COVID-19 and dementia: Are scientists concerned?
Written by
Katharine Lang on February 25, 2022 — Fact checked by Harriet Pike, Ph.D.
For most, COVID-19 causes a few days of mild to moderate symptoms, but others feel the effects for months. Some of these effects are neurological, leading scientists to ask whether COVID-19 could increase the risk of dementia. Medical News Today looked at the evidence and spoke with experts to find out the latest views.
- Does COVID increase dementia risk? Here is what the experts think.
Since the start of the COVID-19 pandemic, more than
425 million SARS-CoV-2 infections have been confirmed worldwide. Globally, almost
6 million people have died from, or with, the infection.
For most, when SARS-CoV-2 infection leads to COVID-19, the symptoms are mild to moderate. But for some, symptoms of the illness are prolonged.
Experts have described this issue,
long COVID, as “not recovering [for] several weeks or months following the start of symptoms that were suggestive of COVID, whether you were tested or not.”
Symptoms of long COVID vary, but some are common COVID-19 symptoms, such as
fatigue, shortness of breath, a cough, and joint pain.
Other respiratory virus infections have been associated with neurological and psychiatric after-effects. The authors of
one review observe that “Numerous respiratory viruses can infect the cells of the peripheral and central nervous systems, elicit inflammatory cascades, and directly and indirectly cause various neurologic manifestations.”
And it seems that COVID-19 is no exception, with many people
reporting neurological symptoms after SARS-CoV-2 infections. These symptoms may include:
- brain fog, a reduced ability to think clearly
- anxiety
- difficulties with memory and concentration
- difficulty sleeping
- changes in mood
Experts are now investigating how COVID-19 might affect
neurocognitive function and whether it may increase dementia risk.
COVID-19 and the nervous system
SARS-CoV-2 usually gains access to the body via droplets that enter the nose or mouth. From there, the virus moves to the throat. It can then travel to the lungs and other organs, and,
various studies suggest, may enter the nervous system.
- The blood-brain barrier stops most viruses from entering the brain. So some studies have investigated whether the neurological effects of COVID-19 stem from either a viral invasion of the central nervous system or the systemic effects of the infection.
One review suggests that both may occur in parallel. In severe infections, oxygen deprivation and a
cytokine storm
may damage the blood-brain barrier and allow SARS-CoV-2 to enter the brain.
- Another review backs this up, suggesting that SARS-CoV-2 may disrupt the blood-brain barrier or infect the peripheral neurons, then enter the central nervous system.
Prof. Harris Gelbard, director of the Center for Neurotherapeutics Discovery at the University of Rochester Medical Center, told
Medical News Today:
- “A recent cerebrospinal fluid study suggests that patients with COVID-19 infection have blood-cerebrospinal fluid barrier dysfunction, with pathology occurring in endothelial cells that line blood vessels in the blood-brain barrier. While this study did not demonstrate evidence for the presence of SARS-CoV-2 in any of the cerebrospinal fluid samples, all patients in this study had PCR-proven COVID-19.”
Evidence is growing that COVID-19 can cause neurological damage. One
2020 review observed that “COVID-19 is also anticipated to take a toll on the nervous system in the long term.”
Another Source asserts that “Respiratory virus
neurotropism and collateral injury due to concurrent inflammatory cascades result in various neurologic pathologies, including
Guillain-Barré syndrome,
encephalopathy,
encephalitis,
ischemic stroke,
intracerebral hemorrhage, and
seizures.”
ACE2 receptors
Some research has suggested that SARS-CoV-2 might invade the nervous system in the same way that it invades other cells, via
agiotensin-converting enzyme 2 (ACE2) receptors.
However, only
certain cells in the nervous system have these receptors. Among them are excitatory and inhibitory neurons and other types of cells, such as
astrocytes,
oligodendrocytes, and endothelial cells.
- One review points out that ACE2 receptors are expressed in small blood vessels in the brain, which could provide a potential entry route for SARS-CoV-2 into the brain.
Prof. Gelbard emphasized that the
evidence so far of how SARS-CoV-2 might enter the central nervous system is not conclusive: “The pathologic evidence for direct infection of neural cell types, particularly neurons, remain equivocal at best. Despite survey studies of neuronal expression of ACE2 receptors from brain transcriptome databases, […] the correlative neuropathology from postmortem human cases is scant.”
Whether or not the virus invades the central nervous system, it is clear that SARS-CoV-2 infection can lead to
cognitive dysfunction that may last for months or even years after the acute phase of COVID-19.
Inflammation
Many people who are hospitalized with COVID-19 have inflammatory complications, which can affect the nervous system.
One study has reported that these patients experience delirium, reduced consciousness, stroke, and other
encephalopathiesTrusted Source following SARS-CoV-2 infection.
