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

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.