The Journal of Prevention of Alzheimer's Disease最新文献

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Clarity AD: Asian regional analysis of a phase III trial of lecanemab in early Alzheimer's disease. Clarity AD:Lecanemab 治疗早期阿尔茨海默病 III 期试验的亚洲地区分析。
IF 4.3
The Journal of Prevention of Alzheimer's Disease Pub Date : 2025-04-05 DOI: 10.1016/j.tjpad.2025.100160
Christopher Chen, Sadao Katayama, Jae-Hong Lee, Jun-Young Lee, Masaki Nakagawa, Kentaro Torii, Tomoo Ogawa, Amitabh Dash, Michael Irizarry, Shobha Dhadda, Michio Kanekiyo, Steve Hersch, Takeshi Iwatsubo
{"title":"Clarity AD: Asian regional analysis of a phase III trial of lecanemab in early Alzheimer's disease.","authors":"Christopher Chen, Sadao Katayama, Jae-Hong Lee, Jun-Young Lee, Masaki Nakagawa, Kentaro Torii, Tomoo Ogawa, Amitabh Dash, Michael Irizarry, Shobha Dhadda, Michio Kanekiyo, Steve Hersch, Takeshi Iwatsubo","doi":"10.1016/j.tjpad.2025.100160","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100160","url":null,"abstract":"<p><strong>Background: </strong>Across Asia, Alzheimer's disease prevalence is expected to rise dramatically due to, among other factors, rapidly aging populations. Alzheimer's disease pathology is triggered by the accumulation of soluble and insoluble aggregated Aβ peptides (oligomers, protofibrils, and fibrils). Lecanemab is a recently approved humanized IgG1 monoclonal antibody that preferentially targets soluble aggregated Aβ species (oligomers, protofibrils), with activity at insoluble fibrils. In the recent 18-month phase 3 Clarity AD study, lecanemab demonstrated a consistent slowing of decline in clinical (global, cognitive, functional, and quality of life) outcomes, and reduction in brain amyloid in early Alzheimer's disease. Lecanemab was well tolerated in Clarity AD, with an increase in incidence of infusion related reactions and amyloid-related imaging abnormalities (ARIA) versus placebo.</p><p><strong>Objectives: </strong>The objective of this manuscript is to present the results for the Asian region population of Clarity AD.</p><p><strong>Design: </strong>The core Clarity AD study was an 18-month, multicenter, double-blind, placebo-controlled, parallel-group study.</p><p><strong>Setting: </strong>Academic and clinical centers in Asia PARTICIPANTS: A total of 294 individuals with early Alzheimer's disease (i.e., mild cognitive impairment or mild Alzheimer's disease).</p><p><strong>Intervention: </strong>Eligible patients were randomized across 2 treatment groups (placebo and lecanemab 10 mg/kg biweekly) according to a fixed 1:1 schedule.</p><p><strong>Measurements: </strong>The primary efficacy endpoint in the core study was change in the Clinical Dementia Rating-Sum-of-Boxes (CDR-SB) from baseline at 18 months. Key secondary endpoints included change from baseline at 18 months in amyloid PET Centiloids (in patients participating in the amyloid PET sub-study), AD COMposite Score (ADCOMS) and AD Assessment Scale-Cognitive Subscale 14 (ADAS-Cog14). Safety was monitored throughout the study in a blinded manner by the sponsor and in an unblinded manner by an independent data safety monitoring committee.</p><p><strong>Results: </strong>Of the total of 1795 subjects randomized in Clarity AD, 294 subjects were in the Asian region (Japan:152; Korea:129; Singapore:13). The efficacy of lecanemab was consistent with the overall population. For the primary endpoint, there was a slowing of decline with lecanemab in the CDR-SB at 18 months compared to placebo in the Asian region (adjusted mean difference: -0.349; 95 % confidence intervals: -0.773, 0.076; 24 % slowing of decline). Results for the secondary efficacy endpoints also favored lecanemab versus placebo in Asians. Lecanemab was well tolerated in Asian subjects, with a safety profile in Asian subjects similar to the overall Clarity AD population. The most common adverse events of special interest were ARIA-H (lecanemab:14.4 %; placebo:16.2 %), ARIA-E (lecanemab:6.2 %; placebo:1.4 %), and in","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100160"},"PeriodicalIF":4.3,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Concerns about Anavex's clinical trial of Blarcamesine. 对 Anavex 公司的 Blarcamesine 临床试验表示担忧。
IF 4.3
The Journal of Prevention of Alzheimer's Disease Pub Date : 2025-04-03 DOI: 10.1016/j.tjpad.2025.100137
Jesse Brodkin
