Lipoprotein(a) and risk of cognitive impairment in Black and White Americans: the Reasons for Geographic and Racial Differences in Stroke cohort

BACKGROUND: Cognitive impairment has a substantial vascular etiology. Higher lipoprotein(a) [Lp(a)] is associated with cardiovascular disease risk, but its association with cognitive function is uncertain. We hypothesized that Lp(a) is a risk factor for cognitive impairment, a relationship that would be modified by race and sex. OBJECTIVES: To study the association of Lp(a) with cognitive impairment in a biracial cohort. METHODS: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study recruited 30,239 Black and White Americans aged >45 years from 2003 to 2007. After 3.4 years, among participants with normal baseline cognition, baseline Lp(a) was measured in 434 cases of incident cognitive impairment and 557 controls. Cognitive impairment was defined as scores below the sixth percentile based on age, sex, race, and education norms on 2 or 3 components of a 3-test battery administered every 2 years. RESULTS: Median Lp(a) was higher in Black than in White individuals. Among Black participants, the adjusted odds ratio (OR) of cognitive impairment per SD higher increment Lp(a) was 1.39 (95% CI: 1.05, 1.84). The OR in White participants was 1.03 (95% CI: 0.87, 1.21; P for race difference = .03). The relationship of Lp(a) with cognitive trajectory differed by sex and race. Elevated Lp(a) was associated with worse baseline memory in Black men and a steeper trajectory of verbal fluency decline in Black men than in White men and women. CONCLUSION: Higher Lp(a) was associated with increased risk of cognitive impairment in Black but not White individuals. Future studies should evaluate the biological and social mechanisms through which race and Lp(a) interact to increase risk of cognitive impairment.