Alzheimer''s and Dementia: Translational Research and Clinical Interventions最新文献

{"title":"The African Initiative for Bioinformatics Online Training in Neurodegenerative Diseases (AI-BOND): Investing in the next generation of African neuroscientists","authors":"Bernard Fongang, Biniyam A. Ayele, Yannick N. Wadop, Emmanuel Epenge, Cyrille D. Nkouonlack, Wepnyu Y. Njamnshi, Xueqiu Jian, Murali Sargurupremraj, Alice B. S. Nono Djotsa, Paul F. Seke Etet, Rebecca Bernal, Abdon Atangana, Jose E. Cavazos, Jayandra Jung Himali, Alfred N. Fonteh, Gladys Maestre, Alfred K. Njamnshi, Sudha Seshadri","doi":"10.1002/trc2.70002","DOIUrl":"https://doi.org/10.1002/trc2.70002","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Neurodegenerative disorders, including Alzheimer's disease and AD-related dementias (AD/ADRD), pose significant challenges to health care systems globally, particularly in Africa. With the advances in medical technology and research capabilities, especially in next-generation sequencing and imaging, vast amounts of data have been generated from AD/ADRD research. Given that the greatest increase in AD/ADRD prevalence is expected to occur in Africa, it is critical to establish comprehensive bioinformatics training programs to help African scientists leverage existing data and collect additional information to untangle AD/ADRD heterogeneity in African populations. The South Texas Alzheimer's Disease Research Center, with efforts from the National Institutes of Health and the Global Brain Health Institute, has partnered with the Brain Research Africa Initiative to develop the <b>A</b>frican <b>I</b>nitiative on <b>B</b>ioinformatics <b>O</b>nline Training in <b>N</b>eurodegenerative <b>D</b>isease (<b>AI-BOND</b>). AI-BOND is a comprehensive and accessible training program, the aim of which is to advance biostatistics and bioinformatics expertise in Africa in studying neurodegenerative diseases. This expertise is essential to enable African scientists to utilize the extensive AD/ADRD data and enhance the continent's ability to contribute to global research efforts in this field. The training addresses the gap in analyzing neurodegenerative disease data by providing skills and knowledge in genetic epidemiology, biostatistics, and bioinformatics to African students and researchers. This innovative online training program will last 6 months and provide training in skill sets R, SAS, and Python programing, genome-wide association studies, genomics, transcriptomics, proteomics, metabolomics, microbiome analysis, and advanced statistical methods. Additional training will include study design and manuscript and grant writing. The first cohort of the AI-BOND program will graduate in June 2024. The AI-BOND program is expected to build research computational capacities in Africa that will improve the ability of graduates to conduct and utilize large-scale studies, with the goal of curbing the growing incidence of neurodegenerative diseases in Africa.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Alzheimer's disease (AD) and AD-related dementias (ADRD) pose significant health challenges globally, particularly in Africa.</li>\u0000 \u0000 <li>The most significant AD/ADRD prevalence increase is predicted to occur in Africa.</li>\u0000 \u0000 <li>It is crucial to establish a bioinformatics training capacity in Africa to leverage the vast number","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting regional tau accumulation with machine learning-based tau-PET and advanced radiomics","authors":"Saima Rathore, Ixavier A. Higgins, Jian Wang, Ian A. Kennedy, Leonardo Iaccarino, Samantha C. Burnham, Michael J. Pontecorvo, Sergey Shcherbinin","doi":"10.1002/trc2.70005","DOIUrl":"https://doi.org/10.1002/trc2.70005","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Alzheimer's disease is partially characterized by the progressive accumulation of aggregated tau-containing neurofibrillary tangles. Although the association between accumulated tau, neurodegeneration, and cognitive decline is critical for disease understanding and clinical trial design, we still lack robust tools to predict individualized trajectories of tau accumulation. Our objective was to assess whether brain imaging biomarkers of flortaucipir-positron emission tomography (PET), in combination with clinical and genomic measures, could predict future pathological tau accumulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We quantified the disease profile of participants (<i>N</i> = 276) using a comprehensive set of descriptors, including clinical/demographic (age, diagnosis, amyloid status, sex, race, ethnicity), genetic (apolipoprotein E [APOE]-ε4), and flortaucipir-PET imaging measures (regional flortaucipir standardized uptake value ratio [SUVr] and comprehensive radiomic texture features extracted from Automated Anatomical Labeling template regions). We trained an AdaBoost machine learning algorithm in a 2:1 split train-test configuration to derive a prognostic index that (i) stratifies individualized brain regions including global (AD-signature region) and lobar regions (frontal, occipital, parietal, temporal) into stable/slow- and fast-progressors based on future tau accumulation, and (ii) forecasts individualized regional annualized-rate-of-change in flortaucipir-PET SUVr. Further, we developed an adaptive model incorporating flortaucipir-PET measurements from the baseline and intermediate timepoints to predict annualized-rate-of-change.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>In binary classification for predicting stable/slow- versus fast-progressors, the area-under-the-receiver-operating-characteristic curve was 0.86 in the AD-signature region and 0.83, 0.82, 0.84, and 0.83 in frontal, occipital, parietal, and temporal regions, respectively. The trained models successfully predicted annualized-rate-of-change of flortaucipir-PET regional flortaucipir SUVr in AD-signature and lobar regions (Pearson-correlation [<i>R</i>]: AD-signature = 0.73; frontal = 0.73; occipital = 0.71; parietal = 0.70; temporal = 0.69). The models’ performance in predicting annualized-rate-of-change slightly increased when imaging features from intermediate timepoints were used in the adaptive setting (<i>R</i>: AD-signature = 0.79; frontal = 0.87; occipital = 0.83; parietal = 0.74; temporal = 0.82).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION<","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142525669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Site-level factors affecting nursing home implementation of a personalized music intervention: Qualitative analyses from Music & Memory: A Pragmatic Trial for Nursing Home Residents with Alzheimer's Disease (METRIcAL)","authors":"Davoodi Natalie, Olson Miranda, Uth Rebecca, Baier Rosa, Rudolph James, Zediker Esme, Shield Renee, Ellen McCreedy","doi":"10.1002/trc2.70006","DOIUrl":"https://doi.org/10.1002/trc2.70006","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> BACKGROUND</h3>\u0000 \u0000 <p>Non-pharmacological interventions (NPIs) are preferred alternatives to using antipsychotic medications to manage disruptive behaviors in nursing home (NH) residents living with dementia. However, the implementation of these interventions is often complex in the NH environment. In this qualitative analysis of data from an embedded pragmatic clinical trial (ePCT) of a personalized music intervention, we describe NH-level implementation barriers and facilitators.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>In a 54-facility trial, we randomized 27 NHs from four US corporations to the personalized music intervention. In this qualitative analysis, we analyzed barriers and facilitators at 9 of the 27 intervention NHs, using (1) routinely collected data collector observations and (2) semi-structured interviews with NH staff. We iteratively developed codes to best describe these data and generated themes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We found five qualitative themes related to the variation of intervention implementation across NHs: (1) turnover and institutional changes interfered with implementation; (2) consistent with pragmatic implementation, delivery strategies varied across NHs; (3) family members influenced residents’ participation; (4) non-clinical program champions needed clinical buy-in, which was challenging and required demonstrating the intervention's clinical benefits; and (5) technological barriers among staff and residents impeded implementation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CONCLUSIONS</h3>\u0000 \u0000 <p>Qualitative results from nine facilities participating in a NH ePCT of personalized music intervention highlight the importance of identifying an intervention's key components to ensure fidelity, while allowing the flexibility necessary for pragmatic implementation. Engaging family caregivers may improve the implementation of NPIs in the NH setting. Results may be helpful to other researchers implementing NPIs to manage neuropsychiatric symptoms for people living with dementia in NHs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>This was a real-world trial of a personalized music for nursing home (NH) residents with dementia.</li>\u0000 \u0000 <li>Pragmatic adaptations to intervention delivery may have compromised fidelity.