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

{"title":"Unveiling Potential Biomarkers in Cerebrospinal Fluid for Amyloid Pathological Positivity in Non-Demented Individuals","authors":"F. Meng, Xi Zhang","doi":"10.14283/jpad.2024.129","DOIUrl":"https://doi.org/10.14283/jpad.2024.129","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaque accumulation and neurofibrillary tangles. The recent approval of anti-amyloid therapeutic medications highlights the crucial need for early detection of Aβ pathological abnormalities in individuals without dementia to facilitate timely intervention and treatment.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>The primary aim of this study was to identify cerebrospinal fluid (CSF) biomarkers strongly associated with Aβ pathological positivity in a non-demented cohort and evaluate their clinical values.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>A comprehensive analysis was conducted on 51 CSF proteins (excluding Aβ42, pTau, and Tau) obtained from 474 non-demented participants sourced from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. By utilizing the Least Absolute Shrinkage and Selection Operator (LASSO) regression, we identified potential proteins indicative of Aβ pathological positivity and evaluated their performance in tracking longitudinal pathological progression.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Our LASSO analysis unveiled three candidates: apolipoprotein E (APOE), chitinase-3-like protein 1 (CHI3L1), and SPARC-related modular calcium-binding protein 1 (SMOC1). While SMOC1 did not correlate with Aβ42-related cognitive alterations, it displayed better abilities in discriminating both CSF-Aβ positivity and Aβ-positron emission tomography (PET) positivity than the other two candidates. It could precisely predict longitudinal Aβ-PET status conversion. Notably, SMOC1 was the only protein showing associations with longitudinal Aβ-PET trajectory and enhancing the diagnostic accuracy of Aβ42. The assessment of combined Aβ42 and SMOC1 yielded valuable clinical insights.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Our findings elucidated SMOC1 as a potential biomarker for detecting Aβ abnormalities. Aβ42 combining SMOC1 offered critical implications in AD pathological diagnosis and management.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"18 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141526643","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}

{"title":"Modulatory Effect of Blood LDL Cholesterol on the Association between Cerebral Aβ and Tau Deposition in Older Adults","authors":"S. M. Han, M. S. Byun, D. Yi, J. H. Jung, N. Kong, Y. Y. Chang, M. Keum, G. J. Jung, J.-Y. Lee, Y.-S. Lee, Y. K. Kim, K. M. Kang, C.-H. Sohn, Dong Young Lee","doi":"10.14283/jpad.2024.131","DOIUrl":"https://doi.org/10.14283/jpad.2024.131","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>This study investigates the synergistic relationship between blood low-density lipoprotein cholesterol (LDL-C) and cerebral beta-amyloid (Aβ) in relation to tau deposition, a key factor in the pathology of Alzheimer’s disease (AD), in older adults across a diverse cognitive spectrum.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>To examine whether higher levels of LDL-C in the blood moderate the association of cerebral Aβ with tau deposition in older adults, including those with normal cognition, mild cognitive impairment, and Alzheimer’s disease dementia.</p><h3 data-test=\"abstract-sub-heading\">Design</h3><p>Cross-sectional design. Setting: The study was conducted as a part of a prospective cohort study. All assessments were done at the Seoul National University Hospital, Seoul, South Korea. Participants: A total of 136 older adults (aged 60–85 years) with normal cognition, mild cognitive impairment or Alzheimer’s disease (AD) dementia were included.</p><h3 data-test=\"abstract-sub-heading\">Measurements</h3><p>Serum lipid measurements, [11C] Pittsburgh Compound B-positron emission tomography (PET), [18F] AV-1451 PET, and magnetic resonance imaging were performed on all participants.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>There was a significant Aβ × LDL-C interaction effect on tau deposition indicating a synergistic moderation effect of LDL-C on the relationship between Aβ and tau deposition. Subsequent subgroup analysis showed that the positive association between Aβ and tau deposition was stronger in higher LDL-C group than in lower LDL-C group. In contrast, other lipids, such as total cholesterol, high-density lipoprotein cholesterol, and triglycerides, did not show a similar moderation effect on the relationship between Aβ deposition and tau deposition.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Our findings suggest that blood LDL-C synergistically enhances the influence of Aβ deposition on tau pathology, emphasizing the need for greater attention to the role of LDL-C in AD progression.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"52 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141526592","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}

