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

{"title":"Machine learning–enhanced screening funnel for clinical trials in Alzheimer's disease","authors":"Scott Gladstein,&nbsp;Liuqing Yang,&nbsp;Dustin Wooten,&nbsp;Xin Huang,&nbsp;Robert Comley,&nbsp;Qi Guo,&nbsp;the Alzheimer's Disease Neuroimaging Initiative","doi":"10.1002/trc2.70084","DOIUrl":"https://doi.org/10.1002/trc2.70084","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) clinical trials with therapeutic interventions require hundreds of subjects to be studied over many months/years due to variable and slow disease progression. This article presents a novel screening paradigm integrating disease progression models to improve trial efficiency by identifying appropriate candidates for early phase clinical studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>A traditional screening funnel is enhanced using machine learning models, including 3D convolutional neural networks and ensemble models, which integrate neuroimaging, demographic, genetic, and clinical data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>This approach predicts clinical progression (2-year Clinical Dementia Rating Sum of Boxes change &gt; 1) with an area under the curve of 0.836. Incorporating it into trials (with maximized sensitivity/specificity optimization) could reduce the number of subjects required by 55%, shorten recruitment by 13 months, and reduce screening amyloid positron emission tomography scans by 72%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>By reducing patient burden and shortening timelines in clinical trials, this enhanced screening funnel could accelerate the development of AD therapies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>An innovative screening funnel was developed to improve Alzheimer's disease clinical trial efficiency.</li>\u0000 \u0000 <li>The funnel incorporates machine learning (ML)–based disease progression models.</li>\u0000 \u0000 <li>The ML model identifies patients with progression rate optimal for clinical trials.</li>\u0000 \u0000 <li>Unsuitable patients would fail early in the funnel before burdensome imaging procedures.</li>\u0000 \u0000 <li>This screening funnel is customizable to specific study needs.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865894","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":"Clinical factors predicting the rate of cognitive decline in a US memory clinic: An electronic health record study","authors":"Roy Adams,&nbsp;Jeannie-Marie Leoutsakos,&nbsp;Milap A. Nowrangi,&nbsp;Esther S. Oh,&nbsp;Paul B. Rosenberg,&nbsp;Konstantina Skolariki,&nbsp;Sevil Yasar,&nbsp;Peter P. Zandi,&nbsp;Constantine G. Lyketsos","doi":"10.1002/trc2.70070","DOIUrl":"https://doi.org/10.1002/trc2.70070","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;Dementia progression is heterogeneous and predicting who will decline quickly remains an open problem. Most work in this area has focused on volunteer-based cohorts, which are subject to recruitment biases. Instead, we examine predictors of rate of cognitive decline in cognitive assessment scores using electronic health record (EHR) data from a US memory clinic.&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;Data include patients with their first memory clinic visit (baseline) between January 1, 2014 and May 31, 2024. We used a discrete-time model to identify significant predictors of baseline and 6 month change in Mini-Mental State Examination (MMSE) scores (Montreal Cognitive Assessment scores were converted to MMSE equivalents for analysis). Inverse probability weighting was used to account for selection and censoring biases and &lt;i&gt;p&lt;/i&gt; values were adjusted for multiple 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;The cohort included 9583 patients, of which 7113 had a baseline cognitive assessment. Average MMSE at baseline was 23.2. Variables associated with lower baseline MMSE included female sex, non-White race, Medicaid enrollment, baseline dementia diagnosis, and cholinesterase inhibitor prescription, while higher scores were associated with prior diagnoses of chronic pain or fatigue. Quicker post-baseline decline was associated with older age, dementia diagnoses, and cholinesterase inhibitor prescription, while slower decline was associated with a higher number of total prescriptions, distance from home to clinic, and Social Deprivation Index. Notably, rate of decline was not associated with mild cognitive impairment, other non-dementia cognitive impairment, or any of the comorbidities considered.&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;While several significant predictors were identified, the lack of associations with broad categories of comorbidities and social determinants of health suggest that finer grained predictors may be needed. Additionally, the finding that cholinesterase inhibitor prescriptions predicted quicker decline merits additional investigation in real-world samples. The model developed in this work may serve as a first step toward an EHR-based progression risk tool.