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

{"title":"Biological effects of sodium phenylbutyrate and taurursodiol in Alzheimer's disease","authors":"Steven E. Arnold, Suzanne Hendrix, Jessie Nicodemus-Johnson, Newman Knowlton, Victoria J. Williams, Jeffrey M. Burns, Monica Crane, Alison J. McManus, Sanjeev N. Vaishnavi, Zoe Arvanitakis, Judith Neugroschl, Karen Bell, Bianca A. Trombetta, Becky C. Carlyle, Pia Kivisäkk, Hiroko H. Dodge, Rudolph E. Tanzi, Patrick D. Yeramian, Kent Leslie","doi":"10.1002/trc2.12487","DOIUrl":"10.1002/trc2.12487","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Sodium phenylbutyrate and taurursodiol (PB and TURSO) is hypothesized to mitigate endoplasmic reticulum stress and mitochondrial dysfunction, two of many mechanisms implicated in Alzheimer's disease (AD) pathophysiology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>The first-in-indication phase 2a PEGASUS trial was designed to gain insight into PB and TURSO effects on mechanistic targets of engagement and disease biology in AD. The primary clinical efficacy outcome was a global statistical test combining three endpoints relevant to disease trajectory (cognition [Mild/Moderate Alzheimer's Disease Composite Score], function [Functional Activities Questionnaire], and total hippocampal volume on magnetic resonance imaging). Secondary clinical outcomes included various cognitive, functional, and neuropsychiatric assessments. Cerebrospinal fluid (CSF) biomarkers spanning multiple pathophysiological pathways in AD were evaluated in participants with both baseline and Week 24 samples (exploratory outcome).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>PEGASUS enrolled 95 participants (intent-to-treat [ITT] cohort); cognitive assessments indicated significantly greater baseline cognitive impairment in the PB and TURSO (<i>n</i> = 51) versus placebo (<i>n</i> = 44) group. Clinical efficacy outcomes did not significantly differ between treatment groups in the ITT cohort. CSF interleukin-15 increased from baseline to Week 24 within the placebo group (<i>n</i> = 34). In the PB and TURSO group (<i>n</i> = 33), reductions were observed in core AD biomarkers phosphorylated tau-181 (p-tau181) and total tau; synaptic and neuronal degeneration biomarkers neurogranin and fatty acid binding protein-3 (FABP3); and gliosis biomarker chitinase 3-like protein 1 (YKL-40), while the oxidative stress marker 8-hydroxy-2-deoxyguanosine (8-OHdG) increased. Between-group differences were observed for the Aβ42/40 ratio, p-tau181, total tau, neurogranin, FABP3, YKL-40, interleukin-15, and 8-OHdG. Additional neurodegeneration, inflammation, and metabolic biomarkers showed no differences between groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>While between-group differences in clinical outcomes were not observed, most likely due to the small sample size and relatively short treatment duration, exploratory biomarker analyses suggested that PB and TURSO engages multiple pathophysiologic pathways in AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918094","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":"Pooling Alzheimer's disease clinical trial data to develop personalized medicine approaches is easier said than done: A proof-of-principle study and call to action","authors":"Mark A. Dubbelman,&nbsp;Eleonora M. Vromen,&nbsp;Betty M. Tijms,&nbsp;Johannes Berkhof,&nbsp;Lois Ottenhoff,&nbsp;Everard G. B. Vijverberg,&nbsp;Niels D. Prins,&nbsp;Wiesje M. van der Flier,&nbsp;Sietske A. M. Sikkes","doi":"10.1002/trc2.12485","DOIUrl":"10.1002/trc2.12485","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>With the advent of the first generation of disease-modifying treatments for Alzheimer's disease, it is clearer now more than ever that the field needs to move toward personalized medicine. Pooling data from past trials may help identify subgroups most likely to benefit from specific treatments and thus inform future trial design. In this perspective, we report on our effort to pool data from past Alzheimer's disease trials to identify patients most likely to respond to different treatments. We delineate challenges and hurdles, from our proof-of-principle study, for which we requested access to trial datasets from various pharmaceutical companies and encountered obstacles in the process of arranging data-sharing agreements through legal departments. Six phase I–III trials from three sponsors provided access to their data (total <i>n</i> = 3170), which included demographic information, vital signs, primary and secondary endpoints, and in a small subset, cerebrospinal fluid amyloid (<i>n</i> = 165, 5.2%) and tau (<i>n</i> = 212, 