{"title":"Safety of switching from lecanemab to donanemab in 20 consecutive patients with Alzheimer's disease.","authors":"Heii Arai, Satoko Aiba, Reiko Arai","doi":"10.1177/13872877251361051","DOIUrl":"https://doi.org/10.1177/13872877251361051","url":null,"abstract":"<p><p>We retrospectively reviewed 20 consecutive patients with Alzheimer's disease who switched from lecanemab to donanemab. No new amyloid-related imaging abnormalities (ARIA) or significant adverse events were observed during the first five donanemab infusions. Prior exposure to lecanemab may reduce ARIA risk. Cognitive function remained stable. These preliminary observations suggest that switching between anti-amyloid therapies may be safe in the short term, though larger prospective studies are warranted.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251361051"},"PeriodicalIF":3.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emma Nichols, Jinkook Lee, Alden L Gross, Masroor Anwar, Abhishek Gupta, Eileen M Crimmins, Bharat Thyagarajan, Sharmistha Dey
{"title":"Associations between blood-based neurodegenerative biomarkers and cognitive functioning and decline in India.","authors":"Emma Nichols, Jinkook Lee, Alden L Gross, Masroor Anwar, Abhishek Gupta, Eileen M Crimmins, Bharat Thyagarajan, Sharmistha Dey","doi":"10.1177/13872877251361934","DOIUrl":"https://doi.org/10.1177/13872877251361934","url":null,"abstract":"<p><p>BackgroundMounting evidence supports the use of blood-based neurodegenerative biomarkers as a low-cost, minimally invasive tool for studying Alzheimer's disease and other dementias, but existing data largely come from clinical samples or high-income settings. Despite emphasis in the literature on the importance of understanding the utility of neurodegenerative biomarkers in diverse populations, published analyses are limited.ObjectiveTo assess the utility of neurodegenerative biomarkers in India by quantifying associations between biomarkers and cognitive outcomes in a nationally representative cohort study.MethodsWe quantified associations between five neurodegenerative blood biomarkers (amyloid-β 42/40 (Aβ<sub>42/40</sub>), total tau, phosphorylated Tau181 (pTau-181), glial fibrillary acidic protein (GFAP), neurofilament light (NfL)) and cross-sectional and longitudinal cognitive outcomes using nationally-representative data from the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (N = 4096).ResultsWe observed associations between biomarkers and cross-sectional cognitive functioning (Aβ<sub>42/40</sub>, GFAP, and NfL) and longitudinal cognitive change (pTau-181 and NfL). NfL had the strongest associations; each SD increase in log NfL was associated with 0.007 (95% CI 0.000 to 0.014) SD unit/year worse cognitive decline, equivalent to about 35% of the mean longitudinal decline in the sample. We saw little evidence of effect modification by demographic variables or <i>APOE</i> ε4 status.ConclusionsNeurodegenerative biomarkers were associated with cross-sectional and longitudinal outcomes as well as mortality, though there was variation in outcome-specific findings across biomarkers. Findings generally support the use of neurodegenerative biomarkers in India. Future research in India should leverage these biomarkers to address a range of research topics, including heterogeneity in dementia phenotypes.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251361934"},"PeriodicalIF":3.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The discriminant ability of the Eating Assessment Tool-10 to detect dysphagia and aspiration according to the stage of Alzheimer's disease.","authors":"Serkan Bengisu, Merve Savaş, Demet Aygün Üstel, Senanur Kahraman Beğen, Burak Manay","doi":"10.1177/13872877251362229","DOIUrl":"https://doi.org/10.1177/13872877251362229","url":null,"abstract":"<p><p>BackgroundAlzheimer's disease (AD) is a progressive neurodegenerative disorder frequently associated with dysphagia, leading to malnutrition, dehydration, and aspiration pneumonia. The Eating Assessment Tool-10 (EAT-10) is widely used for dysphagia screening; however, its reliability in advanced AD, where cognitive impairments hinder self-reporting, remains uncertain.ObjectiveThis study aimed to evaluate the diagnostic accuracy of EAT-10 in detecting dysphagia and aspiration across different AD stages.MethodsThe study included 30 AD patients classified into mild, moderate, and advanced stages based on Clinical Dementia Rating (CDR) scores. Dysphagia was assessed using EAT-10 and validated through