Jpad-Journal of Prevention of Alzheimers Disease最新文献

{"title":"Plasma MMP-9 Levels as the Future Risk of Conversion to Dementia in ApoE4-Positive MCI Patients: Investigation Based on the Alzheimer’s Disease Neuroimaging Initiative Database","authors":"K. Abe, Yuhei Chiba, K. Ide, A. Yoshimi, T. Asami, A. Suda, T. Odawara, A. Hishimoto, Alzheimer's Disease Neuroimaging Initiative","doi":"10.14283/jpad.2022.19","DOIUrl":"https://doi.org/10.14283/jpad.2022.19","url":null,"abstract":"Background Matrix metalloproteinase 9 (MMP-9) has been reported to be correlated with declines in hippocampal volume and cognitive function in ApoE4-positive MCI patients. Objectives The present study was aimed to investigate the effects of plasma matrix MMP-9 on the conversion risk between mild cognitive impairment (MCI) patients with and without ApoE4. Design and Setting Retrospective observational study using the data extracted from the Alzheimer’s Disease Neuroimaging Initiative database. Participants We included 211 ApoE4-positive MCI subjects (ApoE4+ MCI) and 184 ApoE4-negative MCI subjects (ApoE4-MCI). Measurements We obtained demographic and data including plasma MMP-9 levels at baseline and longitudinal changes in Clinical Dementia Rating (CDR) up to 15 years. We compared conversion rates between ApoE4+ MCI and ApoE4- MCI by the Log-rank test and calculated the hazard ratio (HR) for covariates including age, sex, educational attainment, drinking and smoking histories, medications, and plasma MMP-9 levels using a multiple Cox regression analysis of ApoE4+ MCI and ApoE4- MCI. Results No significant differences were observed in baseline plasma MMP-9 levels between ApoE4+ MCI and ApoE4- MCI. High plasma MMP-9 levels increased the conversion risk significantly more than low plasma MMP-9 levels (HR, 2.46 [95% CI, 1.31–4.48]) and middle plasma MMP-9 levels (HR, 1.67 [95% CI, 1.04–2.65]) in ApoE4+ MCI, but not in ApoE4- MCI. CONCLUSION: Plasma MMP-9 would be the risk of the future conversion to dementia in ApoE4+ MCI.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"1 1","pages":"1-7"},"PeriodicalIF":6.4,"publicationDate":"2022-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43280353","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 Association between Sugar-Sweetened Beverages and Cognitive Function in Middle-Aged and Older People: A Meta-Analysis","authors":"Q. Sun, Y. Yang, X. Wang, R. Yang, X. Li","doi":"10.14283/jpad.2021.71","DOIUrl":"https://doi.org/10.14283/jpad.2021.71","url":null,"abstract":"To explore the association between the intake of sugar-sweetened beverages and cognitive dysfunction in middle-aged and older adults, so as to provide an evidence-based basis for the early prevention of cognitive dysfunction. A comprehensive search of relevant literature was conducted in PubMed, EMBase, Cochrane, ScienceDirect, and Web of Science from the inception until January 2021. Odds ratios (OR), hazard ratios (HR) and 95% confidence intervals (CI) were calculated using a random-effects, generic inverse variance method. Meta-analysis of the included studies was performed using Review Manager 5.4. A total of 10 studies on the association between sugary beverages and cognitive dysfunction in middle-aged and older adults were included, of which 3 were cross-sectional studies and the rest were cohort studies. Eight of the ten studies had results suggestive of a negative association. However, Meta-analysis results showed that the association between the intake of sugar-sweetened beverages and the risk of cognitive impairment was not statistically significant (OR=1.59, 95% CI: 0.93–2.74, P=0.08); but from two studies, the hazard ratios of all-cause dementia in middle-aged and older people consuming sugar-sweetened beverages was 2.77 (95%CI: 2.24–3.43, P<0.00001); the hazard ratios of Alzheimer’s disease in middle-aged and older people consuming sugar-sweetened beverages was 2.63 (95%CI: 1.70–4.05, P<0.0001). There is insufficient evidence to state conclusively that sugar-sweetened beverages intake causes cognitive dysfunction in middle-aged and older adults.