Skip to main content

Advertisement

SpringerLink
Log in

Late-onset epilepsy and the risk of dementia: a systematic review and meta-analysis

  • Review
  • Published:
Aging Clinical and Experimental Research Aims and scope Submit manuscript

Abstract

Background

Patients with dementia have higher risk of epilepsy. However, it remains not comprehensively evaluated if late-onset epilepsy (LOE) is associated with higher risk of dementia. We, therefore, performed a meta-analysis to systematically evaluate the association.

Methods

Relevant cohort studies were identified by search of electronic databases including PubMed, Embase, and Web of Science. A randomized-effect model incorporating the possible between-study heterogeneity was used to pool the results.

Results

Overall, seven cohort studies including 873,438 adults were included, and 16,036 (1.8%) of them had LOE. With a mean follow-up duration of 8.7 years, 33,727 of them were diagnosed as dementia. Pooled results showed that LOE was associated with a higher risk of dementia (risk ratio [RR] 2.39, 95% confidence interval [CI] 2.04–2.81, p < 0.001, I2 = 67%). Results of subgroup analysis showed that the association between LOE and the risk of dementia was stronger in hospital-derived participants (RR 4.23, 95% CI 2.67–6.70, p < 0.001) than that in community-derived population (RR 2.25, 95% CI 1.93–2.63, p < 0.001; p for subgroup difference = 0.01). Pooled results of three studies showed that LOE was associated with a higher risk of Alzheimer’s disease (RR 2.35, 95% CI 1.08–5.08, p = 0.03, I2 = 85%). One study suggested a significant association between LOE and risk of vascular dementia (RR 2.0, 95% CI 1.77–2.26, p < 0.001).

Conclusions

Evidence from cohort studies suggests that LOE may be a risk factor of dementia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Sarkis RA, Willment KC, Pennell PB et al (2019) Late-onset unexplained epilepsy: what are we missing? Epilepsy Behav 99:106478. https://doi.org/10.1016/j.yebeh.2019.106478

    Article  PubMed  Google Scholar 

  2. Hildick-Smith M (1994) Late-onset epilepsy. Br J Clin Pract 48:87–90

    CAS  PubMed  Google Scholar 

  3. Sen A, Capelli V, Husain M (2018) Cognition and dementia in older patients with epilepsy. Brain 141:1592–1608. https://doi.org/10.1093/brain/awy022.4915830[pii]

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kotloski RJ, Dowding J, Hermann BP et al (2019) Epilepsy and aging. Handb Clin Neurol 167:455–475. https://doi.org/10.1016/B978-0-12-804766-8.00025-X

    Article  PubMed  Google Scholar 

  5. Brigo F, Lattanzi S (2021) Pharmacotherapeutic considerations for late-onset epilepsy. Expert Opin Pharmacother 22:389–391. https://doi.org/10.1080/14656566.2020.1865311

    Article  CAS  PubMed  Google Scholar 

  6. Loiseau J, Crespel A, Picot MC et al (1998) Idiopathic generalized epilepsy of late onset. Seizure 7:485–487. https://doi.org/10.1016/s1059-1311(98)80007-1

    Article  CAS  PubMed  Google Scholar 

  7. Hanby MF, Al-Bachari S, Makin F et al (2015) Structural and physiological MRI correlates of occult cerebrovascular disease in late-onset epilepsy. Neuroimage Clin 9:128–133. https://doi.org/10.1016/j.nicl.2015.07.016

    Article  PubMed  PubMed Central  Google Scholar 

  8. Gibson LM, Hanby MF, Al-Bachari SM et al (2014) Late-onset epilepsy and occult cerebrovascular disease. J Cereb Blood Flow Metab 34:564–570. https://doi.org/10.1038/jcbfm.2014.25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Gibson LM, Allan SM, Parkes LM et al (2011) Occult cerebrovascular disease and late-onset epilepsy: could loss of neurovascular unit integrity be a viable model? Cardiovasc Psychiatry Neurol 2011:130406. https://doi.org/10.1155/2011/130406

    Article  PubMed  PubMed Central  Google Scholar 

  10. Brigo F, Tezzon F, Nardone R (2014) Late-onset seizures and risk of subsequent stroke: a systematic review. Epilepsy Behav 31:9–12. https://doi.org/10.1016/j.yebeh.2013.11.003

    Article  PubMed  Google Scholar 

  11. Wall J, Knight J, Emsley HCA (2021) Late-onset epilepsy predicts stroke: systematic review and meta-analysis. Epilepsy Behav 115:107634. https://doi.org/10.1016/j.yebeh.2020.107634

