Skip to main content
Log in

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

  • ORIGINAL RESEARCH ARTICLE
  • Published:
Indian Journal of Clinical Biochemistry Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Data Availabilty Statement

The data supporting the findings of this study will be made available by the authors on reasonable request.

References

  1. Janoutová J, Serý O, Hosák L, Janout V. Is mild cognitive impairment a precursor of Alzheimer's disease? Short review. Cent Eur J Public Health. 2015;23(4):365. https://doi.org/10.21101/cejph.a4414

  2. Wortmann M. Dementia: a global health priority-highlights from an ADI and World Health Organization report. Alzheimer’s Res Ther. 2012;4:1–3. https://doi.org/10.1186/alzrt143.

    Article  Google Scholar 

  3. Pais R, Ruano L, Moreira C, Carvalho OP, Barros H. Prevalence and incidence of cognitive impairment in an elder Portuguese population (65–85 years old). BMC Geriatr. 2020;20(1):470.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Das SK, Bose P, Biswas A, Dutt A, Banerjee TK, Hazra A, et al. An epidemiologic study of mild cognitive impairment in Kolkata. India Neurol. 2007;68(23):2019–26. https://doi.org/10.1212/01.wnl.0000264424.76759.e6.

    Article  CAS  Google Scholar 

  5. Sengupta P, Benjamin AI, Singh Y, Grover A. Prevalence and correlates of cognitive impairment in a north Indian elderly population. WHO South-East Asia J Public Health. 2014;3(2):135–43. https://doi.org/10.4103/2224-3151.206729.

    Article  PubMed  Google Scholar 

  6. Khullar S, Kaur G, Dhillon H, Sharma R, Mehta K, Singh M, et al. The prevalence and predictors of cognitive impairment in the type 2 diabetic population of Punjab. India Soc Health Diabetes. 2017;5(1):47–53. https://doi.org/10.4103/2321-0656.193996.

    Article  Google Scholar 

  7. Kaur G, Gaur R, Yadav S, Saraswathy KN. Association of vitamin B12-mediated hyperhomocysteinemia and methylenetetrahydrofolate reductase (C677T) gene polymorphism with cognitive impairment: a population-based study from North India. Psychiatry Res. 2018;270:123–5. https://doi.org/10.1016/j.psychres.2018.08.103.

    Article  CAS  PubMed  Google Scholar 

  8. Singh N, Chaudhary V, Khate K, Bhattacharjee D, Longkumer I, Kataria S, et al. Cognitive impairment viz-a-viz genetic and biochemical variations in the one-carbon metabolic pathway: A population-based study from North India. Gene Rep. 2023;30: 101720. https://doi.org/10.1016/j.genrep.2022.101720.

    Article  CAS  Google Scholar 

  9. Khate K, Chaudhary V, Longkumer I, Saraswathy KN, Devi NK. Gender-specific association of blood lipids and reproductive trajectory with cognitive impairment: A community-based cross-sectional study from India. Front Psychol. 2023;14. https://doi.org/10.3389/fpsyg.2023.1107152

  10. Harman MF, Martín MG. Epigenetic mechanisms related to cognitive decline during aging. J Neurosci Res. 2020;98(2):234–46. https://doi.org/10.1002/jnr.24436.

    Article  CAS  PubMed  Google Scholar 

  11. Chouliaras L, Pishva E, Haapakoski R, Zsoldos E, Mahmood A, Filippini N, et al. Peripheral DNA methylation, cognitive decline and brain aging: pilot findings from the Whitehall II imaging study. Epigenomics. 2018;10(5):585–95. https://doi.org/10.2217/epi-2017-0132. ([PubMed PMID: 29723050]).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Sugden K, Caspi A, Elliott ML, Bourassa KJ, Chamarti K, Corcoran DL, et al. Association of pace of aging measured by blood-based DNA methylation with age-related cognitive impairment and dementia. Neurology. 2022 27;99(13):e1402–13. https://doi.org/10.1212/WNL.0000000000200898. [PubMed PMID: 34260763]

  13. Smith AD, Refsum H. Homocysteine, B vitamins, and cognitive impairment. Annu Rev Nutr. 2016;17(36):211–39. https://doi.org/10.1146/annurev-nutr-071715-050947. ([PubMed PMID: 27146033]).