</li>\u0000 \u0000 <li>Family care","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The HOPE4MCI study: AGB101 treatment slows progression of entorhinal cortex atrophy in APOE ε4 non-carriers with mild cognitive impairment due to Alzheimer's disease","authors":"Arnold Bakker, Nisha Rani, Richard Mohs, Michela Gallagher","doi":"10.1002/trc2.70004","DOIUrl":"https://doi.org/10.1002/trc2.70004","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Hippocampal hyperactivity is a hallmark of prodromal Alzheimer's disease (AD) that predicts progression in patients with amnestic mild cognitive impairment (aMCI). AGB101 is an extended-release formulation of levetiracetam in the dose range previously demonstrated to normalize hippocampal activity and improve cognitive performance in aMCI. The HOPE4MCI study was a 78-week trial to assess the progression of MCI due to AD. As reported in Mohs et al., the decline in the Clinical Dementia Rating Sum of Boxes score (CDR-SB) was reduced by 40% in apolipoprotein E (<i>APOE</i>) ε4 non-carriers over the 78-week duration of the study with a negligible effect in carriers. Here we report an exploratory analysis of the effects of AGB101 on neuroimaging and biomarker measures in the 44 <i>APOE</i> ε4 non-carriers who completed the 78-week protocol.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Structural magnetic resonance imaging scans obtained at baseline and after 78 weeks were analyzed using the Automated Segmentation of Hippocampal Subfields software providing volume measures of key structures of the medial temporal lobe relevant to AD progression. Blood samples collected at 78 weeks in the study were analyzed for plasma biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Treatment with AGB101 significantly reduced atrophy of the left entorhinal cortex (ERC) compared to placebo. This reduction in atrophy was correlated with less decline in the CDR-SB score over 78 weeks and with lower neurofilament light chain (NfL), a marker of neurodegeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>The HOPE4MCI study showed that <i>APOE</i> ε4 non-carriers treated with AGB101 demonstrated a substantially more favorable treatment effect compared to carriers. Here we report that treatment with AGB101 in non-carriers of <i>APOE</i> ε4 significantly reduced atrophy of the left ERC over 78 weeks. That reduction in atrophy was closely coupled with the change in CDR-SB and with plasma NfL indicative of neurodegeneration in the brain. These exploratory analyses are consistent with a reduction in neurodegeneration in <i>APOE</i> ε4 non-carriers treated with AGB101 before a clinical diagnosis of dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>AGB101 slows entorhinal cortex (ERC) atrophy in apolipoprotein E (<i>APOE</i>) ε4 non-carriers wit","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142429849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association of dementia risk symptoms and functional activity in adults with Down syndrome","authors":"Selena E. Washington, Amy E. Bodde, Brian C. Helsel, Rebecca M. Bollinger, Nora Smith, Lauren T. Ptomey, Beau Ances, Susan L. Stark","doi":"10.1002/trc2.70007","DOIUrl":"https://doi.org/10.1002/trc2.70007","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Adults with Down syndrome (DS) have an increased risk of Alzheimer's disease (AD) dementia, often showing neuropathological indicators by age 40. Physical function and activities of daily living (ADLs) are understudied areas of function that may inform dementia risk. We investigated associations among age, physical function (gait/balance, grip strength, and lower extremity strength), ADLs, and dementia risk symptoms in adults with DS. We hypothesized that compromised physical function and lower independence with ADLs would be associated with an informant/caregiver-reported measure of dementia risk symptoms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>A secondary analysis for this cross-sectional study was completed using data from two academic research centers with 43 adults with DS (age 30 ± 12 years). We examined the association of dementia risk symptoms, captured through the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID), with physical function (timed up and go [TUG], sit-to-stand [STS], grip strength) and ADLs (Waisman Activities of Daily Living Scale). A linear regression model for the continuous dementia risk measure in the DSQIID used a log transformation of (1 + log(Y + 1)) to account for a high zero count. Wilcoxon rank-sum tests were used to assess differences in the physical function measures, DSQIID questionnaire, and Waisman ADL by dividing mean age categories.