Videofluoroscopic Swallowing Study (VFSS) and the Penetration-Aspiration Scale (PAS). Statistical analyses included the Mann-Whitney U test, Spearman correlation, and receiver operating characteristic (ROC) curve analysis (p < 0.05).ResultsEAT-10 scores significantly differed across AD stages (p = 0.001), with mean scores of 3.11 ± 1.17 (mild), 11.70 ± 4.64 (moderate), and 18.00 ± 6.90 (advanced). Unsafe swallowing and aspiration were observed in 43.3% and 23.3% of patients, respectively, with higher prevalence in advanced AD. ROC analysis determined an EAT-10 cut-off score of 15 for unsafe swallowing (AUC: 0.96, sensitivity: 88%, specificity: 77%) and 18 for aspiration (AUC: 0.81, sensitivity: 81.2%, specificity: 75%). Strong correlations were found between EAT-10 and PAS scores (r = 0.812, p < 0.001).ConclusionsEAT-10 is an effective screening tool for dysphagia and aspiration risk in early and moderate AD stages. However, in advanced AD, objective assessments like VFSS remain essential to complement EAT-10 results. Integrating EAT-10 into routine evaluations may enhance early detection, enabling timely interventions and improved clinical outcomes.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251362229"},"PeriodicalIF":3.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Application of the Cogstate Brief Battery in assessing cognitive function in older Japanese individuals.","authors":"Takuya Ataka, Noriyuki Kimura","doi":"10.1177/13872877251359968","DOIUrl":"https://doi.org/10.1177/13872877251359968","url":null,"abstract":"<p><p>BackgroundAccurate and simple detection of cognitive decline is important for the prediction of dementia and identification of drug indications. The Cogstate Brief Battery (CBB) is useful in assessing cognitive function during the preclinical and mild cognitive impairment stages. However, whether it is beneficial for assessing brain function in older Japanese adults remains unclear.ObjectiveThis study aimed to assess the association of the CBB score with those of traditional cognitive tests and brain imaging in assessing cognitive function in older Japanese adults with normal cognitive function and those with mild cognitive impairment.MethodsCommunity-dwelling older adults in Usuki city underwent CBB, traditional cognitive tests, magnetic resonance imaging, and amyloid positron emission tomography. The association of the CBB score with the Japanese version of the Montreal Cognitive Assessment (MoCA-J), Japanese version of Mini-Mental State Examination (MMSE), hippocampal atrophy on magnetic resonance imaging, and brain amyloid deposition on <sup>11</sup>C-Pittsburgh compound-B positron emission tomography was examined.ResultsIn total, 170 participants were included in this study. Among them, 59 were positive for the C-Pittsburgh compound-B. The CBB score was significantly associated with the MoCA-J and MMSE score in all patients. Further, it was significantly associated with hippocampal atrophy in the amyloid-positive group.ConclusionsThe CBB is associated with the MoCA-J and MMSE scores and may thus be a useful tool for the assessing cognitive decline in Japanese older adults.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251359968"},"PeriodicalIF":3.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhaohua Huo, Benjamin Hon-Kei Yip, Allen Ting-Chun Lee, Sheung-Tak Cheng, Wai Chi Chan, Ada Wai-Tung Fung, Suk Ling Ma, Calvin Pak-Wing Cheng, Frank Ho-Yin Lai, Samuel Yeung-Shan Wong, Linda Chiu-Wa Lam
{"title":"Healthcare utilization and economic costs of neurocognitive disorders in community-dwelling older Chinese adults: A comparison with 9 Asian economies.","authors":"Zhaohua Huo, Benjamin Hon-Kei Yip, Allen Ting-Chun Lee, Sheung-Tak Cheng, Wai Chi Chan, Ada Wai-Tung Fung, Suk Ling Ma, Calvin Pak-Wing Cheng, Frank Ho-Yin Lai, Samuel Yeung-Shan Wong, Linda Chiu-Wa Lam","doi":"10.1177/13872877251361057","DOIUrl":"https://doi.org/10.1177/13872877251361057","url":null,"abstract":"<p><p>BackgroundIt is increasing recognized that care for people with neurocognitive disorders (NCDs) is costly, and cost of NCDs can be highly context dependent.ObjectiveTo evaluate the healthcare utilization and economic costs of NCDs in Hong Kong, cross referencing with other Asian metropolitan cities.Methods461 older adults aged ≥60 (major NCD: 68, mild NCD: 264, normal cognition: 129) were recruited from a population-based cross-sectional survey, Hong Kong Mental Morbidity Survey for Older People. Healthcare utilization was collected by Resource Utilization