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.