6.7%). Data could be analyzed only within specific data access platforms, limiting potential harmonization with data provided through other platforms. Limited overlap in terms of outcome measures, clinical and biological information hindered analyses. Thus, while it is a commendable advancement that (some) trials now allow researchers to study their data, we conclude that gaining access to past trial datasets is complicated, frustrating the field's communal effort to find the best treatments for the right individuals. We provide a plea to promote harmonization and open access to data, by urging trial sponsors and the academic research community alike to remove barriers to data access and improve collaboration through practicing open science and harmonizing outcome measures, to allow investigators to learn all there is to learn from past failures and successes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> HIGHLIGHTS</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Pooling data from past Alzheimer's disease clinical trials may help identify subgroups most likely to benefit from specific treatments and may help inform future trial design.</li>\u0000 \u0000 <li>Accessing past trial datasets is complicated, frustrating the field's communal effort to find the best treatments for the right individuals.</li>\u0000 \u0000 <li>We urge trial sponsors and the academic research community to remove data access barriers and improve collaboration through practicing open science and harmonizing outcome measures.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903598","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":"Assessing social connection for long-term care home residents: Systematic review using COnsensus-based Standards for the selection of health Measurement INstruments guidelines","authors":"Neha Dewan,&nbsp;Andrew Sommerlad,&nbsp;Hannah Chapman,&nbsp;Sube Banerjee,&nbsp;Kirsten Corazzini,&nbsp;David Edvardsson,&nbsp;Madalena P. Liougas,&nbsp;Gill Livingston,&nbsp;Katherine S. McGilton,&nbsp;Hannah M. O'Rourke,&nbsp;Jennifer Bethell","doi":"10.1002/trc2.12492","DOIUrl":"10.1002/trc2.12492","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;p&gt;Social connection is important for long-term care (LTC) residents' quality of life and care. However, there is a lack of consensus on how to measure it and this limits ability to find what improves and impairs social connection in LTC homes. We therefore aimed to systematically review and evaluate the measurement properties of existing measures of social connection for LTC residents, to identify which, if any, measures can be recommended. We searched eight electronic databases from inception to April 2022 for studies which reported on psychometric properties of a measure of any aspect(s) of social connection (including social networks, interaction, engagement, support, isolation, connectedness, and loneliness) for LTC residents. We used COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines to evaluate the measurement properties reported for each identified measure and make recommendations. We identified 62 studies reporting on 38 measures; 21 measured quality of life, well-being or life satisfaction and included a social connection subscale or standalone items and 17 measures specifically targeted social connection. We found there was little high-quality evidence on psychometric properties such as sufficient content validity (&lt;i&gt;n&lt;/i&gt; = 0), structural validity (&lt;i&gt;n&lt;/i&gt; = 3), internal consistency (&lt;i&gt;n&lt;/i&gt; = 3), reliability (&lt;i&gt;n&lt;/i&gt; = 1), measurement error (&lt;i&gt;n&lt;/i&gt; = 0), construct validity (&lt;i&gt;n&lt;/i&gt; = 4), criterion validity (&lt;i&gt;n&lt;/i&gt; = 0) and responsiveness (&lt;i&gt;n&lt;/i&gt; = 0). No measures demonstrated satisfactory psychometric properties on all these aspects, so none could be recommended for use. Thirty-four measures have the potential to be recommended but require further research to assess their quality and the remaining four are not recommended for use. Our review therefore found that no existing measures have sufficient evidence to be recommended for assessment of social connection in residents of LTC homes. Further validation and reliability studies of existing instruments or the development of new measures are needed to enable accurate measurement of social connection in LTC residents for future observational and interventional studies.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Highlights&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;Social connection is fundamental to person-centered care in long-term care homes.