Contribution of Contextual Factors and Neuropathology to Dementia

痴呆症是全球死亡的主要原因之一，但仍然没有已知的预防，治疗或治疗方法。 治愈在过去的二十年中，痴呆症的患病率有所增加，痴呆症是一种主要的 导致晚年生活质量差和医疗费用高。虽然生物学机制 被认为有助于阿尔茨海默病（AD）已经确定，这些生物因素并不总是 与痴呆症的临床诊断一致。几个个人层面的背景因素是已知的，以减少 痴呆症发作的风险，虽然这些因素改变痴呆症发作的机制，以及它们如何影响痴呆症的发病率， 联合收割机与潜在的神经病理学，仍然未知。此外，不知道宏观层面的背景如何 因素（即，更广泛的社会因素）可能会影响神经病理学和 痴呆拟议的项目将通过评估个人和宏观一级 背景因素与神经病理学相互作用，导致痴呆。该项目将是一个次要项目。 前瞻性队列研究的数据分析。将从四项纵向队列研究（ 阿尔茨海默病神经影像学倡议，捷克大脑老化研究，澳大利亚老年双胞胎研究， 悉尼记忆和老龄化研究）通过数据协调，这将增加样本量， 先进的分析。将基于神经病理学标志物估计潜伏特征，以评估这些特征如何影响神经病理学。 概况联合收割机与环境因素影响痴呆风险。评估个人层面的背景 因素（例如，教育，职业）和神经病理学是独立和相互依赖的关系， 痴呆症会发生。将发生数据链接，以合并来自世界卫生组织、世界不平等和 经合组织iLibrary数据库与协调数据集，以评估如何宏观层面的背景因素（例如， GDP、退休政策、社会水平教育/休闲活动或不平等标志）和神经病理学 与痴呆症有独立和相互依赖的关系。拟议的项目是扩大 现有的研究，包括生物和环境因素的全面措施，可以影响 以及通过检查独立和互动的影响，个人和宏观层面的背景 有神经病理学标记的因素。核心假设是，背景因素会改变 神经病理学和痴呆症之间的联系。拟议项目的调查结果将为 了解导致痴呆症的背景因素和生物因素之间的关系，可以 用于为政策和公共卫生外展提供信息，并制定有针对性的干预措施，以延迟痴呆症的发作。 PI将得到神经认知老化理论、临床标准和临床诊断方面专家的指导。 痴呆症和相关的统计方法，在培训环境中，将加强必要的技能， 成为一名独立的研究员。完成提案和培训后，PI将准备 领导未来的研究项目，评估各种风险因素对痴呆症的相对影响。

Dementia is one of the leading causes of death globally, yet there are still no known preventions, treatments, or cures. The prevalence of dementia has increased over the past two decades and dementia is a major contributor to poor late-life quality of life and to high health care costs. Although the biological mechanisms thought to contribute to Alzheimer’s disease (AD) have been identified, these biological factors do not always align with a clinical diagnosis of dementia. Several individual-level contextual factors are known to reduce the risk of dementia onset, although the mechanism by which these factors modify dementia onset, and how they combine with underlying neuropathology, remains unknown. Further, it is unknown how macro-level contextual factors (i.e., broader societal-level factors) may influence the association between neuropathology and dementia. The proposed project will address these gaps by assessing how individual- and macro-level contextual factors interact with neuropathology resulting in dementia. The proposed project will be a secondary data analysis of prospective cohort studies. Data will be pooled from four longitudinal cohort studies (the Alzheimer’s Disease Neuroimaging Initiative, the Czech Brain Aging Study, the Older Australian Twins Study, the Sydney Memory and Ageing Study) through data harmonization, which will increase sample size for advanced analyses. Latent profiles will be estimated based on markers of neuropathology to assess how these profiles combine with contextual factors to affect dementia risk. Assessment of how individual-level contextual factors (e.g., education, occupation) and neuropathology are independently and interdependently related to dementia will occur. Data linking will occur to merge macro-level factors from the WHO, World Inequality, and OECD iLibrary Databases with the harmonized dataset to assess how macro-level contextual factors (e.g., GDP, retirement policies, societal-level education/leisure activity, or markers of inequality) and neuropathology are independently and interdependently related to dementia. The proposed project represents an expansion of existing research by incorporating thorough measures of biological and contextual factors that can influence dementia as well as by examining independent and interactive effects of individual- and macro-level contextual factors with markers of neuropathology. The central hypothesis is that contextual factors will modify the association between neuropathology and dementia. Findings from the proposed project will inform understanding of the relationship between contextual and biological factors that contribute to dementia, can be used to inform policy and public health outreach, and create targeted interventions to delay dementia onset. The PI will be supported by the mentorship of experts in theories of neurocognitive aging, clinical criteria of dementia, and relevant statistical methodology, in a training environment that will bolster the skills necessary to become an independent researcher. Upon completion of the proposal and training, the PI will be prepared to lead future research projects assessing the relative contributions of various risk factors for dementia.