{"title":"Concerns about Anavex's clinical trial of Blarcamesine.","authors":"Jesse Brodkin","doi":"10.1016/j.tjpad.2025.100137","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100137","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100137"},"PeriodicalIF":4.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The cost-effectiveness of an online intervention to prevent dementia: Results from the Maintain Your Brain (MYB) randomised controlled trial. 预防痴呆症在线干预的成本效益:维护你的大脑(MYB)随机对照试验的结果。
IF 4.3
The Journal of Prevention of Alzheimer's Disease Pub Date : 2025-04-03 DOI: 10.1016/j.tjpad.2025.100151
Heidi J Welberry, Li-Jung Elizabeth Ku, Sophy Tf Shih, Louisa R Jorm, Maria Fiatarone Singh, Michael Valenzuela, Jeewani Anupama Ginige, Kaarin J Anstey, Perminder S Sachdev, John J McNeil, Nicola T Lautenschlager, Megan Heffernan, Tiffany Chau, Henry Brodaty
{"title":"The cost-effectiveness of an online intervention to prevent dementia: Results from the Maintain Your Brain (MYB) randomised controlled trial.","authors":"Heidi J Welberry, Li-Jung Elizabeth Ku, Sophy Tf Shih, Louisa R Jorm, Maria Fiatarone Singh, Michael Valenzuela, Jeewani Anupama Ginige, Kaarin J Anstey, Perminder S Sachdev, John J McNeil, Nicola T Lautenschlager, Megan Heffernan, Tiffany Chau, Henry Brodaty","doi":"10.1016/j.tjpad.2025.100151","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100151","url":null,"abstract":"<p><strong>Background: </strong>The Maintain Your Brain (MYB) randomised controlled trial (RCT) examined the effect of a multi-domain internet-based dementia prevention program against a control group (information only).</p><p><strong>Objectives: </strong>A cost-effective analysis (CEA) quantified the differences in costs (direct healthcare and program costs) and effectiveness outcomes between the intervention and control groups from a healthcare sector perspective.</p><p><strong>Design: </strong>An economic evaluation was conducted alongside the MYB RCT over three years.</p><p><strong>Setting: </strong>Australians aged 55-77 years with at least 2 identified remediable risk factors for cognitive decline/dementia recruited from communities in New South Wales.</p><p><strong>Participants: </strong>There were 3,025 participants in the intervention group and 3,033 in the control group with available linked healthcare data via the Sax Institute's 45 and Up Study out of the 6104 enrolled in the trial (99.2% of total cohort).</p><p><strong>Intervention: </strong>The MYB trial comprised a personalised schedule of online coaching in physical activity, nutrition, cognitive activity, and depression or anxiety management.</p><p><strong>Measurements: </strong>The two effectiveness outcomes were global cognition composite (GCC) scores and the Australian National University-Alzheimer's Disease Risk Index -short form (ANU-ADRI-SF) questionnaire scores. Costs included MYB program costs and the direct healthcare costs incurred by the MYB participants. All costs were reported in Australian dollars (AUD$) during the trial period. The time horizon of this analysis was 3 years after randomisation (2018-2021). Incremental cost-effectiveness ratio (ICERs) between the intervention and the control groups were calculated by comparing the average difference in costs to a mean difference in z score for GCC and ANU-ADRI-SF score using the bootstrapped means and 95% Confidence Intervals.</p><p><strong>Results: </strong>The total unadjusted program and healthcare costs over three years were similar between groups (AUD$16,521 per person in the control group and AUD$16,473 in the intervention group). After adjusting for baseline characteristics, the average difference between groups in total cost per person at three years was not statistically different: AUD$467 favouring the control group (95%CI: -$552 - $1585). This was compared to a significant mean difference (improvement) in GCC z score at three years of 0.18 (95%CI: 0.13, 0.23) and -0.57 (95%CI: -0.95, -0.24) point difference in ANU-ADRI-SF for the intervention versus control. The base case ICERs were AUD$2,568 per 1 standard deviation in z score and $823 per reduction of 1 ANU-ADRI-SF point. With 1000 bootstrapped replications, the scatterplots of ICER ellipses suggest that the MYB intervention was more effective than the control group and with no significant difference in overall healthcare costs.</p><p><strong>Conclusion:","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100151"},"PeriodicalIF":4.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The role of serum vitamins in mediating the effect of neurodegenerative diseases on subcortical brain volume.
