Jpad-Journal of Prevention of Alzheimers Disease最新文献

{"title":"Erratum to: Alzheimer’s Disease Composite Score: a Post-Hoc Analysis Using Data from the LipiDiDiet Trial in Prodromal Alzheimer’s Disease","authors":"S. Hendrix, H. Soininen, A. M. V. van Hees, N. Ellison, P. Visser, A. Solomon, A. Attali, K. Blennow, M. Kivipelto, T. Hartmann","doi":"10.1007/s42414-019-0001-5","DOIUrl":"https://doi.org/10.1007/s42414-019-0001-5","url":null,"abstract":"","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2019-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48953697","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":"Is a Large-Scale Screening for Alzheimer’s Disease Possible? Yes, in a Few Years","authors":"Federica Ribaldi, Federica Ribaldi, D. Altomare, Giovanni B. Frisoni","doi":"10.14283/jpad.2019.29","DOIUrl":"https://doi.org/10.14283/jpad.2019.29","url":null,"abstract":"Recent evidence on blood-based biomarkers is pointing the way towards a new era of large-scale, feasible, cost-effective and non-invasive screening for Alzheimer’s disease (AD). This was one of the main focuses of the recent meeting of the European Union-North American Clinical Trials in AD (EU/US CTAD) Task Force, which took place in Barcelona in October 24-27, 2018, and convened drug and diagnostics developers from industry and academia in order to define a roadmap for the development and marketing of blood-based biomarkers (1).","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.14283/jpad.2019.29","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66893433","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 2018 Revised FDA Guidance for Early Alzheimer’s Disease: Establishing the Meaningfulness of Treatment Effects","authors":"C. Edgar, G. Vradenburg, J. Hassenstab","doi":"10.14283/jpad.2019.30","DOIUrl":"https://doi.org/10.14283/jpad.2019.30","url":null,"abstract":"The present report reviews the revised 2018 FDA guidance for early AD, with an emphasis on meaningfulness of clinical outcome assessments (COAs). A radical shift is evident in the importance given to establishing the meaningfulness of COAs in the 2018 draft versus the 2013 draft. The implications of this shift include the assertion that cognition is clinically meaningful, but that a persuasive effect on cognition, depending upon disease stage of the participants in the trial, is one that is of enough magnitude, established across multiple relevant domains, and can be supported by biomarkers reflecting underlying AD pathological changes. Meaningfulness is established through an understanding of the conceptual relevance of what is being measured and magnitude of any treatment effect. Precedent exists within other FDA guidance and independent good practices publications as to how meaningfulness may be assessed e.g. via evaluation of content validity and concepts such as minimally important difference. Additionally, FDA is developing a series of methodological Patient Focused Drug Development (PFDD) documents to provide further guidance on this topic, which are aimed at addressing gaps in methodology and recommended best practice. Importantly, application of PFDD approaches to AD is behind that in other areas and there is limited published content validity for COAs and a lack of supportive qualitative research. Initiatives to build robust conceptual models of AD and develop novel direct measures of meaningful health outcomes will have a significant impact on measurement of efficacy in clinical trials and on payer determinations of beneficiary value. Greater recognition of what is meaningful from the perspective of the patient and caregiver will inform regulatory reviews and determinations for payment and coverage of treatments.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.14283/jpad.2019.30","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66893016","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":"Alzheimer’s Disease Composite Score: a Post-Hoc Analysis Using Data from the LipiDiDiet Trial in Prodromal Alzheimer’s Disease","authors":"S. Hendrix, Hilkka Soininen, A. V. Hees, N. Ellison, Pieter Jelle Visser, Pieter Jelle Visser, Alina Solomon, Alina Solomon, Alina Solomon, A. Attali, K. Blennow, K. Blennow, M. Kivipelto, M. Kivipelto, M. Kivipelto, T. Hartmann","doi":"10.14283/jpad.2019.33","DOIUrl":"https://doi.org/10.14283/jpad.2019.33","url":null,"abstract":"As research evolves in prodromal AD, the need to validate sufficiently sensitive outcome