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Higher DSQIID scores were associated with lower independence with ADLs (<i>β</i> = −0.103, <i>p</i> = 0.008), slower gait times (TUG; <i>β</i> = 0.112, <i>p</i> = 0.034), and impaired lower extremity strength (STS; <i>β</i> = 0.112, <i>p</i> = 0.017) and grip strength (<i>β</i> = −0.039, <i>p</i> = 0.034). DSQIID scores differed significantly between the ≥30 and <30 age groups. Participants ≥30 years of age scored 5 points higher on the DSQIID than participants <30, suggesting that age was associated with greater dementia risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Greater dementia risk symptoms were associated with age, lower physical function scores, and independence with ADLs, suggesting that declines in physical function and ADLs may be early indicators of subsequent dementia risk in adults with DS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We explor","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142429232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma amyloid beta biomarkers predict amyloid positivity and longitudinal clinical progression in mild cognitive impairment","authors":"Takuya Ataka, Noriyuki Kimura, Naoki Kaneko, Teruaki Masuda, Yosuke Takeuchi, Kenichi Yabuuchi, Takeshi Mizukami, Tsukasa Takeuchi, Temmei Ito, Hideaki Tasai, Takehiko Miyagawa, Shunya Hanai, Shinichi Iwamoto, Etsuro Matsubara","doi":"10.1002/trc2.70008","DOIUrl":"https://doi.org/10.1002/trc2.70008","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Previous studies have examined the predictive accuracy of plasma amyloid beta (Aβ) biomarkers in clinical cohorts. However, their accuracy for predicting amyloid-positive patients in community-based cohorts is unclear. This study aimed to determine the predictive accuracy of Aβ precursor protein 669-711/Aβ1-42, Aβ1-40/1-42 and their composite biomarkers for brain amyloid deposition or the clinical progression in community-dwelling older adults with mild cognitive impairment (MCI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>This prospective cohort study was conducted from August 2015 to September 2019. Subsequently, the participants underwent follow-up cognitive assessments up to 8 years after the start of the study. Blood samples were collected from older adults aged ≥ 65 years with MCI at baseline. Plasma Aβ biomarkers were analyzed using immunoprecipitation-mass spectrometry. The accuracy of plasma biomarkers for brain amyloid status was evaluated using receiver operating characteristic curve analysis. Relationships between comorbidities and plasma Aβ markers were examined using multiple linear regression analysis. Associations of plasma biomarkers with clinical conversion to Alzheimer's disease (AD) dementia were evaluated using Kaplan‒Meier curves.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The participants included 107 patients (57 [53.3%] females, median age: 76.0 [72.0–80.0] years). Plasma biomarkers correlated with cortical amyloid uptake (<i>ρ</i> = 0.667–0.754). The composite biomarker had the best area under the curve (0.943, 95% confidence interval [CI]: 0.901 to 0.985) for predicting amyloid positivity. Apolipoprotein ε4 status showed significant correlations with increased plasma amyloid biomarker levels. Participants with high composite biomarker levels at baseline had a greater risk of conversion to AD dementia (hazard ratio 10.74, 95% CI: 3.51 to 32.84, <i>P</i> < 0.001). The higher composite biomarker was associated with a faster rate of cognitive decline (<i>ρ</i> = −0.575, <i>P</i> < 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Plasma Aβ composite biomarker may serve as a surrogate measure for amyloid deposition and a predictor of disease progression in a community-based cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Plasma amyloid beta (Aβ) biomarkers correlated with 11C-Pittsburgh","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142429835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linking cognitive and behavioral reserve: Evidence from the CAN-PROTECT study","authors":"Dylan X. Guan, Moyra E. Mortby, G Bruce Pike, Clive Ballard, Byron Creese, Anne Corbett, Ellie Pickering, Adam Hampshire, Pamela Roach, Eric E. Smith, Zahinoor Ismail","doi":"10.1002/trc2.12497","DOIUrl":"10.1002/trc2.12497","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Changes to the brain due to Alzheimer's disease and other age-related neuropathologies may present with cognitive and behavioral symptoms, even during preclinical and prodromal stages. While cognitive reserve is known to mitigate cognitive decline in the preclinical stages of Alzheimer's disease, links between cognitive reserve and behavioral symptoms remain unclear. This study investigates the relationship between cognitive reserve and mild behavioral impairment (MBI), a neurodegenerative behavioral prodrome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We analyzed cross-sectional data from 1204 participants in the Canadian Platform for Research Online to Investigate Health, Quality of Life, Cognition, Behavior, Function, and Caregiving in Aging (CAN-PROTECT) study. A cognitive reserve score (CRS) was generated based on education, occupation, and personal cognitive reserve proxies. MBI presence (MBI+) and MBI global and domain symptom severity were evaluated using the self-reported MBI Checklist. Initial analyses examined the convergent validity of the CRS through associations with objective neuropsychological test performance and self-reported cognitive symptoms (Everyday Cognition [ECog-II] scale). Models were also fitted to assess MBI status and severity as functions of the CRS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Higher CRS was associated with better neuropsychological test scores, lower odds of subjective cognitive decline (OR = 0.86, 95% CI: [0.76, 0.98], <i>p</i> = .03), and lower ECog-II total score. Likewise, higher CRS was associated with lower odds of MBI+ (OR = 0.81, 95% CI: [0.71, 0.93], <i>p</i> = .003), and lower MBI symptom severity globally, and in impulse dyscontrol and social inappropriateness domains.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>We provide preliminary evidence that engagement in activities known to preserve cognitive function in aging and disease may also preserve behavioral function. Future research should disentangle possible pathways through which cognitive reserve may preserve both cognition and behavior, explore common etiologies for these symptoms, and observe outcomes longitudinally to better understand these relationships.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Education, occupation, and personal activities are cognitive reserve proxies.</li>\u0000 \u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11450604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing social connection for long-term care home residents: A scoping review of measure content","authors":"Madalena P. Liougas, Andrew Sommerlad, Hannah M. O'Rourke, Hannah Chapman, Neha Dewan, Katherine S. McGilton, Jennifer Bethell","doi":"10.1002/trc2.12488","DOIUrl":"10.1002/trc2.12488","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Social connection comprises distinct but interrelated aspects describing how individuals connect to each other. Various measures have assessed multiple aspects of social connection in long-term care (LTC) home populations, but they use inconsistent terminology, making it unclear what aspects are measured. This scoping review describes how social connection is assessed by measures that have been used in LTC home residents.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>This review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Two systematic literature searches combining search terms for social connection AND LTC home residents AND measurement properties were conducted in eight electronic databases from inception to April 2022. Included studies reported the development or psychometric testing of measures which assessed social connection in LTC home residents. A content analysis with a deductive-inductive approach was used to analyze the measures’ content and an adapted Framework Method was used for data management. Findings report each measure's items and the assessed aspects of social connection. Dementia and non-dementia-specific measures had content, administration, and scoring compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>From 8753 records, 58 studies reporting on 14 dementia-specific and 28 non-dementia-specific social connection measures were identified, including complete measures, subscales, and single items. These measures assessed social network (52.4%), social isolation (11.9%), social interaction (47.6%), social engagement (31.0%), social support (33.3%), social connectedness (21.4%), and loneliness (9.5%). A total of 27 (64.3%) of the measures included more than one aspect of social connection. Dementia-specific measures most often assessed social interaction whereas non-dementia-specific measures most often assessed social network, social interaction, and social support. Dementia-specific measures typically relied on a proxy response, whereas non-dementia-specific measures more often used self-report.