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Epigenetic Aging Clocks Associate with Cognitive Status but Not Cognitive Decline: Evidence from the Parkinson's
Medrxiv : the Preprint Server for Health Sciences
|May 25, 2026
Summary
Epigenetic aging in Parkinsonian disorders may indicate cognitive vulnerability rather than progression. Blood-based epigenetic aging measures correlate with cognitive status, not short-term cognitive decline.
Area of Science:
- Neuroscience
- Genetics
- Aging Research
Background:
- Cognitive impairment is a significant disability in Parkinsonian disorders.
- Biomarkers distinguishing cognitive status from decline are limited.
- Epigenetic aging measures offer insights into biological aging but their role in cognitive changes is unclear.
Purpose of the Study:
- To investigate the association between epigenetic aging measures and global cognition in Parkinsonian disorders.
- To determine if epigenetic aging reflects stable cognitive vulnerability or longitudinal cognitive change.
Main Methods:
- Utilized data from the Parkinson's Progression Markers Initiative (PPMI) cohort.
- Derived seven epigenetic aging measures from peripheral blood DNA methylation.
- Assessed cognition longitudinally using the Montreal Cognitive Assessment (MoCA) and applied linear mixed-effects models.
Main Results:
- Higher epigenetic aging was consistently linked to lower MoCA scores.
- Associations were primarily driven by baseline epigenetic aging, not longitudinal changes.
- Within-person analyses showed no significant association with cognitive change.
Conclusions:
- Blood-based epigenetic aging measures may serve as biomarkers for cognitive status or vulnerability in Parkinsonian disorders.
- These measures appear less informative for tracking short-term cognitive progression.
- Further research with longer follow-up is needed to clarify longitudinal relevance.
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