Jpad-Journal of Prevention of Alzheimers Disease最新文献

{"title":"Erratum to: Cerebral Phospho-Tau Acts Synergistically with Soluble Aβ42 Leading to Mild Cognitive Impairment in AAV-AD Rats","authors":"B. Souchet, M. Audrain, Y. Gu, M. Lindberg, N. S. Orefice, E. Rey, N. Cartier, N. Janel, L. Meijer, J. Braudeau","doi":"10.14283/jpad.2022.74","DOIUrl":"https://doi.org/10.14283/jpad.2022.74","url":null,"abstract":"The authors would like to draw the reader’s attention to the error in the following article.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2022-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47664281","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":"Aducanumab Trials EMERGE But Don’t ENGAGE","authors":"L. Schneider","doi":"10.14283/jpad.2022.37","DOIUrl":"https://doi.org/10.14283/jpad.2022.37","url":null,"abstract":"If at first you don’t succeed, try, try (and try?) again to get that darned manuscript published just the way you want it (1). Which is what 24 authors did after rejections or ‘revise and resubmits’ from JAMA, probably from the New England Journal of Medicine before JAMA, if not another journal afterwards (Just guessing based on an Axios report and the timing of the JAMA submission https://www.axios.com/biogen-jamaaduhelm-clinical-trial-results-publish-fc7c2876-a684-4bfc8462-4165f57d735a.html). The Emerge (302) and Engage (301) manuscript appears to have been withheld over two years because the Biogen and academic authors would not respond or comply with reviewers and editors. The manuscript could have been reviewed by 6 to 12 reviewers before JPAD got its turn. This published version, unfortunately, shows scant evidence of having been critically reviewed (1). There are defensive tones here and there, but little evidence of deliberation or uncertainty in the presentation, conduct and outcomes of the trials. (It’s perhaps notable, that their structured abstract remains in the unique style that JAMA requires for submitted manuscripts and that is reformatted when the revised manuscript is published (https://jamanetwork.com/ journals/jama/pages/instructions-for-authors#SecAb stractsforReportsofOriginalData). Clearly, the authors wanted complete control of their message and not to have to acknowledge the substantial limitations of their trials, outcomes, and inferences they make. The message they want to sell is: High dose aducanumab met its “prespecified” primary and secondary endpoints; showed an association between reduction of biomarkers of “underlying disease pathology” and slowing of clinical decline; and has a “clinically meaningful” effect. Frankly, this is so wrong on many levels.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2022-04-01","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":"Where Do We Go from Here?","authors":"R. C. Petersen","doi":"10.14283/jpad.2022.35","DOIUrl":"https://doi.org/10.14283/jpad.2022.35","url":null,"abstract":"Budd Haeberlein and colleagues presented the data from the two randomized Phase 3 studies of aducanumab in early Alzheimer’s disease (AD) recently in JPAD (1). The data have been carefully evaluated by the field over the past few years and are now finally reported for closer scrutiny. Essentially, the two studies involved 3,285 participants with mild cognitive impairment or mild dementia due to underlying AD as documented by amyloid positivity. One study, EMERGE, demonstrated statistically significant findings on the primary outcome measure, three secondary measures and a tertiary measure. The parallel study, ENGAGE, failed to replicate these results. The sponsor did post hoc analyses on the ENGAGE study to rationalize its failure to replicate the EMERGE results and suggested several plausible hypotheses. Central to this discussion was the implementation of protocol amendments during the conduct of the study that may have differentially influenced the outcomes of the two studies. The studies were stopped for futility in March of 2019 according to predetermined guidelines. The sponsor, however, evaluated an expanded dataset beyond the data available to the iDMC and concluded that EMERGE demonstrated positive results while ENGAGE did not. The socio-political fallout of these studies has been enormous. From the original termination of the studies due to futility through the subsequent analyses of additional double-blinded data, the FDA’s willingness to entertain a filing, the FDA Advisory Committee’s recommendations, the accelerated approval by the FDA on June 7, 2021, and the subsequent consideration for coverage by CMS have resulted in a firestorm. As such, it may be time to step back from the media circus and look at the implications of these studies for the field and, most importantly, our patients. An interpretation of these data could conclude that there is a positive effect of aducanumab on clinical progression of AD, but the effect is modest. The combination of the positive results from the EMERGE study would be statistically quite unlikely to have happened by chance. However, these data need to be interpreted in the context of the negative results from the parallel study, ENGAGE. This may reflect reality. The impact of intervention on amyloid at the stage of plaque development, along with the symptoms of mild cognitive impairment or mild dementia, may be minimal. If one accepts the putative explanation of the development of AD pathophysiology with amyloid accumulation occurring over years to decades subsequently leading to tau hyperphosphorylation, synaptic