Psychology and Neuroscience Graduate Students Database
Psychology and Neuroscience
Arts & Sciences
Duke University

 HOME > Arts & Sciences > pn > Graduate Students    Search Help Login pdf version printable version 

Publications [#363998] of Maxwell Elliott

search PubMed.

Journal Articles

  1. Sugden, K; Caspi, A; Elliott, ML; Bourassa, KJ; Chamarti, K; Corcoran, DL; Hariri, AR; Houts, RM; Kothari, M; Kritchevsky, S; Kuchel, GA; Mill, JS; Williams, BS; Belsky, DW; Moffitt, TE; Alzheimer’s Disease Neuroimaging Initiative, (2022). Association of Pace of Aging Measured by Blood-Based DNA Methylation With Age-Related Cognitive Impairment and Dementia.. Neurology, 10.1212/WNL.0000000000200898. [doi]
    (last updated on 2022/09/07)

    Abstract:

    Background and objectives

    DNA methylation algorithms are increasingly used to estimate biological aging; however, how these proposed measures of whole-organism biological aging relate to aging in the brain is not known. We used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Framingham Heart Study (FHS) Offspring Cohort to test the association between blood-based DNA methylation measures of biological aging and cognitive impairment and dementia in older adults.

    Methods

    We tested three 'generations' of DNA methylation age algorithms (1st generation: Horvath and Hannum clocks; 2nd generation: PhenoAge and GrimAge; and 3rd generation: DunedinPACE, Dunedin Pace of Aging Calculated from the Epigenome) against the following measures of cognitive impairment in ADNI: clinical diagnosis of dementia and mild cognitive impairment; scores on AD/ADRD screening tests (Alzheimer's Disease Assessment Scale; Mini-Mental State Examination; Montreal Cognitive Assessment); and scores on cognitive tests (Rey Auditory Verbal Learning Test; Logical Memory Test; Trail Making Test). In an independent replication in the FHS Offspring Cohort, we further tested the longitudinal association between the DNA methylation algorithms and risk of developing dementia.

    Results

    In ADNI (N = 649 individuals), the 1st generation (Horvath and Hannum DNA methylation age clocks) and the 2nd generation (PhenoAge and GrimAge) DNA methylation measures of aging were not consistently associated with measures of cognitive impairment in older adults. In contrast, a 3rd generation measure of biological aging, DunedinPACE, was associated with clinical diagnosis of Alzheimer's Disease (beta[95%CI]=0.28[0.08-0.47]) and with poorer scores on AD/ADRD screening tests (beta[Robust SE]=-0.10[0.04] to 0.08[0.04]), and cognitive tests (beta[Robust SE]=-0.12[0.04] to 0.10[0.03]). The association between faster pace of aging, as measured by DunedinPACE, and risk of developing dementia was confirmed in a longitudinal analysis of the FHS Offspring Cohort (N = 2,264 individuals, HR[95%CI] =1.27[1.07-1.49]).

    Discussion

    Third generation blood-based DNA methylation measures of aging could prove valuable for measuring differences between individuals in the rate at which they age, in their risk for cognitive decline, and for evaluating interventions to slow aging.

Duke University * Arts & Sciences * Faculty * Staff * Grad * Postdocs * Reload * Login