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

{"title":"Neurovascular de-coupling underlies dual-task cost across cognitive abilities","authors":"Laura K. Fitzgibbon-Collins,&nbsp;Sarah Best,&nbsp;Mamiko Noguchi,&nbsp;Corey Guest,&nbsp;Michael Borrie,&nbsp;J. Kevin Shoemaker,&nbsp;Jaspreet Bhangu","doi":"10.1002/trc2.70156","DOIUrl":"https://doi.org/10.1002/trc2.70156","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We tested the hypothesis that increased middle cerebral artery velocity (MCA velocity) during complex motor (overground walking) and cognitive tasks (e.g., dual task) is associated with cognitive performance in older adults with varying levels of cognitive ability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Fifty-six participants (19 females, 75 ± 7 years old) completed a seated single task that assessed working memory performance; a walking single task, assessing overground walking gait speed; and a dual task, combining both. Continuous MCA velocity was collected, and participants completed a Montreal Cognitive Assessment (MoCA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Higher MCA velocity was associated with faster gait speed, better working memory performance, and greater MoCA scores (all <i>p</i> &lt; 0.05). Participants with lower MoCA scores had lower MCA velocity (<i>p</i> = 0.052), slower gait speed (<i>p</i> = 0.035), and lower working memory performance (<i>p</i> = 0.016) than people with higher MoCA scores. The hyperemic response of MCA velocity from single task walking to the dual task with increased cognitive load significantly contributed to MoCA scores (<i>p</i> = 0.017).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The functional response of cerebral blood flow with these tests suggests vascular properties may be considered a biomarker indicative of subclinical cognitive function during walking tasks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Mobile devices simultaneously assessed neurovascular coupling and dual-task cost.</li>\u0000 \u0000 <li>Middle cerebral artery velocity (MCA velocity) is negatively associated with dual-task cost.</li>\u0000 \u0000 <li>MCA velocity is associated with gait speed, working memory, and Montreal Cognitive Assessment scores.</li>\u0000 \u0000 <li>MCA velocity decreased from controls to mild cognitive impairment to dementia.</li>\u0000 \u0000 <li>Novel methodological approach to utilize MCA velocity during overground walking, single-tasks, and dual-tasks.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237279","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":"Mitochondrial blood-based biomarker is related to cardiorespiratory fitness and aging in a sex-dependent manner","authors":"Riley E. Kemna,&nbsp;Amanda Szabo-Reed,&nbsp;Hana D. Mayfield,&nbsp;Paul J. Kueck,&nbsp;Jenae Pennington,&nbsp;Casey S. John,&nbsp;Brittany M. Hauger,&nbsp;Heather M. Wilkins,&nbsp;Eric D. Vidoni,&nbsp;Jill K. Morris","doi":"10.1002/trc2.70163","DOIUrl":"https://doi.org/10.1002/trc2.70163","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 sedentary lifestyle increases the risk for Alzheimer's disease (AD), whereas exercise has been shown to benefit brain health. Physiological factors, such as female sex, are linked to lower cardiorespiratory fitness and can increase the risk of AD, which might impact exercise benefits to the brain. Exploring cellular mechanisms underlying fitness in older adults is essential to understanding exercise and AD risk and how sex might impact this interaction.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; METHODS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We collected blood from 34 cognitively healthy older adults (age 65+, 18 male, 16 female) enrolled in the COMbined Exercise Trial (COMET; NCT04848038). Subjects underwent a blood draw and clinical assessments for cardiorespiratory fitness and body composition. Blood was collected in ACD tubes, and lymphocytes were isolated. Fluorescent stains used were MitoTracker, Annexin V, MitoSOX, TMRE (tetramethylrhodamine ethyl ester), and Hoechst, analyzed by flow cytometry, and used to calculate a composite mitochondrial function index (MFI).&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;As expected, males had higher lean mass and VO&lt;sub&gt;2peak&lt;/sub&gt; than females (&lt;i&gt;p&lt;/i&gt; = 0.01), but groups did not differ in body mass index (&lt;i&gt;p&lt;/i&gt; = 0.51). Males had a higher MFI compared to females (&lt;i&gt;p&lt;/i&gt; = 0.01). Within each sex, we observed unique metabolic relationships. In males, there was an age-associated decline in MFI (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.382, &lt;i&gt;p&lt;/i&gt; = 0.01). In females, our systemic measure of mitochondrial superoxides had a negative relationship with lean mass (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.648, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) and oxygen uptake efficiency slope (OUES) (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.271, &lt;i&gt;p&lt;/i&gt; = 0.04).