measures, e.g. the Alzheimer’s Disease Composite Score (ADCOMS) is clear. In the LipiDiDiet randomized trial in prodromal AD, cognitive decline in the study population was much less than expected in the timeframe studied. While the primary composite endpoint was insufficiently sensitive to detect a difference in the modified intention to treat population, the per-protocol population showed less decline in the active than the control group, indicating better treatment effects with regular product intake. These results were further strengthened by significant benefits on secondary endpoints of cognition and function, and brain atrophy. The present post-hoc analysis investigated whether ADCOMS could detect a difference between groups in the LipiDiDiet population (138 active, 140 control). The estimated mean change in ADCOMS from baseline (standard error) was 0.085 (0.018) in the active and 0.133 (0.018) in the control group; estimated mean treatment difference −0.048 (95% confidence intervals −0.090, −0.007; p=0.023), or 36% less decline in the active group. This suggests ADCOMS identified the cognitive and functional benefits observed previously, confirming the sensitivity of this composite measure.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66893794","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":"A Turning Point in Alzheimer’s Research: Harmonized Research Strategies and Novel Investments in Public Health Infrastructure Are Reenergizing the Field, and Rekindling Hope for Those Affected by Alzheimer’s and Related Dementias","authors":"M. Carrillo, H. Snyder, R. Conant, S. Worley, R. Egge","doi":"10.14283/jpad.2019.36","DOIUrl":"https://doi.org/10.14283/jpad.2019.36","url":null,"abstract":"Alzheimer’s disease (AD) and related dementias (ADRD) are complex global health issues that require resources and commitments from around the world. The international research community continues to build upon knowledge and generate fresh ideas and strategies to move toward an effective therapy to treat, delay, or prevent ADRD. With accelerated momentum and more funding, the field is poised to hasten the discovery of interventions to stop, slow, or prevent disease progression, and improve care and quality of life for those affected.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66893875","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":"Randomized, Placebo Controlled Trial of NPT088, A Phage-Derived, Amyloid-Targeted Treatment for Alzheimer’s Disease","authors":"D. Michelson, M. Grundman, K. Magnuson, R. Fisher, Jonathan M. Levenson, Paul S. Aisen, K. Marek, Martha Gray, Franz Hefti","doi":"10.14283/jpad.2019.37","DOIUrl":"https://doi.org/10.14283/jpad.2019.37","url":null,"abstract":"The engineered fusion protein NPT088 targets amyloid in vitro and in animal models of Alzheimer’s disease. Previous studies showed that NPT088 treatment reduced β-amyloid plaque and tau aggregate loads in mouse disease models. Here, we present the results from an initial clinical study of NPT088 in patients with mild to moderate Alzheimer’s disease. Patients were treated with 4 dose levels of NPT088 for 6 months to evaluate its safety and tolerability. Exploratory measurements included measurement of change in β-amyloid plaque and tau burden utilizing Positron Emission Tomography imaging as well as measures of Alzheimer’s disease symptoms. At endpoint NPT088 was generally safe and well-tolerated with the most prominent finding being infusion reactions in a minority of patients. No effect of NPT088 on brain plaques, tau aggregates or Alzheimer’s disease symptoms was observed.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.14283/jpad.2019.37","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66893456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of the NIA-AA Research Framework: Towards a Biological Definition of Alzheimer’s Disease using Cerebrospinal Fluid Biomarkers in the AIBL Study","authors":"S. Burnham, Preciosa M. Coloma, Qiao-Xin Li, Steven J. Collins, G. Savage, Simon M. Laws, Simon M. Laws, J. Doecke, P. Maruff, R. Martins, R. Martins, D. Ames, Christopher Rowe, Colin L. Masters, V. Villemagne","doi":"10.14283/jpad.2019.25","DOIUrl":"https://doi.org/10.14283/jpad.2019.25","url":null,"abstract":"BackgroundThe National Institute on Aging and Alzheimer’s Association (NIA-AA) have proposed a new Research Framework: Towards a biological definition of Alzheimer’s disease, which uses a three-biomarker construct: Aß-amyloid, tau and neurodegeneration AT(N), to generate a biomarker based definition of Alzheimer’s disease.ObjectivesTo stratify AIBL participants using the new NIA-AA Research Framework using cerebrospinal fluid (CSF) biomarkers. To evaluate the clinical and cognitive profiles of the different groups resultant from the AT(N) stratification. To compare the findings to those that result from stratification using two-biomarker construct criteria (AT and/or A(N)).DesignIndividuals were classified as being positive or negative for each of the A, T, and (N) categories and then assigned to the appropriate AT(N) combinatorial group: A−T−(N)−; A+T-(N)−; A+T+(N)−; A+T−(N)+; A+T+(N)+; A−T+(N)−; A−T−(N)+; A−T+(N)+. In line with the NIA-AA research framework, these eight AT(N) groups were then collapsed into four main groups of interest (normal AD biomarkers, AD pathologic change, AD and non-AD pathologic change) and the respective clinical and cognitive trajectories over 4.5 years for each group were assessed. In two sensitivity analyses the methods were replicated after assigning individuals to four groups based on being positive or negative for AT biomarkers as well as A(N) biomarkers.SettingTwo study centers in Melbourne (Victoria) and Perth (Western Australia), Australia recruited MCI individuals and individuals with AD from primary care physicians or tertiary memory disorder clinics. Cognitively healthy, elderly NCs were recruited through advertisement or via spouses of participants in the study.ParticipantsOne-hundred and forty NC, 33 MCI participants, and 27 participants with AD from the AIBL study who had undergone CSF evaluation using Elecsys® assays.Intervention (if any)Not applicable.MeasurementsThree CSF biomarkers, namely amyloid β1–42, phosphorylated tau181, and total tau, were measured to provide the AT(N) classifications. Clinical and cognitive trajectories were evaluated using the AIBL Preclinical Alzheimer Cognitive Composite (AIBL-PACC), a verbal episodic memory composite, an executive function composite, California Verbal Learning Test–Second Edition; Long-Delay Free Recall, Mini-Mental State Examination, and Clinical Dementia Rating Sum of Boxes scores.ResultsThirty-eight percent of the elderly NCs had no evidence of abnormal AD biomarkers, whereas 33% had biomarker levels consistent with AD or AD pathologic change, and 29% had evidence of non-AD biomarker change. Among NC participants, those with biomarker evidence of AD pathology tended to perform worse on cognitive outcome assessments than other biomarker groups. Approximately three in four participants with MCI or AD had biomarker levels consistent with the research framework’s definition of AD or AD pathologic change. For MCI participants, a decrease in AIBL-PACC score","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.14283/jpad.2019.25","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66893085","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":"Mediterranean-Dash Intervention for Neurodegenerative Delay (MIND) Diet Slows Cognitive Decline After Stroke.","authors":"L Cherian, Y Wang, K Fakuda, S Leurgans, N Aggarwal, M Morris","doi":"10.14283/jpad.2019.28","DOIUrl":"10.14283/jpad.2019.28","url":null,"abstract":"<p><strong>Objective: </strong>This study sought to determine if the MIND diet (a hybrid of the Mediterranean and Dash diets, with modifications based on the science of nutrition and the brain), is effective in preventing cognitive decline after stroke.</p><p><strong>Design: </strong>We analyzed 106 participants of a community cohort study who had completed a diet assessment and two or more annual cognitive assessments and who also had a clinical history of stroke. Cognition in five cognitive domains was assessed using structured clinical evaluations that included a battery of 19 cognitive tests. MIND diet scores were computed using a valid food frequency questionnaire (FFQ). Dietary components of the MIND diet included whole grains, leafy greens and other vegetables, berries, beans, nuts, lean meats, fish, poultry, and olive oil and reduced consumption of cheese, butter, fried foods, and sweets. MIND diet scores were modeled in tertiles. The influence of baseline MIND score on change in a global cognitive function measure and in the five cognitive domains was assessed using linear mixed models adjusted for age and other potential confounders.