Links between COVID-19 and Alzheimer’s Disease—What Do We Already Know?

Abstract

Alzheimer’s disease (AD) is a life-changing condition whose etiology is explained by several hypotheses. Recently, a new virus contributed to the evidence of viral involvement in AD: the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the COVID-19 coronavirus disease. AD was found to be one of the most common COVID-19 comorbidities, and it was found to increase mortality from this disease as well. Moreover, AD patients were observed to present with the distinct clinical features of COVID-19, with delirium being prevalent in this group. The SARS-CoV-2 virus enters host cells through the angiotensin-converting enzyme 2 (ACE2) receptor. ACE2 is overexpressed in brains with AD, which thus increases the viral invasion. Furthermore, the inhibition of the ACE2 receptor by the SARS-CoV-2 virus may also decrease the brain-derived neurotrophic factor (BDNF), contributing to neurodegeneration. The ApoE ε4 allele, which increases the risk of AD, was found to facilitate the SARS-CoV-2 entry into cells. Furthermore, the neuroinflammation and oxidative stress existing in AD patients enhance the inflammatory response associated with COVID-19. Moreover, pandemic and associated social distancing measures negatively affected the mental health, cognitive function, and neuro-psychiatric symptoms of AD patients. This review comprehensively covers the links between COVID-19 and Alzheimer’s disease, including clinical presentation, molecular mechanisms, and the effects of social distancing.

Investigating the structural network underlying brain-immune interactions using combined histopathology and neuroimaging: a critical review for its relevance in acute and long COVID-19

“…The most commonly applied technique is a T 1-weighted dynamic contrast-enhanced (DCE)-MRI, during which a gadolinium-based contrast agent is injected intravenously; leakage of the contrast agent can be detected when it crosses the damaged BBB (e.g., 70 , 71 ). It should be noted that there is substantial comorbidity between COVID-19 and AD ( 72 , 73 ) and the chronic neurological sequelae in Long COVID are also present in AD clinical phenomenology. Furthermore, there is evidence indicating APOE e4e4 genotype as a potential genetic determinant for the development of severe COVID-19 ( 74 ), and ApoE e4e4 homozygotes are more likely to be COVID-19 test positive ( 75 ).…”

“…Furthermore, there is evidence indicating APOE e4e4 genotype as a potential genetic determinant for the development of severe COVID-19 ( 74 ), and ApoE e4e4 homozygotes are more likely to be COVID-19 test positive ( 75 ). Furthermore, ApoE e4e4 homozygotes were found to be at the highest risk of sporadic AD ( 73 , 76 ). However, the mechanism underlying this association remains unclear ( 74 ).…”

COVID-19 and Alzheimer’s disease: Impact of lockdown and other restrictive measures during the COVID-19 pandemic

“…Social connectivity/family bonding, as a means of overcoming loneliness, is one of the most important social measures that can delay the progression of dementia in patients with Alzheimer’s disease [ 87 , 88 ] and thereby social connectedness and healthy relationships are protective factors for patients with Alzheimer’s disease [ 89–91 ]. The Harvard adult study, the longest longitudinal study on human life that followed 268 Harvard sophomores for a period of 80 years to understand what the key factors that lead to a longer and healthier life, reported that one of the most powerful indicators of good health and happiness is strong, trustworthy and satisfied relationships.…”

Infection with COVID‐19 is no longer a public emergency: But what about degenerative dementia?

“…Despite the aforementioned variations in design and demographics observed in COVID cognition studies, however, there is a growing body of evidence indicating that individuals who have recovered from COVID-19 may be susceptible to the development of mild cognitive impairment and degenerative dementia. [10][11][12] Additionally, there is strong evidence suggesting the presence of certain neuropsychiatric symptoms such as depression and anxiety after COVID-19 infection. 2,13,14 Here, it is noteworthy to remember that the presence of comorbid preexisting conditions, along with strict pandemic restrictions that have significant neuropsychiatric consequences, can mutually reinforce one another in a vicious cycle, ultimately impairing cognition and consequently elevating one's risk to degenerative dementia.…”

“…However, as mentioned above, these studies failed to shed light on how specific cognitive regions relate to the cognitive functions. Despite the aforementioned variations in design and demographics observed in COVID cognition studies, however, there is a growing body of evidence indicating that individuals who have recovered from COVID‐19 may be susceptible to the development of mild cognitive impairment and degenerative dementia 10–12 . Additionally, there is strong evidence suggesting the presence of certain neuropsychiatric symptoms such as depression and anxiety after COVID‐19 infection 2,13,14 .…”