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

{"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}

{"title":"Genetically proxied IL-6 signaling and risk of Alzheimer's disease and lobar intracerebral hemorrhage: A drug target Mendelian randomization study","authors":"Evangelos Pavlos Myserlis,&nbsp;Anushree Ray,&nbsp;Christopher D. Anderson,&nbsp;Marios K. Georgakis","doi":"10.1002/trc2.70000","DOIUrl":"https://doi.org/10.1002/trc2.70000","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Evidence suggests that higher C-reactive protein (CRP) is associated with lower risk of Alzheimer's disease (AD) and lobar intracerebral hemorrhage (ICH). Whether interleukin (IL)-6 signaling, an active pharmacological target upstream of CRP, is associated with these amyloid-related pathologies remains unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We used 26 CRP-lowering variants near the IL-6 receptor gene to perform Mendelian randomization analyses for AD (111,326 cases, 677,663 controls) and ICH (1545 cases, 1481 controls). We explored the effect of genetically proxied IL-6 signaling on serum, cerebrospinal fluid (CSF), and brain proteome (971 individuals).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Genetically upregulated IL-6 receptor-mediated signaling was associated with lower risk of AD (OR per increment in serum logCRP levels: 0.87, 95% CI: 0.79–0.95) and lobar ICH (OR: 0.27, 95% CI: 0.09–0.89). We also found associations with 312, 77, and 79 brain, CSF, and plasma proteins, respectively, some of which were previously implicated in amyloid-clearing mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Genetic data support that CRP-lowering through variation in the gene encoding IL-6 receptor may be associated with amyloid-related outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Genetic variants proxying IL-6 inhibition are associated with AD and lobar ICH risk.</li>\u0000 \u0000 <li>The variants are also associated with amyloid clearing-related proteomic changes.</li>\u0000 \u0000 <li>Whether pharmacologic IL-6 inhibition is linked to AD or lobar ICH merits further study.</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":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142089873","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":"Practical social media recommendations for dementia prevention researchers","authors":"Viorica Hrincu,&nbsp;Katherine T. Roy,&nbsp;Julie M. Robillard","doi":"10.1002/trc2.12496","DOIUrl":"https://doi.org/10.1002/trc2.12496","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Practical social media recommendations are needed to facilitate greater engagement in dementia prevention research. Alongside relevant experts, our aim was to develop a set of consensus recommendations that reflect the values and priorities of prospective participants to guide social media use.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We conducted a three-round, modified Delphi consisting of three online surveys and three conferences calls. The diverse, international Delphi panel comprised 16 experts with lived (<i>n</i> = 10) and professional (<i>n</i> = 6) experiences. Consensus was defined a priori as ≥ 70% agreement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Twenty-six items achieved consensus. Two items reached consensus in round 1: ethical considerations of closed social media groups (88%) and of social media users sharing prevention content with connections who are not on social media (79%). Nine items reached consensus in round 2, related to misinformation (79%), stigma (93%), and other key aspects of social media communication. After revisions, 15 items reached consensus in the final round. These items included: identifying when researchers ought to engage, managing closed social media groups, rankings of short form content, prioritizing lay summaries and multimedia resources, and rankings of preferred language. One item about the language of prevention for audiences living with dementia did not reach consensus. Final consensus items formed the new set of recommendations, which we organized into seven social media use cases. These use cases include setting up a social media page or community, handling online misinformation, actively challenging stigma, handling difficult online interactions, introducing new research to the public, help with study recruitment, and the language of prevention when writing posts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These consensus recommendations can help dementia prevention researchers harness social media use for the purposes of public engagement and uphold the norms and values specific to the dementia research and broader communities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We created social media recommendations with research and community experts.