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

{"title":"Response to: Refining the clinical interpretation of activity variability in cognitive impairment: The need for phenotypic specificity","authors":"Patrick T. Donahue, Jennifer A. Schrack, Johannes Thrul, Michelle C. Carlson","doi":"10.1002/trc2.70128","DOIUrl":"https://doi.org/10.1002/trc2.70128","url":null,"abstract":"<p>Dear Guo et al.,</p><p>We thank Guo et al.<span><sup>1</sup></span> for their interest in our article<span><sup>2</sup></span> and for providing innovative thoughts regarding clinical translation of our activity variability metric.</p><p>We would first like to emphasize that we positioned our work as an exploratory analysis of a conceptually novel metric developed using available accelerometry data. It is fit for application in future longitudinal and clinical studies with accelerometry data, which can replicate our findings and establish clinically meaningful changes relevant to activity variability and cognition. Our cross-sectional study suggests that low activity variability is strongly associated with cognitive impairment, yet we acknowledge that this metric requires further validation before implementation as a digital biomarker of cognitive decline and impairment. We intend to extend this work to other studies and encourage other researchers and clinicians to pursue validation studies, which were beyond the scope of our analysis.</p><p>We agree with Guo et al.<span><sup>1</sup></span> that cognitive impairment is heterogeneous and that it would be useful to distinguish subtypes of dementia, such as vascular versus Alzheimer's disease pathologies. The data we used have strengths and limitations, as noted in our article. As Guo et al. mention, and we discussed in our article, the National Health and Aging Trends Study (NHATS) dementia classification criteria are <i>not</i> equivalent to a dementia diagnosis, nor do they distinguish subtypes of cognitive decline and impairment.<span><sup>2</sup></span> As Guo et al. compellingly state, it is important to further extend the conceptual link between activity variability and cognitive risk to clinical neurological outcomes, not limited to dementia (e.g., traumatic brain injury). Guo et al.’s proposal to link activity variability to specific brain regions via neuroimaging and associated cognitive domains via neuropsychological testing presents exciting additional mechanistic areas of research, which would greatly complement our findings. We agree that identifying underlying brain regions and cognitive domains that may be specifically related to activity variability would enhance this metric's clinical utility for greater sensitivity in detection of cognitive and functional impairment. In addition, if activity variability can be linked to specific brain regions, it may serve as a potential intermediate outcome for cognitive interventions.</p><p>Guo et al. commented that, because activity variability and gait speed were correlated, we cannot disentangle “the cognitive versus biomechanical determinants of variability”. Importantly, our study was not intended to examine the cognitive versus biological determinants of activity variability. Although activity variability and gait speed were correlated, activity variability remained strongly associated with cognitive impairment even after controlling f","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144514970","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 as a resistance or resilience mechanism in Down syndrome Alzheimer's disease","authors":"Victoria L. Fleming,&nbsp;Jamie Peven,&nbsp;Brian C. Helsel,&nbsp;Lauren T. Ptomey,&nbsp;Julianne Clina,&nbsp;Ashlyn Barry,&nbsp;Beau M. Ances,&nbsp;Benjamin L. Handen,&nbsp;Bradley T. Christian,&nbsp;Charles Laymon,&nbsp;Matthew Zammit,&nbsp;Elizabeth Head,&nbsp;Mark Mapstone,&nbsp;Ozioma Okonkwo,&nbsp;Sigan L. Hartley,&nbsp;for the Alzheimer Biomarkers Consortium – Down Syndrome","doi":"10.1002/trc2.70127","DOIUrl":"https://doi.org/10.1002/trc2.70127","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Adults with Down syndrome (DS) are at risk for Alzheimer's disease (AD). Lifestyle factors such as engagement in moderate-to-vigorous physical activity (MVPA) reduce risk or delay the onset of AD. This study aimed to determine whether MVPA confers a <i>resistance</i> (AD pathology) or <i>resilience</i> (cognitive decline) effect on the relationship between AD pathology and cognitive decline in DS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Analyses included 69 adults with DS (aged 26–58) who participated in a longitudinal study across 3.29 years. An actigraphy accelerometer assessed MVPA across 7 days. Directly administered and informant-reported measures assessed cognitive functioning, specifically memory and dementia symptoms. Neuroimaging biomarkers quantified amyloid beta (Aβ) burden, as assessed via positron emission tomography imaging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>In regression models, baseline MVPA was not associated with baseline level or change in global Aβ burden across 32 months. However, baseline MVPA (<i>β</i> = −0.005 to −0.004, <i>p</i> &lt; 0.05) significantly moderated the association between increases in Aβ burden and declines in cognitive functioning. Adults with DS who engaged in greater MVPA experienced less cognitive decline compared to adults with DS who engaged in less MVPA, who had similar Aβ load.