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

{"title":"Perspective: Minimally clinically important “symptomatic” benefit associated with disease modification resulting from anti-amyloid immunotherapy","authors":"John Alam,&nbsp;Marwan N. Sabbagh","doi":"10.1002/trc2.70035","DOIUrl":"10.1002/trc2.70035","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Despite some skepticism regarding the amyloid hypothesis, there is growing evidence that clearing amyloid by targeting specific species of amyloid (plaque, oligomers, fibrils, and protofibrils) for removal has therapeutic benefits. Specifically, there is growing evidence that, in mild cognitive impairment and mild dementia due to Alzheimer's disease (AD), robust and aggressive removal of amyloid can slow cognitive decline as measured by global instruments, composite measures, and cognitive testing. Furthermore, clinical efficacy signals coupled with clear biomarker changes provide the first evidence of disease modification. This effect seems to be in addition to symptomatic treatments and opens speculation that the effect of anti-amyloid monoclonal antibodies might be clinically meaningful through symptomatic amelioration that is a result of disease modification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Clearance of brain amyloid plaques may lead to a clinical benefit in patients with early AD.</li>\u0000 \u0000 <li>Aggregated Aβ may play a role in both disease expression and progression.</li>\u0000 \u0000 <li>Anti-amyloid monoclonal antibodies might be clinically meaningful through symptomatic amelioration resulting from disease modification.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11746071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015974","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":"Developing, implementing, and evaluating the first national Memory and Cognition Clinic Guidelines in Australia","authors":"Inga Mehrani,&nbsp;Matthew Paradise,&nbsp;Lee-Fay Low,&nbsp;Sue Kurrle,&nbsp;Valerie Arsenova,&nbsp;Gemma Jahn,&nbsp;Katrina Fyfe,&nbsp;Johannes C. Michaelian,&nbsp;Katharine Salmon,&nbsp;Jane Alty,&nbsp;Sharon L. Naismith,&nbsp;Perminder S. Sachdev","doi":"10.1002/trc2.70031","DOIUrl":"10.1002/trc2.70031","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>A lack of national consensus on the roles and responsibilities of Australian memory and cognition clinics contributes to the large variability seen across services. The introduction of guidelines and a quality assessment framework could facilitate greater harmonization and quality improvements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We used a modified Delphi process to develop the guidelines. Pilot clinics completed a self-assessment, case-note audit, and review meeting to evaluate their service against the guidelines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The final guidelines included 160 standards on 14 different topics. Standards around maximum waiting times for an assessment and minimum post-diagnostic care responsibilities were particularly controversial. Seven clinics participated in the pilot. On average, clinics achieved 56% of standards (range of 18% to 87%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The Memory and Cognition Clinic Guidelines form the first step toward greater harmonization and quality improvements. Key learnings from the clinics’ feedback included reducing the number of secondary standards and streamlining data collection with the national dementia clinical quality registry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We developed and implemented the first national consensus-based best-practice guidelines for memory and cognition clinics in Australia.</li>\u0000 \u0000 <li>The guidelines are based on consultation with 125 Australian health professionals and 89 Australians living with dementia and care partners.</li>\u0000 \u0000 <li>First-time national agreement on standards around maximum waiting times for an assessment and minimum post-diagnostic care requirements is presented in the guidelines.</li>\u0000 \u0000 <li>The guidelines were implemented in seven memory and cognition clinics from five different states.</li>\u0000 \u0000 <li>Clinicians' feedback included: reducing the number of secondary standards to increase conciseness and practicability should be considered for future iterations.