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

{"title":"A splice-switching antisense oligonucleotide targeting APP reduces accumulation of α-synuclein in a mouse model of Parkinson's disease","authors":"Rijwan U. Ahammad, Brian Spencer, Bao Quach, Sahar Salehi, Robert A. Rissman","doi":"10.1002/trc2.70117","DOIUrl":"https://doi.org/10.1002/trc2.70117","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) and Parkinson's disease (PD) are neurodegenerative disorders characterized by abnormal protein aggregation, with amyloid beta (Aβ) and α-synuclein (α-syn) as key pathological markers. Increasing evidence highlights a pathological interplay between Aβ and α-syn, exacerbating neurodegeneration in both AD and PD. In this study, we evaluated the effects of reducing amyloid precursor protein (APP) processing on α-syn pathology using a splice-switching oligonucleotide (SSO) targeting APP exon 15 in Thy1-α-syn transgenic (α-syn-tg) mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>α-syn-tg mice received systemic APP SSO treatment. Immunohistochemistry and immunoblotting assessed α-syn, phosphorylated α-syn (P-Syn), and APP C-terminal fragments (CTFs) in the cortex, hippocampus, and thalamus. Neuronal integrity in different brain regions were examined, and behavioral assessments evaluated cognitive and motor functions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>APP SSO treatment significantly reduced α-syn and P-Syn in the cortex, hippocampus, and thalamus while also reversing neuronal loss in the hippocampal CA3 region. Interestingly, α-syn-tg mice exhibited elevated levels of alternative APP CTFs, which were reduced by APP SSO treatment, implicating APP processing dysregulation in α-syn pathology. Although behavioral assessments revealed no significant impairments or improvements in female α-syn-tg mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Our findings demonstrate that targeting APP reduces α-syn pathology and rescues neuronal loss, supporting the therapeutic potential of APP modulation in synucleinopathies. While no behavioral changes were observed in transgenic mice, further research exploring different models and conditions may provide additional insights into the full range of therapeutic benefits. Future studies should optimize delivery methods and explore combination therapies to enhance outcomes in neurodegenerative diseases with overlapping proteinopathies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>APP-targeting SSO reduces α-syn and P-Syn in α-syn-tg mice.</li>\u0000 \u0000 <li>APP SSO lowers APP CTFs, linking APP processing to α-syn pathology.</li>\u0000 \u0000 <li>Neuronal loss in the hippocampal CA3 region is restored fol","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367413","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":"Why testing and diagnosis for Alzheimer's disease are mission critical","authors":"Brent W. Beasley","doi":"10.1002/trc2.70126","DOIUrl":"https://doi.org/10.1002/trc2.70126","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>The author, a physician who has younger-onset Alzheimer's disease (AD), recounts his recent lunch with a former coworker who has had a stroke. The author makes the point that because we now have an effective treatment for AD, and phosphorylated tau217 is a sensitive and specific screening test for AD, we should advocate for its usage in Medicare Wellness Visits, given that the adage “Time Is Brain” is just as apropos for AD as it has been in stroke care. However, at this time, Medicare is <i>not</i> paying for the lab test.</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":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339262","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":"Alzheimer's disease genetic risk: Top African American risk allele frequencies and genetic architecture among Mexican-, African-, and non-Hispanic White Americans","authors":"Mohammad Housini,&nbsp;Zhengyang Zhou,&nbsp;Lubnaa Abdullah,&nbsp;Gita Pathak,&nbsp;Reem Ayoub,&nbsp;John Gutierrez,&nbsp;Shea Andrews,&nbsp;Nicole Phillips,&nbsp;Sid O'Bryant,&nbsp;Robert Barber,&nbsp;For the HABS-HD Study Team","doi":"10.1002/trc2.70124","DOIUrl":"https://doi.org/10.1002/trc2.70124","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 (AD) continues to be the sixth leading cause of death in the United States. Significant efforts are spent researching etiology and potential management strategies. Although minorities face a higher disease burden and are anticipated to make up 43% of the US population by 2060, most literature on inherited AD risk has been derived from studying European ancestry. Here we evaluate frequencies of top AD risk alleles for late-onset AD (LOAD) in African- (AA), Mexican- (MA) and non-Hispanic White (NHW)-American participants enrolled in the Health &amp; Aging Brain Study–Health Disparities (HABS-HD) cohort to determine ethnicity-specific differential genetic architecture.