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;There is insufficient evidence for the reliability and validity of existing measures.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;No current measures can be recommended for use based on existing evidence.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;A reliable and valid measure of social connection is needed for fu","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894860","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":"Comparing research attitudes in Down syndrome and non-Down syndrome research decision-makers","authors":"Thuy V. Lu,&nbsp;Paola Campos,&nbsp;Sean Leader,&nbsp;Xavier Lee,&nbsp;Helena Xu,&nbsp;Eric Doran,&nbsp;Joshua D Grill,&nbsp;Ira T. Lott","doi":"10.1002/trc2.12478","DOIUrl":"10.1002/trc2.12478","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; INTRODUCTION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Recruitment challenges in people with and without Down syndrome (DS) can delay research progress and risk sample bias. This study identified and quantified differences in research attitudes across populations of research enrollment decision-makers for individuals with and without 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;We performed analyses using data from two registries: the University of California, Irvine Consent-to-Contact (C2C) Registry and DS-Connect. The former represented a sample of non-DS decision-makers (&lt;i&gt;N&lt;/i&gt; = 4818), while for the latter, we excluded individuals with DS, leaving a population of DS family decision-makers (&lt;i&gt;N&lt;/i&gt; = 976). We assessed scores on the Research Attitudes Questionnaire (RAQ) between DS and non-DS decision-makers. We compared total RAQ scores using linear regression and assessed item-level RAQ differences using proportional odds regression.&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;Mean total RAQ scores were not statistically different between decision-makers in the two registries, after adjusting for age, sex, race and ethnicity, education, and the coronavirus disease 2019 (COVID-19) time frame (Est. Diff = 0.11, 95% confidence interval [CI]: -0.22, 0.43; &lt;i&gt;p&lt;/i&gt; = 0.531). However, in a pre-specified analysis, we did find evidence of differential attitudes on item-level RAQ scores. Specifically, decision-makers for participants with DS had increased odds of a more favorable response to the question of responsibility to help others (DS vs. non-DS: odds ratio [OR] = 1.26, 95% CI: 1.08, 1.48) and decreased odds of a more favorable response to the question regarding the belief that medical research would find cures for major diseases during their lifetime (DS vs. non-DS: OR = 0.77, 95% CI: 0.66, 0.90).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; DISCUSSION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Our findings provide insights for researchers to develop strategies for recruiting individuals with and without DS into clinical research. The observed item-level differences warrant further investigation to instruct precise recruitment strategies.&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;Research attitudes between decision-makers for individuals with Down syndrome (DS) and decision-makers without DS were observed to be similar on average.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Item-level differences in research att","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861639","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":"Meaningful benefit of disease-modifying treatment: Evaluating changes in health-related resource use","authors":"Carolyn W. Zhu,&nbsp;Mary Sano","doi":"10.1002/trc2.12455","DOIUrl":"10.1002/trc2.12455","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Are reductions in the rate of decline from the new disease-modifying treatments (DMTs) in early Alzheimer's disease (AD) meaningful? We examined whether such reductions may be reflected in changes in health-related resource use.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Patients with Clinical Dementia Rating (CDR) = 0.5 or 1 with a clinical diagnosis of mild cognitive impairment or AD, reflecting clinical trial populations. Health-related resource use was reported using the Resource Use Inventory (RUI) including direct medical care, non-medical care, unpaid informal care, and time use.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Faster decline in CDR–Sum of Boxes (CDR-SB) from baseline was independently associated with higher likelihood and hours of informal care received, and lower likelihood of employment/volunteer work, but not with direct medical care.