Associations Between Longitudinal Loneliness, DNA Methylation Age Acceleration, and Cognitive Functioning.

Area of Science:

• Gerontology
• Epigenetics
• Cognitive Neuroscience

Background:

• Loneliness is a growing concern among older adults.
• Loneliness may impact cognitive aging through biological pathways.
• DNA methylation (DNAm) age acceleration is a potential biomarker for aging processes.

Purpose of the Study:

• To investigate if DNA methylation (DNAm) age acceleration mediates the relationship between loneliness and cognitive function in older adults.
• To examine effects of baseline loneliness and longitudinal loneliness trajectories on cognitive outcomes.
• To identify specific DNAm age acceleration measures associated with loneliness and cognitive decline.

Main Methods:

• Utilized data from 1,814 older adults in the Health and Retirement Study.
• Assessed baseline loneliness and five longitudinal loneliness trajectories.
• Measured six common DNAm age acceleration measures and cognitive abilities (general cognitive ability, immediate/delayed memory recall, processing speed).

Main Results:

• Higher baseline loneliness and highest loneliness trajectories were associated with poorer cognitive ability and memory.
• DNAm age acceleration measures linked to comorbidities, lifestyle, and mortality risk mediated loneliness effects on cognition, but not processing speed.
• GrimAge Accel mediated memory outcomes in specific loneliness trajectory groups.

Conclusions:

• DNAm biomarkers of aging, especially GrimAge Accel, show potential in explaining the association between loneliness and cognitive functioning.
• Covariates like self-rated health, depression, social isolation, and BMI significantly influenced the total and mediated effects of loneliness on cognition.