    Article  CAS  Google Scholar 

  14. Chaudhary V, Bhattacharjee D, Devi NK, Saraswathy KN. Global DNA Methylation Levels Viz-a-Viz Genetic and Biochemical Variations in One Carbon Metabolic Pathway: An Exploratory Study from North India. Biochem Genet. 2024 Feb 14. https://doi.org/10.1007/s10528-023-10659-4. Epub ahead of print. PMID: 38356009

  15. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–98 ([PubMed PMID: 1202204]).

    Article  CAS  PubMed  Google Scholar 

  16. Miller S, Dykes D, Polesky H. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16(3):1215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Sukla KK, Raman R. Association of MTHFR and RFC1 gene polymorphism with hyperhomocysteinemia and its modulation by vitamin B12 and folic acid in an Indian population. Eur J Clin Nutr. 2012;66(1):111–8. https://doi.org/10.1038/ejcn.2011.152. (Epub 2011 Aug 31 PMID: 21878957).

    Article  CAS  PubMed  Google Scholar 

  18. Li H, Wu TT, Tang L, Liu Q, Mao XZ, Xu JM, et al. Association of global DNA hypomethylation with post-operative cognitive dysfunction in elderly patients undergoing hip surgery. Acta Anaesth Scand. 2020;64(3):354–60. https://doi.org/10.1111/aas.13502.

    Article  CAS  PubMed  Google Scholar 

  19. Yang X, Yuan Y, Lu X, Yang J, Wang L, Song J, et al. The relationship between cognitive impairment and global DNA methylation decrease among aluminum potroom workers. J Occup Environ Med. 2015;57(7):713–7. https://doi.org/10.1097/JOM.0000000000000474. ([PubMed PMID: 26110289]).

    Article  CAS  PubMed  Google Scholar 

  20. Schiepers OJ, Van Boxtel MP, de Groot RH, Jolles J, Kok FJ, Verhoef P, et al. DNA methylation and cognitive functioning in healthy older adults. Br J Nutr. 2012;107(5):744–8. https://doi.org/10.1017/S0007114511003576. ([PubMed PMID: 21967862]).

    Article  CAS  PubMed  Google Scholar 

  21. Gomes MV, Toffoli LV, Arruda DW, Soldera LM, Pelosi GG, Neves-Souza RD, et al. Age-related changes in the global DNA methylation profile of leukocytes are linked to nutrition but are not associated with the MTHFR C677T genotype or to functional capacities. PLoS ONE. 2012;7(12): e52570. https://doi.org/10.1371/journal.pone.0052570. ([PubMed PMID: 23272203]).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Cui D, Xu X. DNA methyltransferases, DNA methylation, and age-associated cognitive function. Int J Mol Sci. 2018;19(5):1315. https://doi.org/10.3390/ijms19051315. ([PubMed PMID: 29710737]).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kaeberlein M. Time for a new strategy in the war on Alzheimer’s disease. Public Policy Aging Rep. 2019;29(4):119–22. https://doi.org/10.1093/ppar/prz020. ([PubMed PMID: 32189970]).

    Article  Google Scholar 

  24. Ma DK, Jang MH, Guo JU, Kitabatake Y, Chang ML, Pow-Anpongkul N, et al. Neuronal activity–induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science. 2009;323(5917):1074–7. https://doi.org/10.1126/science.1166859. ([PubMed PMID: 19229056]).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lopez-Atalaya JP, Barco A. Can changes in histone acetylation contribute to memory formation? Trends Genet. 2014;30(12):529–39. https://doi.org/10.1016/j.tig.2014.09.003. ([PubMed PMID: 25306222]).

    Article  CAS  PubMed  Google Scholar 

  26. Kaushik A, Chaudhary V, Longkumer I, Saraswathy KN, Jain S. Sex-specific variations in global DNA methylation levels with age: a population-based exploratory study from North India. Front Genet. 2023;14. [PubMed PMID: To be added once available]

  27. Orsitto G. Different components of nutritional status in older inpatients with cognitive impairment. J Nutr Health Aging. 2012;16:468–71. https://doi.org/10.1007/s12603-012-0024-1. ([PubMed PMID: 22689217]).

    Article  CAS  PubMed  Google Scholar 

  28. Scarmeas N, Anastasiou CA, Yannakoulia M. Nutrition and prevention of cognitive impairment. Lancet Neurol. 2018;17(11):1006–15. https://doi.org/10.1016/S1474-4422(18)30338-7. ([PubMed PMID: 30389355]).

