Increased Risk for Neurodegenerative, Cerebrovascular Disorders Post COVID-19 Infection, Similar to Other Infections


Among a large cohort of outpatient and inpatient individuals, the risk of Alzheimer disease, Parkinson disease, ischemic stroke, and intracerebral hemorrhage were all elevated after infection, with stroke risk increased compared with other respiratory infections.

Pardis Zarifkar, MD, neurologist, Rigshospitelet, Copenhagen University Hospital

Pardis Zarifkar, MD

Among outpatient individuals who were COVID-19 positive, the risk of neurodegenerative and cerebrovascular disorders was increased compared with those who were COVID-19 negative, though the majority were not more frequent than after other respiratory infections, with the one standout being ischemic stroke. The risk of neuroimmune disorders was not increased for this population.1

Among a total cohort of 35,362 outpatients in Denmark who tested positive between February 2020 and November 2021, the relative risk (RR) was increased for Alzheimer disease (RR, 3.5; 95% CI, 2.2-5.5) and Parkinson disease (RR, 2.6; 95% CI, 1.7-4.0), ischemic stroke (RR, 2.7; 95% CI, 2.3-3.2), and intracerebral hemorrhage (RR, 4.8; 95% CI, 1.8-12.9). Among 8013 COVID-19 positive inpatients, the risk of ischemic stroke was increased compared with inpatients with influenza (RR, 1.7; 95% CI, 1.2-2.4) and bacterial pneumonia (RR, 2.7; 95% CI, 1.2-6.2). Notably, the latter group consisted of only individuals aged 80 years and older.

The results were presented at the European Academy of Neurology (EAN) Congress, June 25-28, 2022, in Vienna, Austria, by Pardis Zarifkar, MD, neurologist, Rigshospitelet, Copenhagen University Hospital. Zarifkar and colleagues noted that importantly, the frequencies of multiple sclerosis, myasthenia gravis, Guillain-Barré syndrome, and narcolepsy all showed no differences post COVID-19, influenza, and bacterial pneumonia. “Neurological symptoms, including headache and anosmia, are well-described and present in more than 80% of hospitalized COVID-19 patients. To our knowledge, however, epidemiologic studies investigating the incidence of specific neurodegenerative diseases such as Alzheimer disease and Parkinson disease or autoimmune disorders (eg, multiple sclerosis, narcolepsy, and myasthenia gravis) after COVID-19 are still missing,” she and colleagues wrote.

“We found support for an increased risk of neurodegenerative disorders and of cerebrovascular disorders in COVID-19 patients, compared to individuals tested negative for COVID-19. While the risk of ischemic stroke was increased with COVID-19 compared to influenza, reassuringly, most neurological disorders do not appear to occur more frequently after COVID-19 than after other common respiratory tract infections,” Zarifkar and colleagues noted.

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The population-based cohort was utilized via electronic health records that included about 50% of Denmark’s population, totaling 2,972,192 individuals. Those tested for COVID-10 or diagnosed with community-acquired bacterial pneumonia in hospital-based facilities were included, as well as those who tested for influenza in the corresponding prepandemic period (February 2018 to November 2019). Patients were then stratified to cohorts for in- and outpatient status, age, sex, and comorbidities.

The literature on the impact of COVID-19 and its relationship to neurologic disorders, both the increase of risk and its effect on individuals with these disorders, is continuing to grow. Recently, in one of the first studies of its kind, investigators found a very high prevalence of moderate-to-severe sleep disturbances in individuals who had post-acute sequelae (PASC) of COVID-19, including 3-fold higher odds for Black individuals. The study, presented at the 2022 SLEEP Annual Meeting, June 4-8, in Charlotte, North Carolina, also identified several predictors of these disturbances such as obesity and mood symptoms.2

Also, at the 2022 American Headache Society (AHS) Annual Scientific Meeting, June 9-11, in Denver, Colorado, data from Brian LaGrant, MD, et al suggest that the changes in schooling during the COVID-19 pandemic may have affected how children and adolescents who attended outpatient visits for new headache at the Children’s Hospital of Philadelphia (CHOP) coped with headaches. LaGrant et al showed that of all the variables assessed, headache frequency had the most pronounced effect on Pediatric Migraine Disability Assessment (PedMIDAS) scores.3

Similarly, a recent PMD Alliance survey presented in a poster at the 2022 Advanced Therapeutics in Movement and Related Disorders (ATMRD) Congress in Washington, DC, June 17-19, suggest that the pandemic resulted in a decline in social support for patients with Parkinson disease (PD). The data show that this decline, in turn, was negatively associated with a statistically significant burden of nonmotor symptoms of PD, such as those of mood and neuropsychiatric origin.4

1. Zarifkar P, Peinkhofer C, Benros ME, Kondziella D. Frequency of neurological diseases after COVID 19, influenza A/B and bacterial pneumonia. Presented at: EAN Congress; June 25-28, 2022; Veinna, Austria.
2. 1. Pena Orbea C, Lapin B, Katzan I, Englund K, Folvary-Schaefer N, Mehra R. Sleep disturbances in post-acute sequelae of COVID-19 (PASC). Presented at: SLEEP Annual Meeting, 2022; June 4-8; Charlotte, NC. Abstract 0735.
3. Lagrant B, Hershey AD, Szperka C. Headache disability in children and adolescents before and during the COVID-19 pandemic. Presented at: AHS Annual Scientific Meeting; June 9-11, 2022; Denver, CO. Front-02.
4. Hermanowicz N, Ospina MC, Torres-Yaghi Y, et al. Impact of isolation during the COVID-19 pandemic on the patient burden of Parkinson disease: a PMD Alliance survey. Presented at: ATMRD Congress; June 17-19, 2022; Washington, DC.
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