Association of COVID-19 with neurodegenerative and neurological disorders in vaccinated and unvaccinated people
Introduction: COVID-19 has been linked to neuropathology, neurological symptoms, and diagnoses of neurological illnesses. Evidence regarding the long-term impact of COVID-19 on neurodegenerative and neurological disorders is still limited. Methods: We investigated associations of COVID-19 with neurodegenerative and neurological disorders by vaccination status in both hospitalised patients and the general population in the largest and longest study to date. We used OpenSAFELY-TPP to access linked electronic health records from 18.3 million adults registered with English GPs. We defined three cohorts with up to 5.5 years follow-up: pre-vaccination (exposed to COVID-19 January 2020-June 2021), and vaccinated and unvaccinated (exposed June-December 2021). We estimated adjusted hazard ratios (aHRs) comparing the incidence of cognitive impairment and dementia after diagnosis of COVID-19 with before or without COVID-19. We also studied Parkinson's disease, restless leg syndrome, rapid eye movement sleep disorder, motor neuron disease, multiple sclerosis, and migraine. Results: Incidence of most outcomes was elevated during weeks 0-4 after COVID-19 (cognitive impairment/dementia aHRs; pre-vaccination: 4.02 (3.74-4.32)/5.05 (4.63-5.52), vaccinated: 2.24 (2.05-2.45)/2.05 (1.77-2.37), unvaccinated: 4.38 (3.45-5.55)/8.69 (6.13-12.32)). Incidence remained elevated up to 4 years after COVID-19, especially in those hospitalised with COVID-19 (cognitive impairment/dementia aHRs; pre-vaccination: 1.49 (1.35-1.64)/ 1.39 (1.21-1.60), vaccinated: 1.27 (1.04-1.54)/1.32 (1.02-1.71), unvaccinated: 1.55 (1.11-2.16)/1.48 (1.00-2.20)). Conclusion: Incidence of cognitive impairment and dementia were elevated shortly after COVID-19. Incidence of cognitive impairment remained elevated in the longer term, particularly among unvaccinated individuals and/or those hospitalised with COVID-19. These patients may require additional assessment during routine care to evaluate persistent or new cognitive concerns.
Authors
- Amelia C. A. Green (ORCID: https://orcid.org/0000-0002-7246-2074)
- Elizabeth Jane Coulthard (ORCID: https://orcid.org/0000-0002-0017-9595)
- Rachel Denholm (ORCID: https://orcid.org/0000-0002-8067-5440)
- Harry Mason (ORCID: https://orcid.org/0000-0002-4906-8415)
- Jonathan A C Sterne (ORCID: https://orcid.org/0000-0001-8496-6053)
- Mengxuan Zou (ORCID: https://orcid.org/0000-0002-1713-6639)
- Simon Davy (ORCID: https://orcid.org/0000-0001-9890-3619)
- Emily Eyles (ORCID: https://orcid.org/0000-0002-2695-7172)
- Seb Bacon (ORCID: https://orcid.org/0000-0002-6354-3454)
- Amir Mehrkar (ORCID: https://orcid.org/0000-0002-2098-1278)
- Alex J Walker (ORCID: https://orcid.org/0000-0003-4932-6135)
- Louis Fisher (ORCID: https://orcid.org/0000-0002-0295-3812)
- Yinghui Wei (ORCID: https://orcid.org/0000-0002-7873-0009)
- Paul Madley‐Dowd (ORCID: https://orcid.org/0000-0003-2932-9486)
- Ben M. Goldacre (ORCID: https://orcid.org/0000-0002-5127-4728)
- Venexia M. Walker (ORCID: https://orcid.org/0000-0001-5064-446X)
- Tom Palmer (ORCID: https://orcid.org/0000-0003-4655-4511)
- Marwa Al Arab (ORCID: https://orcid.org/0000-0001-7514-1551)
- Genevieve Isabelle Cezard (ORCID: https://orcid.org/0000-0002-3011-7416)
- Nish Chaturvedi (ORCID: https://orcid.org/0000-0002-6211-2775)
- Jose Ignacio Cuitun Coronado
Institutions
- University of Leeds (GB)
- University of Exeter (GB)
- University of Cambridge (GB)
- University of Bristol (GB)
- University of Oxford (GB)
- University College London (GB)
Publication Details
- Journal
- medRxiv
- Published
- 2026-11-01
- DOI
- https://doi.org/10.64898/2026.10.30.26366919
- Primary Topic
- Long-Term Effects of COVID-19
- Type
- preprint
Funders
- Wellcome Trust
- Health and Care Research Wales
- UK Research and Innovation
- Cancer Research UK
- National Institute for Health and Care Research
- British Heart Foundation
- Department of Health and Social Care
- University of Bristol
- Public Health Agency
- Chief Scientist Office, Scottish Government Health and Social Care Directorate
- Medical Research Council
- Engineering and Physical Sciences Research Council
- Economic and Social Research Council
- Health and Social Care Research and Development Division
- NIHR Oxford Biomedical Research Centre
- NIHR Cambridge Biomedical Research Centre
- National Institute for Health and Care Research Applied Research Collaboration Oxford and Thames Valley
- Health Data Research UK