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Existing social connection measures in LTC home settings operationalize seven aspects of social connection and differ according to the target population (dementia or non-dementia-specific). These findings will inform future measure selection and development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perspectives on the clinical use of anti-amyloid therapy for the treatment of Alzheimer's disease: Insights from the fields of cancer, rheumatology, and neurology","authors":"Gregory A. Jicha,&nbsp;Erin L. Abner,&nbsp;Elif P. Coskun,&nbsp;Mark J. Huffmyer,&nbsp;Thomas C. Tucker,&nbsp;Peter T. Nelson","doi":"10.1002/trc2.12500","DOIUrl":"https://doi.org/10.1002/trc2.12500","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The advent of disease-modifying therapies for Alzheimer's disease (AD) has raised many questions and debates in the field as to the clinical benefits, risks, and costs of such therapies. The controversies have resulted in the perception that many clinicians are apprehensive about prescribing these medications to their patient populations. There also remains widespread uncertainty as to the economic impact, cost benefit ratio, and safety oversight for use of these medications in standard clinical care settings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To contextualize such issues, the present study compared anti-amyloid biologic therapy (lecanemab) to four commonly used biologic agents in other fields, including trastuzumab for breast cancer, bevacizumab for lung cancer, etanercept for rheumatoid arthritis, and ocrelizumab for multiple sclerosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The data presented demonstrate comparable costs, clinical benefits, and risks for these biologic agents in their disparate disease states.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>These results provide context for the costs, clinical benefits, and safety regarding the mainstream use of anti-amyloid biologic agents for the prevention of cognitive loss. While the era of disease-modifying therapies for AD is now in its infancy, there is an expectation that these discoveries will be followed by improved therapies and combination treatments leading to greater efficacy in ameliorating the clinical trajectory of AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Anti-amyloid therapy costs are comparable to other commonly used biologics.</li>\u0000 \u0000 <li>Anti-amyloid therapy efficacy is comparable to other commonly used biologics.</li>\u0000 \u0000 <li>Anti-amyloid therapy safety is compatible with other commonly used biologics.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.12500","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-epileptic drug use and subsequent degenerative dementia occurrence","authors":"Naoki Ikegaya,&nbsp;Honoka Nakamura,&nbsp;Yutaro Takayama,&nbsp;Yohei Miyake,&nbsp;Takahiro Hayashi,&nbsp;Masaki Sonoda,&nbsp;Mitsuru Sato,&nbsp;Kensuke Tateishi,&nbsp;Jun Suenaga,&nbsp;Masao Takaishi,&nbsp;Yu Kitazawa,&nbsp;Misako Kunii,&nbsp;Hiroki Abe,&nbsp;Tomoyuki Miyazaki,&nbsp;Tetsuaki Arai,&nbsp;Manabu Iwasaki,&nbsp;Takayuki Abe,&nbsp;Tetsuya Yamamoto","doi":"10.1002/trc2.70001","DOIUrl":"https://doi.org/10.1002/trc2.70001","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The use of anti-epileptic drugs (AEDs) in degenerative dementia (DD) remains uncertain. We aimed to evaluate the association of early AED administration with subsequent DD occurrence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using a large nationwide database, we enrolled patients newly diagnosed with epilepsy from 2014 to 2019 (<i>n</i> = 104,225), and using propensity score matching, we divided them into treatment (those prescribed AEDs in 2014) and control groups. The primary outcome was subsequent DD occurrence in 2019.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Overall, 4489 pairs of patients (2156 women) were matched. The odds ratio (treatment/control) for DD occurrence was 0.533 (95% confidence interval: 0.459–0.617). The DD proportions significantly differed between the treatment (340/4489 = 0.076) and control (577/4489 = 0.129) groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Among patients newly diagnosed with epilepsy, compared to non-use, early AED use was associated with a lower occurrence of subsequent DD. Further investigations into and optimization of early intervention for epilepsy in DD are warranted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Anti-epileptic drug (AED) use before epilepsy diagnosis was linked with a lower subsequent degenerative dementia (DD) occurrence.</li>\u0000 \u0000 <li>Identifying the epileptic phenotype was crucial for justifying early AED use in DD.</li>\u0000 \u0000 <li>AED use with an epilepsy diagnosis did not pose an additional risk of DD.</li>\u0000 \u0000 <li>The potential contribution of combination drug therapy to the strategy was noted.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}