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Reductions in the rate of decline in CDR-SB seen from DMTs significantly affect patients’ work capacity and need for informal care, indicators of economic impact meaningful to patients, families, and health systems. These measures are not readily captured in administrative data sets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Following a cohort of participants with MCI or mild dementia due to AD that mimics participants targeted for AD trials, this study showed slower decline in CDR-SB have significant effects on patients’ work capacity and need for informal care, but not on their direct medical care utilization such as hospitalizations, ED use, and doctors’ visits.</li>\u0000 \u0000 <li>Capturing potential benefits in health-related resource use may require direct measures of informal care and work/volunteer effort which are meaningful outcomes to patients, families and health systems.</li>\u0000 \u0000 <li>Caution is needed in our effort to assess benefits of recently developed disease modifying treatment in AD using electronic health records and administrative data from which utilization of direct medical care are routinely collected as these data sources may not capture the most apparent changes in resource utilization during early disease stages.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861640","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":"Vietnamese Insights into Cognitive Aging Program (VIP): Objectives, study design, and cohort description","authors":"Oanh L. Meyer,&nbsp;Sarah Tomaszewski Farias,&nbsp;Rachel A. Whitmer,&nbsp;Alka M. Kanaya,&nbsp;Danielle Harvey,&nbsp;Ladson Hinton,&nbsp;Quyen Q. Tiet,&nbsp;Quyen Vuong,&nbsp;Brandon Gavett,&nbsp;Van Ta Park","doi":"10.1002/trc2.12494","DOIUrl":"10.1002/trc2.12494","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;There is a dearth of research on cognitive aging and dementia in Asian Americans, particularly in Vietnamese Americans, the fourth largest Asian subgroup in the United States.&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 Vietnamese Insights into Cognitive Aging Program (VIP) investigates early life adversity and war-related trauma and their associations with cognitive health in a community-based sample of older Vietnamese Americans in Northern California (i.e., Sacramento and Santa Clara counties). Baseline measurements include a comprehensive neuropsychological battery, including measures of global cognition along with executive function, semantic memory, and episodic memory. Data also include measures of functioning, early life adversity and trauma exposure, and psychosocial and traditional cardiovascular disease risk factors. Cognitive assessments will be repeated twice over the course of the data collection period, approximately 12- and 24- months post-baseline. Blood samples collected during Wave 2 will be assayed for biochemical risk factors.&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;Baseline assessments were conducted from January 2022 to November 2023, with &lt;i&gt;N&lt;/i&gt; = 548 Vietnamese Americans; mean age ± SD was 73 ± 5.31 years and 55% of participants were women. There were significant differences in social factors by site, with Santa Clara participants having higher education (some college or higher: Sacramento, ≈25%; Santa Clara: ≈48%) and marginally higher incomes compared to Sacramento participants. A higher percentage of Santa Clara participants reported speaking English well or very well (24%) compared to Sacramento participants (13%), although the majority of the entire sample (81%) reported speaking some to no English (response options: not at all; some/a little bit; well/very well).&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 longitudinal study providea a unique opportunity to more fully delineate psychosocial factors that contribute to dementia disparities in diverse and under-engaged populations. Future work will examine cognition, the prevalence of mild cognitive impairment and dementia, and other health outcomes, while controlling for site differences in all analyses.&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;Vietnamese Insights into Cognitive Aging Program (VIP) is a new study.