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016012","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":"Comparison of sample characteristics of Wisconsin Alzheimer's Disease Research Center participants with the Wisconsin state population—An evaluation of the recruitment effort","authors":"Yue Ma,&nbsp;Maria C. Mora Pinzon,&nbsp;William R. Buckingham,&nbsp;Andrew J. Bersch,&nbsp;W. Ryan Powell,&nbsp;Tamara J. LeCaire,&nbsp;Gilda E. Ennis,&nbsp;Yuetiva Deming,&nbsp;Erin M. Jonaitis,&nbsp;Nathaniel A. Chin,&nbsp;Lindsay R. Clark,&nbsp;Dorothy F. Edwards,&nbsp;Art Walaszek,&nbsp;Ozioma C. Okonkwo,&nbsp;Megan Zuelsdorff,&nbsp;Richard J. Chappell,&nbsp;Sterling C. Johnson,&nbsp;Sanjay Asthana,&nbsp;Carey E. Gleason,&nbsp;Amy J. Kind,&nbsp;Barbara B. Bendlin,&nbsp;Cynthia M. Carlsson","doi":"10.1002/trc2.70036","DOIUrl":"10.1002/trc2.70036","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; INTRODUCTION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Understanding how a research sample compares to the population from which it is drawn can help inform future recruitment planning. We compared the Wisconsin Alzheimer's Disease Research Center (WADRC) participant sample to the Wisconsin state population (WI-pop) on key demographic, social exposome, and vascular risk measures.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; METHODS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The WADRC sample included 930 participants. Population statistics were estimated using several national and state data sources. We compared WADRC to WI-pop for two age groups, 45–64 years and ≥65 years, separately.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; RESULTS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Compared to WI-pop, WADRC participants were older and included more women, more Black and American Indian individuals, and fewer Hispanic and Asian individuals. WADRC participants had higher levels of educational attainment, consisted of smaller proportions living in rural areas and disadvantaged neighborhoods, and showed lower vascular risks. Greater differences between WADRC and WI-pop were found for most metrics in the ≥65 group compared to the 45–64 group.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; DISCUSSION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The findings revealed opportunities to increase enrollment from the Hispanic/Latino and Asian American populations, to include participants from a broader range of educational backgrounds, and to enroll more residents from rural areas and disadvantaged neighborhoods, which may lead to a broader distribution of cardiovascular risk factors. Expanding sociodemographic and health profiles represented in the participant candidate pool for study selection and including those who are underrepresented in research may potentially reduce selection bias but not eliminate it. Statistical approaches can be applied to address bias and generalize findings from a study sample to its target population by adjusting for their differences in the joint distribution of covariates. Although research centers have different regional populations and specific recruitment focuses for scientific reasons, evaluating their participant characteristics may help plan engagement efforts to improve the inclusion of underrepresented groups and collaboratively support generalizable research nationwide.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Highlights&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;We compared the characteristics of Wisconsin Alzheimer's Disease Research Center (WADRC) particip","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015536","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":"Statin use and dementia risk: A systematic review and updated meta-analysis","authors":"Fernando Luiz Westphal Filho,&nbsp;Paulo Roberto Moss Lopes,&nbsp;Artur Menegaz de Almeida,&nbsp;Vitor Kendi Tsuchiya Sano,&nbsp;Fernanda Moraes Tamashiro,&nbsp;Ocílio Ribeiro Gonçalves,&nbsp;Francisco Cezar Aquino de Moraes,&nbsp;Michele Kreuz,&nbsp;Francinny Alves Kelly,&nbsp;Pablo Vinícius Silveira Feitoza","doi":"10.1002/trc2.70039","DOIUrl":"10.1002/trc2.70039","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Dementia affects 55 million people globally, with the number projected to triple by 2050. Statins, widely prescribed for cardiovascular benefits, may also have neuroprotective effects, although studies on their impact on dementia risk have shown contradictory results. In this systematic review and meta-analysis, we