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

{"title":"A diagnostic plasma omics-biomarker for Alzheimer's disease informed by microglial single-cell transcriptomics: A pilot study.","authors":"Michael W Lutz, Zhaohui Man, Yifei Zheng, Srilakshmi Venkatesan, Ornit Chiba-Falek","doi":"10.1002/trc2.70273","DOIUrl":"10.1002/trc2.70273","url":null,"abstract":"<p><strong>Background: </strong>The current biomarker framework for the diagnosis and staging of Alzheimer's disease (AD) relies mainly on neuropathological features; thus, its performance for diagnosis is limited prior to the initiation of neurodegeneration. Here, we leveraged transcriptomic data to develop a new framework for omic-informed blood-based diagnostic biomarkers for AD from an early stage.</p><p><strong>Methods: </strong>Microglial gene expression from single nucleus RNA sequencing (snRNA-seq) data was analyzed via six statistical methods to identify candidate panels of genes predictive of AD. A total of 78 gene panels, 30 to 2000 genes in size, were selected and evaluated for their ability to distinguish AD patients from controls. Three top-ranked panels of 300, 50, and 30 genes were transferred to blood (monocyte) transcriptomic data obtained from living subjects via a graph-based mapping approach based on optimal transport statistics.</p><p><strong>Results: </strong>The 300-panel method resulted in an area under the curve (AUC) of 0.7 and moderate accuracy (75%) in classifying AD; however, the accuracy in predicting cognitively normal patients was lower (53%). While the 300 genes provided high accuracy, inspection of the distribution of <i>P</i> values for the gene set revealed that the panel could be greatly reduced in size to capture the most significant differences between AD patients and cognitively normal individuals. The accuracy and specificity of the 50 and 30 panels demonstrated similar AUC values but improved the balance between the prediction of AD patients and normal controls. Specifically, the 50-gene panel resulted in an AUC of 0.7, with 65% AD accuracy and 71% normal accuracy.</p><p><strong>Conclusions: </strong>Integrating multiomics datasets into the AD biomarker discovery pipeline offers a powerful modality to increase precision and comprehensiveness in AD research and clinical applications.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 2","pages":"e70273"},"PeriodicalIF":7.4,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13286739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148320740","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 long-term lecanemab treatment effect on Alzheimer's disease progression.","authors":"Troy Williams, Se Ryeong Jang, Krista L Lanctôt, Ashley Kang, Lisa Bloudek, Guoqiao Wang","doi":"10.1002/trc2.70274","DOIUrl":"10.1002/trc2.70274","url":null,"abstract":"<p><strong>Introduction: </strong>Anti-amyloid therapies such as lecanemab have demonstrated statistically significant slowing of decline on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) in patients with early Alzheimer's disease (AD) in pivotal trials. Converting treatment differences on CDR-SB into time saved from disease progression may help convey clinical relevance for patients and caregivers more effectively.</p><p><strong>Methods: </strong>Disease progression models were developed using Alzheimer's Disease Neuroimaging Initiative and National Alzheimer's Coordinating Center data. A 37% treatment-related time delay, derived from the Clarity AD trial, was applied to estimate long-term efficacy of lecanemab.</p><p><strong>Results: </strong>Natural progression models estimated 11.5 to 13.7 years from mild cognitive impairment due to AD to severe AD. When starting treatment at CDR-SB 3.2, lecanemab delayed progression to severe AD by 2.5 to 3.7 years when assuming patients remained on treatment and 2.0 to 3.0 years when accounting for treatment discontinuation. Results were consistent across different datasets.</p><p><strong>Discussion: </strong>Projections suggest lecanemab substantially delays clinical progression of AD, preserving patients' time in earlier stages of AD.