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"9 1","pages":"323 - 330"},"PeriodicalIF":6.4,"publicationDate":"2022-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45763016","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 Effects of Dual-Task Training on Cognitive and Physical Functions in Older Adults with Cognitive Impairment; A Systematic Review and Meta-Analysis","authors":"N. Ali, H. Tian, L. Thabane, J. Ma, H. Wu, Q. Zhong, Y. Gao, C. Sun, Yi Zhu, Tong Wang","doi":"10.14283/jpad.2022.16","DOIUrl":"https://doi.org/10.14283/jpad.2022.16","url":null,"abstract":"Background and Objective Individuals with Alzheimer disease and dementia experience cognitive decline and reduction in physical capabilities. Engaging in cognitive challenges and physical exercises is effective in reducing age-related cognitive and physical decline. It is believed that physical activity in the context of cognitive challenges might enhance the process of neurogenesis in the adult brain, but how effective are such interventions? Is there enough evidence to support that dual-task training is more effective than cognitive or physical training alone? To what extent can such training improve cognitive and physical functions in patients at various stages of cognitive decline? Methodology This systematic review with meta-analysis summarizes the emerging evidence of dual-task training for enhancing cognitive and physical functions in older individuals with cognitive impairment, dementia or Alzheimer’s disease. A systematic search was carried out in MEDLINE, PubMed, EMBASE, and Cochrane Library with the following search terms: randomized control trials, dual-task training, SCD, MCI, dementia, and Alzheimer’s disease. Results A total of 21 studies with 2,221 participants were identified. The results of dual-task tanning intervention are summarized as change in global cognitive function; SMD = 0.24, (P= 0.002), memory; SMD = 0.28, (P = 0.000), executive function; SMD = 0.35, (P = 0.000), attention; SMD = −0.19, (P = 0.1), gait speed; SMD = 0.26, (P = 0.007), dual-task cost; SMD 0.56, (P = 0.000), and balance; SMD 0.36, (P = 0.004). Conclusion Primary analysis showed a small-to-medium positive effect of dual-task training interventions on cognitive functions and medium-to-large positive effect on gait functions and balance.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"1 1","pages":"1-12"},"PeriodicalIF":6.4,"publicationDate":"2022-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47461876","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 Association of Heart/Vascular Aging with Mild Cognitive Impairment in a Rural Multiethnic Cohort: The Project FRONTIER Study","authors":"D. Appiah, G. Ashworth, A. Boles, N. Nair","doi":"10.14283/jpad.2022.15","DOIUrl":"https://doi.org/10.14283/jpad.2022.15","url":null,"abstract":"Background Cardiovascular disease (CVD) and Alzheimer’s disease and related dementias (ADRD) disproportionately affect rural communities. Identifying strategies to effectively communicate CVD risk to prevent these conditions remains a high priority. Objective We assessed the relation between predicted heart/vascular age (PHA), an easily communicated metric of CVD risk, and mild cognitive impairment (MCI), an early manifestation of ADRD. Design, Setting, Participants Data were from 967 rural West Texas residents aged ≥40 years without CVD at baseline (2009–2012) enrolled in Project FRONTIER, an ongoing, multiethnic cohort study on cognitive aging. Measurements MCI was diagnosed using the standardized consensus review criteria. PHA was calculated using the Framingham CVD risk equation. High excess PHA (HEPHA) was defined as the difference between PHA and chronological age >5 years. Logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI). Result At baseline, the mean age of participants (70% women and 64% Hispanics) was 55 years. Almost 13% had MCI and 65% had HEPHA. After adjusting for socio-demographic and health factors, HEPHA was positively associated with MCI (OR=2.98; 95%CI: 1.72–5.15). Among participants without MCI at baseline who returned for follow-up exam after three years (n=238), a three-year negative change in PHA was seemingly associated with reduced odds for MCI (OR=0.98; 95%CI: 0.96–1.01). Conclusions In this study, PHA was positively associated with MCI, with improvement in CVD risk profile seemingly related to reduced odds for MCI. PHA may provide a low-cost means of communicating CVD risk in rural settings to prevent both CVD and ADRD.