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>MVPA may help maintain cognitive functioning early in the progression of AD pathology in adults with DS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Adults with Down syndrome are genetically at risk for Alzheimer's disease (AD).</li>\u0000 \u0000 <li>Timing of AD clinical onset spans 30+ years.</li>\u0000 \u0000 <li>Physical activity has been linked to less cognitive decline and dementia symptoms.</li>\u0000 \u0000 <li>Physical activity may protect against dementia through resilience mechanisms.</li>\u0000 \u0000 <li>Physical activity could be a low-cost intervention to help prevent cognitive decline.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503156","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":"System readiness and the patient care pathway for Alzheimer's disease diagnosis and treatment","authors":"B. Joy Snider,&nbsp;Alessandro Biffi,&nbsp;Sasha Bozeat,&nbsp;Carolyn Clevenger,&nbsp;Gill Farrar,&nbsp;Darren Gitelman,&nbsp;Rachel Kolster,&nbsp;Soeren Mattke,&nbsp;Michelle Mielke,&nbsp;Debjani Mukherjee,&nbsp;Jennifer Murphy,&nbsp;Hamid Okhravi,&nbsp;Gil D. Rabinovici,&nbsp;Dorene Rentz,&nbsp;Jose Soria,&nbsp;Heather Synder,&nbsp;Gregg Walker,&nbsp;Simin Mahinrad,&nbsp;Maria C. Carrillo,&nbsp;Christopher J. Weber","doi":"10.1002/trc2.70094","DOIUrl":"https://doi.org/10.1002/trc2.70094","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Promising therapeutic interventions that target the underlying pathophysiology are changing the landscape of Alzheimer's disease (AD) research. The AD care pathway must be transformed to meet the challenge of bringing these new therapies to the increasing number of people living with AD within the existing healthcare framework. Challenges include identifying patients who may benefit from treatment interventions early in the course of the disease, ensuring that diagnostic tools are accessible and accurate, and developing capabilities to monitor the effectiveness of interventions over time. These challenges must be addressed at all levels, from primary care settings to tertiary treatment centers; this will require collaborative efforts between health systems, drug manufacturers, and research institutions to navigate this evolving landscape and ensure system readiness for patients and their families with AD. The Spring 2024 Alzheimer's Association Research Roundtable (AARR) meeting gathered industry representatives and clinicians to discuss insights, challenges, and solutions that will help researchers and health systems identify patients in the early stages of AD and deliver emerging therapies efficiently and safely. In this paper, we provide highlights from the Spring 2024 AARR meeting.</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":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70094","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323583","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":"BDNF Val66Met polymorphism moderates associations between physical activity and neurocognitive outcomes in older adults","authors":"Claire J. Cadwallader,&nbsp;Anna M. VandeBunte,&nbsp;D. Luke Fischer,&nbsp;Coty Chen,&nbsp;Valentina E. Diaz,&nbsp;Shannon Y. Lee,&nbsp;Brandon Chan,&nbsp;Argentina Lario-Lago,&nbsp;Julio C. Rojas,&nbsp;Eliana Marisa Ramos,&nbsp;Jessica E. Rexach,&nbsp;Jennifer S. Yokoyama,&nbsp;Joel H. Kramer,&nbsp;Emily W. Paolillo,&nbsp;Rowan Saloner,&nbsp;Kaitlin B. Casaletto","doi":"10.1002/trc2.70106","DOIUrl":"https://doi.org/10.1002/trc2.70106","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;Increased brain-derived neurotrophic factor (BDNF) release through physical activity (PA) is thought to underlie protective effects of PA on brain aging. The &lt;i&gt;BDNF&lt;/i&gt; Val66Met single-nucleotide polymorphism (rs6265) reduces activity-dependent BDNF release and has been linked to early Alzheimer's disease (AD) pathology and cognition. We examined whether &lt;i&gt;BDNF&lt;/i&gt; genotype influences the association of PA with plasma markers of AD, axonal degeneration, and neuroinflammation, along with consequences for cognition, in older adults without 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;One hundred eighty older adults (M&lt;sub&gt;age&lt;/sub&gt; = 73.1; SD&lt;sub&gt;age&lt;/sub&gt; = 9.1; 61% female; 42% &lt;i&gt;BDNF&lt;/i&gt; Met allele carriers) from the University of California San Francisco (UCSF) Memory and Aging Center completed 30 days of actigraphy monitoring, plasma assays of phosphorylated tau (p-tau181), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and &lt;i&gt;BDNF&lt;/i&gt; Val66Met genotyping. One hundred twenty-three of the sample completed comprehensive neuropsychological evaluation. Habitual PA levels were operationalized via average daily step count. Composite z-scores were calculated for cognitive domains of memory and executive functioning.