Jpad-Journal of Prevention of Alzheimers Disease最新文献

{"title":"Editorial: The 'Aducanumab Story': Will the Last Chapter Spell the End of the 'Amyloid Hypothesis' or Mark a New Beginning?","authors":"Z S Khachaturian","doi":"10.14283/jpad.2022.36","DOIUrl":"10.14283/jpad.2022.36","url":null,"abstract":"","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"9 1","pages":"190-192"},"PeriodicalIF":8.5,"publicationDate":"2022-01-01","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":"Unsupervised Performance of the CogState Brief Battery in the Brain Health Registry: Implications for Detecting Cognitive Decline","authors":"T. Banh, C. Jin, J. Neuhaus, R. S. Mackin, P. Maruff, N. Stricker, M. Weiner, R. Nosheny","doi":"10.14283/jpad.2021.68","DOIUrl":"https://doi.org/10.14283/jpad.2021.68","url":null,"abstract":"The feasibility and validity of unsupervised, longitudinal brief computerized cognitive batteries is unknown. Participants aged 56–90 (N = 19476) from the Brain Health Registry (BHR) completed the CogState Brief Battery (CBB) at 6-month intervals over a period of 5 years. We used linear mixed-effects models to assess whether cross-sectional and longitudinal performance on CBB within BHR was associated with demographic and cognitive characteristics. We also defined a group of CBB decliners based on subject-specific slopes and estimated associations between decliner status and participant characteristics. We found weak associations between longitudinal change in CBB and participant characteristics. Cross-sectional CBB scores were significantly associated with participant characteristics such as age, gender, ethnicity, self-reported disease status, and memory concern. CBB decliners were more likely to self-report mild cognitive impairment (MCI) and memory concerns. Cross-sectional, remote CBB shows evidence of construct validity, but our results suggest that longitudinal assessment may not provide additional value for identifying those at risk for and with cognitive impairment.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"9 1","pages":"262 - 268"},"PeriodicalIF":6.4,"publicationDate":"2021-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44925247","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 Scottish Brain Health Service Model: Rationale and Scientific Basis for a National Care Pathway of Brain Health Services in Scotland","authors":"C. Ritchie, J. Waymont, C. Pennington, K. Draper, A. Borthwick, N. Fullerton, M. Chantler, M. E. Porteous, S. Danso, A. Green, L. Mcwhirter, G. Muniz Terrera, S. Simpson, G. Thompson, D. Trépel, T. Quinn, A. Kilgour","doi":"10.14283/jpad.2021.63","DOIUrl":"https://doi.org/10.14283/jpad.2021.63","url":null,"abstract":"In order to address the oft-cited societal, economic, and health and social care impacts of neurodegenerative diseases, such as Alzheimer’s disease, we must move decisively from reactive to proactive clinical practice and to embed evidence-based brain health education throughout society. Most disease processes can be at least partially prevented, slowed, or reversed. We have long neglected to intervene in neurodegenerative disease processes, largely due to a misconception that their predominant symptom — cognitive decline — is a normal, age-related process, but also due to a lack of multi-disciplinary collaboration. We now understand that there are modifiable risk factors for neurodegenerative diseases, that successful management of common comorbidities (such as diabetes and hypertension) can reduce the incidence of neurodegenerative disease, and that disease processes begin (and, crucially, can be detected, reduced, and delayed, prevented, or treated) decades earlier in life than had previously been appreciated. Brain Health Scotland, established by Scottish Government and working in partnership with Alzheimer Scotland, propose far-reaching public health and clinical practice approaches to reduce neurodegenerative disease incidence. Focusing here on Brain Health Scotland’s clinical offerings, we present the Scottish Model for Brain Health Services. To our knowledge, the Scottish Model for Brain Health, built on foundations of personalised risk profiling, targeted risk reduction and prevention, early disease detection, equity of access, and harnessing comprehensive data to assist in clinical decision-making, marks the first example of a nationwide approach to overhauling clinical, societal, and political approaches to the prevention, assessment, and treatment of neurodegenerative disease.