**4. Pathophysiology of neurocognitive disorders in COVID-19**

The pathophysiological mechanisms of neurocognitive impairment after COVID-19 disease have not been determined definitively. SARS-CoV-2 infection causes deficits in the central nervous system by direct and/or indirect mechanisms. The induced psychosocial process contributes to neurocognitive dysfunction. This disease is a complex process with vascular and metabolic disorders. All factors associated with neurocognitive dysfunctions are summarized in **Figure 1**. There are 4 main pathophysiological mechanisms in this process. They are vascular, inflammatory, psychosocial factors and direct neurotropism.

#### **4.1 Cerebrovascular diseases**

The risk of acute cerebrovascular disease increased in COVID-19 disease after SARS-CoV-2 infection. In studies, cerebrovascular disease was detected with a frequency of 2−6% in hospitalized patients with the diagnosis of COVID-19 [12]. In a study reported from Spain, stroke was determined in 23 (1.4%) of 1683 patients. Approximately 75% of stroke patients were ischemic stroke [34]

It has been detected that cerebrovascular diseases are more common in COVID-19 patients with neurological complications. The incidence of stroke is higher in elderly patients with severe disease activity. This rate is higher, especially in patients with comorbid diseases, such as hypertension, diabetes mellitus and cerebrovascular disease [30]. However, stroke associated with large vessel disease after COVID-19 disease may be detected in young adults [35].

*COVID-19 Pandemic and Neurocognitive Process: New Scenarios for Understanding… DOI: http://dx.doi.org/10.5772/intechopen.106687*

**Figure 1.**

*Possible causal factors of cognitive symptoms associated with COVID-19 (coronavirus disease 2019).*

Neurocognitive disorders associated with cerebrovascular diseases occur in COVID-19 patients. The pathophysiological mechanism of this process has not been definitively defined. This process is associated with systemic inflammation and disseminated intravascular coagulation (DIC) [36]. In patients with ARDS associated with COVID-19, a series of reactions including endothelial cell dysfunction, vascular leakage and dysregulated immune activation have been demonstrated for the mechanism of DIC. Activation of kallikrein-bradykinin system, leukocyte adhesion molecules, platelets and neutrophils increase inflammation. This process potentially causes vascular and neuronal damage in patients with COVID-19. SARS-CoV-2 infection damages vascular endothelial structures in cerebral vascular and many other tissues [37]. In many studies, major neurological complications after COVID-19 disease have been associated with cerebral vascular injury and ischemia.

Postmortem neuropathological autopsy studies in COVID-19 patients identified acute hypoxic-ischemic brain injury and perivascular inflammation in the cerebrum and cerebellum. However, SARS-CoV-2 virus could not be isolated in the central nervous system [38]. In the early postmortem period, hemorrhagic lesions and evidence of posterior reversible encephalopathy syndrome (PRES) were detected in patients with COVID-19 [39].

The results of the studies describe that COVID-19 process causes deficits in the central nervous system. The pathophysiological mechanisms of neurocognitive dysfunction in COVID-19 disease are systematically summarized in **Table 1**. It has been demonstrated that brain damage and cognitive impairment are associated with ischemic and inflammatory processes. Cognitive dysfunction associated with hypoxic-ischemic brain injury is explained by these mechanisms.