In this study, the researchers found that the degree of
inflammation was correlated with the severity of COVID-19 symptoms and an increase in pro-inflammatory cytokines.
Prof. Gelbard, who was not involved in this study, explains how experts interpret the findings:
“Our collective view of this is that SARS-CoV-2 infection/COVID-19 impacts elderly patients with underlying neurovascular disease, whether it is from cerebrovascular disease, subclinical Alzheimer’s disease, Parkinson’s disease or other neurodegenerative disease, by creating a pro-inflammatory central nervous system milieu that is permissive for cognitive impairment, either manifesting as acute delirium or delirium superimposed on dementia.”
Dementia and COVID-19
Studies have shown that people with dementia have increased morbidity and mortality from COVID-19. Many have
comorbidities associated with poor COVID-19 outcome, such as cardiovascular disease, diabetes,
hypertension, and
obesity.
Dr. Heather Snyder, Alzheimer’s Association’s vice president of medical and scientific relations, told
MNT:
- “The factors causing or contributing to dementia, including hypertension and diabetes, may be what make individuals with dementia more vulnerable to contracting COVID-19. […] Research published in February 2021 in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association found that risk of contracting COVID-19 was twice as high for people living with dementia than those without it.”
People with dementia are more at risk of COVID-19 — but might the disease worsen existing dementia or cause the development of dementia?
It may be that for people with dementia, SARS-CoV-2 can more easily enter the brain, as the blood-brain barrier
is damaged. This might explain worsening symptoms
reported in people with dementia after COVID-19.
- One study states: “There is evidence for a bidirectional relationship between viral infections and dementia: People with dementia have an increased risk for infection, while a poor immune response to infection places individuals at increased risk for dementia.”
Another risk of COVID-19, and particularly severe forms of this disease,
is thrombosis, a cause of
strokes. According to one large study, a stroke can
double the risk of developing dementia.
Mitigating the risks
People with severe COVID-19 are more likely to have neurological symptoms of the illness, both during its acute phase and afterwards. And severe COVID-19 is
more common in those who are older or have comorbidities, such as overweight or obesity, diabetes, chronic lung disease, and cancers.
Studies suggest that the best way to avoid neurological effects of COVID-19 is to optimize brain and body health in these ways:
- being physically active
- doing cognitively stimulating activities
- sleeping for 7 to 8 hours every night
- having a balanced diet with all the essential vitamins and minerals
- having regular social interactions.
Drug treatments to combat inflammation are also an option. Prof. Gelbard, who is now working on developing such a treatment, commented, “What is sorely needed is an appropriate anti-neuroinflammatory intervention with a brain-penetrant therapy that can mitigate this type of neuroinflammatory response.”
And, as
several experts have noted, vaccination against COVID-19 is one of the most effective ways of minimizing the risk of both severe COVID and long COVID, a view Dr. Snyder reiterated:
“While we work to further understand the lasting impacts of COVID-19 on the brain, the take-home message for protecting your cognition is simple: Don’t get COVID-19. The best way to not get COVID-19 is to get vaccinated.”
No clear answer
As yet, it is unclear whether COVID-19 may be a risk factor for dementia.
Dr. Snyder told
MNT that “The ongoing COVID-19 pandemic gives us an unwelcome opportunity to study the impact of viral infection on the brain in the short and long term.”
She added: “Potential viral contributions to Alzheimer’s and dementia have been long debated within the research community. However, no research to date has shown definitively that a virus can cause Alzheimer’s disease. Because COVID-19 is still relatively new, we won’t know if infection will have an impact on dementia risk for some time.”
Prof. Gelbard concurred: “Unfortunately, we believe this is the tip of the iceberg. Not to sound like an alarmist, but we echo the sentiments of public health experts: We may feel like we are done with COVID-19, but the virus is not done with us. We expect the aftershocks of this pandemic to continue amplifying the challenge of dealing with neurodegenerative disease in the elderly and immunocompromised.”
- “If you have had COVID-19, it doesn’t mean you’re going to get dementia. We’re still trying to understand this relationship.” – Dr. Heather Snyder
While researchers have yet to arrive at conclusive evidence, it appears that the neurological and psychiatric effects of COVID-19 are likely to be with us for many years to come.
References
- The neuroinvasive potential of SARS‐CoV2 may be at least partially responsible for the respiratory failure of COVID‐19 patients. Li, Y. et al. (2020), J. Med. Virol. jmv.25728.
- Insights into RNA synthesis, capping, and proofreading mechanisms of SARS-coronavirus. Sevajol, M. et al. (2014), Virus Res. 194, 90–99.
- COVID-19: what has been learned and to be learned about the novel coronavirus disease. Yi, Y. et al. (2020), Int. J. Biol. Sci. 16, 1753–1766.
- Virus-induced neuronal dysfunction and degeneration. Berth, S. H. et al. (2009), Front. Biosci. 14, 5239.