IF 4.3
The Journal of Prevention of Alzheimer's Disease Pub Date : 2025-04-02 DOI: 10.1016/j.tjpad.2025.100155
Haonan Li, Meng Cheng, Nannan Zhang, Siqi Wang, Caihua Ye, Haodong Li, Shengnan Wang, Zirui Wang, Xuan Yang, Zhixuan Liu, Xingyu Zhang, Jiayuan Xu, Qiang Xu, Junping Wang
{"title":"The role of serum vitamins in mediating the effect of neurodegenerative diseases on subcortical brain volume.","authors":"Haonan Li, Meng Cheng, Nannan Zhang, Siqi Wang, Caihua Ye, Haodong Li, Shengnan Wang, Zirui Wang, Xuan Yang, Zhixuan Liu, Xingyu Zhang, Jiayuan Xu, Qiang Xu, Junping Wang","doi":"10.1016/j.tjpad.2025.100155","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100155","url":null,"abstract":"<p><strong>Background: </strong>Neurodegenerative diseases (NDs) lead to a progressive loss of neuronal cells and link to atrophy of subcortical brain structures, but the causal intermediates are not known. To test whether major NDs (Alzheimer's disease (AD), Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis) causally affects subcortical atrophy, and whether serum vitamin level play a mediating role in this process.</p><p><strong>Methods: </strong>Using large-scale genome-wide association study (GWAS) summary data, we performed two-sample Mendelian randomization (MR) to assess the causal effect of NDs on the volume of seven subcortical structures, and then adopted two-step multivariable MR approach to quantify the proportion of the effect of NDs on the volume of subcortical regions mediated by serum vitamin level. Finally, we utilized animal experiments to validate results and explored the potential molecular mechanisms.</p><p><strong>Results: </strong>Genetically predicted AD was associated with atrophy of the nucleus accumbens (NAc) (β = -0.09; p = 5.13 × 10<sup>-5</sup>), amygdala (β = -0.07; p = 8.44 × 10<sup>-4</sup>), and hippocampus (β = -0.07; p = 0.001), as well as with low serum vitamin D level (β = -0.02; p = 6.84 × 10<sup>-6</sup>). Specifically, decreased serum vitamin D level mediated 3.99 % (95 % CI: -0.006 to -5.82 × 10<sup>-5</sup>) and 3.97 % (95 % CI: -0.007 to -2.94 × 10<sup>-4</sup>) of the total effect of AD on hippocampal and NAc atrophy, respectively. Animal experiments further confirmed significant delays in hippocampal and NAc atrophy, a significant reduction of β-amyloid deposits and an increase of vitamin D receptor expression in hippocampus in AD mice with high-dose vitamin D diet.</p><p><strong>Conclusions: </strong>These findings provide important insights into the effect sizes of vitamin D-mediated roles in AD and atrophy of subcortical structures. Interventions to increase serum vitamin D levels at a population level might attenuate damage to hippocampus in patients with AD.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100155"},"PeriodicalIF":4.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of traditional Thai folk dance combined with cognitive stimulation program on behavior and cognition among older adults with cognitive decline: A randomized controlled trial. 传统泰国民间舞蹈结合认知刺激计划对认知衰退老年人行为和认知的影响:一项随机对照试验。
IF 4.3
The Journal of Prevention of Alzheimer's Disease Pub Date : 2025-04-01 Epub Date: 2025-01-17 DOI: 10.1016/j.tjpad.2025.100066
Panawat Sanprakhon, Wachira Suriyawong, Natsala Longphasuk, Natsuda Khatichop, Churai Arpaichiraratana, Sresuda Wongwiseskul, Peerayut Rattanaselanon, Noppamas Pipatpiboon, Papan Thaipisuttikul
{"title":"Effects of traditional Thai folk dance combined with cognitive stimulation program on behavior and cognition among older adults with cognitive decline: A randomized controlled trial.","authors":"Panawat Sanprakhon, Wachira Suriyawong, Natsala Longphasuk, Natsuda Khatichop, Churai Arpaichiraratana, Sresuda Wongwiseskul, Peerayut Rattanaselanon, Noppamas Pipatpiboon, Papan Thaipisuttikul","doi":"10.1016/j.tjpad.2025.100066","DOIUrl":"10.1016/j.tjpad.2025.100066","url":null,"abstract":"<p><strong>Background: </strong>Older adults with mild behavioral impairment (MBI) are at the higher risk of developing dementia compared to those without MBI, leading to decreased quality of life (QoL). Addressing MBI in older adults provides valuable opportunities to prevent dementia.</p><p><strong>Objectives: </strong>This study aimed to determine the effects of traditional Thai folk dance combined with a cognitive stimulation program on MBI, QoL, subjective cognitive decline (SCD), and cognitive functioning in older Thai adults.