behaviors (Cohen’s d=0.25-0.52, p<0.016). Participants with higher motivational beliefs had greater dementia risk reduction.
CONCLUSIONS: Improving older adults’ motivation and knowledge may help modify lifestyle behaviors to reduce dementia risk. However, program attrition remains a challenge, suggesting the need for strategies to enhance participant engagement and retention in such interventions.
CITATION:
J. Siette ; L. Dodds ; K. Deckers ; S. Köhler ; I. Heger ; P. Strutt ; C. Johnco ; V. Wuthrich ; C.J. Armitage (2024): A Pilot Study of BRAIN BOOTCAMP, a Low-Intensity Intervention on Diet, Exercise, Cognitive Activity, and Social Interaction to Improve Older Adults’ Dementia Risk Scores. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.104
INDEPENDENT AND JOINT ASSOCIATIONS OF SOCIOECONOMIC STATUS AND LIFESTYLE BEHAVIORS WITH COGNITIVE IMPAIRMENT AMONG ELDERLY CHINESE POPULATION
Y. Feng, S. Jia, W. Zhao, X. Wu, Y. Zuo, S. Wang, L. Zhao, M. Ma, X. Guo, C.S. Tarimo, Y. Miao, J. Wu
J Prev Alz Dis 2024;5(11):1513-1522
Show summaryHide summaryBACKGROUND: Numerous studies have shown that there are socioeconomic disparities in people’s health. Health behavior is considered to be an effective strategy to alleviate socio-economic differences. However, the independent or joint relationship between socioeconomic status (SES) and lifestyle behaviors (LBs) on the cognition of Chinese elderly are not clear. Therefore, this study aimed to reveal the impact of SES and LBs on cognitive impairment in elder Chinese.
METHODS: The data from the 2017-2018 wave of Chinese Longitudinal Healthy Longevity Survey was used. SES was created using latent class analysis based on annual per-capita household income, education level, and occupation. Six LBs were considered in calculating LB scores. Restricted cubic splines were used to model the association of LB scores and cognitive impairment to investigate the dose-response relationship. LB scores were divided into three groups: unhealthy, intermediate, and healthy lifestyle. Multivariate Logistic regression models were applied to explore both the independent and joint effects of SES and LB scores on cognitive impairment.
RESULTS: Among 10,116 participants, 1,872 (18.51%) were recorded as having cognitive impariment. After adjusting for multivariable confounding factors, compared with participants of high SES, those of low SES had higher risks of cognitive impairment [Odds ratio (OR): 1.385; 95% confidence interval (CI): 1.137-1.689]. In contrast to those with unhealthy lifestyle, participants adhering to a healthy lifestyle were found to be associated with a reduced risk of cognitive impairment (OR: 0.198; 95%CI: 0.150-0.263). A non-linear relationship was observed between LB scores and cognitive impairment (Pnonlinearity =0.001), indicating a protective effect on cognitive impairment when having more than two LBs. Participants with high SES and engaged in healthy lifestyle had the lowest risk of cognitive impairment compared to those with low SES and unhealthy lifestyle (OR: 0.123; 95% CI 0.073-0.207).
CONCLUSION: Cognitive impairment has socioeconomic disparities among the elderly Chinese population. A healthy lifestyle may attenuate the impact of socioeconomic inequality on cognitive impairment, emphasizing the important role of LBs modification in reducing the disease burden of cognitive impairment, especially in the elderly population with low SES.
CITATION:
Y. Feng ; S. Jia ; W. Zhao ; X. Wu ; Y. Zuo ; S. Wang ; L. Zhao ; M. Ma ; X. Guo ; C.S. Tarimo ; Y. Miao ; J. Wu ; (2024): Independent and Joint Associations of Socioeconomic Status and Lifestyle behaviors with Cognitive Impairment among Elderly Chinese Population. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.127