</p><p><strong>Results: </strong>With adjustment for age, sex, education, APOE-ε4, caloric intake, smoking, and participation in cognitive and physical activities, the top vs lowest tertiles of MIND diet scores had a slower rate of global cognitive decline (β = .08; CI = 0.0074, 0.156) over an average of 5.9 years of follow-up.</p><p><strong>Conclusions: </strong>High adherence to the MIND diet was associated with a slower rate of cognitive decline after stroke.</p>","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66893394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can Digital Technology Advance the Development of Treatments for Alzheimer’s Disease?","authors":"M. Mc Carthy, P. Schueler","doi":"10.14283/jpad.2019.32","DOIUrl":"https://doi.org/10.14283/jpad.2019.32","url":null,"abstract":"The report explores the potential digital technology has to generate novel endpoints and digital biomarkers for Alzheimer’s disease drug development studies. Drawing from literature and novel pilots, we explore the value of innovative digital technology to digitize physiological behaviours such as sleep disturbance and gait changes. Technology now exists to monitor and quantify our use and interaction with electronics in the home, the use of social platforms and smart-phones, geolocation, sleep and activity patterns. These multimodal digital data are a feasible alternative to capturing the more complex activities of daily living that require higher cognitive processes and are a sensitive predictor of disease. The combination of biosensors and the internet of things (IoT), offers the potential to collect highly relevant, objective data in a continuous, passive and low burden manner. Digital endpoints and biomarkers could have value in the diagnosis, monitoring and development of therapies for patients living with Alzheimer’s disease.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66893242","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":"Financial Management Skills in Aging, MCI and Dementia: Cross Sectional Relationship to 18F-Florbetapir PET Cortical β-amyloid Deposition","authors":"Sierra Tolbert, Sierra Tolbert, Y. Liu, C. Hellegers, J. Petrella, Michael W. Weiner, T. Wong, P. Doraiswamy","doi":"10.14283/jpad.2019.26","DOIUrl":"https://doi.org/10.14283/jpad.2019.26","url":null,"abstract":"BackgroundThere is a need to more fully characterize financial capacity losses in the preclinical and prodromal stages of Alzheimer’s disease (AD) and their pathological substrates.ObjectivesTo test the association between financial skills and cortical β-amyloid deposition in aging and subjects at risk for AD.DesignCross-sectional analyses of data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI-3) study conducted across 50 plus sites in the US and Canada.SettingMulticenter biomarker study.Participants243 subjects (144 cognitively normal, 79 mild cognitive impairment [MCI], 20 mild AD).Measurements18F-Florbetapir brain PET scans to measure global cortical β-amyloid deposition (SUVr) and the Financial Capacity Instrument Short Form (FCI-SF) to evaluate an individual’s financial skills in monetary calculation, financial concepts, checkbook/register usage, and bank statement usage. There are five sub scores and a total score (range of 0–74) with higher scores indicating better financial skill.ResultsFCI-SF total score was significantly worse in MCI [Cohen’s d= 0.9 (95%CI: 0.6–1.2)] and AD subjects [Cohen’s d=3.1(CI: 2.5–3.7)] compared to normals. Domain scores and completion times also showed significant difference. Across all subjects, higher cortical β-amyloid SUVr was significantly associated with worse FCI-SF total score after co-varying for age, education, and cognitive score [Cohen’s f2=0.751(CI: 0.5–1.1)]. In cognitively normal subjects, after covarying for age, gender, and education, higher β -amyloid PET SUVr was associated with longer task completion time [Cohen’s f2=0.198(CI: 0.06–0.37)].ConclusionUsing a multicenter study sample, we document that financial capacity is impaired in the prodromal and mild stages of AD and that such impairments are, in part, associated with the extent of cortical β-amyloid deposition. In normal aging, β-amyloid deposition is associated with slowing of financial tasks. These data confirm and extend prior research highlighting the utility of financial capacity assessments in at risk samples.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.14283/jpad.2019.26","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66893162","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}