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"1 1","pages":"1-8"},"PeriodicalIF":6.4,"publicationDate":"2022-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41706789","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":"Evaluation of Memantine in AAV-AD Rat: A Model of Late-Onset Alzheimer’s Disease Predementia","authors":"B. Souchet, M. Audrain, S. Alves, R. Fol, Satoru Tada, N. S. Orefice, B. Potier, P. Dutar, J. Billard, N. Cartier, J. Braudeau","doi":"10.14283/jpad.2021.67","DOIUrl":"https://doi.org/10.14283/jpad.2021.67","url":null,"abstract":"Background Though our understanding of Alzheimer’s disease (AD) remains elusive, it is well known that the disease starts long before the first signs of dementia. This is supported by the large number of symptomatic drug failures in clinical trials and the increased trend to enroll patients at predementia stages with either mild or no cognitive symptoms. However, the design of pre-clinical studies does not follow this attitude, in particular regarding the choice of animal models, often irrelevant to mimic predementia Late Onset Alzheimer’s Disease (LOAD). Objectives We aimed to pharmacologically validate the AAV-AD rat model to evaluate preventive treatment of AD. Methods We evaluated an N-methyl-D-aspartate receptor antagonist, named memantine, in AAV-AD rats, an age-dependent amyloid rat model which closely mimics Alzheimer’s pathology including asymptomatic and prodromal stages. Memantine was used at a clinically relevant dose (20 mg daily oral administration) from 4 (asymptomatic phase) to 10 (mild cognitive impairment phase) months of age. Results A 6-month treatment with memantine promoted a non-amyloidogenic cleavage of APP followed by a decrease in soluble Aβ42. Consequently, both long-term potentiation and cognitive impairments were prevented. By contrast, the levels of hyperphosphorylated endogenous tau remained unchanged, indicating that a long-term memantine treatment is ineffective to restrain the APP processing-induced tauopathy. Conclusions Together, our data confirm that relevant models to LOAD, such as the AAV-AD rat, can provide a framework for a better understanding of the disease and accurate assessment of preventive treatments.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"1 1","pages":"1-10"},"PeriodicalIF":6.4,"publicationDate":"2022-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47765580","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":"Identifying Dementia Risk in Older Veterans Using A Mailing Survey","authors":"Aashaq Shah, O. Ysea-Hill, A. Torres-Morales, C. Gomez, A. Castellanos, J. Ruiz","doi":"10.14283/jpad.2022.14","DOIUrl":"https://doi.org/10.14283/jpad.2022.14","url":null,"abstract":"Evidence suggests that dementia can be prevented. Patients with frailty may be particularly at risk for cognitive impairment (CI). The aim of this study was to determine dementia risk in older Veterans and whether the risk varies according to frailty status. We also evaluated the feasibility of mailed dementia risk screening. Participants were mailed a questionnaire and the Self-Administered Gerocognitive Examination (SAGE). High dementia risk was defined as having mild cognitive impairment (MCI) on SAGE or a CAIDE score ≥6. Out of 5,432 mailed surveys, we obtained a response rate of 19.75%. Most responders completed the questionnaire items. We identified a total of 689 (75.9%) subjects to be at high risk for dementia. Individuals with frailty were at a greater risk for dementia when compared to robust individuals OR:1.921 (95%CI:1.259–2.930), p=.002. The mailed screening represents a convenient, alternative and scalable approach to screen for dementia risk.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"9 1","pages":"371-375"},"PeriodicalIF":6.4,"publicationDate":"2022-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49239042","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":"Study Protocol of a Comprehensive Activity Promotion Program for the Prevention of Dementia: A Randomized Controlled Trial Protocol","authors":"H. Shimada, S. Lee, K. Harada, S. Bae, K. Makino, I. Chiba, O. Katayama, H. Arai","doi":"10.14283/jpad.2022.12","DOIUrl":"https://doi.org/10.14283/jpad.2022.12","url":null,"abstract":"Background Several technical devices are available to monitor and promote changes in behavior toward higher activity. In particular, smartphones are becoming the primary platform for recognizing human activity. However, the effects of behavior change techniques