&lt;/li&gt;\u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749749","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":"Personalized goals of people living with dementia and family carers: A content analysis of goals set within an individually tailored psychosocial intervention trial","authors":"Jessica Budgett,&nbsp;Andrew Sommerlad,&nbsp;Nuriye Kupeli,&nbsp;Sedigheh Zabihi,&nbsp;Kenneth Rockwood,&nbsp;Claudia Cooper","doi":"10.1002/trc2.12493","DOIUrl":"10.1002/trc2.12493","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;Person-centered goals capture individual priorities in personal contexts. Goal Attainment Scaling (GAS) has been used in drug trials involving people living with dementia (PLWD) but GAS has been characterized as difficult to incorporate into trials and clinical practice. We used GAS in a trial of New Interventions for Independence in Dementia Study (NIDUS)-family, a manualized care and support intervention, as the primary outcome and to tailor the interventions to goals set. We aimed to assess the feasibility and content of baseline goal-setting.&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 developed training for nonclinical facilitators to set individualized GAS goals remotely with PLWD and family carer dyads, or carers alone, in the intervention trial, during the COVID-19 pandemic. A qualitative content analysis of the goals set explored participants’ priorities and unmet needs, to consider how existing GAS goal domains might be extended in a psychosocial intervention trial context.&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;Eleven facilitators were successfully trained to set and score GAS goals. A total of 313/328 (95%) participants were able to collaboratively set three to five goals with the facilitators. Of these, 302 randomized participating dyads set 1043 (mean 3.5, range 3 to 5) goals. We deductively coded 719 (69%) goals into five existing GAS domains (mood, behavior, self-care, cognition, and instrumental activities of daily living); 324 (31%) goals were inductively coded into four new domains: carer break, carer mood, carer behavior, and carer sleep. The most frequently set goals pertained to social support. There was little variation in types of goals set based on the context of who set them or level of pandemic restrictions in place.&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;It is feasible for people without clinical training to set GAS holistic goals for PLWD and family carers in the community. GAS has potential to facilitate personalization of care and support interventions, such as NIDUS-family, and facilitate the roll out of more personalized care.&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;Goal Attainment Scaling (GAS) can capture meaningful priorities of people with dementia and their family carers.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;A psychosocial intervention RCT used GAS as t","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11247364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141621734","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":"Correction to “The functional role of the pulvinar in discriminating between objective and subjective cognitive impairment in major depressive disorder”","authors":"","doi":"10.1002/trc2.12489","DOIUrl":"10.1002/trc2.12489","url":null,"abstract":"<p>Yulug B, Ayyildiz S, Sayman D, et al. The functional role of the pulvinar in discriminating between objective and subjective cognitive impairment in major depressive disorder. <i>Alzheimer's Dement</i>. 2024;10(1)e12450. doi:10.1002/trc2.12450</p><p>The second affiliation for Halil Aziz Velioglu was incorrectly listed as “School of Medicine, TUM-NIC Neuroimaging Center, Technical University of Munich, Munich, Germany”</p><p>The correct second affiliation is “Functional Imaging and Cognitive–Affective Neuroscience Lab (fINCAN), Health Sciences and Technology Research Institute (SABITA), Istanbul Medipol University, Istanbul, Turkey”</p><p>We apologize for this error.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617589","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":"Relationships between plasma biomarkers, tau PET, FDG PET, and volumetric MRI in mild to moderate Alzheimer's disease patients","authors":"Dawn C. Matthews,&nbsp;Jefferson W. Kinney,&nbsp;Aaron Ritter,&nbsp;Randolph D. Andrews,&nbsp;Erin N. Toledano Strom,&nbsp;Ana S. Lukic,&nbsp;Lauren N. Koenig,&nbsp;Carolyn Revta,&nbsp;Howard M. Fillit,&nbsp;Kate Zhong,&nbsp;Babak Tousi,&nbsp;James B. Leverenz,&nbsp;Howard H. Feldman,&nbsp;Jeffrey Cummings","doi":"10.1002/trc2.12490","DOIUrl":"10.1002/trc2.12490","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 “A/T/N” (amyloid/tau/neurodegeneration) framework provides a biological basis for Alzheimer's disease (AD) diagnosis and can encompass additional changes such as inflammation (“I”). A spectrum of T/N/I imaging and plasma biomarkers was acquired in a phase 2 clinical trial of rasagiline in mild to moderate AD patients. We evaluated these to understand biomarker distributions and relationships within this population.