Abstract
Hyperhomocysteinemia or high levels (> 15 µmol/L) of homocysteine (Hcy)in the blood has been suggested to affect the brain through vascular and neurodegenerative pathways and potentially impact cognition. The current study aims to explore the association of high homocysteine with cognition and brain volume changes in a cohort of middle and old agedr adults. The study recruited 1296 participants aged ≥ 45 years from Tata Longitudinal Study of Ageing (TLSA), an ongoing cohort study. The participants underwent detailed cognitive assessments using Addenbrooke's Cognitive Examination-III (ACE-III) and Computerized Assessment of Adult Information Processing (COGNITO) neuropsychological battery and MR imaging using a 3T scanner. The participants were classified based on the median homocysteine level (16.89 µmol/L) into low Hcy (≤ median) and high Hcy (> median) groups. When adjusted for age, gender, years of education, vitamin B12, folate and dyslipidaemia, Generalised Linear Model (GLM) found a significant association of high Hcy with vocabulary task [β (95% CI) - 1.354 (- 2.655, - 0.052); p = 0.041]. Significant associations was also obtained between cerebral white matter volume and high Hcy [β (95% CI) - 5617.182 (- 11062.762, - 173.602); p = 0.043]. The results suggest that people with high Hcy levels performed poorer in cognitive tasks related to language domain and had lesser cerebral white matter volume. This indicates that homocysteine might have a profound impact on brain structure as well as function.