Are sex differences in cognitive impairment reflected in epigenetic age acceleration metrics?

Amy M Inkster; Paula Duarte-Guterman; Arianne Y Albert; Cindy K Barha; Liisa A M Galea; Wendy P Robinson; Alzheimer's Disease Neuroimaging Initiative

doi:10.1016/j.neurobiolaging.2021.09.022

Are sex differences in cognitive impairment reflected in epigenetic age acceleration metrics?

Neurobiol Aging. 2022 Jan:109:192-194. doi: 10.1016/j.neurobiolaging.2021.09.022. Epub 2021 Oct 3.

Authors

Amy M Inkster¹, Paula Duarte-Guterman², Arianne Y Albert³, Cindy K Barha⁴, Liisa A M Galea², Wendy P Robinson⁵; Alzheimer's Disease Neuroimaging Initiative

Affiliations

¹ Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.; BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada. Electronic address: ainkster@bcchr.ca.
² Djavad Mowafaghian Centre for Brain Health and Department of Psychology, University of British Columbia, Vancouver, British Columbia, Canada.
³ Women's Health Research Institute of British Columbia, Vancouver, British Columbia, Canada.
⁴ Djavad Mowafaghian Centre for Brain Health and Department of Physical Therapy, University of British Columbia, Vancouver, British Columbia, Canada.
⁵ Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.; BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.

PMID: 34775209
DOI: 10.1016/j.neurobiolaging.2021.09.022

Abstract

Sex differences are well-established in Alzheimer's disease (AD) frequency and pathogenesis, but are not mechanistically understood. Accelerated epigenetic age has been associated with both cognitive aging and AD pathophysiology, but has not been studied by sex in AD or related cognitive impairment. Using the ADNI cohort, we found that none of sex, cognitive impairment diagnosis, nor load of APOEε4 alleles (strongest genetic AD risk factor) were associated with epigenetic age acceleration (DNAmAge, Intrinsic DNAmAge, PhenoAge, or GrimAge), although females exhibit more accelerated epigenetic aging using the Skin & Blood clock in the transition from normal cognition to cognitive impairment than males.

Keywords: APOE genotype; Alzheimer's Disease; DNAmAge, age; Epigenetic age; GrimAge; Sex differences; Skin & Blood clock, PhenoAge.

MeSH terms

Aged
Aged, 80 and over
Aging / genetics*
Alzheimer Disease / etiology
Alzheimer Disease / genetics*
Cognitive Aging*
Cognitive Dysfunction / genetics*
Cohort Studies
Epigenesis, Genetic / genetics*
Female
Humans
Male
Middle Aged
Sex Characteristics*