Could COVID-19 Increase the Risk for Alzheimer's Disease?
Studies show that SARS-CoV-2 enters the brain and may cause damage there.
Posted September 15, 2022 | Reviewed by Devon Frye
- The virus that causes COVID-19 can enter the brain directly and indirectly.
- Post-mortem brain studies show brain pathologies in patients with COVID-19.
- One MRI study shows brain shrinkage by up to 2 percent and cognitive decline in those with COVID-19.
- It's possible that COVID-19 may increase the risk of Alzheimer's disease, though more research is needed to be sure.
Alzheimer's disease (AD) is a brain disease that leads to a gradual decline in memory, thinking, and reasoning. It is a debilitating disorder that interferes with quality of life. The exact causes of AD are unknown, although some researchers have proposed a possible link between AD and infectious disease.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can access the brain by crossing the blood-brain barrier (BBB). This barrier protects the brain from invaders that may harm it. However, the virus has evolved clever ways to enter the BBB.
COVID-19 infection can cause an intense inflammatory reaction that increases the permeability of the BBB, allowing infected cells, cytokines, and viruses to pass into the brain. The virus can also get into the brain through the nasal cavity and rhino-pharynx through the olfactory and trigeminal nerves.1 It then spreads by hijacking the brain's normal mechanisms, such as endocytosis (getting into brain cells), exocytosis (exiting cells), and moving within neurons using its axonal transport system (the highway that transports proteins and important molecules along the brain cell).
COVID-19 and the Brain
Postmortem brain studies have revealed many micro- and macroscopic brain pathologies due to COVID-19.1 On a macroscopic level, the brains of people who got COVID-19 showed edema (swelling), hemorrhage (bleeding), hydrocephalus (abnormal build-up of fluid in the brain), atrophy (brain tissue death), low brain weight, encephalitis (inflammation in the brain), asymmetry in the olfactory bulb (smell area in the brain), and infarcts (small localized areas of dead tissue because of failure of blood supply).
Microscopically, swollen axons and loss of myelin, gliosis (pathologies in supporting cells in the brain), hypoxic-ischemic damage, mild or moderate arteriolosclerosis, leptomeningeal inflammation, microglial nodules, neuron loss, axon degeneration, diffuse or focal spongiosis, vascular congestion, and focal ischemic necrosis have been observed.
In addition, the U.K. Biobank project compared pre-infection brain scans with post-COVID-19-infection brain scans.2 The researchers matched the infected and the uninfected group on age, sex, blood pressure, obesity, smoking, socioeconomic status, and diabetes status. The study showed that even a mild infection was associated with brain shrinkage—specifically, the brain parts related to smell and memory. The overall brain size appeared to have shrunk between 0.2 and 2 percent. The study also showed that the infected group displayed lower cognitive scores.
Unsurprisingly, COVID-19 patients have reported many neurological symptoms. These neurological pathologies may manifest as headaches, dizziness, anosmia (loss of smell), ageusia (loss of taste), neuralgia (pain in nerves such as shooting/jabbing pain like an electric shock), mood disorders, anxiety, fatigue, memory loss, brain fog, tremors, numbness, and altered vision.
The Link Between Alzheimer's Disease and COVID-19
It's possible, therefore, that a bidirectional relationship exists between COVID-19 and AD. A study conducted on a Korean sample of nearly 200,000 people investigated the prevalence of COVID-19 in those with AD and those without AD.3
The prevalence of COVID-19 infection did not differ depending on the presence of AD. But AD was associated with an increased risk for severe COVID-19 complications and increased mortality. The authors point out that the apolipoprotein E4 allele is a common risk factor for both AD and COVID-19 susceptibility and fatality compared with other genotypes for this protein. Perhaps it is this shared genetic vulnerability that leads to both AD and severe COVID-19.
Another important question is whether COVID-19 might cause new-onset AD or accelerate its emergence. A research team analyzed the electronic health records of more than six million adults aged 65 years and older in the United States who received medical treatment between February 2020 and May 2021.4 Critically, they had no prior diagnosis of AD.
The team divided this population into two groups: people who contracted COVID-19 during that period and those with no documented cases of COVID-19. The findings were startling. The study showed that the risk for developing AD in older people nearly doubled (0.35 percent vs. 0.68 percent) over the year following the infection with COVID-19. The most vulnerable group with the highest risk were people over 85 and women. It is unclear from these results whether COVID-19 causes the new development of AD or accelerates its emergence, or whether something else is going on.
I argue that the results of these studies cannot be taken lightly. AD has a colossal economic and social cost. COVID-19 has affected millions of people who, according to these early studies, could be at risk for developing AD. Even individuals who don't develop AD might still suffer cognitive decline, as shown in the U.K. Biobank project study. Policymakers should work on devising prevention programs with these findings in mind.
1. Generoso, J. S. et al. (2020). Neurobiology of COVID-19: how can the virus affect the brain? Brazilian Journal of Psychiatry, 43(6); 650-664.
2. Douaud, G., Lee, S., Alfaro-Almagro, F. et al. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature 604, 697–707 (2022). https://doi.org/10.1038/s41586-022-04569-5
3. Chung, S. J. et al. (2022). Association of Alzheimer's Disease with COVID-19 Susceptibility and Severe Complications: A Nationwide Cohort Study. Journal of Alzheimer's Disease 87 (2): 701–710.
4. Wang, L. et al. (2022). Association of COVID-19 with New-Onset Alzheimer’s Disease. Journal of Alzheimer's Disease 89 (2): 411 – 414.