&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;&lt;i&gt;BDNF&lt;/i&gt; genotype moderated the relationship between PA and plasma p-tau181, whereby higher PA was associated with lower plasma p-tau181 concentration in Val/Val participants only. In moderated mediation analyses examining cognitive outcomes, plasma p-tau181 selectively mediated the relationship between PA and executive function in Val/Val participants. In analyses including sex as a biological factor, there was a three-way interaction of PA, &lt;i&gt;BDNF&lt;/i&gt; genotype, and sex on plasma GFAP concentration, whereby higher PA was associated with lower plasma GFAP only in Val/Val male participants.&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 Val/Val &lt;i&gt;BDNF&lt;/i&gt; genotype may facilitate the neuroprotective relationships of PA, including lower AD-relevant biology and better executive function. We further show there may be a sex-specific negative relationship of PA with neuroinflammation in Val/Val males. These results further elucidate sources of individual variation observed in relationships between PA and brain health and will contribute to guiding personalized neurotrophic treatments for older adults.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Highlights&lt;","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323585","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":"Identification of cerebrospinal fluid pharmacodynamic biomarkers and molecular correlates of brain activity in a Phase 2 clinical trial of the Alzheimer's disease drug candidate CT1812","authors":"Valentina Di Caro,&nbsp;Eunah Cho,&nbsp;Hilary A. North,&nbsp;Jill Caldwell,&nbsp;Kiran Pandey,&nbsp;Duc Duong,&nbsp;Michael Grundman,&nbsp;Willem de Haan,&nbsp;Everard G. Vijverberg,&nbsp;Charlotte E. Teunissen,&nbsp;Anthony O. Caggiano,&nbsp;Nicholas T. Seyfried,&nbsp;Mary E. Hamby","doi":"10.1002/trc2.70119","DOIUrl":"https://doi.org/10.1002/trc2.70119","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;CT1812 (zervimesine) is an orally dosed modulator of the sigma-2 receptor (S2R) currently in clinical development for the treatment of Alzheimer's disease (AD). CT1812 has been shown in preclinical and early clinical trials to selectively prevent and displace binding of amyloid beta oligomers from their synaptic receptors and has improved cognitive function in animal models of AD.&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;SEQUEL (NCT04735536) is a completed Phase 2, randomized, placebo-controlled 4-week crossover trial in adults with mild-to-moderate AD that investigated the effect of CT1812 on safety, synaptic function using quantitative electroencephalography (qEEG), and biomarkers. CT1812 improved established qEEG markers of spontaneous brain activity, suggesting improved neuronal and synaptic function. In the present study, cerebrospinal fluid (CSF)-based tandem mass tag mass spectrometry (TMT-MS) was performed on participant samples to investigate proteomic effects and identify potential biomarkers of CT1812.&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;Biomarkers found through proteomics analyses to be significantly differentially abundant in CT1812- versus placebo-treated participants supported pathway engagement and proof of mechanism for CT1812. Impacted proteins support a role for CT1812 at synapses, in vesicle trafficking, and in lipoprotein biology. Biomarkers correlated with the previously reported improvements in qEEG-based functional connectivity (inferred through alpha band Amplitude Envelope Correlations) with CT1812 treatment were also identified and may be potential early surrogate biomarkers of efficacy for CT1812. The processes and functions supported by biomarkers were congruent with those previously revealed in CSF proteomics analyses from phase 1 and 2 AD clinical trials with CT1812.&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;After 1 month of treatment, the identification of biomarkers supporting pathway engagement, the replication of biomarker findings from prior trials, and the discovery of molecular correlates of improved functional connectivity with CT1812 treatment bolster support for and expound upon the mechanism of action for CT1812 in displacing Aβ oligomers at neuronal synapses, as well as underscores the CT1812 relevance to AD.