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 2","pages":"e70274"},"PeriodicalIF":7.4,"publicationDate":"2026-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13283907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148310505","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":"Aβ- and tau-associated neuroinflammatory signatures in Alzheimer's disease.","authors":"Bruna Bellaver, Guilherme Povala, Marco Antônio De Bastiani, Ilaria Pola, Pamela C L Ferreira, Guilherme Bauer-Negrini, João Pedro Ferrari-Souza, Douglas T Leffa, Firoza Z Lussier, Joseph Therriault, Nesrine Rahmouni, Jenna Stevenson, Stijn Servaes, Riddhi Patira, Serge Gauthier, Dana L Tudorascu, Thomas K Karikari, Nicholas Ashton, Kaj Blennow, Henrik Zetterberg, Eduardo R Zimmer, Andrea L Benedet, Pedro Rosa-Neto, Tharick A Pascoal","doi":"10.1002/trc2.70275","DOIUrl":"10.1002/trc2.70275","url":null,"abstract":"<p><strong>Introduction: </strong>Neuroinflammation is increasingly recognized as a key contributor to Alzheimer's disease (AD) progression, with distinct responses linked to amyloid beta (Aβ) and tau pathology. Two detrimental waves of neuroinflammation have been proposed, the first during early Aβ accumulation, and the second during widespread tau deposition. However, the neuroinflammatory signatures associated with each phase remain unclear.</p><p><strong>Methods: </strong>We studied 63 individuals who underwent Aβ and tau positron emission tomography imaging along with cerebrospinal fluid profiling of 368 inflammation-related proteins. Protein contrasts between cognitively unimpaired Aβ-negative and Aβ-positive individuals defined the signature of the Aβ phase, while comparisons between cognitively impaired Aβ-positive individuals with early versus late tau pathology characterized the tau phase. Gene Ontology enrichment identified biological processes associated with differentially expressed proteins.</p><p><strong>Results: </strong>During the Aβ phase, 34 proteins were downregulated and mapped to 157 biological processes, including Toll-like receptor signaling, nuclear factor kappa beta activation, and cytokine production. The tau phase showed upregulation of 23 proteins associated with 82 biological processes enriched in adaptive immune responses. A set of 48 biological processes and three proteins including interleukin 4 receptor, cystosolic phospholipidase A₂, and secretoglobin family 3A member 2 showed opposite regulation patterns, being downregulated in the Aβ phase and upregulated in the tau phase.</p><p><strong>Discussion: </strong>Our results revealed distinct neuroinflammatory signatures and biological processes associated with Aβ- and tau-dominant stages of AD. The reversal in protein expression patterns across these stages underscores the need for stage-specific neuroimmune therapeutic strategies.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 2","pages":"e70275"},"PeriodicalIF":7.4,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13279462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148297304","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":"Accelerometer-derived daily steps, cognition, and cognitive impairment in U.S. community-dwelling older adults: The Atherosclerosis Risk in Communities Study.","authors":"Pablo Martinez-Amezcua, Wuyang Zhang, Erin E Dooley, Bjoern Hornikel, Lisa Pompeii, Kelly R Evenson, Brady Rippon, B Gwen Windham, Thomas H Mosley, Jennifer A Schrack, Kelley Pettee Gabriel, Priya Palta","doi":"10.1002/trc2.70252","DOIUrl":"10.1002/trc2.70252","url":null,"abstract":"<p><strong>Introduction: </strong>The relationship between daily steps and brain health is relatively underexplored, with inconsistent findings regarding the number of steps that confer cognitive benefits.</p><p><strong>Methods: </strong>We conducted cross-sectional and longitudinal analyses using data from the Physical Activity and Falls Ancillary (PAFA) study of the Atherosclerosis Risk in Communities Study (ARIC) cohort. Participants wore an ActiGraph GT3X on the hip for ≥10 h on ≥3 days in 2016-2017. Daily step counts were analyzed continuously and categorically. Cognitive functioning and its change were assessed using global and domain-specific factor scores from a neuropsychological battery. Cognitive impairment was adjudicated (mild cognitive impairment [MCI] or dementia). Regression models-adjusted for demographics, lifestyle, and chronic conditions-evaluated differences in cognitive scores, their 4-year change, and odds of cognitive impairment by step counts. Spline terms assessed nonlinearity.