that promote physical, cognitive, and social activities on incident dementia in older adults remain unknown. Objectives This randomized controlled trial aims to examine the effects of behavior change techniques on the prevention of dementia among community-dwelling older adults using a smartphone as a behavior change tool. Design A randomized controlled trial. Setting Community in Japan. Participants The study cohort comprises 3,498 individuals, aged ≥60 years, randomized into two groups: the smartphone group (n = 1,749) and the control group (n = 1,749). Intervention. The smartphone group will be asked to use smartphone applications for at least 30 minutes daily to self-manage and improve their physical, cognitive, and social activities. The smartphone group will perform 60-minute group walking sessions using application-linked Nordic walking poles with cognitive stimulation twice a week during the intervention period. The walking poles are a dual-task exercise tool that works with a smartphone to perform cognitive tasks while walking, and the poles are equipped with switches to answer questions for simple calculation and memory tasks. The smartphone and control groups will receive lectures about general health that will be provided during the baseline and follow-up assessments. Measurements Incident dementia will be detected using cognitive tests (at baseline, after 15 months, and after 30 months) and by preparing diagnostic monthly reports based on data from the Japanese Health Insurance System. Participants without dementia at baseline who will be diagnosed with dementia over the 30-month follow-up period will be considered to have incident dementia. Conclusions This study has the potential to provide the first evidence of the effectiveness of information communication technology and Internet of Things in incident dementia. If our trial results show a delayed dementia onset for self-determination interventions, the study protocol will provide a cost-effective and safe method for maintaining healthy cognitive aging.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"9 1","pages":"376 - 384"},"PeriodicalIF":6.4,"publicationDate":"2022-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66893597","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":"Editorial: Aducanumab Trials EMERGE But Don't ENGAGE.","authors":"L S Schneider","doi":"10.14283/jpad.2022.37","DOIUrl":"10.14283/jpad.2022.37","url":null,"abstract":"","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"9 1","pages":"193-196"},"PeriodicalIF":8.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48138090","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":"Anxiety and Depressive Symptoms and Cortical Amyloid-β Burden in Cognitively Unimpaired Older Adults.","authors":"C K Lewis, O M Bernstein, J D Grill, D L Gillen, D L Sultzer","doi":"10.14283/jpad.2022.13","DOIUrl":"10.14283/jpad.2022.13","url":null,"abstract":"<p><strong>Background: </strong>There is evidence of relationships between behavioral symptoms and increased risk for Alzheimer's Disease and/or Alzheimer's Disease biomarkers. However, the nature of this relationship is currently unknown.</p><p><strong>Objectives: </strong>To evaluate the relationship between anxiety and depressive symptoms and amyloid-β deposition in cognitively unimpaired older adults, and to assess mediating effects of either objective or subjective cognitive skills.</p><p><strong>Design: </strong>Cross-sectional analysis of screening data from participants enrolled in the Anti-Amyloid Treatment in Asymptomatic Alzheimer Disease (A4) Study (ClinicalTrials.gov Identifier: NCT02008357).</p><p><strong>Setting: </strong>Data analysis.</p><p><strong>Participants: </strong>4492 cognitively unimpaired adults, age 65-85, enrolled in the Anti-Amyloid Treatment in Asymptomatic Alzheimer Disease (A4) Study.</p><p><strong>Measurements: </strong>We used linear regression to estimate the associations between amyloid-β standard uptake value ratio (SUVR) and Geriatric Depression Scale (GDS) and State Trait Anxiety Inventory (STAI) scores while adjusting for potential confounding factors as well as for Cognitive Function Index (CFI) or Preclinical Alzheimer's Cognitive Composite (PACC) scores as possible mediational variables.