Potential Role Of Citicoline On Cognitive Decline Associated With COVID-19

An early study reported that more than one-third (36.4%) of COVID-19 patients had neurologic symptoms. Furthermore, a study by Miskowiak et al. found that more than 80% of COVID-19 patients with long-term symptoms within 3 to 4 months of discharge reported that they had severe cognitive impairment in daily life, which was associated with more subjective cognitive difficulties, absenteeism and poor of quality of life.

The most common single symptom reported in some cohorts of non-hospitalized COVID-19 patients was fatigue, but 85% of them had four or more neurologic symptoms, the most common being "brain fog," concentration function and Worsening working memory, representing mild form of encephalopathy after COVID-19. Brain fog is an umbrella term for CNS involvement that includes cognitive impairment, difficulty concentrating, confusion, psychological symptoms, and behavioral changes. Neurologic symptoms found in them (regardless of whether they had a positive or negative PCR test for SARS-CoV-2) included brain fog, headache, numbness (tingling), dysgeusia, anosmia, myalgia, dizziness, abnormal Localized pain in the chest, blurred vision, tinnitus, dyskinesias, focal motor and sensory disturbances, dysarthria, ataxia, seizures, dysphagia and aphasia.

Citicoline sodium is an essential substance for cell membrane structure phospholipids, and has been found to have neuroprotective effects on patients with neurological diseases. In clinical stroke trials, citicoline was also found to be the only neuroprotective agent to demonstrate safety and sustained beneficial effects in acute ischemic stroke through confirmatory clinical trials to improve post-stroke cognition decline and functional recovery. A prospective study also demonstrated the efficacy of citicoline for ischemic, hemorrhagic and subarachnoid hemorrhagic stroke in improving MMSE (Mini Mental Scale Examination) and disability scores.

Since neurologic complications due to COVID-19 occur at a relatively higher rate in more severe patients, and increases in cytokines are associated with poorer clinical outcomes, the use of citicoline may also be beneficial because It reduces cytokine MIP-1α, TNFα, IL-1β, MCP-1 secretion, IL-6, RANTES and anti-inflammatory cytokine IL-10 secretion.

Citicoline has anti-inflammatory and neuroprotective effects, and recent studies have found a correlation between the role of phospholipase A2 in the COVID-19 inflammatory cascade and the occurrence of cytokine storm.

Citicoline also shows anti-inflammatory and antiviral potential on the UPS mechanism, as it functions as a proteasome regulator by shifting populations in favor of capped proteasome granules, activating the intrinsic activity of 20S and 19S to form 26s granule, which acts as a regulator by fine-tuning between activating and restricting its activity. Citicoline has also been found to trigger upregulation of SIRT1 expression, which benefits neuronal plasticity and cognitive function by regulating dendritic and axonal growth. Upregulation of SIRT1 expression also reduces neuronal inflammatory responses under hyperinflammatory conditions such as SARS-CoV-2 infection, contributing to neuroprotection and recovery.

Tag: Citicoline

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