</p><p><strong>Results: </strong>Among 430 participants (mean age, 78.4 years; 59.5% female; 19% Black), the baseline mean daily steps were 3492 (SD = 1934). In adjusted cross-sectional models, higher daily steps were associated with better global cognition and executive function/processing speed. Participants in the high-stepping group (≥4025 steps) had a 0.37-point higher executive function/processing speed score (95% confidence interval [CI]: 0.17-0.55) versus the low-step group (<2449). Those in the high-step group had 54% lower odds of prevalent cognitive impairment (odds ratio [OR] = 0.46, 95% CI: 0.24-0.89) compared with the lowest group. Spline models showed better cognition with higher steps, plateauing after ≈4000. Step counts were not associated with 4-year cognitive change.</p><p><strong>Discussion: </strong>Higher daily step counts are associated with better cognitive function in older adults. Modest increases in activity, even among those who moved less (<4000 steps/day), may yield cognitive benefits, although reverse causation cannot be ruled out. Promoting achievable physical activity goals, such as step counts, could benefit older adults.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 2","pages":"e70252"},"PeriodicalIF":7.4,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13272101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148279862","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":"Association of Excessive Daytime Sleepiness With Long-Term Incident Dementia: The Role of β-Amyloid and White Matter Injury.","authors":"Xiaowen Zhou, Guangshi Zhang, Qili Hu, Hanyu Shao, Tao Yang, Jie Wang, Xiaoniu Liang, Qianhua Zhao, Ding Ding","doi":"10.1002/trc2.70272","DOIUrl":"10.1002/trc2.70272","url":null,"abstract":"<p><strong>Introduction: </strong>Excessive daytime sleepiness (EDS) is common in community-dwelling older adults, but its association with long-term incident dementia remains unclear. The roles of Alzheimer's disease (AD) pathology and vascular-related white matter injury in this association were merely studied.</p><p><strong>Methods: </strong>We included 617 dementia-free participants from the Shanghai Aging Study with up to 10 years of follow-up. At baseline, EDS was assessed with the Epworth Sleepiness Scale (ESS) and plasma phosphorylated tau (p-tau)217 was measured using a single-molecule immune-array assay. Cognitive decline was evaluated using the Mini-Mental State Examination (MMSE), and incident dementia was determined by expert consensus during follow-up. A magnetic resonance imaging marker of white matter injury (peak width of skeletonized mean diffusivity [PSMD]) was derived from diffusion tensor imaging, and gray matter volume was assessed from T1-weighted imaging in a subcohort.</p><p><strong>Results: </strong>At baseline, 66 participants (10.7%) had EDS and showed lower MMSE scores. EDS was associated with a higher risk of incident dementia (hazard ratio [HR] 2.06, 95% confidence interval [CI] 1.09-3.92), especially among individuals with low p-tau217 (HR 4.94, 95% CI 1.75-13.93) independent of sleep disturbance after adjusting for age, sex, and education. Higher ESS was related to AD pathology-dependent patterns of brain atrophy and to higher PSMD. PSMD modified the associations between EDS and cognitive decline, and incident dementia. Participants with both high PSMD and EDS showed the highest dementia risk.</p><p><strong>Discussion: </strong>EDS may help identify older adults with low AD biomarker burden who are at increased risk of dementia, independent of nocturnal sleep disturbance. White matter injury may contribute to this risk, supporting a vascular vulnerability pathway.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 2","pages":"e70272"},"PeriodicalIF":7.4,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13239897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148200904","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":"Peripheral immune markers in dementia: A systematic review and meta-analysis of risk, severity, and pathological correlates.","authors":"Ahmad A Toubasi, Thuraya N Al-Sayegh","doi":"10.1002/trc2.70270","DOIUrl":"10.1002/trc2.70270","url":null,"abstract":"<p><strong>Introduction: </strong>Systemic inflammation and innate immune activation have been implicated in dementia; however, prior studies were limited by small sample sizes. We conducted this study to evaluate the association between peripheral immune markers and the future risk of mild cognitive impairment (MCI) and dementia, their ability to differentiate between dementia causes, and their correlation with disease severity and pathological biomarkers.