**7. Approach to cognitive disorders in COVID-19 disease**

The primary cause of cognitive impairment and the etiopathogenetic process should be investigated in patients with COVID-19. It is important to investigate systemic and metabolic causes. Activation of the renin-angiotensin system may also impair the metabolic process. Therefore, patients should also be evaluated for endocrinological status [69, 70]. Cardiopulmonary failure and hemodynamic disorders that cause cognitive impairment should be evaluated in patients with COVID-19. Hypoxic ischemic brain injury and diffuse white matter injury associated with hypoxemia are important for treatment and etiopathogenetic process [38, 39, 57].

Hypercoagulability-related cerebrovascular disease should be considered in COVID-19 patients with acute neurological clinical symptoms. Ischemic stroke in a COVID-19 patient is associated with indirect intravascular coagulation or direct cerebral arterial thrombosis after DIC [36, 71]. Brain neuroradiological imaging is indicated for these patients (Computed tomography (CT) and/or magnetic resonance imaging (MRI)).

Encephalitis may be detected as a result of direct or indirect neuronal invasion in patients with COVID-19. In these patients, diffusion restriction in the central nervous system, particularly in the corpus callosum splenium, has been reported. Patients usually have encephalopathy and neurocognitive symptoms. The neurological examination should be repeated periodically. CT and/or MRI neuroimaging is required. Electroencephalography (EEG) and CSF examination should be performed in some patients [3, 72, 73].

Hyperactive delirium is more common than hypoactive delirium in COVID-19 disease. Treatment and management of this clinical symptom are difficult. Scales associated with cognitive dysfunction and delirium should be applied periodically during the COVID-19 process. Control of risk factors associated with this process, optimum blood oxygenation, fluid and calorie support and cognitive behavioural therapy are important [2, 42].

It should be recommended not to change the living environment of patients during the COVID-19 disease process. Chronic diseases, alcohol and drugs may precipitate cognitive dysfunction. Therefore, it is important to evaluate these factors. Anticholinergic adverse effects of treatments for COVID-19 disease should be evaluated. In addition, anticholinergic adverse effects of treatments for chronic diseases should be evaluated [57, 74]. Agitation and cognitive changes are treated with haloperidol and benzodiazepines. However, these treatments have the potential for respiratory depression and extrapyramidal adverse reactions.

### **8. COVID-19 pandemic and major neurocognitive disorder**

The COVID-19 pandemic has different effects on patients with Alzheimer's disease and other major neurocognitive disorders. These effects are not only associated with SARS-CoV-2 infection. On the other hand, the psychosocial process of the pandemic process also has negative effects. In some clinical studies, patients with major

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

neurocognitive disorder and non-major neurocognitive disorder have been compared. Patients with major neurocognitive disorders have higher risk for COVID-19 disease. There are many etiological risk factors for the COVID-19 disease in patients with major neurocognitive disorder. First, cognitive impairment and neuropsychiatric symptoms are common in patients with major neurocognitive disorders. Therefore, protective factors and their management are difficult in patients with COVID-19 [75]. Moreover, it is not possible for these patients to fulfil the requirements of quarantine.

The potential for the APOE ε4 genetic allele is higher in patients with major neurocognitive disorders. This condition damages the blood-brain barrier and precipitates cognitive dysfunction. It is also known that APOE ε4 induces cognitive dysfunction associated with microglia. This process produces neuroinflammation and neurodegeneration [76]. In addition, APOE ε4 is associated with increased cytokine after inflammation. Cytokine storm is induced by these mechanisms. Cytokine storm is directly associated with serious COVID-19 disease complications, such as lung injury and multi-organ failure [77].

There are severe individual and social isolation precautions in many countries to control the pandemic. Pandemic precautions are higher in patients with major neurocognitive disorders. This situation causes neuropsychiatric effects. Especially social isolation causes serious psychiatric symptoms in this patient group. In addition, the incidence of stress, anxiety and depression has increased [75–78]. Social isolation is higher in patients with major neurocognitive disorders in the care centres. Therefore, these patients have more exposed to neuropsychiatric and neurocognitive effects. This is one of the reasons for increased neuropsychiatric symptoms in patients with major neurocognitive disorders [75, 76]. Social isolation in patients with major neurocognitive disorders has been associated with neuropsychiatric and neurocognitive disorders.

Social isolation causes more agitation and cognitive impairment in major neurocognitive disorder patients than in other patient groups. The neurocognitive dysfunction correlates with the duration of social isolation. Neurocognitive dysfunction, especially in the quarantine period, may be permanent. Older patients with major neurocognitive disorders have higher risk for COVID-19 disease. These patients have more severe disease outcomes than other patients without major neurocognitive disorders [79–81]. A large-scale cohort study in the UK has demonstrated that patients diagnosed with major neurocognitive disorders are at three times higher risk for severe COVID-19 disease than other patients [80]. Risk factors for major neurocognitive disorders – age, obesity, cardiovascular disease, hypertension and diabetes mellitus – are also risk factors for SARS-CoV-2 infection and severe COVID-19 disease [81]. Some genetic risk factors for COVID-19 have been determined. In particular, a study reported from the United Kingdom demonstrated that homozygous genetic mutations for APOE ε4 are a risk factor for hospitalization associated with COVID-19 [82].

In summary, the pieces of evidence demonstrate that: First, older patients with major neurocognitive disorders are at higher risk for COVID-19 disease. These patients are also at higher risk of disease-related morbidity and mortality after COVID-19 infection. Second, major neurocognitive disorder patients were isolated for a long period to control SARS-CoV-2 infection. These patients have a higher risk for neuropsychiatric and severe neurocognitive disorders. Consequently, social networks, occupational therapy, caregivers and staff education are important during and after the pandemic in patients with major neurocognitive disorders.