</li>\u0000 \u0000 <li>Recommendations cover key ethical considerations for dementia pr","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.12496","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980434","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":"APOLLOE4 Phase 3 study of oral ALZ-801/valiltramiprosate in APOE ε4/ε4 homozygotes with early Alzheimer's disease: Trial design and baseline characteristics","authors":"Susan Abushakra,&nbsp;Anton P. Porsteinsson,&nbsp;Marwan Sabbagh,&nbsp;David Watson,&nbsp;Aidan Power,&nbsp;Earvin Liang,&nbsp;Emer MacSweeney,&nbsp;Merce Boada,&nbsp;Susan Flint,&nbsp;Rosalind McLaine,&nbsp;J. Patrick Kesslak,&nbsp;John A. Hey,&nbsp;Martin Tolar","doi":"10.1002/trc2.12498","DOIUrl":"https://doi.org/10.1002/trc2.12498","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The approved amyloid antibodies for early Alzheimer's disease (AD) carry a boxed warning about the risk of amyloid-related imaging abnormalities (ARIAs) that are highest in apolipoprotein E (<i>APOE</i>) ε4/ε4 homozygotes. ALZ-801/valiltramiprosate, an oral brain-penetrant amyloid beta oligomer inhibitor is being evaluated in <i>APOE</i> ε4/ε4 homozygotes with early AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>This Phase 3 randomized, double-blind, placebo-controlled, 78-week study of ALZ-801 administered as 265 mg twice per day tablets, enrolled 50- to 80-year-old homozygotes with Mini-Mental State Examination (MMSE) ≥ 22 and Clinical Dementia Rating–Global Score 0.5 or 1.0. The study is powered to detect a 2.0 to 2.5 drug–placebo difference on the Alzheimer's Disease Assessment Scale 13-item Cognitive subscale primary outcome with 150 subjects/arm. The key secondary outcomes are Clinical Dementia Rating–Sum of Boxes and Instrumental Activities of Daily Living; volumetric magnetic resonance imaging and fluid biomarkers are additional outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The APOLLOE4 Phase 3 trial enrolled 325 subjects with a mean age of 69 years, 51% female, MMSE 25.6, and 65% mild cognitive impairment. Topline results are expected in 2024.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>APOLLOE4 is the first disease-modification AD trial focused on <i>APOE</i> ε4/ε4 homozygotes. Oral ALZ-801 has the potential to be the first effective and safe anti-amyloid treatment for the high-risk <i>APOE</i> ε4/ε4 population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The APOLLOE4 Phase 3, placebo-controlled, 78-week study is designed to evaluate the efficacy and safety of ALZ-801 265 mg twice per day in early Alzheimer's disease (AD) subjects with the apolipoprotein E (<i>APOE</i>) ε4/ε4 genotype.</li>\u0000 \u0000 <li>The enrolled early AD population (<i>N</i> = 325) has 51% females, a mean age = 69 years, and a mean Mini-Mental State Examination = 25.6, with the majority being mild cognitive impairment subjects, a similar disease stage to the lecanemab Phase 3 AD trial (Clarity AD).</li>\u0000 \u0000 <li>The primary outcome is the cognitive Alzheimer's Disease Assessment Scale 13-item Cognitive subscale, with two functional measures as key secondary outc","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.12498","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980440","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":"Rural-Urban mild cognitive impairment comparison in West Michigan through EHR","authors":"Xiaodan Zhang,&nbsp;Martin Witteveen-Lane,&nbsp;Christine Skovira,&nbsp;Aakash A. Dave,&nbsp;Jeffrey S. Jones,&nbsp;Erin R. McNeely,&nbsp;Michael R. Lawrence,&nbsp;David G. Morgan,&nbsp;Dave Chesla,&nbsp;Bin Chen","doi":"10.1002/trc2.12495","DOIUrl":"10.1002/trc2.12495","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Mild cognitive impairment (MCI) is a significant public health concern and a potential precursor to Alzheimer's disease (AD). This study leverages electronic health record (EHR) data to explore rural-urban differences in MCI incidence, risk factors, and healthcare navigation in West Michigan.