&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;Exploratory pr","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323584","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 LATTICE Study: Design of a pilot feasibility randomized controlled trial of lithium to delay cognitive decline in mild cognitive impairment","authors":"Ariel G. Gildengers,&nbsp;Tamer S. Ibrahim,&nbsp;Xuemei Zeng,&nbsp;Howard J. Aizenstein,&nbsp;Salem K. Alkhateeb,&nbsp;Stewart J. Anderson,&nbsp;Cong Chu,&nbsp;Jihui L. Diaz,&nbsp;James E. Emanuel,&nbsp;Thomas K. Karikari,&nbsp;Jinghang Li,&nbsp;Oscar L. Lopez,&nbsp;Brian J. Lopresti,&nbsp;Sarah K. Royse,&nbsp;Andrea N. Sajewski,&nbsp;Tales Santini,&nbsp;Andrea M. Weinstein,&nbsp;Minjie Wu,&nbsp;Meryl A. Butters","doi":"10.1002/trc2.70112","DOIUrl":"https://doi.org/10.1002/trc2.70112","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Interest has grown in lithium's neuroprotective properties in neurodegenerative illnesses. We discuss the design, rationale, and implementation of a pilot feasibility, double-blind, randomized placebo-controlled trial (RCT) examining whether lithium can delay cognitive decline in older adults with mild cognitive impairment (MCI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>The study launched in September 2017. The goal was to enroll 80 community-dwelling participants ≥ 60 years with MCI into an RCT in which they would participate for 2 years with baseline and follow-up assessment of cognition, brain imaging, and plasma-based biomarkers. Participants were randomized to lithium or placebo (1:1).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We enrolled 80 MCI older adults into the RCT. Baseline characteristics included a mean (standard deviation) age of 72 (7.7) years with 35 male and 45 female participants. Seventy-five participants had positron emission tomography imaging for amyloid beta (Aβ), and 66 completed 7T magnetic resonance imaging. Twenty-one participants were Aβ+ and 54 were Aβ–.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The study successfully enrolled 80 participants into an RCT examining whether lithium delays cognitive decline. The main study results will be forthcoming.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Clinical Trial Registration</h3>\u0000 \u0000 <p>NCT03185208.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Eighty adults ≥ 60 years with mild cognitive impairment entered a placebo-controlled randomized controlled trial evaluating lithium's neuroprotective properties.</li>\u0000 \u0000 <li>Participants were followed for 2 years with baseline and follow-up evaluations at 1 and 2 years that included neurocognitive assessment, ultra-high-field structural neuroimaging, positron emission tomography imaging for amyloid beta and tau, and plasma-based biomarkers.</li>\u0000 \u0000 <li>Study results will be forthcoming.</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":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256342","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":"Time saved in activities of daily living and whole-brain volume: Post hoc analysis of a randomized feasibility trial of gamma oscillation treatment in participants with mild or moderate Alzheimer's disease","authors":"Ralph Kern,&nbsp;Benjamin Haaland,&nbsp;Jessie Nicodemus-Johnson,&nbsp;Samuel Dickson,&nbsp;Matthew Morgan,&nbsp;Joshua R. Christensen,&nbsp;Marwan N. Sabbagh,&nbsp;Lily Lee,&nbsp;Mihaly Hajós,&nbsp;Julia Riddle,&nbsp;Chandran V. Seshagiri,&nbsp;Christian Howell,&nbsp;Craig Mallinckrodt,&nbsp;Suzanne Hendrix","doi":"10.1002/trc2.70118","DOIUrl":"https://doi.org/10.1002/trc2.70118","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;Gamma oscillations in the brain are necessary for normal cognitive function, sensory processing, and memory consolidation, and are reduced in Alzheimer's disease (AD). In a 6 month, randomized, feasibility trial in participants with mild-to-moderate AD (OVERTURE [NCT03556280], &lt;i&gt;n&lt;/i&gt; = 76), a non-invasive method for sensory-evoked brain gamma oscillations outperformed sham on the secondary outcomes of slowing decline on the Alzheimer's Disease Cooperative Study–Activities of Daily Living (ADCS-ADL) functional scale, magnetic resonance imaging measures of whole brain volume and the Mini-Mental State Examination (MMSE) cognitive outcome, despite not showing statistical significance on the primary outcome (Mild and Moderate Alzheimer's Disease Composite [MADCOMS]), a composite cognitive-functional score. In this post hoc analysis of OVERTURE, we evaluated the effects of investigational sensory-evoked gamma oscillation treatment in terms of time saved, as an estimate of slowing in disease progression, on ADCS-ADL, MMSE, and whole-brain volume.