{"title":"Independent and Joint Associations of Socioeconomic Status and Lifestyle behaviors with Cognitive Impairment among Elderly Chinese Population","authors":"Y. Feng, S. Jia, W. Zhao, X. Wu, Y. Zuo, S. Wang, L. Zhao, M. Ma, X. Guo, C. S. Tarimo, Y. Miao, Jian Wu","doi":"10.14283/jpad.2024.127","DOIUrl":"https://doi.org/10.14283/jpad.2024.127","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Numerous studies have shown that there are socioeconomic disparities in people’s health. Health behavior is considered to be an effective strategy to alleviate socioeconomic differences. However, the independent or joint relationship between socioeconomic status (SES) and lifestyle behaviors (LBs) on the cognition of Chinese elderly are not clear. Therefore, this study aimed to reveal the impact of SES and LBs on cognitive impairment in elder Chinese.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>The data from the 2017–2018 wave of Chinese Longitudinal Healthy Longevity Survey was used. SES was created using latent class analysis based on annual percapita household income, education level, and occupation. Six LBs were considered in calculating LB scores. Restricted cubic splines were used to model the association of LB scores and cognitive impairment to investigate the dose-response relationship. LB scores were divided into three groups: unhealthy, intermediate, and healthy lifestyle. Multivariate Logistic regression models were applied to explore both the independent and joint effects of SES and LB scores on cognitive impairment.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Among 10,116 participants, 1,872 (18.51%) were recorded as having cognitive impariment. After adjusting for multivariable confounding factors, compared with participants of high SES, those of low SES had higher risks of cognitive impairment [Odds ratio (OR): 1.385; 95% confidence interval (CI): 1.137–1.689]. In contrast to those with unhealthy lifestyle, participants adhering to a healthy lifestyle were found to be associated with a reduced risk of cognitive impairment (OR: 0.198; 95%CI: 0.150–0.263). A non-linear relationship was observed between LB scores and cognitive impairment (Pnonlinearity =0.001), indicating a protective effect on cognitive impairment when having more than two LBs. Participants with high SES and engaged in healthy lifestyle had the lowest risk of cognitive impairment compared to those with low SES and unhealthy lifestyle (OR: 0.123; 95% CI 0.073–0.207).</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Cognitive impairment has socioeconomic disparities among the elderly Chinese population. A healthy lifestyle may attenuate the impact of socioeconomic inequality on cognitive impairment, emphasizing the important role of LBs modification in reducing the disease burden of cognitive impairment, especially in the elderly population with low SES.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"15 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141526593","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}

{"title":"Free Recall Outperforms Story Recall in Associations with Plasma Biomarkers in Preclinical Alzheimer Disease","authors":"Andrew Aschenbrenner, J. J. Hassenstab, S. E. Schindler, S. Janelidze, O. Hansson, J. C. Morris, E. Grober","doi":"10.14283/jpad.2024.130","DOIUrl":"https://doi.org/10.14283/jpad.2024.130","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>A decline in episodic memory is one of the earliest cognitive characteristics of Alzheimer disease and memory tests are heavily featured in cognitive composite endpoints that are used to demonstrate treatment efficacy. Assessments of episodic memory can take many forms including free recall, associate learning, and paragraph or story recall. Plasma biomarkers of Alzheimer disease are now widely available and will likely form the backbone of cohort enrichment strategies for future clinical trials. Thus, it is critical to evaluate which episodic memory measures are most sensitive to plasma markers of Alzheimer disease pathology.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>To compare the associations of common episodic memory tests with plasma biomarkers of Alzheimer disease.</p><h3 data-test=\"abstract-sub-heading\">Design</h3><p>Longitudinal cohort study.</p><h3 data-test=\"abstract-sub-heading\">Setting</h3><p>Academic medical center in the midwestern United States.</p><h3 data-test=\"abstract-sub-heading\">Participants</h3><p>A total of 161 cognitively normal older adults with at least one plasma biomarker assessment and two or more annual clinical and cognitive assessments which included up to three different tests of episodic memory.</p><h3 data-test=\"abstract-sub-heading\">Measurements</h3><p>Episodic memory performance using free recall, paired associates recall or paragraph recall. Plasma Aβ42, Aβ40, ptau217, and neurofilament light chain were measured.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Free recall on the Free and Cued Selective Reminding Test with Immediate Recall (FCSRT + IR) was substantially more sensitive to longitudinal cognitive change associated with abnormal baseline plasma Aβ42/Aβ40 and ptau217 compared to other measures of episodic memory. A cognitive composite that included only free recall showed larger decline associated with baseline Aβ42/Aβ40 when compared to those that included paragraph recall. Differences in decline across composites were minimal when considering baseline ptau217 or NfL.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Episodic memory is a critical domain to assess in preclinical Alzheimer disease. Methods of assessing memory are not equal and longitudinal change in free recall substantially outperformed both paired associates and paragraph recall. Clinical trial results will depend critically on the episodic memory test(s) that are chosen for a composite endpoint and free recall from the FCSRT + IR is an optimal memory measure to include rather than paired associates or paragraph recall.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"5 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141552172","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}

