The World Health Organization has declared the COVID-19 outbreak a pandemic. The causative agent for COVID-19 is an RNA virus of the Coronaviridae family. In addition to the respiratory and other complications, a significant proportion of COVID-19 patients show neurological manifestations. Dementia is a neurocognitive disorder, the prevalence of which is projected to increase in the coming decades. This review provides an overview of the effects of COVID-19 on dementia patients. Keywords Coronavirus, severe acute respiratory syndrome coronavirus 2, COVID-19, SARS-CoV-2, dementia Received 5 December 2020; accepted 23 February 2021 This virus has generated enormous interest in the general Introduction public, clinicians, as well as basic science investigators. Researchers are trying to understand the biology of the virus The world is reeling with coronavirus disease-2019 (COVID- as well as develop newer diagnostic tools and potential 19). The causative agent for this disease is the severe acute therapeutic measures. Major efforts are directed toward the respiratory syndrome coronavirus 2 (SARS-CoV-2). It started development of vaccines against the virus. The scientific with an outbreak of pneumonia of unknown etiology in interest in the virus is evident from the fact that a PubMed Wuhan, Hubei Province of China, in December 2019. The search with the keyword “COVID-19” results in more than coronavirus outbreak has turned into a pandemic. So far, this 133 thousand articles. In addition to respiratory complications, virus has infected more than 161 million individuals and neurological symptoms have also been observed in a caused more than 3.3 million deaths across different countries significant proportion of individuals infected with the virus. (see https://coronavirus.jhu.edu/map.html). The COVID-19 The dementia patients appear to be adversely affected by pandemic has burdened the healthcare system. It has COVID-19. This review provides an overview of the effects negatively affected the world economy also. of COVID-19 on dementia patients, and the potential effects SARS-CoV-2 is a positive-strand RNA virus and is a of COVID-19 on the development of neurodegenerative highly infectious agent requiring unprecedented measures to diseases including dementia. reduce transmission. It is primarily transmitted by sneezing and coughing. Measures including physical distancing, wearing of face masks, and hand hygiene are important to limit the spread of the virus in the population. The virus can cause a wide range of symptoms including fever, sore throat, dry cough, shortness of breath, and diarrhea. A large portion of infected individuals remain asymptomatic, while others National Brain Research Centre, Manesar, Haryana, India show mild, moderate, or severe symptoms. Higher mortality has been observed in patients with comorbid conditions including hypertension, diabetes, and cancer. Determination Corresponding author: of the genetic sequence has allowed the development of Shiv K. Sharma, National Brain Research Centre, Manesar 122052, diagnostic tests utilizing reverse-transcriptase polymerase Haryana, India. E-mails: email@example.com; firstname.lastname@example.org chain reaction to detect the virus in the infected individuals. Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution- NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-Commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https:// us.sagepub.com/en-us/nam/open-access-at-sage). 2 Annals of Neurosciences neuropsychiatric changes. These patients also showed a worse performance on mini-mental state examination in The entry of SARS-CoV-2 in the cells is mediated by a comparison to the patients who did not show neuropsychiatric glycoprotein, the spike protein, that protrudes out of the virus changes. In retirement homes in France, the AD patients envelop. The S1 subunit of the spike protein binds to the showed a higher level of depression and anxiety during the receptor on the host cell, and the S2 subunit helps in the virus crisis than before. These effects could be due to fusion of the virus with the cell membrane. The virus uses restrictions imposed including physical distancing to reduce angiotensin-converting enzyme-2 (ACE-2) as a receptor to the spread of the virus in society. An increase in the anxiety enter the cells. Studies have examined the expression of level in dementia patients has also been observed by Cohen ACE-2 in different organs. Li and colleagues analyzed the and colleagues. Further, worsening of behavioral symptoms datasets from The Cancer Genome Atlas program and the in dementia patients was observed after 8 weeks of quarantine Genotype-Tissue Expression project and found expression of 15 period. During the pandemic situation, the caregivers of ACE-2 in several organs including the brain. The presence of dementia patients are also facing difficulties in providing the SARS-CoV-2 in the brain has not been conclusively required care. Cagnin and colleagues found that one month established. While some studies did not find