Alzheimer’s disease in elderly COVID-19 patients: potential mechanisms and preventive measures

Abstract

Advanced age correlates with higher morbidity and mortality among patients affected with the novel coronavirus disease 2019 (COVID-19). Because systemic inflammation and neurological symptoms are also common in severe COVID-19 cases, there is concern that COVID-19 may lead to neurodegenerative conditions such as Alzheimer’s disease (AD). In this review, we summarize possible mechanisms by which infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, may cause AD in elderly COVID-19 patients and describe preventive measures to mitigate risk. Potential mechanisms include NLRP3 inflammasome activation and IL-1β release, renin-angiotensin system hyperactivation, innate immune activation, oxidative stress, direct viral infection, and direct cytolytic β-cell damage. Anti-inflammatory therapies, including TNF-α inhibitors and nonsteroidal anti-inflammatory drugs, antioxidants such as the vitamin E family, nutritional intervention, physical activity, blood glucose control, and vaccination are proposed as preventive measures to minimize AD risk in COVID-19 patients. Since several risk factors for AD may converge during severe SARS-CoV-2 infection, neurologists should be alert for potential symptoms of AD and actively implement preventive measures in patients presenting with neuropsychiatric symptoms and in high-risk patients such as the elderly.

SARS-CoV-2-Induced Amyloidgenesis: Not One, but Three Hypotheses for Cerebral COVID-19 Outcomes

“…There are also data suggesting that SARS-CoV-2 activates NLR family pyrin domain-containing 3 (NLRP3) [34], which could increase APP processing [35,36] and negatively modulate Aβ clearance [37,38]. Therefore, based on this collection of information, we can say that SARS-CoV-2 may worsen the conditions of individuals affected by AD and/or CAA [39,40] without ceasing to think that the virus itself could trigger the process in many individuals.…”

COVID-19 and the central nervous system: What is the interplay?

“…In AD and COVID-19 patients, it is proposed that the induced NLRP3 activates the pro-inflammatory mediator IL-1β, which in turn triggers a cytokine storm as an innate immunity response. In general, the activation of innate immunity and the induction of some pro-inflammatory mediators, such as IL-6, IL-8, IL-1β, TNF-α and chemokines, have been reported in both disorders (Wang et al, 2021). The induced pro-inflammatory mediators trigger neuroinflammation; hence, a possible neuronal death is suggested (Figure 2).…”

AD-CovNet: An exploratory analysis using a hybrid deep learning model to handle data imbalance, predict fatality, and risk factors in Alzheimer's patients with COVID-19

“…Transsynaptic transfer via olfactory nerve or expression of angiotensin-converting enzyme 2 (ACE2) receptor in the vascular endothelium of the blood-brain-barrier (BBB) could be the route of viral entry into the brain [ 10 ]. Several pathophysiological changes induced by SARS-CoV-2 can aggravate neurodegeneration in AD patients, increasing the risk of having high viral load and fatality risk [ 11 ]. However, theoretical postulations are drawn from empirical data seldom resonate with the complexity of natural biological systems.…”