</p><p><strong>Results: </strong>4399 subjects with complete covariates were included (mean age: 71.3, 59% female), GDS ranged 0-13 (mean: 1.0), and STAI ranged 6-24 (mean: 9.9). Amyloid-β SUVR was modestly associated with STAI; mean STAI score was estimated to be 0.275 points higher (95% CI: 0.038, 0.526; p-value = 0.023) for each 0.5-point increase in cortical amyloid-β SUVR. Subjective cognitive decline (CFI) attenuated the relationship between SUVR and STAI, while objective cognitive function (PACC) did not. No statistically significant relationship between SUVR and GDS was observed (p = 0.326).</p><p><strong>Conclusions: </strong>In cognitively unimpaired adults with low levels of depression and anxiety, cortical amyloid-β deposition is associated with anxiety but not depressive symptoms. Attenuation of this relationship by subjective cognitive difficulties suggests that anxiety may be partly due to such a perception resulting from cortical amyloid-β deposition.</p>","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"1 1","pages":"286-296"},"PeriodicalIF":6.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44060422","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":"Two Randomized Phase 3 Studies of Aducanumab in Early Alzheimer's Disease.","authors":"S Budd Haeberlein, P S Aisen, F Barkhof, S Chalkias, T Chen, S Cohen, G Dent, O Hansson, K Harrison, C von Hehn, T Iwatsubo, C Mallinckrodt, C J Mummery, K K Muralidharan, I Nestorov, L Nisenbaum, R Rajagovindan, L Skordos, Y Tian, C H van Dyck, B Vellas, S Wu, Y Zhu, A Sandrock","doi":"10.14283/jpad.2022.30","DOIUrl":"10.14283/jpad.2022.30","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease is a progressive, irreversible, and fatal disease for which accumulation of amyloid beta is thought to play a key role in pathogenesis. Aducanumab is a human monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta.</p><p><strong>Objectives: </strong>We evaluated the efficacy and safety of aducanumab in early Alzheimer's disease.</p><p><strong>Design: </strong>EMERGE and ENGAGE were two randomized, double-blind, placebo-controlled, global, phase 3 studies of aducanumab in patients with early Alzheimer's disease.</p><p><strong>Setting: </strong>These studies involved 348 sites in 20 countries.</p><p><strong>Participants: </strong>Participants included 1638 (EMERGE) and 1647 (ENGAGE) patients (aged 50-85 years, confirmed amyloid pathology) who met clinical criteria for mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's disease dementia, of which 1812 (55.2%) completed the study.</p><p><strong>Intervention: </strong>Participants were randomly assigned 1:1:1 to receive aducanumab low dose (3 or 6 mg/kg target dose), high dose (10 mg/kg target dose), or placebo via IV infusion once every 4 weeks over 76 weeks.</p><p><strong>Measurements: </strong>The primary outcome measure was change from baseline to week 78 on the Clinical Dementia Rating Sum of Boxes (CDR-SB), an integrated scale that assesses both function and cognition. Other measures included safety assessments; secondary and tertiary clinical outcomes that assessed cognition, function, and behavior; and biomarker endpoints.</p><p><strong>Results: </strong>EMERGE and ENGAGE were halted based on futility analysis of data pooled from the first approximately 50% of enrolled patients; subsequent efficacy analyses included data from a larger data set collected up to futility declaration and followed prespecified statistical analyses. The primary endpoint was met in EMERGE (difference of -0.39 for high-dose aducanumab vs placebo [95% CI, -0.69 to -0.09; P=.012; 22% decrease]) but not in ENGAGE (difference of 0.03, [95% CI, -0.26 to 0.33; P=.833; 2% increase]). Results of biomarker substudies confirmed target engagement and dose-dependent reduction in markers of Alzheimer's disease pathophysiology. The most common adverse event was amyloid-related imaging abnormalities-edema.</p><p><strong>Conclusions: </strong>Data from EMERGE demonstrated a statistically significant change across all four primary and secondary clinical endpoints. ENGAGE did not meet its primary or secondary endpoints. A dose- and time-dependent reduction in pathophysiological markers of Alzheimer's disease was observed in both trials.</p>","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"9 1","pages":"197-210"},"PeriodicalIF":8.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47498884","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}