Cognitive Dysfunction in a Non-Hospitalized COVID-19 Patient: A Case Study on Citicoline and Cognitive Rehabilitation


The COVID-19 pandemic has brought forth a myriad of challenges for healthcare providers worldwide. Beyond the acute respiratory symptoms that many individuals experience, emerging evidence has highlighted the potential for long-lasting neurological sequelae in some COVID-19 patients.

This study delves into the case of a 59-year-old woman who, despite not requiring hospitalization for COVID-19, developed persistent cognitive dysfunction, a condition referred to as Post-COVID Neurological Syndrome (PCNS) [34].

The remarkable aspect of this case is the patient’s positive response to a treatment regimen combining citicoline and cognitive rehabilitation, shedding light on potential therapeutic strategies for COVID-19-related cognitive impairment.

Case Presentation

The patient in question contracted COVID-19 with relatively mild clinical symptoms, including fever, cough, and dizziness. Importantly, she did not require hospitalization for respiratory issues, nor did she have any known vascular risk factors or diseases.

Traditional markers for long COVID, including complete blood biochemistry, yielded normal results. Brain MRI and EEG scans showed no significant structural or electrical abnormalities. Despite these reassuring findings, the patient reported cognitive disturbances, primarily affecting her verbal episodic memory.

This cognitive decline was confirmed through formal neuropsychological testing, which also revealed borderline impairments in executive functioning (inhibitory control and abstract reasoning) and visuospatial organization. Notably, these cognitive deficits did not interfere with her ability to perform daily activities, including work.

Cognitive Impairments in COVID-19

The cognitive effects of SARS-CoV-2 infection have garnered increasing attention within the medical community. Research suggests that attention and working memory are the primary cognitive domains impacted by the virus [6]. Brain imaging studies have shown a prevailing frontoparietal hypometabolism pattern [36].

In this case, however, the most pronounced cognitive impairment pertained to verbal episodic memory. Additionally, there was mild dysfunction in executive functioning and visuospatial organization.

These findings point towards a more diffuse brain involvement, implicating the left mesial temporal cortex [37], in addition to the fronto-parietal regions, characteristically associated with executive functioning [38] and visuospatial skills [39].

Citicoline and Cognitive Rehabilitation

The patient’s journey towards cognitive recovery began with a six-month combined rehabilitation program, which integrated mnemonic and inhibitory control techniques. Cognitive rehabilitation has a well-established role in addressing cognitive decline, particularly concerning memory functioning [18]. In this case, the combination of rehabilitation with citicoline therapy proved particularly effective.

Citicoline, a compound with a diverse range of neuroprotective properties, played a pivotal role in the patient’s treatment. It has been shown to have anti-inflammatory properties through the inhibition of phospholipase 2 activity, contributing to the mitigation of inflammation in the brain.

Citicoline also exhibits antiviral qualities as a proteasome regulator, possibly assisting in the patient’s recovery from COVID-19-related neurological symptoms. Furthermore, it serves as a neuroprotective agent, reducing oxidative damage and improving mitochondrial dysfunction in the neocortex, which can be especially beneficial in cases of cognitive impairment.

Another vital aspect of citicoline’s mechanism is its role as a precursor for acetylcholine synthesis, a neurotransmitter essential for memory and learning. The administration of citicoline can enhance cerebral blood flow and velocity, promoting better brain function [16]. These multifaceted mechanisms help explain the observed positive impact of citicoline in this patient’s cognitive recovery.

Traumatic Brain Injury (TBI)

Traumatic Brain Injury (TBI) is a devastating and widespread medical condition that can lead to a range of neurological and cognitive deficits, and in severe cases, even death. TBI contributes significantly to the global injury burden, with falls being a predominant cause in older patients, while road injuries frequently affect younger individuals [1]. Beyond its impact on individuals, TBI has profound consequences on families and societies, with substantial financial burdens.

Effective management of TBI is crucial to mitigate its devastating effects. Clinically, TBI is categorized into mild, moderate, and severe based on the Glasgow Coma Scale (GCS) scores. These categories have proven predictive of long-term outcomes, although researchers have explored alternative measures such as biomarkers to enhance TBI management [2,3].

The key goal in TBI management is to minimize the severity of sequelae and improve recovery outcomes. Advances in monitoring and understanding the pathophysiology of TBI hold promise for more targeted interventions, potentially enhancing final outcomes and reducing associated disabilities [4]. This progress has been underpinned by an improved understanding of the complex pathophysiology of TBI, with a growing focus on neuroprotection as a treatment strategy [5,6,7,8,9].

Pathophysiological Mechanisms in TBI

TBI involves a cascade of pathophysiological events, including inflammatory processes and disruptions in phospholipid metabolism. These mechanisms contribute significantly to the injury’s progression and impact [10,11,12,13,14,15,16]. As a result, there is a growing consensus on the need for pharmacological interventions that can protect and restore the nervous system, particularly targeting the “traumatic penumbra,” a zone of compromised but potentially salvageable brain tissue [22].