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Analysis was conducted on 1,528,464 patients from Corewell Health West, using face-to-face encounters between 1/1/2015 and 7/31/2022. MCI cases were identified using International Classification of Diseases (ICD) codes, focusing on patients aged 45+ without prior MCI, dementia, or AD diagnoses. Incidence rates, cumulative incidences, primary care physicians (PCPs), and neuropsychology referral outcomes were examined across rural and urban areas. Risk factors were evaluated through univariate and multivariate Cox regression analyses. The geographic distribution of patient counts, hospital locations, and neurology department referrals were examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Among 423,592 patients, a higher MCI incidence rate was observed in urban settings compared to rural settings (3.83 vs. 3.22 per 1,000 person-years). However, sensitivity analysis revealed higher incidence rates in rural areas when including patients who progressed directly to dementia. Urban patients demonstrated higher rates of referrals to and completion of neurological services. While the risk factors for MCI were largely similar across urban and rural populations, urban-specific factors for incident MCI are hearing loss, inflammatory bowel disease, obstructive sleep apnea, insomnia, being African American, and being underweight. Common risk factors include diabetes, intracranial injury, cerebrovascular disease, coronary artery disease, stroke, Parkinson's disease, epilepsy, chronic obstructive pulmonary disease, depression, and increased age. Lower risk was associated with being female, having a higher body mass index, and having a higher diastolic blood pressure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This study highlights rural-urban differences in MCI incidence and access to care, suggesting potential underdiagnosis in rural areas likely due to reduced access to specialists. Future research should explore socioeconomic, environmental, and lifestyle determinants of MCI to refine prevention and management strategies across geographic settings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11317927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972267","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":"Biological effects of sodium phenylbutyrate and taurursodiol in Alzheimer's disease","authors":"Steven E. Arnold,&nbsp;Suzanne Hendrix,&nbsp;Jessie Nicodemus-Johnson,&nbsp;Newman Knowlton,&nbsp;Victoria J. Williams,&nbsp;Jeffrey M. Burns,&nbsp;Monica Crane,&nbsp;Alison J. McManus,&nbsp;Sanjeev N. Vaishnavi,&nbsp;Zoe Arvanitakis,&nbsp;Judith Neugroschl,&nbsp;Karen Bell,&nbsp;Bianca A. Trombetta,&nbsp;Becky C. Carlyle,&nbsp;Pia Kivisäkk,&nbsp;Hiroko H. Dodge,&nbsp;Rudolph E. Tanzi,&nbsp;Patrick D. Yeramian,&nbsp;Kent Leslie","doi":"10.1002/trc2.12487","DOIUrl":"10.1002/trc2.12487","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Sodium phenylbutyrate and taurursodiol (PB and TURSO) is hypothesized to mitigate endoplasmic reticulum stress and mitochondrial dysfunction, two of many mechanisms implicated in Alzheimer's disease (AD) pathophysiology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>The first-in-indication phase 2a PEGASUS trial was designed to gain insight into PB and TURSO effects on mechanistic targets of engagement and disease biology in AD. The primary clinical efficacy outcome was a global statistical test combining three endpoints relevant to disease trajectory (cognition [Mild/Moderate Alzheimer's Disease Composite Score], function [Functional Activities Questionnaire], and total hippocampal volume on magnetic resonance imaging). Secondary clinical outcomes included various cognitive, functional, and neuropsychiatric assessments. Cerebrospinal fluid (CSF) biomarkers spanning multiple pathophysiological pathways in AD were evaluated in participants with both baseline and Week 24 samples (exploratory outcome).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>PEGASUS enrolled 95 participants (intent-to-treat [ITT] cohort); cognitive assessments indicated significantly greater baseline cognitive impairment in the PB and TURSO (<i>n</i> = 51) versus placebo (<i>n</i> = 44) group. Clinical efficacy outcomes did not significantly differ between treatment groups in the ITT cohort. CSF interleukin-15 increased from baseline to Week 24 within the placebo group (<i>n</i> = 34). In the PB and TURSO group (<i>n</i> = 33), reductions were observed in core AD biomarkers phosphorylated tau-181 (p-tau181) and total tau; synaptic and neuronal degeneration biomarkers neurogranin and fatty acid binding protein-3 (FABP3); and gliosis biomarker chitinase 3-like protein 1 (YKL-40), while the oxidative stress marker 8-hydroxy-2-deoxyguanosine (8-OHdG) increased. Between-group differences were observed for the Aβ42/40 ratio, p-tau181, total tau, neurogranin, FABP3, YKL-40, interleukin-15, and 8-OHdG. Additional neurodegeneration, inflammation, and metabolic biomarkers showed no differences between groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>While between-group differences in clinical outcomes were not observed, most likely due to the small sample size and relatively short treatment duration, exploratory biomarker