Cognition and dementia in older patients with epilepsy
Open accessAbstract
With advances in healthcare and an ageing population, the number of older adults with epilepsy is set to rise substantially across the world. In developed countries the highest incidence of epilepsy is already in people over 65 and, as life expectancy increases, individuals who developed epilepsy at a young age are also living longer. Recent findings show that older persons with epilepsy are more likely to suffer from cognitive dysfunction and that there might be an important bidirectional relationship between epilepsy and dementia. Thus some people with epilepsy may be at a higher risk of developing dementia, while individuals with some forms of dementia, particularly Alzheimer's disease and vascular dementia, are at significantly higher risk of developing epilepsy. Consistent with this emerging view, epidemiological findings reveal that people with epilepsy and individuals with Alzheimer's disease share common risk factors. Recent studies in Alzheimer's disease and late-onset epilepsy also suggest common pathological links mediated by underlying vascular changes and/or tau pathology. Meanwhile electrophysiological and neuroimaging investigations in epilepsy, Alzheimer's disease, and vascular dementia have focused interest on network level dysfunction, which might be important in mediating cognitive dysfunction across all three of these conditions. In this review we consider whether seizures promote dementia, whether dementia causes seizures, or if common underlying pathophysiological mechanisms cause both. We examine the evidence that cognitive impairment is associated with epilepsy in older people (aged over 65) and the prognosis for patients with epilepsy developing dementia, with a specific emphasis on common mechanisms that might underlie the cognitive deficits observed in epilepsy and Alzheimer's disease. Our analyses suggest that there is considerable intersection between epilepsy, Alzheimer's disease and cerebrovascular disease raising the possibility that better understanding of shared mechanisms in these conditions might help to ameliorate not just seizures, but also epileptogenesis and cognitive dysfunction.
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A strong link between APOE4 and seizure risk has been well established.
“A strong link between APOE4 and seizure risk has been well established (Sen et al., 2018; Tai et al., 2023; Vossel et al., 2017)”
From APOE4 reduces hippocampal expression of phosphoglycerate kinase 1 and sodium potassium pump to enhance seizure susceptibility in mice (2026) · cites this paper as Sen et al., 2018
The ‘Common risk factors for epilepsy and dementia’ section links APOE4 to greater amyloid deposition in an epilepsy cohort and to dementia risk, but does not establish an APOE4–seizure-risk association. Searches for APOE4 with seizure risk and for apolipoprotein E with epilepsy or seizures found no passage making that claim. Page numbers were not available in our copy. (LLM, conf=0.72)
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Cited by
Sorted by citations
Sen, A., Akinola, M., Tai, X. Y., Symmonds, M., Davis Jones, G., Mura, S., Galloway, J., Hallam, A., Chan, J. Y. C., Koychev, I., et al. (2021) · Trials · doi:10.1186/s13063-021-05404-4 · Cited by 30 · see citing works
Self-citationSingh, T., Bridgeman, E., Baker, A. J., Noblet, H. A., Yang, K. Y., Kang, S., Lim, K. H., Lee, S. S., Amundsen, N. M., Lee, Y., et al. (2026) · Neurobiology of Disease · doi:10.1016/j.nbd.2025.107246 · Cited by 1 · see citing works
- Authors
- Sen, A., Capelli, V., & Husain, M.
- Affiliations
- John Radcliffe Hospital (GB)
- Oxford Epilepsy Research Group, NIHR Biomedical Research Centre, Nuffield Department Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-02-28
- Volume
- 141
- Issue
- 6
- Pages
- 1592-1608
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC5972564
- OpenAlex
- W2793579479
- Cited by
- 280
- References
- 11
- Citations by year
- 2026: 26 · 2025: 48 · 2024: 40 · 2023: 31 · 2022: 39 · 2021: 39 · 2020: 33 · 2019: 19 · 2018: 5
- FWCI
- 3.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Brain (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Oxford University Research Archive (ORA) (University of Oxford) (submittedVersion, cc-by)
- Funders
- NIHR
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- epilepsy, dementia, older adults, cognitive impairment, Alzheimer's disease, vascular dementia, late-onset epilepsy, epileptogenesis, tau pathology, cerebrovascular disease, network dysfunction
- MeSH terms
- Aged, Aged, 80 and over, Aging, Cognition Disorders, Dementia, Epilepsy, Female, Humans, Male
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