THE IMPORTANCE OF RISK FACTOR MODIFICATION OVER THE LIFECOURSE

Abstract

The pathophysiology of Alzheimer's Disease (AD) probably develops over decades, but the majority of epidemiological studies have focused on risk factor exposure from mid or later life. In addition, the timing and duration of effective AD prevention strategies remains unclear. A small but growing body of evidence suggests that risk factors earlier in the lifecourse may also contribute to an increased risk of cognitive aging. We present data from the Coronary Artery Risk Development in Young Adults Study (CARDIA), a biracial cohort of 3,499 adults (18-30 years old at enrollment). Risk factors including demographics, comorbidities, and lifestyle behaviors were evaluated over 25 years. At Year 25, cognitive function was assessed using the Digit Symbol Substitution Test (DSST), Stroop Interference Score, and Rey Auditory Verbal Learning Test (RAVLT). We also review findings from a study designed to determine the effect of midlife risk factor modification on projected prevalence of AD. Results from CARDIA suggest that early adult risk factors could contribute to midlife cognitive aging. Over 25 years, elevated levels of blood pressure, fasting blood glucose, and cholesterol were associated with worse cognitive performance on RAVLT, DSST, and Stroop in midlife (p<0.05 for all). Relationships were similar for other modifiable risk factors in early adulthood, including those defined by existing guidelines for healthy behaviors such as physical activity, nutrition and the American Heart Association's recommendations for ideal cardiovascular health. Epidemiological data also support a relationship between risk of AD and several potentially modifiable risk factors in mid and late life including diabetes, midlife hypertension, midlife obesity, smoking, depression, cognitive inactivity or low educational attainment, and physical inactivity. As a group, these risk factors could account for up to 50% of AD cases worldwide, and reduction of these risk factors could have a significant impact on AD prevalence. While there is robust evidence for modifiable risk factors and AD risk among older adults, recent findings also indicate that cognitive aging may begin even in midlife. Interventions that target risk factor exposure earlier in the lifecourse could play an important role in AD prevention.