dysfunction and cognitive impairment, then results of these types of amyloid interventions may be comprehensible. That is, if amyloid has built up over decades and if one is able to successfully reduce the plaque burden over the course of 12 to 18 months, what might be a reasonable clinical manifestation of that intervention? One could argue that the expectations should be quite modest b","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47443804","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 ‘Aducanumab Story’: Will the Last Chapter Spell the End of the ‘Amyloid Hypothesis’ or Mark a New Beginning?","authors":"Z. Khachaturian","doi":"10.14283/jpad.2022.36","DOIUrl":"https://doi.org/10.14283/jpad.2022.36","url":null,"abstract":"The paper entitled “Two Randomized Phase 3 Studies of Aducanumab in Early Alzheimer’s Disease” by Budd Haeberlein, S., Aisen, P., Barkhof, F. et al in the current issue of J Prev Alzheimers Dis [https://doi.org/10.14283/jpad.2022.30] presents the much-anticipated results of two pivotal trials to demonstrate the safety and efficacy aducanumab as a therapy for early-stage Alzheimer’s disease [AD]. This phase 3 study shows a reduction of molecular imaging and biofluid markers of AD is associated with a slowing of cognitive decline. These results received an accelerated approval by FDA in June 2021 based on the drug’s effect on a surrogate endpoint that is ‘...reasonably likely to predict a clinical benefit to patients ...’ (1). This ‘conditional’ regulatory ruling requires further confirmatory [phase-4] trials to verify that drug effect on the surrogate endpoints actually predicts a clinically meaningful benefit. The subsequent decisions by EMA [in the EU] and the CMS [in the US] have not been favorable for the routine clinical use of this drug for treatment of dementia-AD. These landmark regulatory determinations by FDA, EMA and CMS have created controversy with passionate debates regarding: the methodological flaws of the two pivotal trials, questionable scientific rational, weak association between surrogate marker and cognitive function, financial implication of high cost of treatment and the uncertainty of the ultimate clinical utility; pending validation of a clinically meaningful benefit for the patient (2). Regardless of the various stances in ongoing debate over the regulatory ruling and the clinical merits of aducanumab, it is important to publish the results of the first phase-3 trial to show a putative association between a surrogate marker and a behavioral/clinical feature of dementia-AD. This study, and the ensuing ‘conditional’ regulatory decision, is a significant ‘teaching’ milestone in the 40-year struggle to develop effective diseasemodifying interventions of dementia-AD. Heated debates over controversial issues in science is not a new phenomenon or necessarily detrimental to progress. For example, nearly thirty years ago the study and the regulatory ruling regarding Tacrine, the first drug approved for AD, was also controversial. [DOI: 10.1177/106002809402800612]. The study was plagued with methodological problems; adverse events [re: liver toxicity] halted the trial before completion and as in the present situation FDA was concerned with the adequacy/validity/relevance of the outcome measures. Eventually by 2013 Tacrine [Cognex] was withdrawn from the market due to its limited clinically meaningful benefit and concerns over its link to liver toxicity. But, Tacrine was an important ‘teaching event’ in the history of therapy development for AD. In retrospect one of the important aspects of the Tacrine experiences was the fact that FDA set the regulatory hurdle-requirement for approval at ‘just right’ level, which might be the case","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45466549","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. Aisen, F. Barkhof, S. Chalkias, T. Chen, S. Cohen, G. Dent, O. Hansson, K. Harrison, C. von Hehn, T. Iwatsubo, C. Mallinckrodt, C. Mummery, K. Muralidharan, I. Nestorov, L. Nisenbaum, R. Rajagovindan, L. Skordos, Y. Tian, C. V. van Dyck, B. Vellas, S. Wu, Y. Zhu, A. Sandrock","doi":"10.14283/jpad.2022.30","DOIUrl":"https://doi.org/10.14283/jpad.2022.30","url":null,"abstract":"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. We evaluated the efficacy and safety of aducanumab in early Alzheimer’s disease. EMERGE and ENGAGE were two randomized, double-blind, placebo-controlled, global, phase 3 studies of aducanumab in patients with early Alzheimer’s disease. These studies involved 348 sites in 20 countries. 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. 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. 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. 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. 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.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2022-03-18","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}