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; DISCUSSION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We combined an MFI with measures related to fitness in a cognitively healthy older adult population. We explored physiological factors that impact cardiorespiratory fitness, such as sex. We observed relationships between mitochondrial superoxides and OUES and lean mass in females, whereas males had higher MFI overall. Sex-dependent differences in mitochondrial function and superoxide might be an underlying factor of variable cardiorespiratory fitness between sexes and could help explain differences in AD risk.&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;Mitochondrial blood-biomarker shows sex-","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70163","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237102","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":"Recruitment and eligibility in a Phase 1 early Alzheimer's disease trial of Sabirnetug","authors":"Robyn Moxon,&nbsp;Todd Feaster,&nbsp;Gopalan Sethuraman,&nbsp;Alyssa Carroll,&nbsp;Siew Tin Gan,&nbsp;Vladimir Skljarevski,&nbsp;Karen Sundell,&nbsp;Janice Hitchcock,&nbsp;Eric Siemers","doi":"10.1002/trc2.70161","DOIUrl":"https://doi.org/10.1002/trc2.70161","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;Historically underrepresented racial and ethnic groups may face a higher risk and burden of dementia but continue to be underrepresented in Alzheimer's disease (AD) clinical research. Recent efforts have been insufficient to identify and address race-related disparities in recruitment and eligibility for AD clinical trials.&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;INTERCEPT-AD was a Phase 1 randomized, placebo-controlled, double-blind, first-in-human study of sabirnetug (ACU193) in participants with early symptomatic AD (mild cognitive impairment [MCI] or mild dementia due to AD). Participants were referred through seven site-selected recruitment strategies across 17 study sites in the United States (June 2021–January 2023). Numbers of pre-screened (&lt;i&gt;n&lt;/i&gt; = 1025), screened (&lt;i&gt;n&lt;/i&gt; = 260), and eligible (&lt;i&gt;n&lt;/i&gt; = 70) participants were compared by recruitment strategy. Recruitment strategy effectiveness (percentage of eligible participants among screened participants) and reasons for screening ineligibility were compared between non-Hispanic White participants and participants from other racial and ethnic groups (i.e., participants who self-identified as American Indian or Alaska Native, Asian, Black or African American, or Hispanic or Latino).&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;Local site databases were used at 13 of 17 sites (76%) and accounted for the most screened (&lt;i&gt;n&lt;/i&gt; = 107, 41%) and eligible (&lt;i&gt;n&lt;/i&gt; = 32, 46%) participants. Non-Hispanic White participants were recruited from all seven recruitment strategies, whereas participants of other racial and ethnic groups were recruited primarily from site databases. Significantly more participants of other racial and ethnic groups were ineligible for the study after screening, largely due to ineligible amyloid positron emission tomography (PET) scans (+13.9%).&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;Diverse recruitment tactics, customized to capabilities of study sites and patient populations, may be more successful in recruiting diverse populations than a one-size-fits-all approach. Although a diverse pool of potential participants was screened, a less diverse group was enrolled, largely due to race- and ethnicity-related disparities in screening eligibility rates. Further investigation is needed to assess equitable screening methods for AD clinical trials.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Highlights&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70161","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237147","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":"Simulation of Alzheimer's diagnostic flows with blood biomarker test options in Japan","authors":"Ataru Igarashi,&nbsp;Noriyuki Kimura,&nbsp;Takuya Ataka,&nbsp;Temmei Ito,&nbsp;Kotaro Sasaki,&nbsp;Chizuru Kobayashi,&nbsp;Mayaka Tani,&nbsp;Yukinori Sakata,&nbsp;Mie Azuma,&nbsp;Ayano Chida,&nbsp;Tomomi Takeshima,&nbsp;Kosuke Iwasaki,&nbsp;Etsuro Matsubara","doi":"10.1002/trc2.70157","DOIUrl":"https://doi.org/10.1002/trc2.70157","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>This study projected the diagnostic testing landscape for lecanemab treatment in Japan under different workflows.