{"title":"A Statistical Framework for Assessing the Relationship between Biomarkers and Clinical Endpoints in Alzheimer’s Disease","authors":"Tianle Chen, R. M. Hutchison, C. Rubel, J. Murphy, J. Xie, P. Montenigro, W. Cheng, K. Fraser, G. Dent, S. Hendrix, O. Hansson, P. Aisen, Y. Tian, J. O’Gorman","doi":"10.14283/jpad.2024.126","DOIUrl":"https://doi.org/10.14283/jpad.2024.126","url":null,"abstract":"<p>Changes in biomarker levels of Alzheimer’s disease (AD) reflect underlying pathophysiological changes in the brain and can provide evidence of direct and downstream treatment effects linked to disease modification. Recent results from clinical trials of anti–amyloid β (Aβ) treatments have raised the question of how to best characterize the relationship between AD biomarkers and clinical endpoints. Consensus methodology for assessing such relationships is lacking, leading to inconsistent evaluation and reporting. In this review, we provide a statistical framework for reporting treatment effects on early and late accelerating AD biomarkers and assessing their relationship with clinical endpoints at the subject and group levels. Amyloid positron emission tomography (PET), plasma p-tau, and tau PET follow specific trajectories during AD and are used as exemplar cases to contrast biomarkers with early and late progression. Subject-level correlation was assessed using change from baseline in biomarkers versus change from baseline in clinical endpoints, and interpretation of the correlation is dependent on the biomarker and disease stage. Group-level correlation was assessed using the placebo-adjusted treatment effects on biomarkers versus those on clinical endpoints in each trial. This correlation leverages the fundamental advantages of randomized placebo-controlled trials and assesses the predictivity of a treatment effect on a biomarker or clinical benefit. Harmonization in the assessment of treatment effects on biomarkers and their relationship to clinical endpoints will provide a wealth of comparable data across clinical trials and may yield new insights for the treatment of AD.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"111 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141526591","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}

{"title":"Update to: Two Randomized Phase 3 Studies of Aducanumab in Early Alzheimer’s Disease","authors":"C. Rubel, T. Chen, Gersham Dent","doi":"10.14283/jpad.2024.147","DOIUrl":"https://doi.org/10.14283/jpad.2024.147","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"61 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141737781","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}

