Cognitive and neural signatures of the APOE E4 allele in mid-aged adults
Open accessAbstract
The apolipoprotein E (APOE) e4 allele is strongly associated with increased risk of cognitive impairments in older adulthood. There is also a possible link to enhanced cognitive performance in younger adults, and the APOE e4 allele may constitute an example of antagonistic pleiotropy. The aim of this work was to investigate the cognitive and neural (functional) effects of the APOE e4 allele during mid-age (45-55 years), where a transition toward cognitive deficit might be expected. APOE e4 carriers (e4+) were compared with non-e4 carriers (e4-) on tasks of sustained and covert attention and prospective memory, and functional magnetic resonance imaging data acquired. Performance by e4+ was equivalent or better than e4- on all 3 tasks, although performance benefits were less pronounced than in youth. Neurally, e4+ showed less task-related recruitment of extrastriate and parietal areas. This became more evident when neural activation data were compared with that of young adults acquired in a parallel study. As expected, mid-age participants showed more diffuse neural activation. Notable was the fact that e4+ showed a relative inability to recruit parietal regions as they aged. This was coupled with a tendency to show greater recruitment of frontal regions, and underactivation of extrastriate visual regions. Thus, mid-age e4+ show a pattern of neural recruitment usually seen later in life, possibly reflecting the source of an accelerated aging profile that describes the e4 genotype.
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Human studies have shown that impaired cognitive performance in ApoE4 carriers is prominent after middle age.
“Indeed, human studies have shown that impaired cognitive performance in ApoE4 carriers is prominent after middle age.25”
From ApoE4-dependent lysosomal cholesterol accumulation impairs mitochondrial homeostasis and oxidative phosphorylation in human astrocytes (2023) · cites this paper as [25]
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- Authors
- Evans, S., Dowell, N. G., Tabet, N., Tofts, P. S., King, S. L., & Rusted, J. M.
- Affiliations
- University of Sussex (GB)
- Brighton and Sussex Medical School (GB)
- Corresponding author
- Rusted, Jennifer M.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 35
- Issue
- 7
- Pages
- 1615-1623
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC4001126
- OpenAlex
- W2093891993
- Cited by
- 86
- References
- 6
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 4 · 2023: 11 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 6 · 2018: 9 · 2017: 9 · 2016: 13 · 2015: 9 · 2014: 2
- FWCI
- 7.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Neurobiology of Aging (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Sussex Research Online (University of Sussex) (submittedVersion, cc-by)
- Funders
- BBSRC (BB/H000518/1)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Functions and Memory
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
- Keywords
- APOE ε4, apolipoprotein E, sustained attention, covert attention, prospective memory, neural recruitment, parietal activation, extrastriate cortex, frontal cortex, brain aging, antagonistic pleiotropy, cognitive aging
- MeSH terms
- Adolescent, Adult, Aging, Alleles, Attention, Cognition, Cognition Disorders, Female, Frontal Lobe, Genotype, Heterozygote, Humans, Magnetic Resonance Imaging, Male, Memory, Middle Aged, Neurons, Parietal Lobe, Apolipoprotein E4, Young Adult, Genetic Association Studies
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