&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;In a memory clinic setting, faster decline in Mini-Mental State Examinat","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865911","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":"Clinically meaningful benefit and real-world evidence in Alzheimer's disease research and care","authors":"Robert Perneczky,&nbsp;Lutz Froelich","doi":"10.1002/trc2.70090","DOIUrl":"https://doi.org/10.1002/trc2.70090","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>In the realm of medical research, assessing novel therapies extends beyond statistical significance. The concept of meaningful benefits plays a pivotal role in determining the practical impact of interventions on patient outcomes. Clinical trials, which form the bedrock of evidence-based medicine, guide treatment decisions and shape health-care practices. While statistical significance remains a fundamental criterion, it falls short in fully evaluating the clinical relevance of therapeutic interventions. Clinically meaningful benefits focus on tangible improvements in patient health and well-being, transcending mere statistical thresholds. Key considerations include survival rates, symptom relief, functional status, and other patient-oriented outcomes. Determining meaningful benefits varies across diseases, patient populations, and available treatments. Balancing statistical rigor with clinical relevance is crucial. Overpowered trials may detect smaller differences than anticipated, necessitating careful interpretation. Researchers must view trial results through a patient-centric lens. Beyond survival, evaluating quality of life and side effects is equally relevant. Quantifying meaningful benefits involves metrics like numbers needed to treat and progression-free survival. Consistency across outcomes matters, as clinicians weigh gains in survival against improvements in quality of life. The pursuit of meaningful benefits elevates clinical trials from mere statistical exercises to patient-centered endeavors. Researchers, clinicians, and regulators must prioritize outcomes that genuinely matter to patients, ensuring that medical progress translates into meaningful improvements for them and their families.</p>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871607","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":"Care staff perspectives of clinically meaningful outcomes for dementia residents","authors":"Alaine E. Reschke-Hernández,&nbsp;Martina Vasil,&nbsp;Emma King,&nbsp;Carson Woolums","doi":"10.1002/trc2.70091","DOIUrl":"https://doi.org/10.1002/trc2.70091","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;Non-pharmacological complementary and supportive care programs (CSCP, e.g., music therapy) are provided in addition to standard medical care for persons with dementia (PWD). Care staff observations are critical in assessing the clinical impact of CSCP on PWD. However, little is known about care staff experiences of CSCP and what factors influence documentation of outcomes. We sought to understand how care staff in Kentucky describe the clinically meaningful impact of CSCP on residents and themselves and learn what conditions enable and prohibit documentation.&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;Four care staff from four dementia care facilities in Kentucky (representing non-profit, for-profit; rural, suburban, and urban areas) participated in this qualitative multiple case study. Participants were selected to reflect diverse care roles, identities, and experience. We collected data from eight semi-structured interviews (two per participant), 24 journal entries, four observations, photographs, and publicly available facility data. The use of multiple data types helped triangulate findings and enrich the analysis. Data were coded and analyzed for emerging themes.&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;Participants described CSCP as enhancing residents’ holistic well-being and being person-centered. CSCP also improved participants’ well-being and enhanced their sense of purpose. Primary documentation barriers were lack of time, prioritizing resident care over documentation, and top-down regulations. Technology both enabled and prohibited documentation, with routine being a key facilitator.&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;Our findings indicate that CSCP improve PWD's quality of life by fostering engagement, joy, and personalized care, consistent with person-centered care principles. Staff also benefit from reduced stress and improved morale. However, barriers exist, including time constraints and documentation challenges. Results may inform directions for future research, translation of CSCP from research to practice, and feasible measurement of clinically meaningful outcomes. The study underscores the importance of addressing systemic issues and advocating for policies that support sustainable, quality dementia care while enhancing both resident and staff well-being.