Contribution of Contextual Factors and Neuropathology to Dementia

痴呆症是全球死亡的主要原因之一，但目前仍没有已知的预防、治疗或治疗方法

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.