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Research Paper|Volume 17, Issue 10|pp 2455—2474

Longitudinal associations of epigenetic aging with cognitive aging in Hispanic/Latino adults from the Hispanic Community Health Study/Study of Latinos

Myriam Fornage1,2, Wassim Tarraf3, Rui Xia1, Adriana Ordonez1, Tamar Sofer4,5,6, Freddie Márquez7, Bharat Thyagarajan8, Gregory A. Talavera9, Linda C. Gallo9, Charles DeCarli10, Hector M. González7
  • 1Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
  • 2Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
  • 3Institute of Gerontology and Department of Healthcare Sciences, Wayne State University, Detroit, MI 48202, USA
  • 4Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
  • 5CardioVascular Institute, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
  • 6Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
  • 7Department of Neurosciences, University of California San Diego, La Jolla, CA 92093, USA
  • 8Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA
  • 9Department of Psychology, San Diego State University, San Diego, CA 92182, USA
  • 10Department of Neurology, University of California, Sacramento, CA 95817, USA
Received: April 4, 2025Accepted: July 22, 2025Published: September 10, 2025
https://doi.org/10.18632/aging.206317

Copyright: © 2025 Fornage et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Due to the paucity of longitudinal DNA methylation data (DNAm), especially among Hispanic/Latino adults, the association between changes in epigenetic clocks over time and cognitive aging phenotypes has not been investigated.

This longitudinal study included 2671 Hispanic/Latino adults (57 years; 66% women) with blood DNAm data and neurocognitive function assessed at two visits ~7 years apart. We evaluated the associations of 5 epigenetic clocks and their between-visit change with multiple measures of cognitive aging that included a global and domain-specific cognitive function score at each visit, between-visit change in global and domain-specific cognitive function score, and MCI diagnosis at visit 2 (V2).

There were significant associations between greater acceleration of all clocks and lower cognitive function at each visit and MCI at V2. The strongest associations were observed for GrimAge and DunedinPACE. There were significant associations of between-visit increase in PhenoAge and GrimAge acceleration with decline in cognitive function and greater risk of MCI diagnosis at V2.

Epigenetic aging is associated with lower global and domain-specific cognitive function, greater cognitive decline, and greater risk of MCI in Hispanic/Latino adults. Longitudinal assessment of change in age acceleration for second-generation clocks, GrimAge and PhenoAge may provide additional value in predicting cognitive aging beyond a single time point assessment.