{"title":"Multidomain Intervention Trial for Preventing Cognitive Decline among Older Adults with Type 2 Diabetes: J-MIND-Diabetes","authors":"T. Sugimoto, A. Araki, H. Fujita, K. Fujita, K. Honda, N. Inagaki, T. Ishida, J. Kato, M. Kishi, Y. Kishino, K. Kobayashi, K. Kouyama, Y. Kuroda, S. Kuwahata, N. Matsumoto, T. Murakami, H. Noma, J. Ogino, M. Ogura, M. Ohishi, H. Shimada, K. Sugimoto, T. Takenaka, Y. Tamura, H. Tokuda, K. Uchida, H. Umegaki, Takashi Sakurai","doi":"10.14283/jpad.2024.117","DOIUrl":"https://doi.org/10.14283/jpad.2024.117","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>No multidomain intervention trials have been designed for the prevention of cognitive decline in older adults with type 2 diabetes.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>To investigate the efficacy of a multidomain intervention in preventing cognitive decline in older adults with type 2 diabetes and cognitive impairment.</p><h3 data-test=\"abstract-sub-heading\">Design</h3><p>Eighteen-month, multi-centered, randomized controlled trial.</p><h3 data-test=\"abstract-sub-heading\">Setting</h3><p>Twelve hospitals in Japan.</p><h3 data-test=\"abstract-sub-heading\">Participants</h3><p>Outpatients with type 2 diabetes aged 70–85 years with cognitive impairment.</p><h3 data-test=\"abstract-sub-heading\">Intervention</h3><p>The multidomain intervention program includes management of metabolic and vascular risk factors, exercise, nutritional counseling, and promotion of social participation. Participants in the control group received usual care and treatment for type 2 diabetes.</p><h3 data-test=\"abstract-sub-heading\">Measurements</h3><p>The primary outcome was the change in a composite score combining several neuropsychological tests from baseline to the 18-month follow-up. To assess the differences in cognitive changes between the intervention and control groups, a mixed-effects model for repeated measures was used.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Between March 13, 2019, and May 8, 2020, 361 participants were screened, and 154 were randomly assigned to either the intervention group (n = 81) or the control group (n = 73). Finally, 110 participants completed the trial. The between-group difference in the composite score changes was 0.068 (95% confidence interval, −0.091 to 0.226). Analyses for secondary outcomes indicated a positive impact of the intervention on memory and indicated that the intervention led to changes in dietary habits with increased intakes of niacin and meat, along with weight reduction compared to the control group.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The multidomain intervention did not demonstrate efficacy in preventing cognitive decline. However, this trial provided proof-of-concept evidence that multidomain interventions may offer cognitive benefits and contribute to changes in dietary behavior and weight reduction in older adults with type 2 diabetes and cognitive impairment. These findings should be confirmed in future studies.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"14 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141552192","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}

{"title":"Leveraging Diverse Regulated Cell Death Patterns to Identify Diagnosis Biomarkers for Alzheimer’s Disease","authors":"L. Ren, Q. Zhang, J. Zhou, X. Wang, D. Zhu, Xueyan Chen","doi":"10.14283/jpad.2024.119","DOIUrl":"https://doi.org/10.14283/jpad.2024.119","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>The functions of regulated cell death (RCD) are closely related to Alzheimer’s disease (AD). However, very few studies have systematically investigated the diagnosis and immunologic role of RCD-related genes in AD patients.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>8 multicenter AD cohorts were included in this study, and then were merged into a meta cohort. Then, an unsupervised clustering analysis was carried out to detect unique subtypes of AD based on RCD-related genes. Subsequently, differently expressed genes (DEGs) and weighted correlation network analysis (WGCNA) between subtypes were identified. Finally, to establish an optimal risk model, an RCD. score was constructed by using computational algorithm (10 machine-learning algorithms, 113 combinations).</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>We identified two distinct subtypes based on RCD-related genes, each exhibiting distinct hallmark pathway activity and immunologic landscape. Specifically, cluster.A patients had a higher immune infiltration, a higher immune modulators and poor AD progression. Utilizing the shared DEGs and WGCNA of these subtypes, we constructed an RCD. score that demonstrated excellent predictive ability in AD across multiple datasets. Furthermore, RCD.score was identified to exhibit the strongest association with poor AD progression. Mechanistically, we observed activation of signaling pathways and effective immune infiltration and immune modulators in the high RCD.score group, thus leading to a poor AD progression. Additionally, Mendelian randomization screening revealed four genes (CXCL1, ENTPD2, METTL7A, and SERPINB6) as feature genes for AD.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The RCD model is a valuable tool in categorizing AD patients. This model can be of great assistance to clinicians in determining the most suitable personalized treatment plan for each individual AD patient.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"52 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141552173","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}