</p><p><strong>Design: </strong>Single-blinded, two-armed, randomized controlled trial, with a three-month follow-up period.</p><p><strong>Setting: </strong>Outpatient chronic disease clinics at two districts in Suphan Buri province, Thailand.</p><p><strong>Participants: </strong>One-hundred twenty-eight older adults with MBI were randomly assigned to either the experimental (n = 64) and cognitive education control group (n = 64).</p><p><strong>Intervention: </strong>The 14-session, 7-week traditional Thai folk-dance program combined with cognitive stimulation focused on enhanced moderate intensity physical activity and cognitive stimulation engagement to improve MBI of older adults.</p><p><strong>Measurements: </strong>The primary outcome was MBI assessed using Mild Behavioral Impairment Checklist. Secondary outcomes were QoL, SCD, and cognitive tests of memory and executive functions.</p><p><strong>Results: </strong>Compared to the control group, participants in the experimental group demonstrated significantly reduced MBI (p <.01), improved QoL (p <.01), decreased SCD (p <.01), and enhanced cognitive functioning (p <.01) after the 7-week intervention and at the 12-week follow-up.</p><p><strong>Conclusion: </strong>The traditional Thai folk dance combined with cognitive stimulation improved outcomes related to early signs of dementia and enhanced the overall QoL of older adults.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100066"},"PeriodicalIF":4.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The impact of pre-analytical factors on plasma biomarkers for Alzheimer's disease: The ASPREE Healthy Ageing Biobank.
IF 4.3
The Journal of Prevention of Alzheimer's Disease Pub Date : 2025-04-01 Epub Date: 2025-02-12 DOI: 10.1016/j.tjpad.2025.100058
Zimu Wu, Michelle M Mielke, Anne M Murray, James Phung, Alice Owen, Robyn L Woods, Danni Li, Jo Wrigglesworth, Joanne Ryan
{"title":"The impact of pre-analytical factors on plasma biomarkers for Alzheimer's disease: The ASPREE Healthy Ageing Biobank.","authors":"Zimu Wu, Michelle M Mielke, Anne M Murray, James Phung, Alice Owen, Robyn L Woods, Danni Li, Jo Wrigglesworth, Joanne Ryan","doi":"10.1016/j.tjpad.2025.100058","DOIUrl":"10.1016/j.tjpad.2025.100058","url":null,"abstract":"<p><strong>Background: </strong>The conditions under which samples were collected, processed, and stored in biobanks may influence Alzheimer's disease (AD) biomarker levels.</p><p><strong>Objectives: </strong>This study aims to investigate whether a range of pre-analytical factors influence plasma levels of AD biomarkers.</p><p><strong>Methods: </strong>Data were obtained from the ASPREE Healthy Ageing Biobank, a cohort of healthy community-dwelling older individuals aged 70+ years in Australia. Five biomarkers were measured using plasma from 11,868 individuals: phosphorylated-tau181 (p-tau181), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and amyloid-beta 42 and 40 (Aβ42/Aβ40). Linear regression examined the association between pre-analytical factors and biomarker levels.</p><p><strong>Results: </strong>Participants were aged 70-96 years, and 54 % were female. The mean storage time for samples was 10.6 years (range: 7.7-13.5). Some significant associations were identified between pre-analytical factors and biomarkers, in particular for p-tau181, but the effect sizes were small. Weak negative associations were found between p-tau181 and the time from venepuncture to laboratory (transport) (β: -0.82, p = 0.03), laboratory processing to frozen storage (β:-1.56, p < 0.001), and total years of storage (β: -0.45, p = 0.007), while a positive association was found with intermediate storage at -20 °C/-30 °C compared to -80 °C (β: 2.24, p = 0.004). Longer fasting time was associated with higher levels of both NfL (β: 0.15, p < 0.001) and GFAP (β: 1.75, p < 0.001).</p><p><strong>Conclusion: </strong>Following standard operating procedures, AD biomarkers can be measured in plasma from biobanks stored for up to 13 years, with minimal impact from long-term storage or other pre-analytical factors.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100058"},"PeriodicalIF":4.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Patient eligibility for amyloid-targeting immunotherapies in Alzheimer's disease.
