Aladdin H Shadyab1, Linda K McEvoy1,2, Steve Horvath3, Eric A Whitsel4, Stephen R Rapp5, Mark A Espeland6, Susan M Resnick7, JoAnn E Manson8, Jiu-Chiuan Chen9, Brian H Chen1, Wenjun Li10, Kathleen M Hayden11, Wei Bao12, Cynthia D J Kusters3, Andrea Z LaCroix1. 1. Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla, USA. 2. Department of Radiology, University of California, San Diego, School of Medicine, La Jolla, USA. 3. Department of Human Genetics, University of California, Los Angeles, USA. 4. Departments of Epidemiology and Medicine, University of North Carolina, Chapel Hill, USA. 5. Department of Psychiatry and Behavioral Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. 6. Division of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA. 7. Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, Maryland, USA. 8. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School and Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. 9. Departments of Preventive Medicine and Neurology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. 10. Department of Public Health, University of Massachusetts, Lowell, USA. 11. Departments of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA. 12. Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, USA.
Abstract
BACKGROUND: Epigenetic age acceleration (AgeAccel), which indicates faster biological aging relative to chronological age, has been associated with lower cognitive function. However, the association of AgeAccel with mild cognitive impairment (MCI) or dementia is not well-understood. We examined associations of 4 AgeAccel measures with incident MCI and dementia. METHODS: This prospective analysis included 578 older women from the Women's Health Initiative Memory Study selected for a case-cohort study of coronary heart disease (CHD). Women were free of CHD and cognitive impairment at baseline. Associations of AgeAccel measures (intrinsic AgeAccel [IEAA], extrinsic AgeAccel [EEAA], AgeAccelPheno, and AgeAccelGrim) with risks for incident adjudicated diagnoses of MCI and dementia overall and stratified by incident CHD status were evaluated. RESULTS: IEAA was not significantly associated with MCI (HR, 1.23; 95% CI, 0.99-1.53), dementia (HR, 1.10; 95% CI, 0.88-1.38), or cognitive impairment (HR, 1.18; 95% CI, 0.99-1.40). In stratified analysis by incident CHD status, there was a 39% (HR, 1.39; 95% CI, 1.07-1.81) significantly higher risk of MCI for every 5-year increase in IEAA among women who developed CHD during follow-up. Other AgeAccel measures were not significantly associated with MCI or dementia. CONCLUSIONS: IEAA was not significantly associated with cognitive impairment overall but was associated with impairment among women who developed CHD. Larger studies designed to examine associations of AgeAccel with cognitive impairment are needed, including exploration of whether associations are stronger in the setting of underlying vascular pathologies.
BACKGROUND: Epigenetic age acceleration (AgeAccel), which indicates faster biological aging relative to chronological age, has been associated with lower cognitive function. However, the association of AgeAccel with mild cognitive impairment (MCI) or dementia is not well-understood. We examined associations of 4 AgeAccel measures with incident MCI and dementia. METHODS: This prospective analysis included 578 older women from the Women's Health Initiative Memory Study selected for a case-cohort study of coronary heart disease (CHD). Women were free of CHD and cognitive impairment at baseline. Associations of AgeAccel measures (intrinsic AgeAccel [IEAA], extrinsic AgeAccel [EEAA], AgeAccelPheno, and AgeAccelGrim) with risks for incident adjudicated diagnoses of MCI and dementia overall and stratified by incident CHD status were evaluated. RESULTS: IEAA was not significantly associated with MCI (HR, 1.23; 95% CI, 0.99-1.53), dementia (HR, 1.10; 95% CI, 0.88-1.38), or cognitive impairment (HR, 1.18; 95% CI, 0.99-1.40). In stratified analysis by incident CHD status, there was a 39% (HR, 1.39; 95% CI, 1.07-1.81) significantly higher risk of MCI for every 5-year increase in IEAA among women who developed CHD during follow-up. Other AgeAccel measures were not significantly associated with MCI or dementia. CONCLUSIONS: IEAA was not significantly associated with cognitive impairment overall but was associated with impairment among women who developed CHD. Larger studies designed to examine associations of AgeAccel with cognitive impairment are needed, including exploration of whether associations are stronger in the setting of underlying vascular pathologies.
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