- Novel coronavirus and central nervous system. Sun, T. et al. (2020), Eur. J. Neurol.
- Activation of human monocytes after infection by human coronavirus 229E. Desforges, M. et al. (2007), Virus Res. 130, 228–240.
- Human coronaviruses: Viral and cellular factors involved in neuroinvasiveness and neuropathogenesis. Desforges, M. et al. (2014), Virus Res. 194, 145–158.
- Neuroinfection may potentially contribute to pathophysiology and clinical manifestations of COVID-19. Steardo, L. et al. (2020), Steardo, L., Zorec, R. & Verkhratsky, A. Acta Physiol. e13473.
- Long-term cognitive impairment after acute respiratory distress syndrome: a review of clinical impact and pathophysiological mechanisms. Sasannejad, C. et al. (2019), Crit. Care 23, 352.
- Coronavirus infection of rat dorsal root ganglia: Ultrastructural characterization of viral replication, transfer, and the early response of satellite cells. Li, Y.-C. et al (2012), Virus Res. 163, 628–635.
- Severe Acute Respiratory Syndrome Coronavirus Infection Causes Neuronal Death in the Absence of Encephalitis in Mice Transgenic for Human ACE2. Netland, J. et al. (2008), J. Virol. 82, 7264–7275.
- Lethal Infection of K18-hACE2 Mice Infected with Severe Acute Respiratory Syndrome Coronavirus. McCray, P. B. et al. (2007), J. Virol. 81, 813–821.
- Angiotensin II regulation of angiotensin-converting enzymes in spontaneously hypertensive rat primary astrocyte cultures. Gowrisankar, Y. V et al. (2016), J. Neurochem. 138, 74–85.
- Angiotensin-Converting Enzyme 2: Central Regulator for Cardiovascular Function. Xia, H. et al. (2010), Curr. Hypertens. Rep. 12, 170–175.
- The Vagus Nerve is One Route of Transneural Invasion for Intranasally Inoculated Influenza A Virus in Mice. Matsuda, K. et al. (2004), Vet. Pathol. 41, 101–107.
- Dementia care during COVID-19. Wang, H. et al. (2020), Lancet 395, 1190–1191.
- Anticipating and Mitigating the Impact of the COVID-19 Pandemic on Alzheimer’s Disease and Related Dementias. Brown, E. E. et al. (2020), Am. J. Geriatr. Psychiatry.
- Outcome of Parkinson’s Disease patients affected by <scp>COVID</scp> ‐19. Antonini, A. et al. (2020), Mov. Disord. mds.28104.
- Impact of the <scp>COVID</scp> ‐19 Pandemic on Parkinson’s Disease and Movement Disorders. Papa, S. M. et al. (2020), Mov. Disord. 35, 711–715.
- The Invisible Hand — Medical Care during the Pandemic. Kittleson, M. M. (2020), N. Engl. J. Med. 382, 1586–1587.
- Management of Advanced Therapies in Parkinson’s Disease Patients in Times of Humanitarian Crisis: The <scp>COVID</scp> ‐19 Experience. Fasano, A. et al. (2020), Mov. Disord. Clin. Pract. 7, 361–372.
- Parkinson’s Disease and <scp>COVID</scp> ‐19: Perceptions and Implications in Patients and Caregivers. Prasad, S. et al. (2020), Mov. Disord. mds.28088.
- The Neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia. Cummings, J. L. et al. (1994), Neurology 44, 2308–2308.
- Facetime to reduce behavioral problems in a nursing home resident with Alzheimer’s dementia during COVID-19. Padala, S. P. et al. (2020), Psychiatry Res. 288, 113028.
- The Promise of Telemedicine for Movement Disorders: an Interdisciplinary Approach. Ben-Pazi, H. et al. (2018), Curr. Neurol. Neurosci. Rep. 18, 26.
- COVID-19: An Early Review of Its Global Impact and Considerations for Parkinson’s Disease Patient Care. Bhidayasiri, R. et al. (2020), J. Mov. Disord. 13, 105–114.
- COVID-19 is catalyzing the adoption of teleneurology. Klein, B. C. et al. (2020), Neurology 94, 903–904.
- Interactive video conferencing: A means of providing interim care to parkinson’s disease patients. Hubble, J. P. et al. (1993), Mov. Disord. 8, 380–382.
- Remotely Assessing Symptoms of Parkinson’s Disease Using Videoconferencing: A Feasibility Study. Stillerova, T. et al. (2016), Neurol. Res. Int. 1–8.
- The Impact of the COVID-19 Pandemic on Parkinson’s Disease: Hidden Sorrows and Emerging Opportunities. Helmich, R. C. et al. (2020), J. Parkinsons. Dis. 10, 351–354.
wrbtrader