searched PubMed, Embase, and Cochrane following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We assessed the risk of dementia, Alzheimer's disease (AD), and vascular dementia (VaD), with subgroup analyses by gender, statin type, and diabetes status. Fifty-five observational studies including over 7 million patients were analyzed. Statin use significantly reduced the risk of dementia compared to nonusers (hazard ratio [HR] 0.86; 95% confidence interval [CI]: 0.82 to 0.91; <i>p</i> &lt; 0.001). It was also associated with reduced risks of AD (HR 0.82; 95% CI: 0.74 to 0.90; <i>p</i> &lt; 0.001) and VaD (HR 0.89; 95% CI: 0.77 to 1.02; <i>p</i> = 0.093). Subgroup analyses revealed significant dementia risk reductions among patients with type 2 diabetes mellitus (HR 0.87; 95% CI: 0.85 to 0.89; <i>p</i> &lt; 0.001), those with exposure to statins for more than 3 years (HR 0.37; 95% CI: 0.30 to 0.46; <i>p</i> &lt; 0.001), and populations from Asia, where the greatest protective effect was observed (HR 0.84; 95% CI: 0.80 to 0.88). Additionally, rosuvastatin demonstrated the most pronounced protective effect for all-cause dementia among specific statins (HR 0.72; 95% CI: 0.60 to 0.88). Our findings underscore the neuroprotective potential of statins in dementia prevention. Despite the inherent limitations of observational studies, the large dataset and detailed subgroup analyses enhance the reliability of our results. Future randomized clinical trials are necessary to confirm these findings and enlighten clinical guidelines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Largest meta-analysis to date on statins and dementia risk, including 55 studies and more than 7 million patients.</li>\u0000 \u0000 <li>Statin use linked to lower risks of all-dementia, AD, and VaD.</li>\u0000 \u0000 <li>Numerous significant subgroup results highlight statins' diverse neuroprotective effects.</li>\u0000 \u0000 <li>Findings support statins as a public health tool, especially in low-income countries.</li>\u0000 \u0000 <li>Future research should explore the impact of statins across diverse patient populations.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016006","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":"LD-informed deep learning for Alzheimer's gene loci detection using WGS data","authors":"Taeho Jo,&nbsp;Paula Bice,&nbsp;Kwangsik Nho,&nbsp;Andrew J. Saykin,&nbsp;Alzheimer's Disease Sequencing Project","doi":"10.1002/trc2.70041","DOIUrl":"10.1002/trc2.70041","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; INTRODUCTION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The exponential growth of genomic datasets necessitates advanced analytical tools to effectively identify genetic loci from large-scale high throughput sequencing data. This study presents Deep-Block, a multi-stage deep learning framework that incorporates biological knowledge into its AI architecture to identify genetic regions as significantly associated with Alzheimer's disease (AD). The framework employs a three-stage approach: (1) genome segmentation based on linkage disequilibrium (LD) patterns, (2) selection of relevant LD blocks using sparse attention mechanisms, and (3) application of TabNet and Random Forest algorithms to quantify single nucleotide polymorphism (SNP) feature importance, thereby identifying genetic factors contributing to AD risk.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; METHODS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The Deep-Block was applied to a large-scale whole genome sequencing (WGS) dataset from the Alzheimer's Disease Sequencing Project (ADSP), comprising 7416 non-Hispanic white (NHW) participants (3150 cognitively normal older adults (CN), 4266 AD).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; RESULTS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;30,218 LD blocks were identified and then ranked based on their relevance with Alzheimer's disease. Subsequently, the Deep-Block identified novel SNPs within the top 1500 LD blocks and confirmed previously known variants, including &lt;i&gt;APOE&lt;/i&gt; rs429358 and rs769449. Expression Quantitative Trait Loci (eQTL) analysis across 13 brain regions provided functional evidence for the identified variants. The results were cross-validated against established AD-associated loci from the European Alzheimer's and Dementia Biobank (EADB) and the GWAS catalog.