Global DNA Methylation and Cognitive Impairment: A Population-Based Study from Haryana, North India

Epigenetic modifications have been implicated in the development of cognitive impairment. However, the relationship between DNA methylation levels and cognitive impairment can be greatly influenced by environmental factors some blood-based nutrition markers. The present study aims to understand the relationship between global DNA methylation levels and cognitive impairment independently and in light of micronutrient status among North Indian adults. This study was conducted among 614 individuals, aged 30 to 79 years from Palwal, Haryana. Cognitive impairment (CI) was assessed using Mini-Mental State Examination (MMSE). Folate, vitamin B12, and homocysteine levels were estimated using chemiluminescence technique. Estimation of global DNA methylation (5mC) levels was performed using the ELISA-based colorimetric technique. Appropriate comparison tests (based on normality distribution) were applied to compare the levels of global DNA methylation in different study groups. Logistic regression models were run to examine association between global DNA methylation and CI. Median 5mC levels of both mild and moderate/severe CI groups were significantly lower than that of the control group. Individuals in the 1st quartile of 5mC, with those in the 4th quartile as the reference, were at a significantly increased risk of both mild and moderate/severe CI. Vitamin B12, but not folate, appeared to mediate global DNA hypomethylation among CI cases. Cognitive impairment may be associated with Global DNA hypomethylation in the studied North Indian population. Vitamin B12 sufficiency may help improve the methylation levels among the cases of cognitive impairment. There is a need to develop population and context-specific epigenetic markers for cognitive impairment.