Abstract
BACKGROUND: Cross-sectional and longitudinal studies have inconsistently linked cognitive performance and change over time to an elevated level of homocysteine (Hcy), with few conducted among urban adults. METHODS: Longitudinal data [Visit 1 (2004-2009) and Visit 2 (2009-2013)] were analyzed from up to 1430 selected Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) participants. Baseline and follow-up blood Hcy was measured, while 11 cognitive function test scores were assessed at either of these two visits. Overall, sex- and race-stratified associations were evaluated using mixed-effects linear regression models, adjusting for key potential confounders. Interaction effects between Hcy and serum levels of folate and vitamin B-12 were also tested. RESULTS: We found that greater LnHcy(v1) was significantly associated with poorer baseline attention based on higher Log(e) (TRAILS A, in seconds) [β (SE): 0.101 (0.031), P = 0.001]. Heterogeneity was also found by sex and by race. Most notably, among men only, LnHcy(v1) was associated with faster decline on the BVRT (# of errors), a measure of visuo-spatial memory (β (SE): 0.297(0.115), P = 0.010, reduced model); while among African American adults only, an elevated and increasing LnHcy over time was associated with faster rate of decline on Log(e) (TRAILS B, in seconds) [β (SE): +0.012 (0.005), p = 0.008], a measure of executive function. Interactions between Hcy, folate and vitamin B-12 blood exposures were also detected. CONCLUSIONS: In summary, sex- and race-specific adverse association between elevated Hcy and cognitive performance over time were detected among middle-aged urban adults, in domains of attention, visuo-spatial memory and executive functioning.