evidence of the from the declaration of quarantine in Italy, more than 60% of 5,6 virus, other studies have detected it in the cerebrospinal caregivers of dementia patients reported stress-related 7,8 fluid of COVID-19 patients. It is unclear how the virus may symptoms. Further, the stress level of caregivers of dementia reach the brain. Many patients show cytokine “storm” which patients was found to be increased after 4 weeks of may compromise the blood brain barrier and facilitate the lockdown. Thus, being confined due to the virus crisis "virus" entry into the brain. Olfactory pathway may be increases neuropsychiatric symptoms in dementia patients, involved in virus entry to the brain and the hypothalamus and increases the stress levels in the caregivers. could also serve as an entry route. As mentioned earlier, ACE-2 serves as the receptor for Dementia is a progressive decline in cognitive abilities SARS-CoV-2 for entry into the cells. An increase in ACE-2 which interferes with daily activities. Dementia is devastating 16,17 expression has been observed in the AD patient brain with respect to not only the affected person but also the raising the possibility that AD patients may be more caregivers. The prevalence of dementia cases is projected to susceptible to developing severe COVID-19 symptoms. increase in the coming years, which is likely to put tremendous People with dementia are likely to have comorbid conditions burden on the healthcare system and society. Alzheimer’s and thus may develop a more severe form of COVID-19. In disease (AD) accounts for majority of the cases. Other fact, dementia has been suggested to be a risk factor for dementia conditions include vascular dementia, hospitalization in COVID-19 patients. Further, dementia, frontotemporal dementia (FTD), and Lewy body dementia. especially in the late stage, increases mortality risk in these Pulmonary complications are well recognized in COVID- patients. 19 patients. In addition, impairment of the sense of smell and Apolipoprotein E (ApoE) plays an important role in lipid taste has also been widely reported in these patients. It has metabolism and other processes. ApoE4 allele is an been reported that about 30% of COVID-19 patients requiring established risk factor for the development of AD. In a hospitalization develop neurological manifestations including Biobank community cohort in the UK, it was observed that dizziness, impairment in consciousness, seizure, stroke, the ApoE e4e4 allele increases the risk for severe COVID- olfactory and gustatory dysfunctions, encephalitis, and 3,9 19. Furthermore, the ApoE e4e4 allele is associated with headache. In addition to the acute effects, it is important to higher mortality in COVID-19 patients. Although these understand the potential long-term consequences of COVID- studies need to be extended to a larger population, they raise 19 on neurological functions. the possibility that AD patients may be more susceptible to Several studies have examined the effects of COVID-19 on dementia patients. A study by Cagnin and colleagues adverse effects of SARS-CoV-2. evaluated the effects of quarantine on behavioral and other In a study conducted to examine postdischarge symptoms, parameters in dementia patients in Italy. It was found that one a significant number of survivors reported impairment in month from the declaration of quarantine, AD patients memory about 100 days after hospitalization. The severely showed more anxiety and depression. Worsening of affected COVID-19 patients show higher levels of cytokines. hallucination and sleep disorder were associated with Considering that systemic inflammation could contribute to dementia with Lewy body, and wondering and change in the development of neurodegenerative diseases, the COVID- appetite were associated with FTD. In addition, during the 19 survivors may be at higher risk for developing these lockdown period in Spain, the neuropsychiatric symptoms conditions. Evidence of neuronal injury has been found in such as apathy and anxiety worsened in AD patients and in severe COVID-19 cases, and activation of glial cells has been individuals with mild cognitive impairment. Another study 25 found in moderate and severe COVID-19 patients. Autopsy found that about 26% of AD patients who were confined to studies have shown neuronal loss in brain areas including their homes for about two months demonstrated 26 hippocampus in the these patients. Sharma 3 In this pandemic situation, dementia patients need special Ethical Statement attention as they may not be able to properly follow the No experiments were conducted by the author for this review article. preventive measures that help reduce the chances of infection, Hence, ethical approval was not required. such as hand hygiene, wearing a face mask while in public places, and maintaining physical distancing. Some dementia ORCID ID patients do not use the facial mask properly or they even Shiv K. 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Annals of Neurosciences – SAGE
Published: Jan 1, 2021