Default mode network connectivity and cognition in the aging brain: the effects of age, sex, and APOE genotype.
Open accessAbstract
The default mode network (DMN) overlaps with regions showing early Alzheimer's Disease (AD) pathology. Age, sex, and apolipoprotein E ɛ4 are the predominant risk factors for developing AD. How these risk factors interact to influence DMN connectivity and connectivity-cognition relationships before the onset of impairment remains unknown. Here, we examined these issues in 475 cognitively normal adults, targeting total DMN connectivity, its anticorrelated network (acDMN), and the DMN-hippocampal component. There were four main findings. First, in the ɛ3 homozygous group, lower DMN and acDMN connectivity was observed with age. Second, sex and ɛ4 modified the relationship between age and connectivity for the DMN and hippocampus with ɛ4 vs. ɛ3 males showing sustained or higher connectivity with age. Third, in the ɛ3 group, age and sex modified connectivity-cognition relationships with the oldest participants having the most differential patterns due to sex. Fourth, ɛ4 carriers with lower connectivity had poorer cognitive performance. Taken together, our results show the three predominant risk factors for AD interact to influence brain function and function-cognition relationships.
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The default mode network (DMN) shows altered activity patterns with ageing, and older adults often exhibit decreased deactivation of the DMN during task performance, which is thought to contribute to attentional deficits.
“The default mode network (DMN), which is active during rest and is involved in self-referential thinking, shows altered activity patterns with ageing. Older adults often exhibit decreased deactivation of the DMN during task performance, which is thought to contribute to attentional deficits.167”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [167]
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References 87 · Cited by 16
- Authors
- Shafer, A. T., Beason-Held, L., An, Y., Williams, O. A., Huo, Y., Landman, B. A., Caffo, B. S., & Resnick, S. M.
- Affiliations
- National Institute on Aging (US)
- Vanderbilt University (US)
- Johns Hopkins University (US)
- Corresponding author
- Shafer, Andrea T.
- Resnick, Susan M.
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2021-08
- Volume
- 104
- Pages
- 10-23
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC12004503
- OpenAlex
- W3142205708
- Cited by
- 16
- References
- 87
- Citations by year
- 2025: 4 · 2024: 1 · 2023: 1 · 2022: 10
- FWCI
- 1.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- default mode network, functional connectivity, brain aging, Alzheimer's disease risk factors, APOE ε4, sex differences, age effects, cognitively normal adults, hippocampus
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Apolipoproteins E, Cognition, Female, Genotype, Hippocampus, Humans, Male, Middle Aged, Nerve Net, Risk Factors, Sex Characteristics
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