There is a robust consensus, most recently articulated by the 2017 Lancet Commission, that the roots of dementia?and thus the possibility for prevention of dementia?can be traced back to early life. Yet, the influence of the early life period on dementia risk, as well as adult behaviors that can offset that risk, remains poorly understood. There is a lack of longitudinal studies with richly characterized full life course measures of genetic, cognitive, geographic, socioeconomic, educational and behavioral factors. Rooted in life course epidemiology, this project aims to help clarify biological and behavioral processes that operate across the life course to influence dementia risk. Key to this framework is the critical influence of early life. Findings from this study could have important public policy and public health implications by providing evidence as to how, especially, early life socioeconomic conditions and adult modifiable behaviors can alter the risk for AD/ADRD. Consequently, the study aims are as follows:
Aim 1 : Track the progression of dementia across cognitive phenotypes (normal, AD dementia, non-AD dementia), including the use of rigorous AD diagnostic protocols, in the Wisconsin Longitudinal Study (WLS), a 60 year longitudinal study. Participants will be in their late 70s at baseline.
Aim 2 : Test the role of early life disadvantage/advantage on the risk for AD/ADRD in later life. In particular, we will test how persistent socioeconomic disadvantage in childhood, lower levels of cognitive functioning, and living in rural communities influence the risk for AD/ADRD in later life. The measures available in the WLS to capture these early life factors are unparalleled in existing dementia studies.
Aim 3 : Test whether early life disadvantage may be offset by adult behavioral protective factors. Can subsequent educational attainment, even when gained in ones 30s and 40s, and engagement in healthy behaviors (e.g. not smoking, maintaining a normal weight, and engaging in exercise), offset early life disadvantages such as lower levels of cognitive functioning and growing up socioeconomically disadvantaged? Sibling models, a unique feature of these data, will provide a mechanism to partially address potential genetic and familial environment confounders. We will also test how these adult behaviors mediate the relationship between sex and AD/ADRD.
Aim 4 : Test whether adolescent IQ and educational attainment moderate genetic risk for AD/ADRD.
Aim 5 : We will create a public good: a data resource that can facilitate cutting edge dementia research. All researchers-via our website- will have access to all the data WLS has to offer?this includes all phenotypic and genetic data.

Public Health Relevance

We propose to track the progression into dementia (AD dementia, non-AD dementia) in the Wisconsin Longitudinal Study (WLS), one of the nation's longest running longitudinal cohort study (nearly 60 years duration). The project will clarify the influence of the early life period on dementia risk?as well as adult behaviors that can offset risk. The findings from these aims will provide supporting evidence for policy and individual level interventions that could modify the risk for AD/ADRD.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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King, Jonathan W
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University of Wisconsin Madison
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United States
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