Citicoline: A Potential Neuroprotective Agent

Citicoline, also known as cytidine-5′-diphosphocholine or CDP-choline, is a naturally occurring component in human metabolism. It serves as an intermediate in the synthesis of phosphatidylcholine, a crucial phospholipid in cellular membranes (Figure 1). When administered as a drug, citicoline exhibits a broad range of biochemical and pharmacological actions, making it a promising candidate for the treatment of various neurological diseases, including TBI [41].

The multifaceted actions of citicoline make it particularly appealing as a neuroprotective agent for TBI [22]. Here are some of the key mechanisms through which citicoline may exert its beneficial effects:

  • Phospholipid Metabolism: Citicoline supports the synthesis of phosphatidylcholine, a vital component of cell membranes. This action can help repair damaged cell membranes in the injured brain tissue.
  • Anti-Inflammatory Effects: Inflammatory processes play a significant role in TBI pathology. Citicoline has demonstrated anti-inflammatory properties that can potentially reduce the neuroinflammation associated with TBI [10,11,12,13,14,15,16].
  • Neuroprotection: Citicoline’s neuroprotective properties extend to reducing oxidative damage and improving mitochondrial function in the neocortex. These actions can help preserve neuronal integrity in the face of TBI-induced stressors [22].
  • Acetylcholine Synthesis: Citicoline serves as a precursor for the synthesis of acetylcholine, a neurotransmitter essential for memory and learning. This role can potentially enhance cognitive recovery in TBI patients.

Traumatic Brain Injury is a major public health concern, impacting individuals across the lifespan and burdening societies with significant healthcare costs. While TBI management traditionally focused on symptom relief and supportive care, recent advancements have illuminated the potential for neuroprotective interventions.

Citicoline, with its diverse mechanisms of action, has emerged as a promising neuroprotective agent in the treatment of TBI. Its ability to support phospholipid metabolism, combat inflammation, and promote neuroprotection make it an attractive candidate for improving outcomes in TBI patients. As our understanding of TBI’s pathophysiology continues to evolve, citicoline represents a valuable tool in the pursuit of more effective and targeted treatments for this devastating condition.


This case study sheds light on the intricate and diverse neurological consequences of COVID-19, extending beyond the acute phase of the disease. Even in patients with mild clinical manifestations and no significant respiratory or vascular symptoms, cognitive dysfunction can manifest and persist. In this particular case, the combination of cognitive rehabilitation techniques and citicoline therapy showed promising results, offering a potential avenue for the treatment of post-COVID cognitive impairment.

The implications of this study extend beyond the individual case, highlighting the importance of a multidisciplinary approach to long COVID-19 syndrome. The complex and varied manifestations of the condition demand comprehensive clinical assessment and tailored treatment strategies. As we continue to learn more about the long-term effects of COVID-19, research and clinical experiences like this will play a critical role in advancing our understanding and improving patient outcomes.

Citicoline, also known as CDP-choline or cytidine diphosphate choline, is a naturally occurring compound that is involved in many important functions in the body, including:

  • Metabolism. Citicoline is a precursor to the neurotransmitter acetylcholine, which is essential for memory, learning, and concentration. It is also involved in the metabolism of fats and cholesterol.
  • Brain health. Citicoline can help to protect the brain from damage caused by stroke, traumatic brain injury, and neurodegenerative diseases such as Alzheimer’s disease. It can also improve cognitive function in people with these conditions.
  • Eye health. Citicoline can help to improve vision and protect the eyes from damage caused by glaucoma and other eye diseases.
  • Liver health. Citicoline can help to protect the liver from damage caused by alcohol, drugs, and other toxins.

How does citicoline work?

Citicoline works by increasing the production of acetylcholine, a neurotransmitter that is essential for memory, learning, and concentration. It also helps to protect the brain from damage caused by free radicals, which are unstable molecules that can damage cells. Citicoline also promotes the growth of new blood vessels in the brain, which can improve blood flow and oxygen delivery to the brain.

What are the benefits of citicoline?

Citicoline has been shown to be beneficial for a variety of conditions, including:

  • Stroke. Citicoline can help to improve cognitive function and reduce the risk of disability after a stroke.
  • Traumatic brain injury. Citicoline can help to improve cognitive function and reduce the risk of long-term complications after a traumatic brain injury.
  • Alzheimer’s disease. Citicoline can help to improve cognitive function and slow the progression of Alzheimer’s disease.
  • Parkinson’s disease. Citicoline can help to improve motor function and reduce the risk of dementia in people with Parkinson’s disease.
  • Glaucoma. Citicoline can help to improve vision and slow the progression of glaucoma.
  • Fatigue. Citicoline can help to improve energy levels and reduce fatigue.

How is citicoline taken?

Citicoline is available as a dietary supplement and as a prescription medication. It can be taken orally, by injection, or by intravenous infusion. The dosage and form of citicoline will vary depending on the condition being treated.

Is citicoline safe?

Citicoline is generally considered safe when taken as directed. However, some people may experience side effects such as headache, nausea, and vomiting. If you experience any side effects, stop taking citicoline and talk to your doctor.

Is citicoline legal?

Citicoline is legal in the United States and most other countries. However, it is important to note that citicoline is a prescription medication in some countries.

Where can I buy citicoline?

Citicoline is available as a dietary supplement at most health food stores and online retailers. It is also available as a prescription medication from your doctor.

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