IF 4.3
The Journal of Prevention of Alzheimer's Disease Pub Date : 2025-04-01 Epub Date: 2025-02-25 DOI: 10.1016/j.tjpad.2025.100102
Jurij Rosen, Frank Jessen
{"title":"Patient eligibility for amyloid-targeting immunotherapies in Alzheimer's disease.","authors":"Jurij Rosen, Frank Jessen","doi":"10.1016/j.tjpad.2025.100102","DOIUrl":"10.1016/j.tjpad.2025.100102","url":null,"abstract":"<p><strong>Background: </strong>Amyloid beta (Aβ) targeting immunotherapies have evolved as promising treatment options for patients with early symptomatic Alzheimer's disease (AD). Understanding how eligibilty criteria impact on the number of patients potentially qualifying for treatment is of high relevance for designing diagnostic workflows in clinical practice and for estimating required ressources and costs.</p><p><strong>Objectives: </strong>We aimed at estimating the number of potentially eligible patients for treatment with the Aβ targeting antibodies aducanumab, lecanemab and donanemab in a specialized center real-world sample by the applying the phase 3 clinical trial and the appropriate use recommendations (AUR) inclusion and exclusion criteria to the data set. The post-mortem report was used for defining amyloid positivity and the presence of AD pathology in this study.</p><p><strong>Design: </strong>Retrospective, descriptive study.</p><p><strong>Setting: </strong>The multicenter National Alzheimer's Coordinating Center-Uniform Data Set (NACC-UDS) and Neuropathology Data Set (NACCNP).</p><p><strong>Participants: </strong>We included all 3,343 participants of the NACC dataset with available post-mortem pathology reports.</p><p><strong>Measurements/results: </strong>887 participants were potential candidates for anti-Aβ immunotherapy as they presented with amnestic mild cognitive impairment or mild dementia and the clinical diagnosis of AD (amnestic AD syndrome). Applying the criterion of amyloid positivity (post mortem report) and the clinical trial inclusion and exclusion criteria to this sample resulted in 83 (9 %), 275 (31 %), and 172 (19 %) participants eligible for treatment with aducanumab, lecanemab, and donanemab, respectively. Applying the criteria of the AUR resulted in 242 (27 %) and 266 (30 %) participants eligible for treatment with aducanumab or lecanemab, respectively. The eligible participant groups for each antibody showed partial, but not full overlap. Co-pathologies were common.</p><p><strong>Conclusions: </strong>The number of eligible participants varies between the different antibodies and the selected groups only partly overlap, indicating partly different groups of eligible participants for each antibody. Since not all inclusion and exclusion criteria can be extracted from the NACC-UDS dataset, the real number of eligible patients will be smaller.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100102"},"PeriodicalIF":4.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterizing and validating 12-month reliable cognitive change in Early-Onset Alzheimer's Disease for use in clinical trials.
