Alzheimer's dementia onset and progression in international cohorts (Amended)

项目总结/摘要 该R 01申请题为“国际队列中阿尔茨海默氏症痴呆症的发病和进展（修订）” 是对PAR-17-054的重新提交。到2050年，预计将有1350万人 美国阿尔茨海默病（AD）患者的成本为1.1万亿美元。AD及相关疾病的发病率增加 痴呆症提出了一个巨大的全球健康挑战，需要研究人员作出承诺的反应， 临床医生和资助机构。痴呆症诊断的增加给研究人员带来了多重挑战， 临床医生一样。其中最重要的是早期，准确识别痴呆症及其病因， 在确保将临床研究结果转化为切实的预防成果的同时， 诊断、治疗和护理有痴呆症风险或表现出痴呆症的人。为了实现这一点，更好的 了解导致或延迟痴呆症诊断的风险和保护因素， 具有本质意义 我们的建议将利用五个主要的阿尔茨海默氏症人群的力量来澄清风险， 阿尔茨海默病和相关痴呆的保护因素：成人儿童研究（ACS）， 阿尔茨海默病神经影像学倡议（ADNI），澳大利亚成像，生物标志物和生活方式旗舰 老龄化研究（Aibl），显性遗传阿尔茨海默氏症网络（DIAN）和国家阿尔茨海默氏症 协调中心。这个国际财团将为我们提供跨越 整个疾病生命周期;从临床前阶段到尸检分析。参与者提供的数据 在三个或更多时间点呈现将用于确保稳健的结果。 本申请将建立并验证人口统计学、基因型和合并症对 阿尔茨海默氏痴呆症的发病率和进展率。这项工作将使我们能够建立和验证危险 使用跨认知，神经成像， 和生物标志物。 将统一这些队列的数据集，以便更好地了解风险， 老年痴呆症的保护因素。此应用程序将导致风险危害评分的生成 基于临床可用的技术。这些发现将直接转移到临床环境中， 还将能够更准确地识别针对阿尔茨海默氏症的临床试验的合适候选人 疾病

PROJECT SUMMARY / ABSTRACT This R01 application, entitled ‘Alzheimer’s dementia onset and progression in international cohorts (Amended)’ is a resubmission in response to PAR-17-054. By the year 2050 it is projected that there will be 13.5 million Americans with Alzheimer’s disease (AD) at a cost of $1.1 trillion. The increasing incidence of AD and related dementias presents a massive global health challenge requiring a committed response from researchers, clinicians and funding bodies. The rise in dementia diagnoses presents multiple challenges for researchers and clinicians alike. Paramount amongst these are early, accurate identification of dementia and its aetiology, in parallel with ensuring that clinical research findings are translated into tangible outcomes in the prevention, diagnosis, treatment, and care for people at risk of or manifesting dementia. To facilitate this, a better understanding of the risk and protective factors which precipitate or delay a dementia diagnosis is essential. Our proposal will leverage the power of five leading well characterized Alzheimer’s cohorts to clarify risk and protective factors for Alzheimer’s disease and related dementias: the Adult Children Study (ACS), the Alzheimer’s Disease Neuroimaging Initiative (ADNI), the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL), the Dominantly Inherited Alzheimer Network (DIAN) and the National Alzheimer's Coordinating Center (NACC). This international consortium will provide us with access to data spanning the entire disease lifespan; from its preclinical stages through to post mortem analyses. Data from participants presenting at three or more timepoints will be used to ensure robust findings. This application will establish and validate the impact of demographics, genotype and comorbidities on the onset and progression rates of Alzheimer’s dementia. This work will enable us to establish and validate hazard scores for disease onset and severity using clinical markers across the domains of cognition, neuroimaging, and biomarkers. The datasets of these cohorts will be harmonized to enable an improved understanding of the risk and protective factors for Alzheimer’s dementia. This application will lead to the generation of risk hazard scores based on clinically available technologies. These findings will be directly transferable to the clinical setting and will also enable more accurate identification of suitable candidates for clinical trials targeting Alzheimer’s disease.