COVID-19 and Alzheimer’s disease: how one crisis worsens the other

Abstract

Alzheimer’s disease (AD) has emerged as a key comorbidity of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The morbidity and mortality of COVID-19 are elevated in AD due to multiple pathological changes in AD patients such as the excessive expression of viral receptor angiotensin converting enzyme 2 and pro-inflammatory molecules, various AD complications including diabetes, lifestyle alterations in AD, and drug-drug interactions. Meanwhile, COVID-19 has also been reported to cause various neurologic symptoms including cognitive impairment that may ultimately result in AD, probably through the invasion of SARS-CoV-2 into the central nervous system, COVID-19-induced inflammation, long-term hospitalization and delirium, and post-COVID-19 syndrome. In addition, the COVID-19 crisis also worsens behavioral symptoms in uninfected AD patients and poses new challenges for AD prevention. In this review, we first introduce the symptoms and pathogenesis of COVID-19 and AD. Next, we provide a comprehensive discussion on the aggravating effects of AD on COVID-19 and the underlying mechanisms from molecular to social levels. We also highlight the influence of COVID-19 on cognitive function, and propose possible routes of viral invasion into the brain and potential mechanisms underlying the COVID-19-induced cognitive impairment. Last, we summarize the negative impacts of COVID-19 pandemic on uninfected AD patients and dementia prevention.

Post-COVID Syndrome: An Insight on Its Pathogenesis

“…and cerebrovascular disorders, such as ischemic stroke, cerebral vasculitis and hemorrhage [44][45][46][47][48][49], and irreversible hearing loss [11], however, these severe conditions are rare [47]. Several psychiatric and neurologic conditions that are observed in post-COVID syndrome may also be linked with Alzheimer's disease [50]. These include post-traumatic stress disorder, Guillain-Barré syndrome, depression, and cognitive impairment [50].…”

“…Several psychiatric and neurologic conditions that are observed in post-COVID syndrome may also be linked with Alzheimer's disease [50]. These include post-traumatic stress disorder, Guillain-Barré syndrome, depression, and cognitive impairment [50]. The worsening of motor function (51.9%) and an increased levodopa daily dose requirement (48.2%), followed by fatigue (40.7%) and cognitive and sleep disturbances (22.2% each), were present in 23 (85.2%) of 27 patients with Parkinson's disease and COVID-19, who developed post-COVID syndrome [51].…”

Biomarkers of ageing and frailty may predict COVID-19 severity

“…Hypertension is a risk factor for neurodegeneration and a common comorbidity of Alzheimer’s disease ( Kim et al, 2017 ). In the elderly, cognitive impairment (e.g., Alzheimer’s disease) appears to be one of the most common comorbidities that negatively impacts COVID-19 prognosis ( Martins et al, 2019 , Wu et al, 2020 , Xia et al, 2021 ). Alzheimer’s patients often have increased levels of inflammatory cytokines such as IL-6, which as discussed above is elevated in COVID-19 patients with hyperinflammation ( Kim et al, 2017 ) and may serve as a clinical marker of reduced disease tolerance ( Chan et al, 2021 ).…”

Can SARS-CoV-2 Infection Lead to Neurodegeneration and Parkinson’s Disease?

“…GABAergic impairments are usually common in frontotemporal dementia and executive dysfunction [ 120 , 121 ]. However, it has to be noted that cognitive impairment is a common problem after suffering from acute respiratory distress syndrome (ARDS), which can have multiple reasons other than COVID-19 [ 116 , 122 , 123 , 124 ]. After ARDS, cognitive disturbances persisted in long-term follow-ups in about 10% of cases [ 116 , 122 ].…”