</p><p><strong>Methods: </strong>On September 8, 2025, we searched PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL). Eligible articles included cohort and case-control studies assessing the association between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), or systemic inflammatory index (SII) and the risk of developing MCI or dementia, as well as their association with disease severity and pathological biomarkers. Outcomes were the risk of MCI and dementia (Alzheimer's disease, vascular dementia, and Parkinson's disease dementia), dementia severity assessed by the Mini-Mental State Examination, and cerebrospinal fluid or pathological markers including amyloid beta (Aβ)42, Aβ40, and tau. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled as effect estimates.</p><p><strong>Results: </strong>Our analysis included 947,020 participants from 23 studies. NLR and SII, but not PLR, were associated with increased risk of dementia (NLR: HR = 1.24, 95% CI: 1.15-1.34; SII: HR = 1.08, 95% CI: 1.03-1.13) and MCI (NLR: HR = 2.78, 95% CI: 1.57-4.90; SII: HR = 1.28, 95% CI: 1.04-1.56). No differential associations were observed across dementia causes. NLR and SII were correlated with worse dementia (NLR: <i>r</i> = -0.22, <i>p</i> = 0.033; SII: <i>r</i> = -0.17, <i>p</i> = 0.041) and MCI severity (NLR: <i>r</i> = -0.30, <i>p</i> = 0.010; SII: <i>r</i> = -0.23, <i>p</i> = 0.025). NLR, but not SII, was associated with Aβ42, Aβ40, and tau.</p><p><strong>Discussion: </strong>NLR and SII may provide valuable insights when advanced biomarker testing is limited by technological or financial barriers.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 2","pages":"e70270"},"PeriodicalIF":7.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13239776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148200976","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":"Virtual reality-based cognitive-motor training in middle-aged adults at high Alzheimer's disease risk improves frontal cortex cerebral blood flow: A randomized controlled trial.","authors":"Maayan Harel, Anat Leibovici, Nofar Itzhaki, Ramit Ravona-Springer, Erin Moshier, Glen M Doniger, Amihai Gottlieb, Yotam Bahat, Barbara B Bendlin, Gabi Zeilig, Meir Plotnik, Michal Schneider Beeri, Abigail Livny","doi":"10.1002/trc2.70265","DOIUrl":"10.1002/trc2.70265","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease (AD) pathological processes begin decades before symptom onset. Early intervention in high-risk populations may be crucial for prevention. We investigated the effect of an intervention utilizing virtual reality (VR) cognitive-motor training on cerebral blood flow (CBF) and cognitive functioning in middle-aged adults at high AD risk due to parental history.</p><p><strong>Methods: </strong>In this randomized controlled trial, participants (<i>n</i> = 79) were randomly assigned to: VR cognitive-motor training while walking on a treadmill (VR+T, <i>n</i> = 24, treatment); VR cognitive training without treadmill (VR-T, <i>n</i> = 21, active control); treadmill walking while watching documentaries (TV+T, <i>n</i> = 20, active control); or no intervention (<i>n</i> = 14, passive control). Training consisted of 45-min sessions, twice weekly, for 12 weeks. CBF was measured at resting state using arterial spin labeling (ASL) at baseline, 3-month, and 6-month follow-up. Cognition was assessed using a comprehensive neuropsychological battery. We applied the intent-to-treat approach.