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Association of Pace of Aging Measured by Blood-Based DNA Methylation With Age-Related Cognitive Impairment and Dementia.

Publication ,  Journal Article
Sugden, K; Caspi, A; Elliott, ML; Bourassa, KJ; Chamarti, K; Corcoran, DL; Hariri, AR; Houts, RM; Kothari, M; Kritchevsky, S; Kuchel, GA ...
Published in: Neurology
September 2022

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.We tested 3 "generations" of DNA methylation age algorithms (first generation: Horvath and Hannum clocks; second generation: PhenoAge and GrimAge; and third 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 Alzheimer disease (AD) / Alzheimer disease and related dementias (ADRD) screening tests (Alzheimer's Disease Assessment Scale, Mini-Mental State Examination, and Montreal Cognitive Assessment), and scores on cognitive tests (Rey Auditory Verbal Learning Test, Logical Memory test, and Trail Making Test). In an independent replication in the FHS Offspring Cohort, we further tested the longitudinal association between the DNA methylation algorithms and the risk of developing dementia.In ADNI (N = 649 individuals), the first-generation (Horvath and Hannum DNA methylation age clocks) and the second-generation (PhenoAge and GrimAge) DNA methylation measures of aging were not consistently associated with measures of cognitive impairment in older adults. By contrast, a third-generation measure of biological aging, DunedinPACE, was associated with clinical diagnosis of Alzheimer disease (beta [95% CI] = 0.28 [0.08-0.47]), poorer scores on Alzheimer disease/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, hazard ratio [95% CI] = 1.27 [1.07-1.49]).Third-generation blood-based DNA methylation measures of aging could prove valuable for measuring differences between individuals in the rate at which they age and in their risk for cognitive decline, and for evaluating interventions to slow aging.

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Published In

Neurology

DOI

EISSN

1526-632X

ISSN

0028-3878

Publication Date

September 2022

Volume

99

Issue

13

Start / End Page

e1402 / e1413

Related Subject Headings

  • Neuropsychological Tests
  • Neurology & Neurosurgery
  • Humans
  • DNA Methylation
  • Cognitive Dysfunction
  • Alzheimer Disease
  • Aging
  • Aged
  • 3209 Neurosciences
  • 3202 Clinical sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Sugden, K., Caspi, A., Elliott, M. L., Bourassa, K. J., Chamarti, K., Corcoran, D. L., … 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, 99(13), e1402–e1413. https://doi.org/10.1212/wnl.0000000000200898
Sugden, Karen, Avshalom Caspi, Maxwell L. Elliott, Kyle J. Bourassa, Kartik Chamarti, David L. Corcoran, Ahmad R. Hariri, et al. “Association of Pace of Aging Measured by Blood-Based DNA Methylation With Age-Related Cognitive Impairment and Dementia.Neurology 99, no. 13 (September 2022): e1402–13. https://doi.org/10.1212/wnl.0000000000200898.
Sugden K, Caspi A, Elliott ML, Bourassa KJ, Chamarti K, Corcoran DL, et al. Association of Pace of Aging Measured by Blood-Based DNA Methylation With Age-Related Cognitive Impairment and Dementia. Neurology. 2022 Sep;99(13):e1402–13.
Sugden, Karen, et al. “Association of Pace of Aging Measured by Blood-Based DNA Methylation With Age-Related Cognitive Impairment and Dementia.Neurology, vol. 99, no. 13, Sept. 2022, pp. e1402–13. Epmc, doi:10.1212/wnl.0000000000200898.
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*. Association of Pace of Aging Measured by Blood-Based DNA Methylation With Age-Related Cognitive Impairment and Dementia. Neurology. 2022 Sep;99(13):e1402–e1413.

Published In

Neurology

DOI

EISSN

1526-632X

ISSN

0028-3878

Publication Date

September 2022

Volume

99

Issue

13

Start / End Page

e1402 / e1413

Related Subject Headings

  • Neuropsychological Tests
  • Neurology & Neurosurgery
  • Humans
  • DNA Methylation
  • Cognitive Dysfunction
  • Alzheimer Disease
  • Aging
  • Aged
  • 3209 Neurosciences
  • 3202 Clinical sciences