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>A dynamic simulation estimated wait times and treatment-eligible patient numbers under four scenarios: current diagnostic workflow, blood biomarker (BBM) tests as triage tools, BBM tests for confirmatory diagnostics, and both combined. Willingness-to-pay (WTP) and intangible costs were assessed via an online survey to estimate testing demand.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The maximum mean wait time under the current workflow was projected at 6.4 months, decreasing with BBM integration. The number of treatment-eligible patients increased considerably with BBM-based confirmatory diagnostics. BBM triage testing reduced wait times but temporarily increased treatment-eligible patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Replacing positron emission tomography (PET) or cerebrospinal fluid with BBM-based diagnostics may increase treatment eligibility because of lower costs, driving higher demand for testing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>A dynamic simulation models Alzheimer's diagnostic workflows in Japan.</li>\u0000 \u0000 <li>Blood biomarker (BBM) tests reduce diagnostic wait times for Alzheimer's in Japan.</li>\u0000 \u0000 <li>Implementing BBM tests improves access to Alzheimer's diagnostics.</li>\u0000 \u0000 <li>Study quantifies demand for diagnostic testing based on costs and accessibility.</li>\u0000 \u0000 <li>Testing costs impact the number of treatment-eligible Alzheimer's patients.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237268","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":"Yuchan Wang,&nbsp;Qian Liu,&nbsp;Wenyong Li","doi":"10.1002/trc2.70166","DOIUrl":"https://doi.org/10.1002/trc2.70166","url":null,"abstract":"&lt;p&gt;To the Editor,&lt;/p&gt;&lt;p&gt;We read the article entitled “Clinical factors predicting the rate of cognitive decline in a US memory clinic: An electronic health record study” that was published in 2025, by Roy Adams et al. in &lt;i&gt;Translational Research &amp; Clinical Interventions&lt;/i&gt;.&lt;sup&gt;1&lt;/sup&gt; This study used real-world clinical data to examine predictors of cognitive decline after an initial memory care visit. It reveals that more rapid deterioration in Mini-Mental State Examination (MMSE) scores was linked to older age, a diagnosis of dementia, and the use of cholinesterase inhibitors or memantine. A slower decline was associated with the patient's total number of prescriptions. Neither race nor ethnicity was associated with rate of decline, and nor was baseline mild cognitive impairment, other non-dementia cognitive impairment, diabetes, hypertension, obesity, depression, anxiety, chronic pain, fatigue, or hearing loss. The authors utilized real-world electronic health records as the data foundation, which best reflects patients’ conditions in actual clinical settings. However, we note that some issues need to be further elucidated.&lt;/p&gt;&lt;p&gt;First, this study reveals that hypertension is not associated with a decline in cognitive scores, but some studies contradict this conclusion.&lt;span&gt;&lt;sup&gt;2-4&lt;/sup&gt;&lt;/span&gt; For example, a study by Ding L et al. showed that a longer hypertension duration was associated with worse memory test; in addition, the Framingham Offspring cohort study by McGrath et al. revealed that midlife hypertension is associated with increased risk of a late life dementia. We speculate that the reason this study&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; concluded that there is no association between hypertension and cognitive decline may be due to its relatively short follow-up period (6 months) and minimal changes in blood pressure. However, this does not definitively rule out a relationship between hypertension and cognitive decline, and further research is warranted.&lt;/p&gt;&lt;p&gt;Second, the authors mentioned in the abstract that faster decline in MMSE scores was associated with cholinesterase inhibitor or memantine prescription. We believe that this expression may mislead readers into thinking that the cognitive decline was caused by increased medication use. However, as the authors clarified in the discussion, this is expected and reflects increased prescribing in sicker patients.&lt;/p&gt;&lt;p&gt;In summary, we believe that this study offers valuable empirical evidence for the investigation of cognitive decline. Building on these findings, the authors could consider extending the follow-up duration and incorporating insights from additional studies&lt;span&gt;&lt;sup&gt;5, 6&lt;/sup&gt;&lt;/span&gt; to account for the causal effects of these medications, so as to further clarify the risk factors for cognitive decline.