&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 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871608","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":"Effect of long-term treatment with memantine on mortality in patients with major cognitive disorders: A systematic review and meta-analysis","authors":"Victoria Zolnowski-Kolp,&nbsp;Bruno Oquendo,&nbsp;Charlotte Havreng-Théry,&nbsp;Carmelo Lafuente-Lafuente,&nbsp;Joël Belmin","doi":"10.1002/trc2.70071","DOIUrl":"https://doi.org/10.1002/trc2.70071","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> BACKGROUND</h3>\u0000 \u0000 <p>Dementia is responsible for a reduction in life expectancy, and the effect of memantine on mortality is still poorly understood. Our aim was to evaluate the effect of long-term treatment with memantine on all-cause mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>In this systematic review and meta-analysis, we searched five databases from their creation to June 2024.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We found 12 randomized trials (<i>n</i> = 4266) and 7 observational studies (<i>n</i> = 20,216). Treatment with memantine was associated with a reduction in all-cause mortality (risk ratios [RRs] 0.81, 95% CI: 0.72–0.92, <i>p</i> = 0.001). In the sensitivity analysis, the pooled RR was similar for randomized controlled trials (RCT) (RR 0.86) and non-randomized studies (RR 0.81) but pooled results from RCTs did not reach statistical significance (95% confidence interval [CI]: 0.59–1.26, <i>p</i> = 0.45), while they did for observational studies (95% CI: 0.70–0.95, <i>p</i> = 0.008), so we consider the overall evidence as of low certainty.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CONCLUSION</h3>\u0000 \u0000 <p>Our results suggest that the use of memantine in patients with dementia may be associated with a reduction in all-cause mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Dementia reduces patients’ survival and the effect of long-term use of memantine on all-cause mortality is not well known.</li>\u0000 \u0000 <li>This systematic review and metanalysis included 19 studies including more than 24000 patients.</li>\u0000 \u0000 <li>We found that memantine in patients with dementia may be associated with a reduction in all-cause mortality.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850996","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":"Physical activity modifies associations between cerebrospinal fluid tau measures and executive function","authors":"Ryan J. Dougherty,&nbsp;Anja Soldan,&nbsp;Corinne Pettigrew,&nbsp;Barry Greenberg,&nbsp;Adam P. Spira,&nbsp;Abhay Moghekar,&nbsp;Marilyn Albert","doi":"10.1002/trc2.70085","DOIUrl":"https://doi.org/10.1002/trc2.70085","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; BACKGROUND&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Alzheimer's disease (AD) is characterized by the abnormal accumulation of amyloid-beta (Aβ) and tau that can be quantified in vivo through cerebrospinal fluid (CSF) sampling. Physical activity has emerged as a possible modifier of AD risk; however, its impact on CSF biomarkers and cognitive function is not yet fully understood. We examined whether higher levels of physical activity modifies associations between AD CSF biomarkers and cognitive function.&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;One hundred and seventeen adults free of dementia from the BIOCARD study (mean age 72.2 ± 8.0 years, 70% women) wore a wrist accelerometer for 1 week, underwent lumbar puncture to collect CSF, and completed a comprehensive neuropsychological exam. Multivariable linear regression analyses were used to examine whether physical activity (total activity counts over the 10 most active hours of the day) moderates the association between AD CSF biomarkers [Aβ42/40, phosphorylated tau (p-tau181), and total tau] and cognitive composite scores (episodic memory, executive function).&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;There were significant interactions between physical activity and p-tau181 (&lt;i&gt;p&lt;/i&gt; = 0.016) as well as between physical activity and total tau (&lt;i&gt;p&lt;/i&gt; = 0.004) in relation to the executive function composite score. Among participants with higher levels of physical activity, the adverse relationship between CSF-measured tau and executive function was diminished. In contrast, there were no significant interactions for episodic memory, and physical activity did not interact with Aβ42/40 (all interactions &lt;i&gt;p &lt;/i&gt;&gt; 0.05).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; CONCLUSION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A physically active lifestyle may provide protection against AD-related cognitive decline by reducing the impact of tau pathology.&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;Older age was associated with lower levels of physical activity, worse CSF biomarker profiles, and poorer cognition.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Physical activity moderates the impact of tau pathology on executive function but shows no significant effect on amyloid-beta pathology.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Physical activity may enhance cognitive reserve, thereby attenuating the influence of accumulating AD pathology on cognition.