</p><p><strong>Results: </strong>All groups improved in executive functions and memory over time (all <i>p</i>-values < 0.05), with no consistent between-group differences at follow-up. CBF of the VR+T group significantly increased at 3 months in the superior (<i>p</i> = 0.013, middle (<i>p</i> = 0.014), and inferior (<i>p</i> = 0.003) frontal gyri compared to the passive control group, which showed a decline in CBF over the same period. No significant differences in frontal CBF change were observed between VR+T and the TV+T active control group. This increase was sustained for 6 months in the superior (<i>p</i> = 0.035) and middle (<i>p</i> = 0.028) frontal gyri. In contrast, in the middle temporal gyrus, the VR+T group had lower CBF at 3 months, compared to the VR-T (<i>p</i> = 0.033) and to the passive control groups (<i>p</i> = 0.004).</p><p><strong>Discussion: </strong>Cognitive-motor VR training increased CBF in frontal regions susceptible to early AD-related changes in middle-aged adults at high AD risk. This intervention shows promise as a preventive approach and may be suitable for implementation as a home-based program for individuals at high risk.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 2","pages":"e70265"},"PeriodicalIF":7.4,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13240019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148201050","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":"<i>APOE</i>-associated disease risk and sex-specific effects in Egyptian Alzheimer's disease: an exploratory study.","authors":"Mai Othman, Eman Khedr, Shimaa Heikal, Mohamed H Yousef, Gharib Fawi, Sara El Farrash, Samer Salama, Muhammad Abdelshafi, Nesma G Elsheikh, Heba M Tawfik, Hany I Hassanin, Nourelhoda A Haridy, Gellan K Ahmed, Noha Abo Elftoh, Amna Ibrahim, Ahmed Qayaty, Eman M Ali, Agsha Atputhavadivel, Samir Shamma, Noha A Yousri, Mie Rizig, Mohamed Salama","doi":"10.1002/trc2.70268","DOIUrl":"10.1002/trc2.70268","url":null,"abstract":"<p><strong>Introduction: </strong>The apolipoprotein E (<i>APOE</i>) gene is the strongest known genetic risk factor for late-onset Alzheimer's disease (AD), particularly the ε4 allele. Evidence suggests that women carrying at least one <i>APOE</i> ε4 allele have a higher risk of developing AD compared to men. However, data addressing genetic risk and sex-specific effects in Middle Eastern and North African populations remain limited.</p><p><strong>Methods: </strong>To address this gap, we evaluated <i>APOE</i> allele frequencies, their association with AD risk, and their contribution to sex-specific variability in a cohort of 63 clinically diagnosed AD patients and 201 cognitively healthy controls recruited across Egypt.</p><p><strong>Results: </strong>The <i>APOE</i> ε3 allele was the most prevalent in both AD cases (83.3%) and controls (83.6%). The ε4 allele was more frequent among AD patients (12.7%) than controls (8.0%) (adjusted odds ratio [OR] = 1.09, 95% confidence interval [CI]: 0.46 to 2.49, <i>p</i> = 0.85), while the ε2 allele was less frequent in AD patients (4.0%) compared to controls (8.5%) (adjusted OR = 0.82, 95% CI: 0.24 to 2.36, <i>p</i> = 0.73). However, neither association reached statistical significance after Benjamini-Hochberg false discovery rate correction. Sex-stratified analyses revealed no significant sex-specific effects of <i>APOE</i> alleles.</p><p><strong>Conclusion: </strong>This pilot study provides the first characterization of <i>APOE</i> genotype and allele frequencies in Egyptians with clinically confirmed AD. No statistically significant association was observed between <i>APOE</i> status and AD risk in either males or females. Larger, geographically representative studies are needed to further elucidate the role of <i>APOE</i> in AD susceptibility within the Egyptian population and to explore potential alternative genetic or environmental contributors.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 2","pages":"e70268"},"PeriodicalIF":7.4,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13240464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148200906","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":"Economic evaluations of strategies targeting pre-diagnosis dementia populations: A systematic review.","authors":"Men Thi Hoang, Alina Mona Zenker, Sanjib Saha, Ulf-Göran Gerdtham, Dominic Trépel","doi":"10.1002/trc2.70236","DOIUrl":"10.1002/trc2.70236","url":null,"abstract":"<p><p>This review aims to appraise and summarize the best available evidence from economic evaluations (EEs) of strategies targeting populations prior to a diagnosis of dementia. A