&lt;/p&gt;&lt;p&gt;Yuchan Wang: manuscript writing, final approval. Qian Liu: revision for academic advice in the field of neurology. Wenyong Li: critical revision for important intelle","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70166","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237267","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 changes in cognitive and functional outcomes in a population-based study of cognitive aging","authors":"Jeremiah A. Aakre,&nbsp;Anna M. Castillo,&nbsp;Jonathan Graff-Radford,&nbsp;Prashanthi Vemuri,&nbsp;Mary M. Machulda,&nbsp;Clifford R. Jack Jr,&nbsp;David S. Knopman,&nbsp;Ronald C. Petersen,&nbsp;Maria Vassilaki","doi":"10.1002/trc2.70160","DOIUrl":"10.1002/trc2.70160","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Research is limited regarding meaningful change thresholds for individual patients on clinical outcome assessments (COAs) frequently used in clinical trials for Alzheimer's disease and related dementias (ADRD), particularly in population-based studies early in the disease course.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>There were 646 study participants in the population-based Mayo Clinic Study of Aging (MCSA), 54–99 years old (47% females), who developed the clinical syndromes of mild cognitive impairment (MCI) with complete data to establish clinically meaningful within-patient change thresholds in cognitive and functional COAs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Using the diagnosis of incident MCI as the anchor, mean (95% confidence interval [CI]) annualized estimates of change were: Clinical Dementia Rating (CDR) scale Sum of Boxes (SB) 0.49 (0.43, 0.55), Mini-Mental State Examination (MMSE) −1.01 (−1.12, −0.91), and Functional Activities Questionnaire (FAQ) score 1.04 (0.82, 1.26).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This study provides within-patient estimates of clinically meaningful change early in disease progression in a community-based sample.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We studied incident mild cognitive impairment (MCI) participants from a population-based study.</li>\u0000 \u0000 <li>Within-patient change thresholds were estimated for clinical outcome assessments (COAs) used in clinical trials for Alzheimer's disease and related dementia (ADRD).</li>\u0000 \u0000 <li>These estimates may be used to plan and evaluate clinical trials involving disease-modifying therapies (DMTs).</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":6.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129360","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":"Mental health counseling for caregivers is associated with a slower rate of health-care use in people with dementia","authors":"Mia Yang,&nbsp;Natasha Collier,&nbsp;Joseph Rigdon,&nbsp;Christina E. Hugenschmidt","doi":"10.1002/trc2.70159","DOIUrl":"10.1002/trc2.70159","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;Caregiver support interventions can reduce depression symptoms for caregivers of persons living with cognitive impairment and dementia (PwCI). However, few studies have assessed the effect of caregiver counseling support on the health-care use of the PwCI. The objective of this study was to assess if caregiver participation in mental health counseling can slow health-care use in PwCI.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; METHODS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The analysis included all PwCI with cognitive impairment identified through the electronic health records as seen in either the Wake Forest Memory Counseling Program (MCP), providing mental health counseling, and/or the Kulynych Geriatric Consult Clinic (KGCC), providing memory assessment and care, between August 1, 2016, and February 28, 2020. Health-care use (emergency department [ED] use and hospitalization) pre- and post-index date were compared between PwCI who received only medical care (MC) and those who received both medical and mental health care (MC+MHC) using a mixed effects logistic regression model adjusted for age, sex, race, ethnicity, KGCC visit type, and primary diagnosis. Hypothesis testing was accomplished with two-sided Wald tests, and odds ratios (ORs) were used to characterize effect sizes.&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 the 1 year pre-index visit, PwCI who received medical care (MC) only experienced an increase in ED visits (OR 1.73, &lt;i&gt;P&lt;/i&gt; &lt; 0.0001) and hospitalizations (OR 1.42, &lt;i&gt;P&lt;/i&gt; &lt; 0.0001) in the 1 year post-index visit. In contrast, PwCI and caregivers who received medical + mental health care (MC+MHC) did not experience increases in ED visits (OR 1.13, &lt;i&gt;P&lt;/i&gt; = 0.5104) or hospitalizations (OR 1.15, &lt;i&gt;P&lt;/i&gt; = 0.4849). Compared to MC only, PwCI who received MC+MHC had significantly lower odds of post- versus pre-ED visits (OR 0.65, &lt;i&gt;P&lt;/i&gt; = 0.0322) but not hospitalizations (OR 0.81, &lt;i&gt;P&lt;/i&gt; = 0.3270).&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;Providing mental health counseling to caregivers in addition to medical care for the PwCI may reduce ED visits among PwCI.