&lt;/li&gt;\u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836205","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":"Generating real-world evidence in early Alzheimer's disease: Considerations for applying the target trial emulation framework to study the safety of anti-amyloid therapies","authors":"Xiaojuan Li,&nbsp;Sonal Singh,&nbsp;Bahareh Rasouli,&nbsp;Jennifer Lyons,&nbsp;Noelle M. Cocoros,&nbsp;Richard Platt,&nbsp;Ivan Abi-Elias,&nbsp;Jerry H. Gurwitz","doi":"10.1002/trc2.70080","DOIUrl":"https://doi.org/10.1002/trc2.70080","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Anti-amyloid beta monoclonal antibodies (anti-Aβ mAbs) have received approval from the US Food and Drug Administration for the treatment of patients with mild cognitive impairment or mild dementia due to Alzheimer's disease (collectively known as early AD) based on evidence from clinical trials. However, whether findings from these trials are generalizable to the real world is uncertain. We need reliable evidence on the real-world safety of these treatments to inform decision making for clinicians, patients, and caregivers. Using lecanemab as an exemplar, we outline the key considerations in designing and implementing an observational study on safety and utilization outcomes using established administrative healthcare claims data sources with the target trial emulation framework. The target trial emulation framework is a rigorous causal inference framework that minimizes common biases in observational studies. The approach proposed here can be applied to evaluation of additional mAbs as they become available.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Little is known about real-world safety of anti-amyloid beta monoclonal antibodies for early Alzheimer's disease.</li>\u0000 \u0000 <li>Existing real-world data can support studies of their safety and utilization outcomes.</li>\u0000 \u0000 <li>Target trial emulation can guide the design of these studies while minimizing bias.</li>\u0000 \u0000 <li>We provide key design and analytical considerations for future studies.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836268","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":"Directionality between cognitive function and daily physical activity patterns","authors":"Francesca R. Marino,&nbsp;Jennifer A. Deal,&nbsp;Alden L. Gross,&nbsp;Yang An,&nbsp;Qu Tian,&nbsp;Eleanor M. Simonsick,&nbsp;Luigi Ferrucci,&nbsp;Susan M. Resnick,&nbsp;Jennifer A. Schrack,&nbsp;Amal A. Wanigatunga","doi":"10.1002/trc2.70068","DOIUrl":"https://doi.org/10.1002/trc2.70068","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Physical activity is a modifiable risk factor for dementia, but cognitive function is also important for physical activity engagement. This study evaluated the directionality of associations between daily physical activity and cognitive function in a sample of cognitively and physically intact older adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Cognitive factor scores for domains including global cognition, memory, language, executive function/attention, and visuospatial processing, and physical activity patterns from wrist accelerometry were measured at two visits (mean: 1.8 years) among 237 cognitively intact older adults in the Baltimore Longitudinal Study of Aging (BLSA) (mean age: 76.5 years). Bivariate latent change score models estimated directionality of associations between changes in cognitive factor scores and physical activity patterns. Models were adjusted for age, sex, race, education, comorbidities, and body mass index.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Higher total amount of activity, longer activity bouts, less sedentary time, and less activity fragmentation at baseline were associated with less annual cognitive decline across multiple cognitive domains (<i>X</i>²&gt; 4.11, 1 df for all). In contrast, baseline cognitive factor scores were not associated with changes in any activity pattern (<i>X</i>² &lt; 3.20, 1 df for all).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Increasing movement and/or decreasing sedentary behavior is associated with less prospective cognitive decline. Targeting reductions in sedentary time and lengthening activity bouts may slow cognitive decline among older adults at risk for dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Greater activity engagement is related to less annual cognitive decline.</li>\u0000 \u0000 <li>Baseline cognition is not associated with short-term changes in activity patterns.