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; DISCUSSION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The Deep-Block framework effectively processes large-scale high throughput sequencing data while preserving SNP interactions during dimensionality reduction, minimizing bias and information loss. The framework's findings are supported by tissue-specific eQTL evidence across brain regions, indicating the functional relevance of the identified variants. Additionally, the Deep-Block approach has identified both known and novel genetic variants, enhancing our understanding of the genetic architecture and demonstrating its potential for application in large-scale sequencing studies.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Highlights&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;Growing genomic datasets require adva","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015954","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":"Cognitive and Alzheimer's disease biomarker effects of oral nicotinamide riboside (NR) supplementation in older adults with subjective cognitive decline and mild cognitive impairment","authors":"Chao-Yi Wu,&nbsp;Ashley C. Kupferschmid,&nbsp;Liu Chen,&nbsp;Alison J. McManus,&nbsp;Pia Kivisäkk,&nbsp;Jake A. Galler,&nbsp;Nadine A. Schwab,&nbsp;Libby A. DesRuisseaux,&nbsp;Victoria J. Williams,&nbsp;Jessica Gerber,&nbsp;Misha Riley,&nbsp;Cathrine Young,&nbsp;Edmarie Guzmán-Vélez,&nbsp;Hiroko H. Dodge,&nbsp;Rudolph E. Tanzi,&nbsp;Clifford M. Singer,&nbsp;Steven E. Arnold","doi":"10.1002/trc2.70023","DOIUrl":"10.1002/trc2.70023","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; INTRODUCTION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Age-associated depletion in nicotinamide adenine dinucleotide (NAD+) concentrations has been implicated in metabolic, cardiovascular, and neurodegenerative disorders. Supplementation with NAD+ precursors, such as nicotinamide riboside (NR), offers a potential therapeutic avenue against neurodegenerative pathologies in aging, Alzheimer's disease, and related dementias. A crossover, double-blind, randomized placebo (PBO) controlled trial was conducted to test the safety and efficacy of 8 weeks' active treatment with NR (1 g/day) on cognition and plasma AD biomarkers in older adults with subjective cognitive decline and mild cognitive impairment.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; METHODS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The primary efficacy outcome was the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Secondary outcomes included plasma phosphorylated tau 217 (pTau&lt;sup&gt;217&lt;/sup&gt;), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL). Exploratory outcomes included Lumosity gameplay (&lt;i&gt;z&lt;/i&gt;-scores) for cognition and step counts from wearables. Mixed model for repeated measures was used for between-group comparisons; paired &lt;i&gt;t&lt;/i&gt;-tests were used for within-individual comparisons.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; RESULTS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Forty-six participants aged over 55 were randomized to NR-PBO or PBO-NR groups; 41 completed baseline visits, and 37 completed the trial. NR supplementation was safe and well tolerated with no differences in adverse events reported between NR and PBO treatment phases. For the between-group comparison, there was a 7% reduction in pTau&lt;sup&gt;217&lt;/sup&gt; concentrations after taking NR, while an 18% increase with PBO (&lt;i&gt;p&lt;/i&gt; = 0.02). No significant between-group differences were observed for RBANS, other plasma biomarkers(GFAP and NfL), Lumosity gameplay scores or step counts. For the within-individual comparison, pTau&lt;sup&gt;217&lt;/sup&gt; concentrations significantly decreased during the NR phase compared to the PBO (&lt;i&gt;p&lt;/i&gt; = 0.02), while step counts significantly increased during the NR phase than PBO (&lt;i&gt;p&lt;/i&gt; = 0.04).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; DISCUSSION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Eight weeks NR supplementation is safe and lowered pTau&lt;sup&gt;217&lt;/sup&gt; concentrations but did not alter cognition as measured by conventional or novel digital assessments. Further research is warranted to validate NR's efficacy in altering pathological brain aging processes.