analyses suggested that PB and TURSO engages multiple pathophysiologic pathways in AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918094","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":"Pooling Alzheimer's disease clinical trial data to develop personalized medicine approaches is easier said than done: A proof-of-principle study and call to action","authors":"Mark A. Dubbelman,&nbsp;Eleonora M. Vromen,&nbsp;Betty M. Tijms,&nbsp;Johannes Berkhof,&nbsp;Lois Ottenhoff,&nbsp;Everard G. B. Vijverberg,&nbsp;Niels D. Prins,&nbsp;Wiesje M. van der Flier,&nbsp;Sietske A. M. Sikkes","doi":"10.1002/trc2.12485","DOIUrl":"10.1002/trc2.12485","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>With the advent of the first generation of disease-modifying treatments for Alzheimer's disease, it is clearer now more than ever that the field needs to move toward personalized medicine. Pooling data from past trials may help identify subgroups most likely to benefit from specific treatments and thus inform future trial design. In this perspective, we report on our effort to pool data from past Alzheimer's disease trials to identify patients most likely to respond to different treatments. We delineate challenges and hurdles, from our proof-of-principle study, for which we requested access to trial datasets from various pharmaceutical companies and encountered obstacles in the process of arranging data-sharing agreements through legal departments. Six phase I–III trials from three sponsors provided access to their data (total <i>n</i> = 3170), which included demographic information, vital signs, primary and secondary endpoints, and in a small subset, cerebrospinal fluid amyloid (<i>n</i> = 165, 5.2%) and tau (<i>n</i> = 212, 6.7%). Data could be analyzed only within specific data access platforms, limiting potential harmonization with data provided through other platforms. Limited overlap in terms of outcome measures, clinical and biological information hindered analyses. Thus, while it is a commendable advancement that (some) trials now allow researchers to study their data, we conclude that gaining access to past trial datasets is complicated, frustrating the field's communal effort to find the best treatments for the right individuals. We provide a plea to promote harmonization and open access to data, by urging trial sponsors and the academic research community alike to remove barriers to data access and improve collaboration through practicing open science and harmonizing outcome measures, to allow investigators to learn all there is to learn from past failures and successes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> HIGHLIGHTS</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Pooling data from past Alzheimer's disease clinical trials may help identify subgroups most likely to benefit from specific treatments and may help inform future trial design.</li>\u0000 \u0000 <li>Accessing past trial datasets is complicated, frustrating the field's communal effort to find the best treatments for the right individuals.</li>\u0000 \u0000 <li>We urge trial sponsors and the academic research community to remove data access barriers and improve collaboration through practicing open science and harmonizing outcome measures.</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":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903598","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: Systematic review using COnsensus-based Standards for the selection of health Measurement INstruments guidelines","authors":"Neha Dewan,&nbsp;Andrew Sommerlad,&nbsp;Hannah Chapman,&nbsp;Sube Banerjee,&nbsp;Kirsten Corazzini,&nbsp;David Edvardsson,&nbsp;Madalena P. Liougas,&nbsp;Gill Livingston,&nbsp;Katherine S. McGilton,&nbsp;Hannah M. O'Rourke,&nbsp;Jennifer Bethell","doi":"10.1002/trc2.12492","DOIUrl":"10.1002/trc2.12492","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Social connection is important for long-term care (LTC) residents' quality of life and care. However, there is a lack of consensus on how to measure it and this limits ability to find what improves and impairs social connection in LTC homes. We therefore aimed to systematically review and evaluate the measurement properties of existing measures of social connection for LTC residents, to identify which, if any, measures can be recommended. We searched eight electronic databases from inception to April 2022 for studies which reported on psychometric properties of a measure of any aspect(s) of social connection (including social networks, interaction, engagement, support, isolation, connectedness, and loneliness) for LTC residents. We used COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines