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

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection initially results in respiratory distress symptoms but can also lead to central nervous system (CNS) and neurological manifestations, significantly impacting coronavirus disease 2019 (COVID-19) patients with neurodegenerative diseases. Additionally, strict lockdown measures introduced to curtail the spread of COVID-19 have raised concerns over the wellbeing of patients with dementia and/or Alzheimer's disease. The aim of this review was to discuss the overlapping molecular pathologies and the potential bidirectional relationship between COVID-19 and Alzheimer's dementia, as well as the impact of lockdown/restriction measures on the neuropsychiatric symptoms (NPS) of patients with Alzheimer's dementia. Furthermore, we aimed to assess the impact of lockdown measures on the NPS of caregivers, exploring its potential effects on the quality and extent of care they provide to dementia patients.We utilized the PubMed and Google Scholar databases to search for articles on COVID-19, dementia, Alzheimer's disease, lockdown, and caregivers. Our review highlights that patients with Alzheimer's disease face an increased risk of COVID-19 infection and complications. Additionally, these patients are likely to experience greater cognitive decline. It appears that these issues are primarily caused by the SARS-CoV-2 infection and appear to be further exacerbated by restrictive/lockdown measures. Moreover, lockdown measures introduced during the pandemic have negatively impacted both the NPSs of caregivers and their perception of the wellbeing of their Alzheimer's patients. Thus, additional safeguard measures, along with pharmacological and non-pharmacological approaches, are needed to protect the wellbeing of dementia patients and their caregivers in light of this and possible future pandemics.

Figure 1.

Key molecular links between COVID-19 and Alzheimer’s disease pathology. The SARS-CoV-2 virus enters the human body through ACE2 receptors expressed in the lung, gut, brain, and potentially other organs [17, 54]. COVID-19 can also increase expression of ACE2 receptors which may further increase entry of more SARS-CoV-2 [101]. The entry of the virus in the lungs can result in a cytokine storm that gives rise to several pro-inflammatory processes [34]. The resulting cytokine storm and inflammation can lead to cerebrovascular dysfunction that can consequently cause hypoxia. Chronic hypoxia can accelerate hyperphosphorylation of tau protein, a hallmark of pathogenesis in Alzheimer’s dementia [47]. The aggregation of beta-amyloid (Aβ) triggered by the SARS-CoV-2 could also potentially be a mechanism through which COVID-19 elevates the risk of acquiring Alzheimer’s disease, leading to the accumulation of Aβ in neurons and the subsequent loss of synapses [37]. COVID-19 can also lead to neuroinflammation which results in increased tau hyperphosphorylation [41]. These pro-inflammatory processes give rise to several cytokines, such as IL-1, IL-6, CKPA4, and Galectin-9 which are involved in the development of Alzheimer’s disease [35]. These pro-inflammatory processes and cytokines can lead to the development of Alzheimer’s disease. However, they also lead to endothelial dysfunction of blood–brain barrier, allowing neurotoxins to enter the brain and further increasing the risk of Alzheimer’s disease [49]. COVID-19 infection also causes gut dysbiosis which can also potentially cause Alzheimer’s disease [51]. Thus, there is much overlap in the pathology of COVID-19 and Alzheimer's diease (see main text for further details). SARS-CoV-2: Severe acute respiratory syndrome coronavirus-2; ACE-2: Angiotensin-converting enzyme 2; COVID-19: Coronavirus disease 2019; IL: Interleukin; CKAP4: Cytoskeleton-associated protein 4. Figure 1 was made with BioRender.com.