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Highlights&lt;/h3&gt;\u0000 \u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016144","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":"Evaluation of efficiency and effectiveness of different recruitment strategies for the FINGER-NL multidomain lifestyle intervention trial via the Dutch Brain Research Registry","authors":"Lisa Waterink,&nbsp;Sietske A. M. Sikkes,&nbsp;Lion M. Soons,&nbsp;Sonja Beers,&nbsp;Yvonne Meijer-Krommenhoek,&nbsp;Ondine van de Rest,&nbsp;Smidt Nynke,&nbsp;Joukje M. Oosterman,&nbsp;Erik Scherder,&nbsp;Kay Deckers,&nbsp;Yannick Vermeiren,&nbsp;Rianne A. A. de Heus,&nbsp;Sebastian Köhler,&nbsp;Wiesje M. van der Flier,&nbsp;MOCIA consortium, FINGER-NL consortium,&nbsp;Marissa D. Zwan","doi":"10.1002/trc2.70017","DOIUrl":"10.1002/trc2.70017","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; INTRODUCTION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Recruitment of participants for intervention studies is challenging. We evaluated the effectiveness and efficiency of a participant recruitment campaign through an online registry for the FINGER-NL study, a multi-domain lifestyle intervention trial targeting cognitively healthy individuals aged 60–79 with dementia prevention potential. Additionally, we explored which recruitment strategy successfully reached individuals from underrepresented groups in research.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; METHODS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The campaign entailed seven recruitment strategies referring to The Dutch Brain Research Registry (DBRR): (1) Facebook advertisements, (2) appearance on national television, (3) newspaper articles, (4) researcher outreach, (5) patient organizations, (6) search engines, and (7) other. For each strategy, we describe the number of individuals (a) registered, (b) potentially eligible, and (c) included in FINGER-NL. Subsequently, the efficiency, defined by the eligibility ratio (eligible/registered), and effectiveness, defined by the inclusion ratio (included/registered) were calculated. Associations between recruitment strategies and sociodemographic factors of underrepresented groups were tested with binomial logistic regressions.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; RESULTS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The campaign resulted in 13,795 new DBRR registrants, of which &lt;i&gt;n&lt;/i&gt; = 3475 were eligible (eligibility ratio = 0.25) and &lt;i&gt;n&lt;/i&gt; = 1008 were included (inclusion ratio = 0.07). The Facebook advertisements and television appearance resulted in the highest numbers of registrants (&lt;i&gt;n&lt;/i&gt; = 4678 and &lt;i&gt;n&lt;/i&gt; = 2182) which translated to the highest number of inclusions (&lt;i&gt;n&lt;/i&gt; = 288 and &lt;i&gt;n&lt;/i&gt; = 262). The appearance on national television (eligibility ratio = 0.35), newspaper articles (0.26), and Facebook campaigns (0.26) were the most efficient strategies. The national television appearance (inclusion ratio = 0.13) was the most effective strategy. The Facebook campaign and appearance on national television performed relatively better in recruiting individuals from underrepresented groups.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; DISCUSSION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A multipronged recruitment campaign via a national online recruitment registry is efficient and effective in recruiting and prescreening an adequate number of individuals aged 60–79 years with prevention potential for a multi-site intervention trial within a limited time frame of 15 months. Social media advertisements and television are preferred strategies to recruit individuals from underrepresent","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11712179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958835","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":"Cost-effectiveness of a multicomponent intervention against cognitive decline","authors":"Christian Brettschneider,&nbsp;Elżbieta Buczak-Stec,&nbsp;Melanie Luppa,&nbsp;Andrea Zülke,&nbsp;Bernhard Michalowsky,&nbsp;Anika Rädke,&nbsp;Alexander Bauer,&nbsp;Christine Brütting,&nbsp;Robert P. Kosilek,&nbsp;Isabel Zöllinger,&nbsp;Juliane Döhring,&nbsp;Martin Williamson,&nbsp;Birgitt Wiese,&nbsp;Wolfgang Hoffmann,&nbsp;Thomas Frese,&nbsp;Jochen Gensichen,&nbsp;Hanna Kaduszkiewicz,&nbsp;Jochen René Thyrian,&nbsp;Steffi G. Riedel-Heller,&nbsp;Hans-Helmut König,&nbsp;the AGEWELL.DE study group","doi":"10.1002/trc2.70028","DOIUrl":"10.1002/trc2.70028","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; INTRODUCTION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The societal costs of dementia and cognitive decline are substantial and likely to increase during the next decades due to the increasing number of people in older age groups. The aim of this multicenter cluster-randomized controlled trial was to assess the cost-effectiveness of a multi-domain intervention to prevent cognitive decline in older people who are at risk for dementia.