of Dementia. Per person cost was estimated from a societal perspective and expressed in 2022 US dollars. Cost-associative factors were explored. Our findings were compared to cost-of-illness evidence in major Asian metropolitan cities by a systematic review.ResultsAnnual costs per community-living adult with mild and major NCD were US$5677 (95%CI: 4985-6465) and US$12,841 (9940-16,590) in Hong Kong. For those with major NCD, costs doubled in severer stages, and diagnosed cases incurred nearly 30% more costs than hidden cases. Dementia cost in Hong Kong was lower than other high-income Asian economies and mainland China, mainly due to methodological heterogeneities and lower utilization of social care services.ConclusionsThe great economic burden of NCDs in Hong Kong reflects a striking social and care needs, particularly in moderate and severe stages. Care planning should prepare for the blowout needs being revealed by hidden cases and the diversified needs by different stages and family caregivers. Region- and population-specific studies with rigor design are warranted to estimate cost-effectiveness of upcoming treatment strategies.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251361057"},"PeriodicalIF":3.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tsz-Lok Lee, Timothy Chi-Yui Kwok, Linda Chiu-Wa Lam, Helene Hoi-Lam Fung, Mei-Chun Cheung, Yvonne Ming Yee Han, Agnes Sui-Yin Chan
{"title":"Improved cognitive function, efficiency, saccadic eye movement, and depressive symptoms in mild cognitive impairment with transcranial photobiomodulation.","authors":"Tsz-Lok Lee, Timothy Chi-Yui Kwok, Linda Chiu-Wa Lam, Helene Hoi-Lam Fung, Mei-Chun Cheung, Yvonne Ming Yee Han, Agnes Sui-Yin Chan","doi":"10.1177/13872877251361033","DOIUrl":"https://doi.org/10.1177/13872877251361033","url":null,"abstract":"<p><p>BackgroundMild cognitive impairment (MCI) is a critical stage with higher progression to Alzheimer's disease, yet effective interventions are still lacking.ObjectiveSome empirical studies have shown that transcranial photobiomodulation (tPBM) may be effective in enhancing cognitive function. To further investigate its effectiveness, a controlled experiment was conducted.MethodsIn this study, 36 community-dwelling older adults with MCI were assigned to receive either real tPBM (experimental group; <i>n</i> = 25) and others without intervention (control group; <i>n</i> = 11) over three weeks. Participants underwent comprehensive assessments before and after the intervention, including neuropsychological tests, measurements of oxygenated hemoglobin (HbO) using function near-infrared spectroscopy during a visual working memory task, saccadic movement measurement using an eye-tracking device, and a questionnaire assessing depressive symptoms.ResultsCompared to the control group, the experimental group demonstrated significant improvements. They showed enhanced cognitive efficiency, as evidenced by improved visual working memory performance, reduced anti-saccade latency, higher scores in the Montreal Cognitive Assessment, and faster completion time in the Shape Trail Test B. In addition, significantly more participants in the experimental group showed improvement in depressive symptoms after the intervention.ConclusionsThese findings provide preliminary evidence that tPBM may effectively improve neuropsychological, physiological, and psychological outcomes in individuals with MCI. This trial was registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn, registration number: ChiCTR2400090408).</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251361033"},"PeriodicalIF":3.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xin Wang, Meng Wang, Han Wang, Guosheng Yin, Yan Dora Zhang
{"title":"Drug repurposing for Alzheimer's disease integrating transcriptome-wide association study and biological network analysis.","authors":"Xin Wang, Meng Wang, Han Wang, Guosheng Yin, Yan Dora Zhang","doi":"10.1177/13872877251360009","DOIUrl":"https://doi.org/10.1177/13872877251360009","url":null,"abstract":"<p><p>BackgroundThe accumulation of particular protein deposits connected to molecular mechanisms is one of the many brain abnormalities associated with Alzheimer's disease (AD), a complex neurodegenerative illness. There are currently no effective disease-modifying treatments for AD.ObjectiveThis study attempts to identify potential AD therapeutics through a biological network-based drug repurposing strategy, focusing on drugs targeting important proteins and biological pathways