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"9 1","pages":"348 - 358"},"PeriodicalIF":6.4,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42079355","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 Polymorphism Cluster at the 2q12 locus May Predict Response to Piromelatine in Patients with Mild Alzheimer’s Disease","authors":"L. Schneider, M. Laudon, T. Nir, J. Caceres, G. Ianniciello, M. Capulli, N. Zisapel","doi":"10.14283/jpad.2021.61","DOIUrl":"https://doi.org/10.14283/jpad.2021.61","url":null,"abstract":"Piromelatine is a novel melatonin MT1/2/3 and serotonin 5-HT-1A/1D receptors agonist developed for mild Alzheimer’s disease (AD). In a randomized, placebo-controlled, dose-ranging study (ReCognition) of piromelatine (5, 20, and 50 mg daily for 6 months) in participants with mild dementia due to AD (n=371, age 60–85 years), no statistically significant differences were found between the piromelatine and placebo-treated groups on the primary (i.e., computerized neuropsychological test battery (cNTB)) and secondary outcomes (ADCS-CGIC, ADCS-MCI-ADL, ADAS-cog14, NPI, and Pittsburgh Sleep Quality Index (PSQI)) nor were there safety concerns (https://clinicaltrials.gov/ct2/show/NCT02615002). This study was aimed at identifying genetic markers predicting piromelatine treatment response using a genome-wide association approach (GWAS). Variant genotyping of a combined whole genome and whole exome sequencing was performed using DNA extracted from lymphocytes from consenting participants. The general case-control allelic test was performed on piromelatine-treated participants, taking “responders” (i.e., >0.125 change from baseline in the cNTB) as cases and “non responders” as controls, using a Cochran-Armitage trend test. 58 outpatient clinics in the US. 371 participants were randomized in the trial; 107 provided informed consent for genotyping. The GWAS sample did not differ from the full study cohort in demographics, baseline characteristics, or response to piromelatine. Six single-nucleotide polymorphisms (SNPs) in chromosome 2q12 (2:107,510,000-107,540,000) were associated with response (p-value < 1×10 −4 each). Post hoc analyses suggested that the carriers of the 2q12 polymorphism cluster (27% of the GWAS sample) improved significantly on the cNTB on piromelatine as compared to placebo but significantly worsened on the ADAS-Cog14 and PSQI. By contrast, “non-carriers” improved significantly with piromelatine compared to placebo on the ADAS-Cog14 (2.91 (N=23) with piromelatine 20 mg vs 1.65 (N=19) with placebo (p=0.03)) and PSQI. The 2q12 (2:107,510,000-107,540,000) 5–6 SNPs cluster may predict efficacy of piromelatine for mild AD. These findings warrant further investigation in a larger, prospective early-stage AD clinical trial for patients who are non-carriers of the 2q12 polymorphism cluster.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"9 1","pages":"247 - 254"},"PeriodicalIF":6.4,"publicationDate":"2021-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47815172","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":"Disease Burden and Attributable Risk Factors of Alzheimer’s Disease and Dementia in China from 1990 to 2019","authors":"Rui Li, J. Qi, Yin Yang, Yinglin Wu, Yanpeng Yin, Maigeng Zhou, Z. Qian, M. LeBaige, S. McMillin, Hualiang Lin, Haoyan Guo","doi":"10.14283/jpad.2021.69","DOIUrl":"https://doi.org/10.14283/jpad.2021.69","url":null,"abstract":"Background Updated information on the burden of Alzheimer’s disease and other forms of dementia are of great importance for evidence-based health care planning. However, such an estimate has been lacking in Chinese populations at both national and provincial levels. Objective To estimate the temporal trends and the attributable burdens of selected risk factors of Alzheimer’s disease and other forms of dementia in China. Design, Setting, and Participants This is an observational description of the Global Burden of Diseases Study 2019 (GBD 2019). Data on incidence, mortality, prevalence, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) of Alzheimer’s disease and other forms of dementia were derived from the GBD 2019 study at both national and provincial levels in China. Measurements Six indicators were used: incidence, mortality, prevalence, DALYs, YLLs, and YLDs. Absolute numbers in detail by age, sex, region, and age-standardized rates (with 95% uncertainty intervals) were calculated. Results There were notable increasing trends in the number of deaths (247.9%), incidence (264.8%), prevalence (296.5%), DALYs (228.1%), YLDs (308.7%) and YLLs (201.7%) from 1990 to 2019, respectively. The corresponding age-standardized rates increased by 6.2%, 19.3%, 33.6%, 10.7%, 33.4% and 3.1%. Smoking, high body mass index, high fasting plasma glucose levels, and metabolic risks were the four leading risk factors. Higher burden was observed among females versus males and in the more developed regions. Conclusions The disease burden in China were increasing substantially. Regional differences of the disease burden are accompanied by discrepancies of economic level and geographical location, as well as different levels of exposure to risk factors. Targeted prevention and control strategies are urgently needed to reduce the disease burden.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"1 1","pages":"1-9"},"PeriodicalIF":6.4,"publicationDate":"2021-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45093865","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":"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":"10 1","pages":"151 - 151"},"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":"1 1","pages":"1-2"},"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":"1 1","pages":"1-5"},"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":"6 1","pages":"232 - 236"},"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":"6 1","pages":"214 - 216"},"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}