&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 DNA extracted from this community-based diverse cohort (&lt;i&gt;N&lt;/i&gt; = 3207), we calculated the genotype frequencies in each population to determine whether a significant difference is detected among the three populations. DNA genotyping was performed per manufacturer's protocols. Imputation was used for single nucleotide polymorphisms (SNPs) that were not directly genotyped. Statistical analysis was performed using R Studio.&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;Genotype frequencies for 12 out of 15 SNPs (2 apolipoprotein E [&lt;i&gt;APOE&lt;/i&gt;] variants&lt;i&gt;, SIPA1L2, PIK3C2G, GPC6, RBFOX1, ABCA7, VRK3, ALCAM, EDEM1, NSG/MSX2&lt;/i&gt;, and &lt;i&gt;WDR70)&lt;/i&gt; differed significantly between 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;This analysis expands on our previous study supporting the notion that genetic risk for AD is heterogeneous across racial and ethnic populations. Our results continue to demonstrate the valuable nature of diversity in genetic risk investigations and suggest the importance of including diverse and underrepresented racial and ethnic populations in medical research. Perhaps the most interesting finding is observed in the SNPs not found to be significantly different between groups, indicating there may be shared pleiotropic gene architecture across ethnicities.&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;Alzheimer's disease (AD) burden is rapidly increasing in the United States; minorities are disproportionally affected.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;We investigate genetic health disparities in our community-based diverse cohort.&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":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315028","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 promotion of physical activity for use in Alzheimer's disease prevention trials in adults with Down syndrome: Results from a 12-month randomized trial","authors":"Lauren T. Ptomey,&nbsp;Brian C. Helsel,&nbsp;Richard A. Washburn,&nbsp;Robert N. Montgomery,&nbsp;Ron Krebill,&nbsp;Jessica C. Danon,&nbsp;Joseph R. Sherman,&nbsp;Daniel Forsha,&nbsp;Amy Bodde,&nbsp;Amanda N. Szabo-Reed,&nbsp;Anna M. Gorczyca,&nbsp;Joseph E. Donnelly","doi":"10.1002/trc2.70115","DOIUrl":"https://doi.org/10.1002/trc2.70115","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 (AD) is the leading cause of death in individuals with Down syndrome (DS). Participation in moderate-to-vigorous physical activity (MVPA) may prevent or delay the onset of AD. Therefore, we evaluated the potential effectiveness of a remotely delivered home-based group exercise (≈8/group) to increase daily MVPA and cardiorespiratory fitness in adults with DS to a level that may be associated with delaying AD in adults with DS.&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;Adults with DS (&lt;i&gt;n&lt;/i&gt; = 81, age ≈27 years 55% female) without dementia were randomized (2:2:1) to a 12-month intervention, which included 40-min exercise sessions scheduled once (remote low (RL), &lt;i&gt;n&lt;/i&gt; = 32) or 3 times per week (remote high (RH), &lt;i&gt;n&lt;/i&gt; = 34) plus twice monthly 20-min individual remotely delivered support/education sessions or to a control arm who attended twice monthly support/education sessions only (SE, &lt;i&gt;n&lt;/i&gt; = 15). MVPA (minutes/day) was assessed by accelerometer, and cardiorespiratory fitness (VO&lt;sub&gt;2 Peak,&lt;/sub&gt; mL/kg/min) was assessed using a maximal treadmill test&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;Participant retention at 12 months was 100%. Attendance at exercise and support/education sessions averaged ~85% and ~86%, respectively. Linear mixed modeling revealed no significant differences in change in MVPA from baseline to 12 months between the RH (10 min/day) and the RL arms (2 min/day, &lt;i&gt;p &lt;/i&gt;= 0.06) or the RH and SE arms (1 min/day &lt;i&gt;p&lt;/i&gt; = 0.13). The change in VO₂ &lt;sub&gt;Peak&lt;/sub&gt; differed significantly between the RH (2.0 ± 4.6 mL/kg/min) and RL arms (−1.1 ± 3.0 mL/kg/min, &lt;i&gt;p&lt;/i&gt; = 0.04) but not between the RH and SE arms (1.2 ± 5.3 mL/kg/min, &lt;i&gt;p &lt;/i&gt;= 0.85).&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 results suggest that remotely delivered group exercise (3 times/week) in conjunction with twice-monthly support/education is feasible and may increase daily MVPA and cardiorespiratory fitness to a level that may be associated with improvements in health and cognitive parameters in adults with DS.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; CLINICAL TRIALS REGISTRATION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This trial was approved by the Institutional Review Board at the University of Kansas Medical Center and was registered on clinicaltrials.gov (NCT04048759).&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 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273125","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}