to evaluate the measurement properties reported for each identified measure and make recommendations. We identified 62 studies reporting on 38 measures; 21 measured quality of life, well-being or life satisfaction and included a social connection subscale or standalone items and 17 measures specifically targeted social connection. We found there was little high-quality evidence on psychometric properties such as sufficient content validity (<i>n</i> = 0), structural validity (<i>n</i> = 3), internal consistency (<i>n</i> = 3), reliability (<i>n</i> = 1), measurement error (<i>n</i> = 0), construct validity (<i>n</i> = 4), criterion validity (<i>n</i> = 0) and responsiveness (<i>n</i> = 0). No measures demonstrated satisfactory psychometric properties on all these aspects, so none could be recommended for use. Thirty-four measures have the potential to be recommended but require further research to assess their quality and the remaining four are not recommended for use. Our review therefore found that no existing measures have sufficient evidence to be recommended for assessment of social connection in residents of LTC homes. Further validation and reliability studies of existing instruments or the development of new measures are needed to enable accurate measurement of social connection in LTC residents for future observational and interventional studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Social connection is fundamental to person-centered care in long-term care homes.</li>\u0000 \u0000 <li>There is insufficient evidence for the reliability and validity of existing measures.</li>\u0000 \u0000 <li>No current measures can be recommended for use based on existing evidence.</li>\u0000 \u0000 <li>A reliable and valid measure of social connection is needed for fu","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894860","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":"Comparing research attitudes in Down syndrome and non-Down syndrome research decision-makers","authors":"Thuy V. Lu,&nbsp;Paola Campos,&nbsp;Sean Leader,&nbsp;Xavier Lee,&nbsp;Helena Xu,&nbsp;Eric Doran,&nbsp;Joshua D Grill,&nbsp;Ira T. Lott","doi":"10.1002/trc2.12478","DOIUrl":"10.1002/trc2.12478","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Recruitment challenges in people with and without Down syndrome (DS) can delay research progress and risk sample bias. This study identified and quantified differences in research attitudes across populations of research enrollment decision-makers for individuals with and without DS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We performed analyses using data from two registries: the University of California, Irvine Consent-to-Contact (C2C) Registry and DS-Connect. The former represented a sample of non-DS decision-makers (<i>N</i> = 4818), while for the latter, we excluded individuals with DS, leaving a population of DS family decision-makers (<i>N</i> = 976). We assessed scores on the Research Attitudes Questionnaire (RAQ) between DS and non-DS decision-makers. We compared total RAQ scores using linear regression and assessed item-level RAQ differences using proportional odds regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Mean total RAQ scores were not statistically different between decision-makers in the two registries, after adjusting for age, sex, race and ethnicity, education, and the coronavirus disease 2019 (COVID-19) time frame (Est. Diff = 0.11, 95% confidence interval [CI]: -0.22, 0.43; <i>p</i> = 0.531). However, in a pre-specified analysis, we did find evidence of differential attitudes on item-level RAQ scores. Specifically, decision-makers for participants with DS had increased odds of a more favorable response to the question of responsibility to help others (DS vs. non-DS: odds ratio [OR] = 1.26, 95% CI: 1.08, 1.48) and decreased odds of a more favorable response to the question regarding the belief that medical research would find cures for major diseases during their lifetime (DS vs. non-DS: OR = 0.77, 95% CI: 0.66, 0.90).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Our findings provide insights for researchers to develop strategies for recruiting individuals with and without DS into clinical research. The observed item-level differences warrant further investigation to instruct precise recruitment strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Research attitudes between decision-makers for individuals with Down syndrome (DS) and decision-makers without DS were observed to be similar on average.</li>\u0000 \u0000 <li>Item-level differences in research att","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861639","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}