Abstract
The relationship between blood levels of homocysteine (HCY), vitamin B12, folic acid and cognitive impairment is inconclusive. Since HCY is an independent risk factor for cardiovascular diseases, understanding its association with Framingham risk score (FRS) may provide insight into the shared underlying mechanism between cardiovascular disease and cognitive impairment. Cross-sectional analyses utilized baseline data from two ongoing longitudinal studies: the Tata Longitudinal Study of Ageing (n = 923), an urban cohort, and Srinivaspura Ageing, NeuroSenescence and COGnition (n = 4239), a rural cohort. The study compared the HCY, vitamin B12 and folic acid levels across cohorts and normal versus mild cognitive impairment (MCI) participants. The association between HCY and cognitive status was established using regression models. Three models were analysed: model 1-unadjusted; model 2-adjusted for age, gender, smoking, alcohol consumption, diet, hypertension, cardiac illness, diabetes; and model 3-adjusted for variables in model 2 plus vitamin B12 and folic acid. Correlation was calculated between HCY and FRS. The urban cohort exhibited a significantly higher level of HCY [median (IQR) (17.70 (10.2) versus 14.70 (9.7); P < 0.001)], vitamin B12 (251 (231) versus 219 (138); P < 0.001) and folic acid (8.21 (8) versus 5.48 (4); P < 0.001) levels compared to rural cohort. HCY, vitamin B12 and folic acid levels did not differ significantly between normal and MCI participants in the urban cohort. In the rural cohort, among the age-gender matched MCI-normal, participants with normal cognition had higher levels of vitamin B12 (≥60 years) [227 (152) versus 217 (175); P = 0.03] and folic acid (<60 years) [5.91 (4) versus 5.40 (4); P = 0.04] compared to MCI. There was no association between HCY and cognitive status in both the cohorts, but there was a significant positive relationship between vitamin B12 deficiency and Clinical Dementia Rating-Sum of the Boxes (CDR-SOB), as well as folic acid deficiency and CDR-SOB in rural and urban cohorts, respectively, within a specific age group. A significant correlation was observed between FRS and HCY in the rural cohort (r = 0.17, P < 0.001), but not in the urban cohort. This study revealed significant differences in HCY, vitamin B12 and folic acid levels between the cohorts. In the rural cohort, participants with MCI had lower vitamin B12 and folic acid levels in a certain age group. Association between HCY and cognitive status was insignificant in both the cohorts. A small significant correlation between FRS and HCY was seen in the rural cohort.