    Article  PubMed  Google Scholar 

  12. Subota A, Pham T, Jette N et al (2017) The association between dementia and epilepsy: a systematic review and meta-analysis. Epilepsia 58:962–972. https://doi.org/10.1111/epi.13744

    Article  PubMed  Google Scholar 

  13. Xu Y, Lavrencic L, Radford K et al (2021) Systematic review of coexistent epileptic seizures and Alzheimer’s disease: incidence and prevalence. J Am Geriatr Soc 69:2011–2020. https://doi.org/10.1111/jgs.17101

    Article  PubMed  Google Scholar 

  14. Johnson EL, Krauss GL, Kucharska-Newton A et al (2021) Mortality in patients with late-onset epilepsy: results from the atherosclerosis risk in communities study. Neurology 97:e1132–e1140. https://doi.org/10.1212/WNL.0000000000012483

    Article  PubMed  Google Scholar 

  15. Carter MD, Weaver DF, Joudrey HR et al (2007) Epilepsy and antiepileptic drug use in elderly people as risk factors for dementia. J Neurol Sci 252:169–172. https://doi.org/10.1016/j.jns.2006.11.004

    Article  CAS  PubMed  Google Scholar 

  16. Cordonnier C, Henon H, Derambure P et al (2007) Early epileptic seizures after stroke are associated with increased risk of new-onset dementia. J Neurol Neurosurg Psychiatry 78:514–516. https://doi.org/10.1136/jnnp.2006.105080

    Article  PubMed  PubMed Central  Google Scholar 

  17. Johnson EL, Krauss GL, Kucharska-Newton A et al (2020) Dementia in late-onset epilepsy: the atherosclerosis risk in communities study. Neurology 95:e3248–e3256. https://doi.org/10.1212/WNL.0000000000011080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kawakami O, Koike Y, Ando T et al (2018) Incidence of dementia in patients with adult-onset epilepsy of unknown causes. J Neurol Sci 395:71–76. https://doi.org/10.1016/j.jns.2018.09.010

    Article  PubMed  Google Scholar 

  19. Keret O, Hoang TD, Xia F et al (2020) Association of late-onset unprovoked seizures of unknown etiology with the risk of developing dementia in older veterans. JAMA Neurol 77:710–715. https://doi.org/10.1001/jamaneurol.2020.0187

    Article  PubMed  Google Scholar 

  20. Schnier C, Duncan S, Wilkinson T et al (2020) A nationwide, retrospective, data-linkage, cohort study of epilepsy and incident dementia. Neurology 95:e1686–e1693. https://doi.org/10.1212/WNL.0000000000010358

    Article  PubMed  Google Scholar 

  21. Tsai ZR, Zhang HW, Tseng CH et al (2021) Late-onset epilepsy and subsequent increased risk of dementia. Aging (Albany NY) 13:3573–3587. https://doi.org/10.18632/aging.202299

    Article  Google Scholar 

  22. Page MJ, McKenzie JE, Bossuyt PM et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71. https://doi.org/10.1136/bmj.n71

    Article  PubMed  PubMed Central  Google Scholar 

  23. Page MJ, Moher D, Bossuyt PM et al (2021) PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ 372:n160. https://doi.org/10.1136/bmj.n160

    Article  PubMed  PubMed Central  Google Scholar 

  24. Higgins J, Thomas J, Chandler J et al (2021) Cochrane Handbook for Systematic Reviews of Interventions version 6.2. The Cochrane Collaboration www.training.cochrane.org/handbook

  25. Wells GA, Shea B, O'Connell D et al. (2010) The Newcastle–Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp

  26. Higgins J, Green S (2011) Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration www.cochranehandbook.org

  27. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558. https://doi.org/10.1002/sim.1186

    Article  PubMed  Google Scholar 

  28. Egger M, Davey Smith G, Schneider M et al (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  CAS  Google Scholar 

  29. Beghi E, Giussani G (2018) Aging and the epidemiology of epilepsy. Neuroepidemiology 51:216–223. https://doi.org/10.1159/000493484

    Article  PubMed  Google Scholar 

  30. Lopez OL, Kuller LH (2019) Epidemiology of aging and associated cognitive disorders: prevalence and incidence of Alzheimer’s disease and other dementias. Handb Clin Neurol 167:139–148. https://doi.org/10.1016/B978-0-12-804766-8.00009-1

    Article  PubMed  Google Scholar 

  31. Johnson EL, Krauss GL, Lee AK et al (2018) Association between midlife risk factors and late-onset epilepsy: results from the atherosclerosis risk in communities study. JAMA Neurol 75:1375–1382. https://doi.org/10.1001/jamaneurol.2018.1935