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; METHODS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We used data from a multi-centric, two-armed, cluster-randomized controlled trial (&lt;i&gt;AgeWell.de&lt;/i&gt; trial, ID: DRKS00013555). Eligible participants with increased dementia risk at baseline (Cardiovascular Risk Factors, Aging, and Incidence of Dementia/CAIDE Dementia Risk Score ≥ 9), 60–77 years of age, were recruited by their general practitioners, and assigned randomly to a multi-domain lifestyle intervention or general health advice. We performed a cost-effectiveness analysis from the societal perspective. The time horizon was 2 years. Health care utilization was measured using the “Questionnaire for Health-Related Resource Use in Older Populations.” As effect measure, we used quality-adjusted life-years (QALYs) based on the 5-level EQ-5D version (EQ-5D-5L). We calculated the incremental cost-effectiveness ratios (ICER) and cost-effectiveness acceptability curves (CEAC) using the net-benefit approach. Exploratory analyses considering women and the EQ visual analogue scale (EQ VAS) were conducted.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; RESULTS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Data were available for 819 participants (mean age 69.0 [standard deviation (SD)5-level EQ-5D version 4.9]); 378 were treated in the intervention group and 441 in the control group. The participants in the intervention group caused higher costs (+€445.88 [SD: €1,244.52]) and gained additional effects (+0.026 QALY [SD: 0.020]) compared to the participants in the control group (the difference was statistically significant). The ICER was €17,149.23/QALY. The CEAC showed that the probability of the intervention being cost-effective was moderate, reaching 59% at a willingness-to-pay (WTP) of €50,000/QALY. The exploratory analyses showed promising results, especially in the female subsample.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; DISCUSSION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Considering aspects like the WTP and the limited time horizon, the multi-domain intervention was cost-effective compared to general health advice.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Highlights&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933501","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":"Association of corneal endothelial cell morphology with neurodegeneration in mild cognitive impairment and dementia","authors":"Georgios Ponirakis,&nbsp;Hanadi Al Hamad,&nbsp;Alaa S. Al-Waisy,&nbsp;Ioannis N. Petropoulos,&nbsp;Adnan Khan,&nbsp;Hoda Gad,&nbsp;Mani Chandran,&nbsp;Masharig Gadelseed,&nbsp;Salah Mahmoud,&nbsp;Ahmed Elsotouhy,&nbsp;Marwan Ramadan,&nbsp;Shafi Khan,&nbsp;Rustu E. Akcan,&nbsp;Priya V. Gawhale,&nbsp;Noushad Thodi,&nbsp;Tala Nakouzi,&nbsp;Moayad Homssi,&nbsp;Nebras Hadid,&nbsp;Aisha Al Obaidan,&nbsp;Rawan Hussein,&nbsp;Ahmed Own,&nbsp;Ashfaq Shuaib,&nbsp;Rayaz A. Malik","doi":"10.1002/trc2.70025","DOIUrl":"10.1002/trc2.70025","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; INTRODUCTION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Corneal confocal microscopy (CCM) detects neurodegeneration in mild cognitive impairment (MCI) and dementia and identifies subjects with MCI who develop dementia. This study assessed whether abnormalities in corneal endothelial cell (CEC) morphology are related to corneal nerve morphology, brain volumetry, cerebral ischemia, and cognitive impairment in MCI and dementia.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; METHODS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Participants with no cognitive impairment (NCI), MCI, and dementia underwent CCM to quantify corneal endothelial cell density (CECD) and area (CECA), corneal nerve fiber morphology, magnetic resonance imaging (MRI) brain volumetry, and severity of brain ischemia.