Citicoline Useful For Long COVID Individuals With Persistent Cognitive Dysfunction As A Result Asymptomatic, Mild Or Moderate COVID-19 Infections

Long COVID: The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has brought with it a myriad of health challenges, including severe respiratory symptoms and a range of neurological manifestations. Among these, persistent cognitive dysfunction has emerged as a concerning issue for individuals affected by COVID-19, even those with asymptomatic, mild, or moderate cases.


 
This news study by researchers from the Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo-Italy delves into the potential benefits of citicoline, a cognitive enhancer, in addressing cognitive deficits in non-hospitalized long-hauler patients with COVID-19.
 
A past Long COVID news article by Thailand Medical News on a Belgium study also noted the benefits of using Citicoline to treat Post COVID cognitive issues.
https://www.thailandmedical.news/news/covid-19-news:-bulgarian-study-reveals-promising-neuroprotective-agents-for-cognitive-impairment-in-post-covid-patients
 
The study team also presents a case study that highlights the positive outcomes of cognitive rehabilitation combined with citicoline treatment, shedding light on the importance of early identification and intervention in managing Post COVID-19 Neurological Syndrome (PCNS).
 
The Neurological Impact of COVID-19
While COVID-19 primarily affects the respiratory system, it has become evident that the nervous system can also be significantly involved, impacting over one-third of patients. Neurological manifestations commonly include symptoms like headaches, fatigue, and brain fog. The pathophysiological mechanisms of SARS-CoV-2 infection are complex and encompass innate, humoral, and cellular immune responses, leading to a cytokine storm, endothelial dysfunction, and mitochondrial impairments. These mechanisms contribute to the neurological sequelae seen in COVID-19 patients.
 
Long COVID, characterized by persistent symptoms beyond the acute phase of the illness, has become a concern. It affects both hospitalized and non-hospitalized individuals, with the latter group sometimes experiencing more debilitating symptoms. The spectrum of symptoms in Long COVID includes not only respiratory issues but also persistent neurological symptoms, such as fatigue, brain fog, headache, numbness, and cognitive dysfunction.
 
Cognitive Impairment in COVID-19
Cognitive impairment in COVID-19 patients can manifest as deficits in attention, working memory, and mild-to-moderate cognitive dysfunction. This cognitive decline can occur even in patients who have recovered from mild or moderate cases of the virus. Interestingly, cognitive impairment seems to correlate with the degree of inflammation, and while some associations have been made with c ertain markers of severity during acute infection, much remains to be understood. Long-term cognitive impairment affects more than 2% of individuals three months after SARS-CoV-2 infection.
 
Citicoline as a Potential Treatment
Citicoline is a cognitive enhancer known for its role in intracellular phospholipid synthesis and as an exogenous source of choline and cytidine. It has been shown to improve cerebral blood flow, brain activity, and mitochondrial function.
 
Beyond these effects, citicoline exhibits anti-inflammatory properties by inhibiting phospholipase 2 activity, upregulating the expression of the SIRT1 protein (associated with improved neuronal plasticity and cognitive functioning), and addressing mitochondrial dysfunction while reducing oxidative damage. Additionally, citicoline is a substrate for acetylcholine synthesis, a neurotransmitter crucial for memory and learning.
 
The Benefits of Cognitive Rehabilitation
Cognitive rehabilitation, a therapeutic approach aimed at improving cognitive functioning, has shown promise in addressing cognitive decline in various contexts, including memory training programs for mild cognitive impairment.
 
While there is limited data on cognitive rehabilitation specifically for COVID-19-related cognitive dysfunction, recent research suggests its potential benefits in preventing long-term cognitive complications from the virus.
 
Case Presentation: A Tale of Recovery
In this study, the researchers presented the case of a 59-year-old female who contracted COVID-19 in early 2021. Her COVID-19 experience was mild, characterized by symptoms such as cough, fever, and dizziness, without the need for hospitalization. However, after recovering from the acute phase, she began experiencing cognitive issues, including forgetfulness and anomia. Over time, these cognitive disturbances gradually progressed, albeit without significantly affecting her daily life and work performance.
 
In April 2021, she sought medical evaluation at the Memory Clinic of the University Hospital of Palermo, Italy. A comprehensive diagnostic work-up and neuropsychological assessment were conducted. The patient's blood biochemistry panel for long COVID biomarkers, which included markers such as d-dimer, fibrinogen, albumin, ferritin, C-reactive protein, and interleukin 6, all returned normal results. Brain MRI with gadolinium and an EEG revealed no significant abnormalities.
 
Neuropsychological assessment revealed deficits in verbal long-term episodic memory and borderline performance in executive functioning and visuo-constructional abilities. Specifically, the patient exhibited difficulty with encoding, learning, and delayed recall, indicating a significant impairment in verbal memory.
 
Additionally, mild executive dysfunction was observed, affecting inhibitory control and abstract reasoning. Cognitive performance in other domains, such as attention, working memory, and language, remained within the normal range. Anxiety levels were mildly elevated, likely linked to the reported cognitive difficulties, while there were no significant signs of depression. Subjective memory impairment was confirmed through the Memory Assessment Clinics Questionnaire (MAC-Q).
 
Diagnosis and Treatment
Based on the cognitive and mood disorders observed in this patient following her COVID-19 infection, she was diagnosed with Post COVID-19 Neurological Syndrome (PCNS). The patient was prescribed a treatment regimen consisting of 1000 mg/daily oral citicoline and a six-month cognitive rehabilitation program. The rehabilitation program included two 40-minute sessions per week, combining relaxation techniques with mnemonic strategies focused on verbal memory and spatial information retrieval through repeated presentations.
 
Positive Outcomes
After six months of treatment and rehabilitation, a follow-up neuropsychological examination revealed significant improvements in cognitive performance. The patient achieved normal scores in all cognitive tests administered, with only borderline performance in delayed recall of verbal episodic memory, suggesting residual impairment. This marked improvement was accompanied by a reduction in anxiety levels and subjective reports of memory deficits.
 
Discussion: Unveiling the Mechanisms
This case study provides valuable insights into the potential of citicoline and cognitive rehabilitation in addressing cognitive dysfunction in non-hospitalized long-hauler patients with COVID-19. The patient's mild clinical manifestations, combined with her normal blood biomarker profile for long COVID, brain MRI, and EEG results, suggested that hypoxemia, vascular comorbidity, or systemic inflammation were unlikely to be the primary contributors to her neurological symptoms.
 
Instead, the study suggests that microvasculopathy and brain damage, potentially triggered by SARS-CoV-2 infection, may have played a role in the cognitive deficits observed in this patient. Citicoline, with its neuroprotective, anti-inflammatory, and cognitive-enhancing properties, seemed to address these issues effectively. Furthermore, cognitive rehabilitation, with a focus on memory and inhibitory control techniques, likely synergized with citicoline to bring about cognitive improvement.
 
Conclusion
To mitigate the long-term consequences of COVID-19 and improve the quality of life for individuals affected by PCNS, a multi-disciplinary approach to patient care is essential. Early clinical assessments, identification of at-risk patients, and tailored rehabilitation programs, coupled with potential nootropic treatments like citicoline, can play a pivotal role in preventing disability and restoring cognitive function. As our understanding of the neurological impact of COVID-19 evolves, it becomes increasingly clear that proactive interventions are crucial for long-hauler patients on their journey to recovery.
 
The study findings were published in the peer reviewed journal: Brain Sciences.
https://www.mdpi.com/2076-3425/13/9/1275
 
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