involved in AD pathology.MethodsA comprehensive biological network of AD-associated molecules and their transcription regulatory interactions is constructed. This computational approach integrates data from genome-wide association studies, multiple AD-related magnetic resonance imaging (MRI) derived phenotypes, biomolecular interactions, and gene expression profiles.ResultsThe constructed AD sub-regulatory network reveals significant correlations between transcription factors showing changed gene expression in AD patients relative to controls. This strategy prioritizes drug candidates based on their mechanisms of action, reducing the risk of clinical trial failures and enhancing patient outcomes related to AD. A total of 43 drug candidates have been identified, including 28 FDA-approved drugs, 15 experimental and investigational drugs that may alter biological processes pertaining to important facets of AD pathology. Baricitinib and Gabapentin emerge as promising candidates for targeting AD-related biological processes in the cerebral cortex and hippocampus regions.ConclusionsBy combining biological network analysis and MRI-driven transcriptome-wide association study, this systematic drug repurposing strategy demonstrates promise for identifying novel therapeutic options for AD and offers potential implications for addressing other complex neurological disorders.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251360009"},"PeriodicalIF":3.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abdullah-J Alzhrani, Leo Stockfelt, Yiyi Xu, Florencia Harari, Susanna Gustafsson, Gunnar Engström, Oskar Hansson, Anna Oudin
{"title":"Long-term exposure to air pollution and validated cases of Alzheimer's disease and vascular dementia in the Malmö diet and cancer cohort.","authors":"Abdullah-J Alzhrani, Leo Stockfelt, Yiyi Xu, Florencia Harari, Susanna Gustafsson, Gunnar Engström, Oskar Hansson, Anna Oudin","doi":"10.1177/13872877251360225","DOIUrl":"https://doi.org/10.1177/13872877251360225","url":null,"abstract":"<p><p>BackgroundDementia is a global public health challenge, with Alzheimer's disease (AD) and vascular dementia (VaD) being the most prevalent subtypes. Air pollution is a potential risk factor for dementia, but few studies separate AD and VaD.ObjectiveThis study aims to investigate whether exposure to air pollution is associated with the incidence of AD and VaD.MethodsThis study involved 30,247 participants from the Malmö Diet and Cancer Study (1991-2014), with 1216 AD cases (including mixed type) and 531 VaD cases, clinically validated. Long-term exposure to PM<sub>2.5</sub> and NO<sub>x</sub> was modeled using the past 5-years or 10-year mean concentration with 50m × 50 m spatial resolution at residential addresses. The association between AD and VaD and air pollution was assessed using adjusted Cox-proportional hazards.ResultsFor AD the hazard ratios (HRs (95% CIs) were 1.06 (0.89-1.27) for PM<sub>2.5</sub> and 1.08 (0.96-1.22) for NO<sub>x</sub> per interquartile range (IQR) increase in past 10-year mean pollution-levels. Nonsignificant associations were observed in two-pollutant models. For past 5-year exposure, we observed a statistically significant association between NO<sub>x</sub> and AD 1.14 (1.00-1.30). For VaD, we found no evidence for associations in any models.ConclusionsWe found that while both PM<sub>2.5</sub> and NO<sub>x</sub> seemed linked to increased AD risk in single-pollutant models, only the associations with NO<sub>x</sub> remained in two-pollutant models, particularly for exposures in the past five years. No associations were observed for VaD. The results underscore the importance of distinguishing dementia subtypes, identifying critical exposure windows, and applying multi-pollutant models in future studies.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251360225"},"PeriodicalIF":3.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuanjun Zeng, Zhenxue Song, Ling Zhang, Wenqi Zhao, Jianguo Xie, Yuchi Meng, Murong Cheng, Dongfeng Zhang, Suyun Li