    Article  PubMed  PubMed Central  Google Scholar 

  32. Brigo F, Lochner P, Nardone R et al (2020) Increased risk of stroke and myocardial infarction in patients with epilepsy: a systematic review of population-based cohort studies. Epilepsy Behav 104:106307. https://doi.org/10.1016/j.yebeh.2019.05.005

    Article  PubMed  Google Scholar 

  33. Terrone G, Balosso S, Pauletti A et al (2020) Inflammation and reactive oxygen species as disease modifiers in epilepsy. Neuropharmacology 167:107742. https://doi.org/10.1016/j.neuropharm.2019.107742

    Article  CAS  PubMed  Google Scholar 

  34. Rosenberg GA (2017) Extracellular matrix inflammation in vascular cognitive impairment and dementia. Clin Sci (Lond) 131:425–437. https://doi.org/10.1042/CS20160604

    Article  CAS  Google Scholar 

  35. Tonnies E, Trushina E (2017) Oxidative stress, synaptic dysfunction, and alzheimer’s disease. J Alzheimers Dis 57:1105–1121. https://doi.org/10.3233/JAD-161088

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Gourmaud S, Shou H, Irwin DJ et al (2020) Alzheimer-like amyloid and tau alterations associated with cognitive deficit in temporal lobe epilepsy. Brain 143:191–209. https://doi.org/10.1093/brain/awz381

    Article  PubMed  Google Scholar 

  37. Paudel YN, Angelopoulou E, Jones NC et al (2019) Tau related pathways as a connecting link between epilepsy and Alzheimer’s disease. ACS Chem Neurosci 10:4199–4212. https://doi.org/10.1021/acschemneuro.9b00460

    Article  CAS  PubMed  Google Scholar 

  38. Giorgi FS, Saccaro LF, Busceti CL et al (2020) Epilepsy and Alzheimer’s disease: potential mechanisms for an association. Brain Res Bull 160:107–120. https://doi.org/10.1016/j.brainresbull.2020.04.009

    Article  CAS  PubMed  Google Scholar 

  39. Vossel KA, Tartaglia MC, Nygaard HB et al (2017) Epileptic activity in Alzheimer’s disease: causes and clinical relevance. Lancet Neurol 16:311–322. https://doi.org/10.1016/S1474-4422(17)30044-3

    Article  PubMed  PubMed Central  Google Scholar 

  40. Johnson EL, Krauss GL, Walker KA et al (2020) Late-onset epilepsy and 25-year cognitive change: the Atherosclerosis Risk in Communities (ARIC) study. Epilepsia 61:1764–1773. https://doi.org/10.1111/epi.16616

    Article  PubMed  PubMed Central  Google Scholar 

  41. Reyes-Miranda A, Chan S, Gowda S et al (2020) Assessing the personal impact of epilepsy in a population-based cohort of veterans. Epilepsy Behav 106:107047. https://doi.org/10.1016/j.yebeh.2020.107047

    Article  PubMed  Google Scholar 

  42. Lattanzi S, Trinka E, Del Giovane C et al (2019) Antiepileptic drug monotherapy for epilepsy in the elderly: a systematic review and network meta-analysis. Epilepsia 60:2245–2254. https://doi.org/10.1111/epi.16366

    Article  PubMed  Google Scholar 

Download references

Funding

No funding was received for this study.

Author information

Authors and Affiliations

  1. Department of Neurology, The First People’s Hospital of Yibin, No. 65 Wenxing Street, Cuiping District, Yibin City, 644000, Sichuan, China

    Lei Huang, Chi Fu, Jie Li & Shijun Peng

Authors
  1. Lei Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chi Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jie Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shijun Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

LH designed the study. LH and CF performed database search, study identification, quality evaluation and data collection. LH, JL, and SP performed statistical analysis and interpreted the results. LH drafted the manuscript. All authors revised the manuscript and approved the submission.

Corresponding author

Correspondence to Lei Huang.

Ethics declarations

Conflict of interest

The authors declared that they have no potential conflict of interest.

Ethics approval

The study did not require ethics committee approval, because of its non-experimental design and search strategy.

Statement of human and animal rights

This review does not contain any experiments involving human participants or animals performed by any authors.

Informed consent

For this review, informed consent forms were not required.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huang, L., Fu, C., Li, J. et al. Late-onset epilepsy and the risk of dementia: a systematic review and meta-analysis. Aging Clin Exp Res 34, 1771–1779 (2022). https://doi.org/10.1007/s40520-022-02118-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40520-022-02118-8

Keywords

Search

Navigation