&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;This study tests whether caregiver participation in mental health counseling can slow health-care use in the person living with dementia (PLWD).&lt;/li&gt;\u0000 \u0000 &lt;li&gt;PLWDs who received medical o","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129361","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":"Transcriptome profiling of cerebrospinal fluid in Alzheimer's disease reveals molecular dysregulations associated with disease","authors":"Rhys E. De Sota,&nbsp;Bojk A. Berghuis,&nbsp;Samantha J. Khoury,&nbsp;Jiali Zhuang,&nbsp;Robert A. Rissman,&nbsp;James B. Brewer,&nbsp;Stephen R. Quake,&nbsp;John J. Sninsky,&nbsp;Shusuke Toden","doi":"10.1002/trc2.70152","DOIUrl":"10.1002/trc2.70152","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;Despite the increasing prevalence of neurodegenerative diseases, the molecular characterization of brain pathologies remains challenging due to limited tissue access. Cerebrospinal fluid (CSF) contains a significant proportion of brain-derived molecular contents, and characterizing these molecules has served as a proxy for evaluating molecular dysregulation in the brain. Here we have characterized the CSF cell-free messenger RNA (cf-mRNA) transcriptome and identified genes and pathways altered in Alzheimer's disease (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;We performed cf-mRNA sequencing on 52 human CSF samples and further compared their transcriptomic profiles to matched plasma samples. In addition, we also investigated the cf-mRNA profiles of CSF in individuals with AD as well as non-cognitively impaired (NCI) controls.&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 molecular content of CSF cf-mRNA was distinct from that of plasma cf-mRNA, with a substantially higher number of brain-associated genes identified in CSF. A large set of dysregulated gene transcripts from CSF was detected in the AD subjects, and these gene transcripts were able to discriminate AD from NCI subjects. Notably, the gene transcripts were enriched in biological processes closely associated with AD, such as brain development and synaptic signaling. In addition, we discovered a subset of gene transcripts that exhibited a high correlation in matched CSF and plasma samples from AD subjects.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; CONCLUSIONS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study not only reveals the novel cf-mRNA content of CSF but also highlights the potential of CSF cf-mRNA profiling as a tool to garner pathophysiological insights into 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;Cell-free messenger RNA (cf-mRNA) sequencing was performed on 52 human cerebrospinal fluid (CSF) samples.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;CSF exhibited a distinct transcriptional profile with a higher prevalence of brain-associated genes compared to plasma.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Dysregulated genes in Alzheimer's disease (AD) CSF effectively distinguished AD from non-cognitively impaired controls.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;CSF cf-mRNA profiling holds potential as a tool for gaining pathophysiological insights into AD.&lt;/li&gt;","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12438960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082321","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":"Vestibular-related dizziness duration and cognitive deficits in older adults","authors":"Xiaobao Ma,&nbsp;Jiali Shen,&nbsp;Wei Wang,&nbsp;Lu Wang,&nbsp;Yulian Jin,&nbsp;Maoli Duan,&nbsp;Qing Zhang,&nbsp;Jun Yang,&nbsp;Jianyong Chen","doi":"10.1002/trc2.70153","DOIUrl":"10.1002/trc2.70153","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; OBJECTIVE&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The objective of this study is to investigate the relationship between symptom duration of vestibular-related dizziness/vertigo and cognitive function in elderly patients, and to establish clinical guidance for assessing and intervening in vestibular-related cognitive impairments.&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 study included 100 elderly patients with vestibular dysfunction presenting dizziness, vertigo, or balance disorders, categorized into short-duration (&lt;i&gt;n&lt;/i&gt; = 64) and long-duration (&lt;i&gt;n&lt;/i&gt; = 36) groups based on symptom duration. A control group of 21 healthy elderly individuals was included. Cognitive assessments comprised P300 event-related potentials (latency/amplitude) and Montreal Cognitive Assessment (MoCA) with domain-specific analysis.