&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;Plasma biomarkers of pTau-181, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), other inflammation-related proteins, imaging measures including fluorodeoxyglucose (FDG) positron emission tomography (PET), flortaucipir PET, and volumetric magnetic resonance imaging (MRI), and cognitive endpoints were analyzed to assess characteristics and relationships for the overall population (&lt;i&gt;N&lt;/i&gt; = 47 at baseline and &lt;i&gt;N&lt;/i&gt; = 21 for longitudinal cognitive comparisons) and within age-decade subgroups (57-69, 70-79, 80-90 years).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; RESULTS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Data demonstrate wide clinical and biomarker heterogeneity in this population influenced by age and sex. Plasma pTau-181 and GFAP correlate with tau PET, most strongly in left inferior temporal cortex (&lt;i&gt;p&lt;/i&gt; = 0.0002, &lt;i&gt;p&lt;/i&gt; = 0.0006, respectively). In regions beyond temporal cortex, tau PET uptake decreased with age for the same pTau-181 or GFAP concentrations. FDG PET and brain volumes correlate with tau PET in numerous regions (such as inferior temporal: &lt;i&gt;p&lt;/i&gt; = 0.0007, &lt;i&gt;p&lt;/i&gt; = 0.00001, respectively). NfL, GFAP, and all imaging modalities correlate with baseline MMSE; subsequent MMSE decline is predicted by baseline parahippocampal and lateral temporal tau PET (&lt;i&gt;p&lt;/i&gt; = 0.0007) and volume (&lt;i&gt;p&lt;/i&gt; = 0.0006). Lateral temporal FDG PET (&lt;i&gt;p&lt;/i&gt; = 0.006) and volume (&lt;i&gt;p&lt;/i&gt; = 0.0001) are most strongly associated with subsequent ADAS-cog decline. NfL correlates with FDG PET and baseline MMSE but not tau PET. Inflammation biomarkers are intercorrelated but correlated with other biomarkers in only the youngest 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;Associations between plasma biomarkers, imaging biomarkers, and cognitive status observed in this study provide insight into relationships among biological processes in mild to moderate AD. Findings show the potential to characterize AD patients regarding likely tau pathology, neurodegeneration, prospective clinical decline, and the importance of covariates such as age.&lt;/p&gt;\u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11233274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581498","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":"Dementia severity at incident diagnosis in a population representative sample of older Americans","authors":"Shengjia Xu,&nbsp;Niloofar Fouladi-Nashta,&nbsp;Yi Chen,&nbsp;Julie Zissimopoulos","doi":"10.1002/trc2.12491","DOIUrl":"10.1002/trc2.12491","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We provide the first analysis of distribution of dementia severity at incident diagnosis for a population representative sample of older Americans.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using data from the Aging, Demographics, and Memory Study (ADAMS), the Health Retirement Study (HRS), and traditional Medicare claims, we estimated the Clinical Dementia Rating Scale for ADAMS respondents and applied parameter estimates to predict dementia severity for HRS respondents with claims-based incident dementia diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Seventy percent of older adults received a dementia diagnosis of mild cognitive impairment or mild dementia (early stages). Fewer individuals were diagnosed at early stages in years 2000 to 2008 (65%) compared to years 2009 to 2016 (76%). About 72% of non-Hispanic white persons were diagnosed at early stages, compared to 63% non-Hispanic black and 59% Hispanic persons. More males than females were diagnosed at early stages (75% vs 67%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These data linkages allow population surveillance of early and equitable dementia detection in the older US population to assess clinical and policy levers to improve detection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>For the US population 70 and older, 30% were diagnosed with dementia at a moderate or severe stage.</li>\u0000 \u0000 <li>Fewer were diagnosed at early stages in years 2000 to 2008 compared to 2009 to 2016 (65% vs 76%).</li>\u0000 \u0000 <li>A total of 72% of white persons were diagnosed at early stages, compared to 63% black and 59% Hispanic persons.</li>\u0000 \u0000 <li>More males than females were diagnosed at early stages (75% vs 67%).</li>\u0000 \u0000 <li>High wealth and education level were associated with diagnosis at early stages disease.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581497","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}