Abstract
The proportion of aging populations affected by dementia is increasing. There is an urgent need to identify biological aging markers in mid-life before symptoms of age-related dementia present for early intervention to delay the cognitive decline and the onset of dementia. In this cohort study involving 1,676 healthy participants (mean age 40) with up to 15 years of follow up, we evaluated the associations between cognitive function and two classes of novel biological aging markers: blood-based epigenetic aging and neuroimaging-based brain aging. Both accelerated epigenetic aging and brain aging were prospectively associated with worse cognitive outcomes. Specifically, every year faster epigenetic or brain aging was on average associated with 0.19-0.28 higher (worse) Stroop score, 0.04-0.05 lower (worse) RAVLT score, and 0.23-0.45 lower (worse) DSST (all false-discovery-rate-adjusted p <0.05). While epigenetic aging is a more stable biomarker with strong long-term predictive performance for cognitive function, brain aging biomarker may change more dynamically in temporal association with cognitive decline. The combined model using epigenetic and brain aging markers achieved the highest accuracy (AUC: 0.68, p<0.001) in predicting global cognitive function status. Accelerated epigenetic age and brain age at midlife may aid timely identification of individuals at risk for accelerated cognitive decline and promote the development of interventions to preserve optimal functioning across the lifespan.
Original language | English (US) |
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Pages (from-to) | 1691-1712 |
Number of pages | 22 |
Journal | Aging |
Volume | 14 |
Issue number | 4 |
DOIs | |
State | Published - 2022 |
Funding
The study was funded by NIH/NIA grant R01AG069120. The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201800005I and HHSN2682018 00007I), Northwestern University (HHSN2682018000 03I), University of Minnesota (HHSN268201800006I), and Kaiser Foundation Research Institute (HHSN 268201800004I). CARDIA was also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intra-agency agreement between NIA and NHLBI (AG0005). The DNA methylation laboratory work and analytical component were funded by American Heart Association (17SFRN33700278 and 14SFRN20790000, Northwestern University, PI: Dr. Lifang Hou). This manuscript has been reviewed by CARDIA for scientific content.
Keywords
- Brain age
- Cognitive function
- Dna methylation
- Epigenetic age
- Magnetic resonance imaging
ASJC Scopus subject areas
- Aging
- Cell Biology