George, Kristen2019-09-172019-09-172019-07https://hdl.handle.net/11299/206665University of Minnesota Ph.D. dissertation. July 2019. Major: Epidemiology. Advisor: Aaron Folsom. 1 computer file (PDF); xi, 151 pages.Dementia and mild cognitive impairment (MCI) are often caused by progressive and irreversible pathologic brain changes. Alzheimer’s disease, cerebrovascular disease, and Lewy body-related diseases are the most common causes with many individuals having mixed etiologies. Characterizing risk factors for dementia and MCI is complex due to overlapping etiologies, long latency periods, and the influence of cognitive reserve. While major risk factors including advanced age, hypertension, and the ApoE4 allele have been identified, further investigation of early- and mid-life risk factors is needed. Using data from the Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study, we examined prospectively risk factors for dementia and MCI. In the first manuscript, we assessed the association between life course socioeconomic status (LC-SES) and dementia and MCI. Low individual-level LC-SES was associated with an increased risk of dementia. Low individual-level economic factors of LC-SES (e.g. income, home ownership) were associated with increased risk of dementia independent of educational attainment. However, neighborhood-level LC-SES was not associated with risk of dementia or MCI. The second manuscript assessed the association between thyroid dysfunction (measured via autoimmune thyroid disease (AITD) and thyroid hormone levels) and risk of dementia and MCI. We found no association between AITD and dementia and MCI. Subclinical hypothyroidism was associated with a lower risk of dementia while overt hyperthyroidism, particularly with very elevated serum FT4 hormone levels, was associated with an increased risk of dementia compared to euthyroid participants. The third manuscript examined the association between lifetime history of migraine symptoms and risk of dementia and MCI. Despite published evidence of brain abnormalities in migraineurs, which might lead to cognitive impairment, we found no association between migraine and dementia and MCI. This dissertation extends our understanding of risk factors for cognitive impairment underscoring the importance of early- and mid-life exposures on late-life risk of dementia and MCI.enCohortDementiaMild Cognitive ImpairmentRisk FactorsThesis or Dissertation