&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;Significant between-group differences in P300 latency were observed (control vs short-duration vs long-duration: &lt;i&gt;p&lt;/i&gt; &lt; 0.001), whereas amplitude showed no difference (&lt;i&gt;p&lt;/i&gt; = 0.817). MoCA total scores differed significantly across groups (&lt;i&gt;p&lt;/i&gt; = 0.001), although abnormality rates were comparable (&lt;i&gt;p&lt;/i&gt; = 0.093). Domain analysis revealed significant differences in visuospatial (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) and abstract abilities (&lt;i&gt;p&lt;/i&gt; = 0.005). Symptom duration correlated with: MoCA total (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.113), visuospatial ability (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.181), attention (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.068), and orientation (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.157). P300 latency correlated with: MoCA total (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.141), visuospatial ability (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.090), delayed recall (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.112), and orientation (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.082).&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;Prolonged vestibular-related dizziness/vertigo in elderly patients is associated with cognitive deficits, particularly in visuospatial and executive functions. P300 latency demonstrates greater sensitivity than both P300 amplitude and MoCA screening, suggesting that combined electrophysiological and neuropsychological assessment enhances early detection of vestibular-related cognitive impairment.&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;Long-duration vestibular-related dizziness or balance disorders are associated with a higher risk of cognitive impairment in el","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057753","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":"Low intrinsic capacity is associated with a blunted exercise-induced cognitive enhancement in physically active middle-aged and older adults","authors":"Brandon A. Yates,&nbsp;Ariela R. Orkaby,&nbsp;Jakob L. Vingren,&nbsp;Lawrence E. Armstrong","doi":"10.1002/trc2.70141","DOIUrl":"10.1002/trc2.70141","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; INTRODUCTION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The World Health Organization supports intrinsic capacity (IC) as a framework for assessing and monitoring an older person's cognitive health. Low IC is associated with higher dementia risk. Regular exercise participation improves cognitive health, reduces dementia risk, and may increase IC. However, the long-term chronic brain benefits of regular exercise training are dependent upon the effectiveness of single exercise bouts to augment cognition. Yet, how IC influences the magnitude of improvement following a single exercise bout has not been elucidated.&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;A convenience sampling of 40 physically active adults (55 ± 6 years; mean ± SD) with a body mass index ≥ 24.9 kg/m&lt;sup&gt;2&lt;/sup&gt; (range: 24.9 to 36.3) were included in this study. IC domains were operationally defined as follows: &lt;i&gt;cognitive&lt;/i&gt; (Mini Cog and Trail Making Test Parts A and B [TMT A+B] performance), &lt;i&gt;vitality&lt;/i&gt; (body composition and exercise performance), and &lt;i&gt;locomotor function&lt;/i&gt; (habitual gait speed). Participants were stratified by &lt;i&gt;locomotor function&lt;/i&gt; into a slow group (≤1.0 m/s; LOW-IC) and a normal group (&gt;1.0 m/s; NORM-IC). Immediately prior to and following the exercise session (161-km cycling event) participants completed the executive function task (TMT A+B). An analysis of covariance, controlling for baseline TMT A+B performance, was used to detect a significant improvement in TMT A+B (&lt;i&gt;p&lt;/i&gt; &lt; 0.05).&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 had similar &lt;i&gt;cognitive abilities&lt;/i&gt; and &lt;i&gt;vitality&lt;/i&gt;, but groups significantly differed by &lt;i&gt;locomotor function&lt;/i&gt;. A significant interaction (&lt;i&gt;p&lt;/i&gt; = 0.004) was revealed where improvement for NORM-IC (−13 s [−18 to −8]; &lt;i&gt;p&lt;/i&gt; &lt; 0.001; partial &lt;i&gt;η&lt;sup&gt;2&lt;/sup&gt;&lt;/i&gt; = 0.47; adjusted mean [95% confidence interval]) was greater than for LOW-IC (−3 s [−9 to 2]; &lt;i&gt;p&lt;/i&gt; = 0.25; partial &lt;i&gt;η&lt;sup&gt;2&lt;/sup&gt;&lt;/i&gt; = 0.04) following the exercise session.&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;Low IC is associated with a blunted acute exercise-induced cognitive enhancement in mid to late adulthood. Future research is justified to determine the physiological mechanisms underpinning this novel finding.&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;Adults with overweight/obesity show cognitive gains after endurance exercise.&lt;/l","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70141","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037568","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}