{"title":"Development and Concurrent Validity of the Short-Form CogDrisk Dementia Risk Assessment Tool","authors":"Kaarin J. Anstey, M. H. Huque, S. Kootar, R. Eramudugolla, M. Li","doi":"10.14283/jpad.2024.108","DOIUrl":"https://doi.org/10.14283/jpad.2024.108","url":null,"abstract":"<p>Evidence-based dementia risk assessment is required to inform individual and policy-level dementia risk reduction interventions. We developed the CogDrisk Short Form (CogDrisk-SF) to assess dementia risk factors, for situations where time and resources are limited. To evaluate concurrent validity with the original CogDrisk, we conducted an online survey using a repeated-measures, counterbalanced design. Community dwelling participants (n = 647, 50.1% were female, mean age 62.2 years, age range 40–89) completed the survey. The mean(sd) score for CogDrisk-SF and the CogDrisk was 9.7 (5.3) and 9.9 (5.5), respectively. The intraclass correlation between the risk score obtained from CogDrisk and CogDrisk-SF was 0.92. Fish intake, insomnia and depression had percentage agreements of 79%, 87% and 89% respectively. Other items had &gt;95% agreement except for loneliness (94%), hypertension (94%), cholesterol (93%), atrial fibrillation (91%) and cognitive activity (90%). Very high agreement between the CogDrisk-SF and original CogDrisk shows that CogDrisk-SF is valid for use in research and clinical practice.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"20 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141552174","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}

{"title":"Performance of Plasma Biomarkers Combined with Structural MRI to Identify Candidate Participants for Alzheimer’s Disease-Modifying Therapy","authors":"M. Manjavong, J. M. Kang, A. Diaz, M. T. Ashford, J. Eichenbaum, A. Aaronson, M. J. Miller, S. Mackin, R. Tank, M. Weiner, Rachel L. Nosheny","doi":"10.14283/jpad.2024.110","DOIUrl":"https://doi.org/10.14283/jpad.2024.110","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Recently, two monoclonal antibodies that lower amyloid plaques have shown promising results for the treatment of Mild Cognitive Impairment (MCI) and mild dementia due to Alzheimer’s disease (AD). These treatments require the identification of cognitively impaired older adults with biomarker evidence of AD pathology using CSF biomarkers or amyloid-PET. Previous studies showed plasma biomarkers (plasma Aβ42/Aβ40 and p-tau181) and hippocampal volume from structural MRI correlated with brain amyloid pathology. We hypothesized plasma biomarkers with hippocampal volume would identify patients who are suitable candidates for disease-modifying therapy.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>To evaluate the performance of plasma AD biomarkers and hippocampal atrophy to detect MCI or AD with amyloid pathology confirmed by amyloid-PET or CSF biomarkers in ADNI.</p><h3 data-test=\"abstract-sub-heading\">Design</h3><p>A cross-sectional and longitudinal study.</p><h3 data-test=\"abstract-sub-heading\">Setting and Participants</h3><p>Data were from the Alzheimer’s Disease Neuroimaging Initiative. Participants were aged 55–90 years old with plasma biomarker and structural MRI brain data.</p><h3 data-test=\"abstract-sub-heading\">Measurements</h3><p>The optimum cut-off point for plasma Aβ42/Aβ40, p-tau181, and NFL and the performance of combined biomarkers and hippocampal atrophy for detecting cognitive impairment with brain amyloid pathology were evaluated. The association between baseline plasma biomarkers and clinical progression, defined by CDR-Sum of Boxes (CDR-SB) and diagnostic conversion over two years, was evaluated using a Weibull time-to-event analysis.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>A total of 428 participants were included; 167 had normal cognition, 245 had MCI, and 16 had mild AD. Among MCI and AD, 140 participants had elevated amyloid levels by PET or CSF. Plasma Aβ42/Aβ40 provided the best accuracy (sensitivity 79%, specificity 66%, AUC 0.73, 95% CI 0.68–0.77) to detect drug candidate participants at baseline. Combined plasma Aβ42/40, p-tau181, and hippocampal atrophy increased the specificity for diagnosis (96%), but had lower sensitivity (34%), and AUC (0.65). Hippocampal atrophy combined with the abnormal plasma p-tau181 or hippocampal atrophy alone showed high sensitivity to detect clinical progression (by CDR-SB worsening) of the drug-candidate participants within the next 2 years (sensitivity 93% and 89%, respectively).</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Plasma biomarkers and structural MRI can help identify patients who are currently eligible for anti-amyloid treatment and are likely to progress clinically, in cases where amyloid-PET or CSF biomarkers are not available.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"34 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141526647","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}