{"title":"Associations of absolute and relative grip strength with cognitive performance in Chinese middle-aged and older populations.","authors":"Yuanjun Zeng, Zhenxue Song, Ling Zhang, Wenqi Zhao, Jianguo Xie, Yuchi Meng, Murong Cheng, Dongfeng Zhang, Suyun Li","doi":"10.1177/13872877251360241","DOIUrl":"https://doi.org/10.1177/13872877251360241","url":null,"abstract":"<p><p>BackgroundRecent meta-analyses indicate that the relationship between grip strength (GS) and cognition is more complex than that was previously assumed. Multiple studies have established a significant correlation between body composition and GS.ObjectiveTo assess longitudinal relationships between absolute and relative GS trajectories and cognitive function.MethodsThe China Health and Retirement Longitudinal Study (CHARLS) data with 2549 participants were analyzed using the Group-Based Trajectory Model (GBTM) to ascertain GS trajectories over time. Absolute GS was defined as the raw force, while relative GS was defined as grip strength adjusted by body weight. Directed Acyclic Graphs (DAGs) were used to identify confounding variables, which were subsequently adjusted for in generalized estimating equation (GEE) models that assessed associations between these trajectories and changes in cognitive function over time.ResultsWe observed that relative GS exhibited three distinct trajectories: The three relative GS trajectories were labeled as Low-decline (n = 823, 32.29%), Medium-decline (n = 1292, 50.69%), and High-decline (n = 434, 17.03%). Absolute GS showed similar downward trends. GEE revealed a uniform five-year decline in cognitive function across all GS trajectory groups (all p<sub>time</sub> < 0.001). The overall interaction between the timing and patterns of changes in both absolute and relative GS and cognitive function was statistically significant (p < 0.001).ConclusionsIn middle-aged and older adults, lower grip strength trajectories align with accelerated cognitive decline, while higher grip strength is associated with slower cognitive deterioration. Monitoring grip strength may serve as a practical marker for cognitive health in aging populations.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251360241"},"PeriodicalIF":3.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anderson Matheus Pereira da Silva, Luciano Falcão, Filipe Virgilio, Isabelle Rodrigues Menezes, Marianna Leite, Elizabeth Farias, Maria Nascimento, Mariana Lee Han, João Paulo Mota Telles, Eryvelton de Souza Franco, Maria Bernadete de Sousa Maia
{"title":"Efficacy and <i>APOE</i> ε4-stratified risk of donanemab in Alzheimer's disease: A systematic review and meta-analysis of randomized clinical trials.","authors":"Anderson Matheus Pereira da Silva, Luciano Falcão, Filipe Virgilio, Isabelle Rodrigues Menezes, Marianna Leite, Elizabeth Farias, Maria Nascimento, Mariana Lee Han, João Paulo Mota Telles, Eryvelton de Souza Franco, Maria Bernadete de Sousa Maia","doi":"10.1177/13872877251361044","DOIUrl":"https://doi.org/10.1177/13872877251361044","url":null,"abstract":"<p><p>BackgroundDonanemab, a monoclonal antibody targeting amyloid-β (Aβ) plaques, has shown the ability to reduce cerebral amyloid burden in early Alzheimer's disease (AD). However, uncertainties remain regarding its clinical relevance, particularly in relation to tau pathology, <i>APOE</i> ε4 genotype, and methodological limitations in existing trials.ObjectiveTo conduct a systematic review and exploratory meta-analysis to evaluate the efficacy, safety, and tolerability of donanemab in patients with mild to moderate AD.MethodsWe conducted a systematic review and exploratory meta-analysis following PRISMA guidelines. Randomized controlled trials comparing donanemab to placebo in individuals aged ≥65 years with biomarker-confirmed mild to moderate AD were included. Outcomes included cognitive measures (ADAS-Cog13, MMSE, CDR-SB, iADRS, ADCS-iADL) and adverse events (ARIA-E, ARIA-H, infusion reactions, discontinuations). Random-effects models were used to estimate pooled mean difference (MD) or risk ratio (RR) with 95% confidence intervals. Subgroup analyses were performed by baseline tau burden and <i>APOE</i> ε4 genotype.ResultsThree trials (n = 2054) were included. Donanemab modestly reduced cognitive decline compared to placebo: ADAS-Cog13 (MD, -1.86), CDR-SB (MD, -0.36), MMSE (MD, 0.64), and iADRS (MD, 3.19), with similar effects across tau subgroups. The risk of ARIA-E was markedly increased (RR, 12.39), especially among <i>APOE</i> ε4 homozygotes. Infusion reactions (RR, 11.90) and discontinuations (RR, 3.22) were also more frequent.ConclusionsDonanemab demonstrated modest cognitive benefits, the clinical significance of which remains uncertain. Independent, longer-term trials with rigorous methodology and active comparators are warranted to more clearly define its therapeutic value in the treatment of AD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251361044"},"PeriodicalIF":3.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}