Biomarkers

Area of Science:

• Epigenetics and Aging
• Neurodegenerative Diseases
• Biomarkers of Aging

Background:

• Epigenetic age estimators assess biological versus chronological age and link to health outcomes like CVD and mortality.
• Few large studies have prospectively examined epigenetic age estimators concerning mild cognitive impairment (MCI) or dementia.

Purpose of the Study:

• To investigate the association between multiple epigenetic age estimators and the risk of developing MCI or dementia.
• To evaluate the predictive power of various epigenetic age acceleration measures in a large cohort of women.

Main Methods:

• Utilized data from 5923 women in the Women's Health Initiative Memory Study, without MCI/dementia at baseline.
• Calculated Horvath AA, Hannum AA, AgeAccelPheno, Intrinsic/extrinsic epigenetic AA, AgeAccelGrim2, and DunedinPACE.
• Employed multivariable Cox proportional hazards models and evaluated effect modification by demographic and lifestyle factors.

Main Results:

• Over 9.3 years, 1267 incident MCI/dementia events occurred.
• Higher quartiles of DunedinPACE (HR=1.22) and AgeAccelGrim2 (HR=1.21) were associated with increased MCI/dementia risk (p-trend=0.02 and 0.01, respectively).
• Non-linear association observed for DunedinPACE; other estimators showed no significant association.

Conclusions:

• Accelerated epigenetic age, indicated by AgeAccelGrim2 and DunedinPACE, predicts incident MCI/dementia in older women.
• These findings suggest that epigenetic age acceleration could serve as a risk indicator for cognitive decline.
• The study provides insights into the pathophysiological mechanisms linking biological aging to neurodegeneration.