&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;Disease trajectories based on the ADCS-ADL, MMSE, and whole-brain volume changes from baseline within each treatment group were constructed using mixed-effects models. Horizontal projection from active to sham arm yielded time saved from baseline at each visit. Data from the open label extension (OLE) phase of the OVERTURE study have also been used to analyze the time-saving effect of active treatment in an extended period.&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 sham, time savings of 4.83, 4.59, and 4.09 months over 6 months of active treatment on ADCS-ADL, MMSE, and whole-brain atrophy were observed in the randomized controlled trial phase. When including the OLE phase, time savings of 8.66, 10.00, and 7.48 months over 14.64, 15.98, and 13.46 months of active treatment on ADCS-ADL, MMSE, and whole-brain atrophy were observed relative to the sham 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;These findings suggest that further exploration of the effect of evoked gamma oscillations in participants with mild-to-moderate AD, as well as the evaluation of treatment effects using time saved, is merited.&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;Evoked gamma oscillation slows functional loss and brain atrophy in Alzheimer's ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70118","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144255841","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":"Translation with ongoing adaptation and improvement (ToAI) framework: A community-informed, structured, iterative approach to culturally adapting cognitive assessment tools","authors":"Quyen Q. Tiet,&nbsp;Sarah Tomaszewski Farias,&nbsp;Duyen Tran,&nbsp;Van T. Park,&nbsp;Brandon E. Gavett,&nbsp;Ladson Hinton,&nbsp;Lauren G. Mai,&nbsp;Christopher Nguyen,&nbsp;Rachel A. Whitmer,&nbsp;Quyen Vuong,&nbsp;Danielle Harvey,&nbsp;Oanh L. Meyer","doi":"10.1002/trc2.70105","DOIUrl":"https://doi.org/10.1002/trc2.70105","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) and related dementias (ADRD) are increasing globally, including in the United States, but the fast-growing Vietnamese American population remains understudied, with a significant lack of culturally adapted neuropsychological assessment tools. The Vietnamese Insights into Cognitive Aging Program (VIP) addresses this gap as the first longitudinal cohort study focused on this community.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>This paper (1) describes the assessment instruments, including a neuropsychological battery selected for the VIP, and (2) introduces the Translation with Ongoing Adaptation and Improvement (ToAI) framework, an innovative and practical method for culturally informed translation and adaptation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The ToAI framework followed a nine-step process: preparation, translation, native-speaker review, VIP team review, external panel review, pilot testing, proofreading, final formatting, and ongoing review and improvement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The ToAI framework was efficient, and the ongoing improvement component was particularly beneficial. It is recommended for inclusion in future cross-cultural research involving translation and adaptation processes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The Translation with Ongoing Adaptation and Improvement (ToAI) framework.</li>\u0000 \u0000 <li>Cross-cultural translation and adaptation of psychological assessment instruments.</li>\u0000 \u0000 <li>Neuropsychological assessment for Vietnamese American older adults.</li>\u0000 \u0000 <li>The Vietnamese Insights into Cognitive Aging Program (VIP).</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":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144255843","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":"Programmatic research outcomes used to establish the evidence-base of dementia caregiving support programs: An analysis of Best Programs for Caregiving","authors":"Morgan J. Minyo,&nbsp;Sara M. Powers,&nbsp;David M. Bass,&nbsp;Rachel M. Cannon,&nbsp;Katie Maslow,&nbsp;Zoe F. Fete,&nbsp;Megan K. Huth","doi":"10.1002/trc2.70092","DOIUrl":"https://doi.org/10.1002/trc2.70092","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;A substantial number of evidence-based dementia caregiving support programs positively impact family and friend caregivers. Researchers and service organizations have successfully translated and delivered a subset of these programs to caregivers and are included in &lt;i&gt;Best Programs for Caregiving&lt;/i&gt; (BPC). This investigation examined the programmatic caregiver research outcomes reported in peer-reviewed articles of BPC programs to understand how programs impact caregivers in the community and identify underrepresented outcomes.