    Article  PubMed  Google Scholar 

  29. Alosco ML, Spitznagel MB, Cohen R, Raz N, Sweet LH, Josephson R, et al. Decreased physical activity predicts cognitive dysfunction and reduced cerebral blood flow in heart failure. J Neurol Sci. 2014;339(1–2):169–75. https://doi.org/10.1016/j.jns.2014.02.008. ([PubMed PMID: 24461454]).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Nakakubo S, Makizako H, Doi T, Tsutsumimoto K, Lee S, Lee S, et al. Impact of poor sleep quality and physical inactivity on cognitive function in community‐dwelling older adults. Geriatr Gerontol Intl. 2017;17(11):1823–8. https://doi.org/10.1111/ggi.12973 [PubMed PMID: 28294469]

  31. Matyas N, Aschenberger FK, Wagner G, Teufer B, Auer S, Gisinger C, et al. Continuing education for the prevention of mild cognitive impairment and Alzheimer’s-type dementia: a systematic review and overview of systematic reviews. BMJ Open. 2019;9(7): e027719. https://doi.org/10.1136/bmjopen-2018-027719. ([PubMed PMID: 31272929]).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Wang AY, Hu HY, Ou YN, Wang ZT, Ma YH, Tan L, et al. Socioeconomic status and risks of cognitive impairment and dementia: a systematic review and meta-analysis of 39 prospective studies. J Prev Alz Dis. 2023;10(1):83–94. https://doi.org/10.14283/jpad.2022.81 [PubMed PMID: To be added once available]

  33. Maugeri A, Barchitta M. How dietary factors affect DNA methylation: lesson from epidemiological studies. Medicina. 2020;56(8):374. https://doi.org/10.3390/medicina56080374. ([PubMed PMID: 32722698]).

    Article  PubMed  PubMed Central  Google Scholar 

  34. Cerutti J, Lussier AA, Zhu Y, Liu J, Dunn EC. Associations between indicators of socioeconomic position and DNA methylation: a scoping review. Cli Epigenetics. 2021;13:1–20. https://doi.org/10.1186/s13148-021-01189-0. ([PubMed PMID: 34945607]).

    Article  CAS  Google Scholar 

  35. Van Dongen J, Bonder MJ, Dekkers KF, Nivard MG, van Iterson M, Willemsen G, et al. DNA methylation signatures of educational attainment. NPJ Sci Learn. 2018;3(1):7. https://doi.org/10.1038/s41539-018-0020-2. ([PubMed PMID: 29594135]).

    Article  PubMed  PubMed Central  Google Scholar 

  36. Wang Z, Zhu W, Xing Y, Jia J, Tang Y. B vitamins and prevention of cognitive decline and incident dementia: a systematic review and meta-analysis. Nutr Rev. 2022;80(4):931–49. https://doi.org/10.1093/nutrit/nuab057. ([PubMed PMID: 35001561]).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge all the kind participants for their invaluable time and cooperation in the present study. We also thank the Department of Anthropology, University of Delhi for providing the required facilities to conduct the study.

Funding

The present study was supported by the Department of Science and Technology, Ministry of Science and Technology, Government of India (DST/CSRI/2018/162G) and Indian Council of Medical Research (45/01/2022-ANTHRO/BMS).

Author information

Authors and Affiliations

Authors

Contributions

KNS and NB supervised the project and data collection. KNS conceptualised the manuscript. DB and AK performed lab analyses for global DNA methylation. KK performed data analyses and wrote the first draft. VC, GKW, NKD and KNS critically revised the manuscript for intellectual content. All the authors approved the final version of the manuscript for publication.

Corresponding author

Correspondence to Naorem Kiranmala Devi.

Ethics declarations

Conflict of interests

The authors declare no competing interests.

Human Ethics

The present study was conducted following the principles of the Declaration of Helsinki for biomedical studies involving human subjects. Moreover, the present study was approved by the Institutional Ethics Committee, Department of Anthropology, University of Delhi (Ref No. Anth/2018/2890/1/28-12-2018). Prior to recruitment and data collection, pre-informed voluntary written consent, transcribed in local language was obtained from each participant.

Consent for publication

All the authors have provided consent for the publication of this manuscript.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khate, K., Chaudhary, V., Bhattacharjee, D. et al. Global DNA Methylation and Cognitive Impairment: A Population-Based Study from Haryana, North India. Ind J Clin Biochem (2024). https://doi.org/10.1007/s12291-024-01205-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12291-024-01205-z

Keywords

Navigation