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; RESULTS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Of the 114 participants, 14 had NCI, 77 had MCI, and 23 had dementia. CECD (1971.3 ± 594.6 vs 2316.1 ± 499.5 cells/mm&lt;sup&gt;2&lt;/sup&gt;, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) was significantly lower in the dementia compared to the NCI group. CECD and CECA were comparable between the MCI and NCI groups (&lt;i&gt;p&lt;/i&gt; = 0.13–0.65). Corneal nerve fiber density (CNFD) (31.7 ± 5.6 vs 24.5 ± 9.2 and 17.3 ± 5.3 fibers/mm&lt;sup&gt;2&lt;/sup&gt;, &lt;i&gt;p&lt;/i&gt; &lt; 0.01), corneal nerve branch density (CNBD) (111.8 ± 58.1 vs 50.4 ± 36.4 and 52.7 ± 21.3 branches/mm&lt;sup&gt;2&lt;/sup&gt;, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001), and corneal nerve fiber length (CNFL) (24.6 ± 6.6 vs 16.5 ± 6.8 and 16.2 ± 5.0 mm/mm&lt;sup&gt;2&lt;/sup&gt;, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) were lower in the MCI and dementia groups compared to the NCI group. Lower CECD partially mediated the impact of age and diabetes on CNFL reduction (&lt;i&gt;p&lt;/i&gt; &lt; 0.05), whereas CECA lost its significance after adjustment (&lt;i&gt;p&lt;/i&gt; = 0.20). CEC morphology does not affect the association between corneal nerve fiber loss and MCI/dementia. CECD and CECA had no significant association with cerebral ischemic lesions (&lt;i&gt;p&lt;/i&gt; = 0.21–0.47), dementia (&lt;i&gt;p&lt;/i&gt; = 0.11–0.35), or cognitive decline (&lt;i&gt;p&lt;/i&gt; = 0.37–0.38). However, lower CECD and higher CECA were associated with decreased cortical gray matter volume (&lt;i&gt;p&lt;/i&gt; &lt; 0.05–0.01).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; DISCUSSION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;CEC loss occurs in patients with dementia, and both endothelial cell loss and hypertrophy are associated with cortical gray matter atrophy. CNF loss occurs in individuals with MCI and dementia. Corneal nerve and endothelial cell abnormalities could act as biomarkers for neurovascular pathology in dementia.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Highlights&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933500","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 problem of multiple adjustments in the assessment of minimal clinically important differences","authors":"Fabricio Ferreira de Oliveira","doi":"10.1002/trc2.70032","DOIUrl":"10.1002/trc2.70032","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Anthropometric, demographic, genetic, and clinical features may affect cognitive, behavioral, and functional decline, while clinical trials seldom consider minimal clinically important differences (MCIDs) in their analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>MCIDs were reviewed taking into account features that may affect cognitive, behavioral, or functional decline in clinical trials of new disease-modifying therapies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The higher the number of comparisons of different confounders in statistical analyses, the lower <i>P</i> values will be significant. Proper selection of confounders is crucial to accurately assess MCIDs without compromising statistical significance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Statistical adjustment of the significance of MCIDs according to multiple comparisons is essential for the generalizability of research results. Wider inclusion of confounding variables in the statistics may help bring trial results closer to real-world conditions and improve the prediction of the efficacy of new disease-modifying therapies, though such factors must be carefully selected not to compromise the statistical significance of the analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Anthropometric, demographic, and clinical features may affect cognitive, behavioral, and functional decline.</li>\u0000 \u0000 <li>Clinical trials seldom take minimal clinically important differences (MCIDs) or their confounders into account.</li>\u0000 \u0000 <li>Generalizability of research results requires the assessment of multiple confounding factors.</li>\u0000 \u0000 <li>The higher the number of comparisons involved, the lower <i>P</i> values will be considered significant.</li>\u0000 \u0000 <li>Use of MCIDs adjusted for confounding factors should be implemented when outcomes are not susceptible to translation into absolute benefits.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933529","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}