IF 4.3
The Journal of Prevention of Alzheimer's Disease Pub Date : 2025-04-01 Epub Date: 2025-02-16 DOI: 10.1016/j.tjpad.2025.100075
Dustin B Hammers, Jane Musema, Ani Eloyan, Maryanne Thangarajah, Alexander Taurone, Renaud La Joie, Alexandra Touroutoglou, Prashanthi Vemuri, Joel Kramer, Paul Aisen, Jeffrey L Dage, Kelly N Nudelman, Kala Kirby, Alireza Atri, David Clark, Gregory S Day, Ranjan Duara, Neill R Graff-Radford, Ian Grant, Lawrence S Honig, Erik C B Johnson, David T Jones, Joseph C Masdeu, Mario F Mendez, Kyle Womack, Erik Musiek, Chiadi U Onyike, Meghan Riddle, Emily Rogalski, Steven Salloway, Sharon J Sha, Raymond Scott Turner, Thomas S Wingo, David A Wolk, Maria C Carrillo, Gil D Rabinovici, Bradford C Dickerson, Liana G Apostolova
{"title":"Characterizing and validating 12-month reliable cognitive change in Early-Onset Alzheimer's Disease for use in clinical trials.","authors":"Dustin B Hammers, Jane Musema, Ani Eloyan, Maryanne Thangarajah, Alexander Taurone, Renaud La Joie, Alexandra Touroutoglou, Prashanthi Vemuri, Joel Kramer, Paul Aisen, Jeffrey L Dage, Kelly N Nudelman, Kala Kirby, Alireza Atri, David Clark, Gregory S Day, Ranjan Duara, Neill R Graff-Radford, Ian Grant, Lawrence S Honig, Erik C B Johnson, David T Jones, Joseph C Masdeu, Mario F Mendez, Kyle Womack, Erik Musiek, Chiadi U Onyike, Meghan Riddle, Emily Rogalski, Steven Salloway, Sharon J Sha, Raymond Scott Turner, Thomas S Wingo, David A Wolk, Maria C Carrillo, Gil D Rabinovici, Bradford C Dickerson, Liana G Apostolova","doi":"10.1016/j.tjpad.2025.100075","DOIUrl":"10.1016/j.tjpad.2025.100075","url":null,"abstract":"<p><strong>Background: </strong>As literature suggests that Early-Onset Alzheimer's Disease (EOAD) and late-onset AD may differ in important ways, need exists for randomized clinical trials for treatments tailored to EOAD. Accurately measuring reliable cognitive change in individual patients with EOAD will have great value for these trials.</p><p><strong>Objectives: </strong>The current study sought to characterize and validate 12-month reliable change from the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) neuropsychological battery.</p><p><strong>Design: </strong>Standardized regression-based (SRB) prediction equations were developed from age-matched cognitively intact participants within LEADS, and applied to clinically impaired participants from LEADS.</p><p><strong>Setting: </strong>Participants were recruited from outpatient academic medical centers.</p><p><strong>Participants: </strong>Participants were enrolled in LEADS and diagnosed with amyloid-positive EOAD (n = 189) and amyloid-negative early-onset cognitive impairment not related to AD (EOnonAD; n = 43).</p><p><strong>Measurement: </strong>12-month reliable change (Z-scores) was compared between groups across cognitive domain composites, and distributions of individual participant trajectories were examined. Prediction of Z-scores by common AD biomarkers was also considered.</p><p><strong>Results: </strong>Both EOAD and EOnonAD displayed significantly lower 12-month follow-up scores than were predicted based on SRB equations, with declines more pronounced for EOAD across several domains. AD biomarkers of cerebral β-amyloid, tau, and EOAD-specific atrophy were predictive of 12-month change scores.</p><p><strong>Conclusions: </strong>The current results support including EOAD patients in longitudinal clinical trials, and generate evidence of validation for using 12-month reliable cognitive change as a clinical outcome metric in clinical trials in EOAD cohorts like LEADS. Doing so will enhance the success of EOAD trials and permit a better understanding of individual responses to treatment.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100075"},"PeriodicalIF":4.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433814","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}
引用次数: 0
Association between L-α glycerylphosphorylcholine use and delayed dementia conversion: A nationwide longitudinal study in South Korea.
