Plasma homocysteine and longitudinal change in cognitive function among urban adults

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. 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. We found that greater LnHcyv1 was significantly associated with poorer baseline attention based on higher Loge (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, LnHcyv1 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 Loge (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. 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. •This study analyzed longitudinal data from 1430 Healthy Aging in Neighborhoods of Diversity across the Life Span participants.•Higher levels of homocysteine (Hcy) were associated with poorer baseline attention and slower decline in visuo-spatial memory.•This was particularly true among men and African American adults.•The study also found that increased Hcy was associated with faster decline in executive function.•The findings suggest a sex- and race-specific adverse association between elevated Hcy and cognitive performance in middle-aged urban adults.