Abstract
Observational research studies serve as the cornerstone for gathering evidence on risk factors and contributors to cognitive decline and impairment. The evidence can then be combined with data from preclinical studies and randomized controlled trials to ultimately inform the development of effective interventions and the content of guidance statements. Observational cohort designs on modifiable risk factors and brain health can be particularly beneficial for studying questions that are unethical or impractical for a clinical trial setting, associations with dementia which may develop over decades, and underrepresented populations typically not included in clinical trials. This chapter will review the major observational, epidemiologic studies pertaining to the traditional vascular risk factors - hypertension, diabetes mellitus, hypercholesterolemia, smoking, and physical inactivity - and how they may impact brain health.