IF 4.3
The Journal of Prevention of Alzheimer's Disease Pub Date : 2025-04-01 Epub Date: 2025-01-10 DOI: 10.1016/j.tjpad.2025.100059
Han-Kyeol Kim, Sojeong Park, Sung-Woo Kim, Eun Seok Park, Jin Yong Hong, Ickpyo Hong, Min Seok Baek
{"title":"Association between L-α glycerylphosphorylcholine use and delayed dementia conversion: A nationwide longitudinal study in South Korea.","authors":"Han-Kyeol Kim, Sojeong Park, Sung-Woo Kim, Eun Seok Park, Jin Yong Hong, Ickpyo Hong, Min Seok Baek","doi":"10.1016/j.tjpad.2025.100059","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100059","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease and vascular dementia are two of the most common causes of dementia. While early diagnosis and intervention are crucial, available treatments and research concerning the mild cognitive impairment stage remain limited. This study aimed to evaluate the real-world effectiveness and safety of L-α glycerylphosphorylcholine in this context.</p><p><strong>Objectives: </strong>To investigate the impact of L-α glycerylphosphorylcholine on the risk of conversion from mild cognitive impairment to Alzheimer's disease dementia and vascular dementia, as well as its influence on stroke risk DESIGN: A nationwide, population-based cohort study SETTING: Data from South Korea's National Health Insurance Service PARTICIPANTS: Overall, 508,107 patients newly diagnosed with mild cognitive impairment between 2013 and 2016 were included.</p><p><strong>Intervention: </strong>Patients were classified as users or non-users of L-α glycerylphosphorylcholine based on prescription records.</p><p><strong>Measurements: </strong>The primary outcomes were the risk of progression to Alzheimer's disease dementia and vascular dementia. Stroke risk was examined as a secondary outcome. A time-dependent Cox regression analysis was used to adjust for demographic and clinical factors.</p><p><strong>Results: </strong>Compared to non-users, L-α glycerylphosphorylcholine users had a lower risk of progression to Alzheimer's disease dementia (hazard ratio = 0.899, 95 % confidence interval: 0.882-0.918) and vascular dementia (hazard ratio = 0.832, 95 % confidence interval: 0.801-0.865) within 2,435,924 and 662,281.6 person-years, respectively. In patients under 65, L-α glycerylphosphorylcholine significantly reduced the risk of progression to Alzheimer's and vascular dementia. Stroke risk significantly decreased in patients who did not progress to dementia but not in those who did.</p><p><strong>Conclusions: </strong>L-α Glycerylphosphorylcholine reduces dementia conversion and stroke risk in patients with mild cognitive impairment, making it a viable early intervention. Future large-scale randomized controlled studies should examine its effects on other dementia subtypes and long-term cognitive outcomes.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 4","pages":"100059"},"PeriodicalIF":4.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Joint ensemble learning-based risk prediction of Alzheimer's disease among mild cognitive impairment patients.
IF 4.3
The Journal of Prevention of Alzheimer's Disease Pub Date : 2025-04-01 Epub Date: 2025-02-05 DOI: 10.1016/j.tjpad.2025.100083
Tianyuan Guan, Lei Shang, Peng Yang, Zhijun Tan, Yue Liu, Chunling Dong, Xueying Li, Zuxuan Hu, Haixia Su, Yuhai Zhang
{"title":"Joint ensemble learning-based risk prediction of Alzheimer's disease among mild cognitive impairment patients.","authors":"Tianyuan Guan, Lei Shang, Peng Yang, Zhijun Tan, Yue Liu, Chunling Dong, Xueying Li, Zuxuan Hu, Haixia Su, Yuhai Zhang","doi":"10.1016/j.tjpad.2025.100083","DOIUrl":"10.1016/j.tjpad.2025.100083","url":null,"abstract":"<p><strong>Objective: </strong>Due to the recognition for the importance of early intervention in Alzheimer's disease (AD), it is important to focus on prevention and treatment strategies for mild cognitive impairment (MCI). This study aimed to establish a risk prediction model for AD among MCI patients to provide clinical guidance for primary medical institutions.</p><p><strong>Methods: </strong>Data from MCI subjects were obtained from the NACC. Importance ranking and the SHapley Additive exPlanations (SHAP) method for the Random Survival Forest (RSF) and Extreme Gradient Boosting (XGBoost) algorithms in ensemble learning were adopted to select the predictors, and hierarchical clustering analysis was used to mitigate multicollinearity. The RSF, XGBoost and Cox proportional hazard regression (Cox) models were established to predict the risk of AD among MCI patients. Additionally, the effects of the three models were evaluated.</p><p><strong>Results: </strong>A total of 3674 subjects with MCI were included. Thirteen predictors were ultimately identified. In the validation set, the concordance indices were 0.781 (RSF), 0.781 (XGBoost), and 0.798 (Cox), and the Integrated Brier Score was 0.087 (Cox). The prediction effects of the XGBoost and RSF models were not better than those of the Cox model.</p><p><strong>Conclusion: </strong>The ensemble learning method can effectively select predictors of AD risk among MCI subjects. The Cox proportional hazards regression model could be used in primary medical institutions to rapidly screen for the risk of AD among MCI patients once the model is fully clinically validated. The predictors were easy to explain and obtain, and the prediction of AD was accurate.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100083"},"PeriodicalIF":4.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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