comprehensive search was conducted in EMBASE, PubMed, EconLit, Web of Science, Cumulative Index to Nursing and Allied Health (CINAHL), and The NHS Economic Evaluation Database (NHS EED). Publications were dually screened and assessed against eligibility criteria, and reporting quality was appraised using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) framework. Seventeen full EEs met the inclusion criteria; all were conducted in high-income countries and covered strategies in identification (29%), risk reduction (65%), and other strategies (6%). The number of publications from 2016 to 2025 tripled compared to the preceding periods. Most risk-reduction strategies were cost-effective and exhibited high reporting quality. The average reporting quality, based on the CHEERS framework, was 72%, with a noticeable improvement observed in articles published after 2020. Overall, the findings suggest that most risk-reduction strategies may offer good value for money. However, evidence remains limited, specifically in low- and middle-income countries; therefore, additional EEs are needed to guide future investment in strategies targeting pre-diagnosis dementia populations.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 2","pages":"e70236"},"PeriodicalIF":7.4,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13239084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148200931","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 utility of a composite endpoint for tracking disease progression in Lewy body dementia.","authors":"Elie Matar, Simon R White, John-Paul Taylor, Alan Thomas, Ian McKeith, Joseph Kane, Simon Lewis, Ajenthan Surendranathan, John O'Brien","doi":"10.1002/trc2.70260","DOIUrl":"10.1002/trc2.70260","url":null,"abstract":"<p><strong>Introduction: </strong>Dementia with Lewy bodies (DLB) or Parkinson's disease dementia (PDD), collectively termed Lewy body dementia (LBD), show heterogenous progression across cognitive, motor, and neuropsychiatric symptom domains, yet disease-specific endpoints are lacking. We evaluated whether a composite clinical endpoint using validated scales across different symptom domains could sensitively track disease progression and align with functional and caregiver outcomes.</p><p><strong>Methods: </strong>One hundred sixteen participants (DLB = 72; PDD = 44) were assessed at baseline, 3, and 6 months in a cluster-randomized trial comparing usual care versus management informed by an evidence-based toolkit. The Lewy Body Symptom Severity (LBSS) index was constructed by summing rescaled Mini-Mental State Examination, Movement Disorder Society Unified Parkinson's Disease Rating Scale (Part III), Dementia Cognitive Fluctuations Scale, and Neuropsychiatric Inventory 4-item subscore (including hallucinations). Linear mixed-effects models tested change over time. Validity was examined against caregiver Clinical Rating of Change (CRC), Bristol Activities of Daily Living (ADL) Scale, and caregiver Zarit Burden Interview.</p><p><strong>Results: </strong>Over 6 months, LBSS increased significantly (<i>β</i> = 0.0307; <i>P</i> = 0.0006). Simulation-based power analyses indicated greater statistical efficiency for LBSS than for any individual component. LBSS also detected a significant intervention effect (<i>P</i> = 0.0365) not observed with single-domain measures. LBSS correlated with caregiver burden (Zarit; <i>ρ</i> = 0.53, <i>P</i> < 0.001), functional dependence (Bristol ADL; <i>ρ</i> = 0.57, <i>P</i> < 0.001), and CRC (<i>ρ</i> = -0.33, <i>P</i> = 0.002), permitting derivation of a minimal clinically important difference.</p><p><strong>Discussion: </strong>A simple composite spanning cognition, parkinsonism, cognitive fluctuations, and neuropsychiatric symptoms sensitively detected short-interval progression, with improved statistical efficiency over single-domain measures, and was aligned with functional/caregiver outcomes. These findings support composite endpoints for LBD trials and can inform the design of disease-specific scales.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 2","pages":"e70260"},"PeriodicalIF":7.4,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13239424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148201021","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}