{"title":"Digital Therapeutics for MCI and Alzheimer’s disease: A Regulatory Perspective — Highlights From The Clinical Trials on Alzheimer’s Disease conference (CTAD)","authors":"J. Shuren, P. Doraiswamy","doi":"10.14283/jpad.2022.28","DOIUrl":"https://doi.org/10.14283/jpad.2022.28","url":null,"abstract":"","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2022-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43231002","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":"Sensitivity of the Preclinical Alzheimer’s Cognitive Composite (PACC), PACC5, and Repeatable Battery for Neuropsychological Status (RBANS) to Amyloid Status in Preclinical Alzheimer’s Disease -Atabecestat Phase 2b/3 EARLY Clinical Trial","authors":"K. Papp, H. Rofael, A. Veroff, M. Donohue, S. Wang, C. Randolph, E. Grober, H. Brashear, G. Novak, K. Ernstrom, R. Raman, P. Aisen, R. Sperling, G. Romano, D. Henley","doi":"10.14283/jpad.2022.17","DOIUrl":"https://doi.org/10.14283/jpad.2022.17","url":null,"abstract":"Cognitive composites commonly serve as primary outcomes in Alzheimer’s disease (AD) secondary prevention trials. To evaluate the association between amyloid (Aβ) burden level (+/−) and performance on three separate composite endpoints: Preclinical Alzheimer’s Cognitive Composite (PACC), PACC+Semantic Fluency (PACC5), and Repeatable Battery for Neuropsychological Status (RBANS). Screening data from the randomized, double-blind, placebo-controlled, phase 2b/3 atabecestat EARLY study in preclinical AD participants were used in this analysis. The EARLY study was conducted at 143 centers across 14 countries. 3,569 cognitively unimpaired older adults (Clinical Dementia Rating of 0; aged 60–85 years) screened for inclusion in the EARLY study with Aβ status and at least PACC or RBANS at screening were included. Participants were categorized as those with non-pathological Aβ levels (Aβ−, n=2,824) and those with pathological Aβ levels (Aβ+, n=745) based on florbetapir uptake or levels of cerebrospinal fluid Aβ1–42. Analysis of Covariance models controlling for age, sex, and education were used to examine the difference in PACC, PACC5, and RBANS between Aβ groups. Nonparametric bootstrap was used to compare sensitivity of composites to differentiate between Aβ status. Of 3,569 participants, 2,116 were women (59%); 3,006 were Caucasian (84%); mean (SD) age was 68.98 (5.28) years. Aβ+ participants performed worse versus Aβ− participants on all cognitive composites though the magnitude of the Aβ effect was generally small. The Aβ+/− effect size for the PACC (Cohen’s d=−0.15) was significantly greater than the RBANS (d=−0.097) while the PACC5 effect size (d=−0.139) was numerically larger than the RBANS. When examining subscores from the composites, memory tests (i.e., Free and Cued Selective Reminding Test, Figure Recall) and speed of processing (i.e., Digit-Symbol/Coding on the PACC/RBANS) exhibited the largest Aβ+/− effect sizes. Cross-sectional relationships between Aβ and cognition among clinically unimpaired older adults are detectable on multi-domain cognitive composites but are relatively small in magnitude. The Aβ+/− group effect was statistically larger for PACC and marginally larger for PACC5 versus RBANS. However, interpretation of composite sensitivity to Aβ status cross-sectionally cannot be generalized to sensitivity to change over time.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2022-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42097536","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":"Detection and Management of Amyloid-Related Imaging Abnormalities in Patients with Alzheimer’s Disease Treated with Anti-Amyloid Beta Therapy","authors":"J. Barakos, D. Purcell, J. Suhy, S. Chalkias, P. Burkett, C. M. Grassi, C. Castrillo‐Viguera, I. Rubino, E. Vijverberg","doi":"10.14283/jpad.2022.21","DOIUrl":"https://doi.org/10.14283/jpad.2022.21","url":null,"abstract":"Amyloid-related imaging abnormalities (ARIA) are adverse events reported in Alzheimer’s disease trials of anti-amyloid beta (Aβ) therapies. This review summarizes the existing literature on ARIA, including bapineuzumab, gantenerumab, donanemab, lecanemab, and aducanumab studies, with regard to potential risk factors, detection, and management. The pathophysiology of ARIA is unclear, but it may be related to binding of antibodies to accumulated Aβ in both the cerebral parenchyma and vasculature, resulting in loss of vessel wall integrity and increased leakage into surrounding tissues. Radiographically, ARIA-E is identified as vasogenic edema in the brain parenchyma or sulcal effusions in the leptomeninges/ sulci, while ARIA-H is hemosiderin deposits presenting as microhemorrhages or superficial siderosis. ARIA tends to be transient and asymptomatic in most cases, typically occurring early in the course of treatment, with the risk decreasing later in treatment. Limited data are available on continued dosing following radiographic findings of ARIA; hence, in the event of ARIA, treatment should be continued with caution and regular monitoring. Clinical trials have implemented management approaches such as temporary suspension of treatment until symptoms or radiographic signs of ARIA have resolved or permanent discontinuation of treatment. ARIA largely resolves without concomitant treatment, and there are no systematic data on potential treatments for ARIA. Given the availability of an anti-Aβ therapy, ARIA monitoring will now be implemented in routine clinical practice. The simple magnetic resonance imaging sequences used in clinical trials are likely sufficient for effective detection of cases. Increased awareness and education of ARIA among clinicians and radiologists is vital.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2022-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43934024","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":"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":null,"pages":null},"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":null,"pages":null},"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}