&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;Peer-reviewed, published research articles that (1) reported at least one dementia caregiver outcome, and (2) used a controlled trial or pre/posttest study design were abstracted from the BPC database. Across 45 evidence-based programs in BPC, 128 articles met inclusion criteria for data coding and descriptive analysis. Research outcomes (e.g., stress, depressive symptoms), efficacy findings (e.g., beneficial, no effect), and the type of study design used (e.g., pre/posttest, treatment/control) were coded from each article.&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;Twelve programmatic outcomes were identified focusing on &lt;i&gt;Caregiver Well-Being&lt;/i&gt; and &lt;i&gt;Caregiver Support&lt;/i&gt;. &lt;i&gt;Caregiver Well-Being&lt;/i&gt; outcomes were frequently assessed by BPC programs, including symptoms of depression, reported in 81 (63.3%) articles, and care-related stress, strain, and/or burden, reported in 75 (58.6%) articles. By comparison, &lt;i&gt;Caregiver Support&lt;/i&gt; outcomes were infrequently measured including quantity of family/friend support, reported in 17 (13.3%) articles, and quantity of community service use, reported in 13 (10.2%) articles. High percentages of beneficial findings were reported for both &lt;i&gt;Caregiver Well-Being&lt;/i&gt; and &lt;i&gt;Caregiver Support&lt;/i&gt; outcomes. Articles reported beneficial findings using pre/posttest and treatment/control group designs similarly across caregiver outcomes.&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 majority of BPC programs positively impact caregiver well-being outcomes but limited attention is given to other person-centered and strength-based research outcomes including supports for caregivers, unmet needs, and positive aspects of caregiving. Additional research is needed by both established and new non-pharmacological caregiving interventions to target and evaluate the impact of these underrepresented outcomes.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144255840","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":"Profiling the needs of dementia caregivers in a Brazilian cross-sectional study","authors":"Alan Cronemberger Andrade,&nbsp;Mariel Carolina Montiel-Aponte,&nbsp;Ronaldo Cristiano Prati,&nbsp;Sheilla de Medeiros Correia Marin,&nbsp;Emanuela Bezerra Torres Mattos,&nbsp;Flavio Shigeo Yamamoto,&nbsp;Marcia Maria Pires Camargo Novelli,&nbsp;Walter Teixeira Lima Junior","doi":"10.1002/trc2.70067","DOIUrl":"https://doi.org/10.1002/trc2.70067","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;Alzheimer's disease is an increasingly critical public health concern in aging populations. Characterized by progressive impairments, it can lead to dementia and significant dependence on family caregivers, who often face cognitive and behavioral challenges and heightened health risks. The study investigates the demands and unmet needs of these family caregivers using an electronic data-capture approach.&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;This observational, descriptive, cross-sectional study was conducted in Brazil from February 2022 to January 2023. Non-professional dementia caregivers were surveyed through asynchronous digital data collection. A novel, context-specific questionnaire developed by an interdisciplinary expert group was administered, and a subset of randomly selected caregivers participated in focused interviews to enhance data quality.&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 711 potential participants screened, 381 completed the questionnaire (53% response rate). Among them, 311 (82%) identified as non-professional caregivers. The results indicate that these caregivers often feel unprepared (46%), may have a negative self-perception of their role (39%), but also may feel rewarded with being a caregiver (44%). The primary needs expressed included additional assistance from others (87%) and emotional support (62%).&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;Findings indicate that care responsibilities were predominantly assumed by middle-aged female relatives, primarily in unpaid roles, with many providing more than 8 hours of direct care daily. A substantial proportion left their jobs to fulfill caregiving duties, underscoring the urgency of implementing policies that address the extensive needs of individuals with dementia and their caregivers. Given the complexity of dementia, public policies should be informed by rigorous situational analysis and delivered through targeted social, health, and educational programs that equip caregivers with effective management strategies and technologies while enhancing personalized emotional support systems.&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;Lack of preparedness: Brazilian family caregivers often feel unprepared for their responsibilities (33%), which may lead to negative self-satisfaction with their role as caregivers (38%).&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":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144213896","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}