Among older adults, an accelerated pace of biological aging was associated with a higher risk for incident dementia, decreased gray matter volume, and increased white matter lesion load. Accelerated biological aging is associated with lower brain volumes and increased risk for incident dementia, according to a study published in Alzheimer’s & Dementia DNA methylation–based algorithms are used to estimate biological aging. Prior studies have found that individuals whose biological age exceeds their chronological age are more likely to develop white matter lesions, white matter loss, and cognitive decline. However, the relationship between biological aging and brain pathology remains unclear. Researchers from the National Institute on Aging in the United States analyzed data from the Age, Gene/Environment Susceptibility–Reykjavik Study (AGES-RS) to examine whether changes in biological aging were associated with brain MRI measures, cognitive outcomes, and incident dementia. The analysis included 2081 participants with whole-blood DNA methylation data at baseline and follow-up who were evaluated for changes in biological aging measured by DunedinPACE (DDPACE), as well as brain magnetic resonance imaging (MRI) and cognitive outcomes. Accelerated aging was defined as a DDPACE score at least 1 SD above the mean. Our findings underscore the potential of biological aging not only to identify individuals at elevated risk of brain damage when their pace of aging accelerates, but also to capture the cumulative effects of lifestyle and environmental exposures on brain aging.*nbsp;At baseline and follow-up, the participants had mean ages of 75.51 and 80.71 years, respectively (
P <.001), 57.6% were women, and mean BMI was 27.25 and 26.74 kg/m², respectively (
P <.001). From baseline to follow-up, the participants had significant increases in DDPACE score and white matter lesion volume, and significant decreases in white matter volume, gray matter volume, total brain volume, and memory, processing speed, working memory, and global cognitive function scores (all
P <.001). Higher baseline DDPACE was associated with higher odds of having 1 infarct (odds ratio [OR], 1.19; 95% CI, 1.01–1.40;
P =.0324) or 2 or more infarcts (OR, 1.24; 95% CI, 1.02–1.51;
P =.0299). In analyses evaluating changes in DDPACE over time, individuals with a decrease in biological aging pace had greater gray matter volume compared with average agers (β, 0.09; P =.0270). Individuals with an increase in biological aging pace had lower gray matter volume (β, -0.06;
P =.022) and higher white matter lesion load (β, 0.05; P =.0090) compared with average agers. The DDPACE scores mediated 15.4% to 17.7% of the association between midlife cardiovascular health and late-life brain volume outcomes, including white matter, white matter lesions, gray matter, and total brain volume (all
P <.001). Similar mediation effects were observed between midlife American Heart Association Life’s Simple 7 score and late-life
cognitive function, accounting for 16.9% to 25% of the association.
At a median follow-up of 5.6 years, 129 incident dementia cases occurred among average agers, 11 among decelerators, and 64 among accelerators. Compared with average agers, individuals with accelerated aging had a higher risk of developing dementia (HR, 1.66; 95% CI, 1.21-2.28; P =.00167), which remained similar after adjusting for baseline DDPACE (adjusted HR, 1.65; 95% CI, 1.20-2.27; P =.00217).
Sensitivity analyses using a 2-year lag time or excluding individuals with an apolipoprotein E (APOE) ε2/ε4 genotype produced results consistent with the main analysis.
Study limitations include the lack of an external cohort to validate these findings.
The study authors concluded, “Our findings underscore the potential of biological aging not only to identify individuals at elevated risk of brain damage when their pace of aging accelerates, but also to capture the cumulative effects of lifestyle and environmental exposures on brain aging.”
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