</li>\u0000 \u0000 <li>Promoting daily movement and lowering sedentary time may have cognitive 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 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822230","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":"Measuring time saved in Alzheimer's disease: What is a meaningful slowing of progression?","authors":"Krista Lanctot,&nbsp;Linus Jönsson,&nbsp;Alireza Atri,&nbsp;Russ Paulsen,&nbsp;Soeren Mattke,&nbsp;Julie Hviid Hahn-Pedersen,&nbsp;Pepa Polavieja,&nbsp;Thomas Maltesen,&nbsp;Teresa León,&nbsp;Anders Gustavsson,&nbsp;Alzheimer's Disease Neuroimaging Initiative","doi":"10.1002/trc2.70081","DOIUrl":"https://doi.org/10.1002/trc2.70081","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Minimal clinically important differences (MCIDs) for Alzheimer's disease (AD) have previously been estimated using clinician-based anchors. However, MCIDs have been criticized for not reflecting the preferences of people living with AD (PLWAD). Furthermore, interpretations of clinical trial results have been criticized for conflating within-person meaningfulness thresholds and between-group differences. Here, we simulate scenarios of disease slowing and compare those to published MCIDs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Scenarios of 5%–95% disease slowing were simulated using Alzheimer's Disease Neuroimaging Initiative (ADNI) data. Time saved and point differences on the Clinical Dementia Rating scale—Sum of Boxes (CDR-SB) were estimated for these scenarios and compared to published MCIDs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Scenario analyses resulted in estimates of time saved at ∼3 weeks–17 months and mean changes at 0.08–1.5 CDR-SB points over 18 months. The often referenced MCID for mild cognitive impairment (0.98) thereby corresponded to 11 months slowing, whereas the MCID for mild dementia (1.63) corresponded to &gt;17 months slowing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Translating trial endpoints to estimates of time saved supports that often-referenced MCIDs may not be aligned with realistic and meaningful slowing of clinical progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>AD slowing of clinical progression by 5%–95% resulted in 0.74–17 months saved and 0.08–1.5 CDR-SB points change at 18 months.</li>\u0000 \u0000 <li>Slowing of at least 60% or 11 months of time saved over 18 months met an often-cited MCID threshold of 0.98 points for mild cognitive impairment.</li>\u0000 \u0000 <li>For mild AD dementia, an MCID of 1.63 meant that even an 18-month delay over 18 months would be considered only borderline meaningful—a face invalid and unrealistic proposition.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822231","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":"Activity variability: A novel physical activity metric and its association with cognitive impairment","authors":"Patrick T. Donahue,&nbsp;Jennifer A. Schrack,&nbsp;Johannes Thrul,&nbsp;Michelle C. Carlson","doi":"10.1002/trc2.70079","DOIUrl":"https://doi.org/10.1002/trc2.70079","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;Evidence suggests that engaging in a high volume of daily or weekly physical activity may reduce the risk of cognitive impairment due to Alzheimer's disease and related dementias (ADRD). However, activity variability and its associations with cognition are underexplored. We examined whether activity variability, measured at the minute level, may capture movement patterns that provide insight into cognitive impairment 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;Using a cross-sectional sample of 711 older adults (mean [standard deviation] age = 79.1 [6.0] years]) from the National Health and Aging Trends Study in 2021, we calculated a novel metric of activity variability, defined as the standard deviation of minute-to-minute changes in accelerometer activity counts across the 7 day wear period. We investigated associations between activity variability and other activity metrics with cognitive impairment using logistic regression models.&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;Lower activity variability was associated with increased odds of cognitive impairment (odds ratio [OR] = 2.23; 95% confidence interval [CI: 1.26–3.97]), even after accounting for total activity counts and other covariates. In receiver operating characteristic curve analyses, activity variability was the strongest predictor of prevalent cognitive impairment compared to other activity metrics (area under the curve = 0.787; 95% CI [0.742–0.832]).&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;Activity variability, measured at the minute level, may capture complexity of daily activities and may serve as a novel indicator of cognitive health. Low activity variability may signal underlying neurological processes that contribute to ADRD risk. Further investigation into potential biological mechanisms that may explain the observed associations between activity variability and cognition is warranted.&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 created a novel metric using variability of minute-level changes in activity counts.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Low activity variability was associated with a greater prevalence of cognitive impairment.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Activity variability outperformed other activity metrics in area under the receiver operating characteristic curve analyses.&lt;/li&gt;\u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809428","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}