The effect of donepezil hydrochloride on post-COVID memory impairment: A randomized controlled trial.

BACKGROUND: Post-Coronavirus Disease (COVID-19) condition, known as "post-COVID syndrome," is associated with a range of complications persisting even after recovery. Among these complications, cognitive dysfunction, including memory impairment, has been relatively common observed, impacting executive function and quality of life. To date, no approved treatment exists for this specific complication. Therefore, the present clinical trial aimed to investigate the impact of Donepezil Hydrochloride on post-COVID memory impairment. METHODS: A randomized, controlled trial (Approval ID: IRCT20210816052203N1) was conducted, enrolling 25 patients with post-COVID memory impairment. Participants with a history of hospitalization were randomly assigned to either the drug group (n = 10) or the control group (n = 15). Memory indices were assessed at baseline, one month, and three months later using the Wechsler Memory Scale-Revised test. SPSS software and appropriate statistical tests were employed for data analysis. RESULTS: The statistical analysis revealed no significant difference in WMS-R subtest and index scores between the drug and control groups at the 4-week and 12-week follow-up periods. However, within the drug group, there was a notable increase in the visual reproduction I and verbal paired associates II subtests during the specified time intervals. CONCLUSION: While donepezil 5 mg did not exhibit a significant overall increase in memory scales compared to the control group over time, our findings suggest that this medication may exert a positive effect on specific memory subtests. Further research and exploration are warranted to better understand the potential benefits of donepezil in managing post-COVID-related memory impairment. TRIAL REGISTRATION: The study was approved by the Research Ethics Committee of Aja University of Medical Sciences (Approval ID: IR.AJAUMS.REC.1400.125) and registered in the Iranian Registry of Clinical Trials (IRCT) (Approval ID: IRCT20210816052203N1).

Neuropathology of 30 deceased patients with COVID-19: a case series in Tehran, Iran.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect the nervous system and result in neurological symptoms. The most common feature of central nervous system involvement is hypoxia and congestion. This study aimed to evaluate the histopathology of cerebral tissue in deceased patients with coronavirus disease 2019 (COVID-19). Methods: In a case series study, we took cerebral samples of 30 deceased patients with COVID-19 through supraorbital bone from January to May 2021. The samples were fixed in a formalin solution, stained with haematoxylin-eosin dyes and studied by two expert pathologists. The Ethics Committee of AJA University of Medical Sciences approved this study with code IR.AJAUMS.REC.1399.030. Results: The mean age of the patients was 73.8 years, and the most common underlying disease was hypertension. Cerebral tissue samples showed hypoxic-ischaemic changes in 28 (93.3%), microhaemorrhage in six (20%), lymphocytic infiltration in five (16.7%) and thrombosis in three samples (10%). Conclusion: Hypoxic-ischaemic change was the most common neuropathology in our patient. Our study showed that many patients with severe COVID-19 may develop central nervous system involvement.

Cardio-Pulmonary Histopathology with Clinical Correlations of Deceased Patients with COVID-19: A Case Series in Tehran, Iran.

BACKGROUND: SARS-CoV-2 may affect vital organs. The present study investigated the histopathology of pulmonary and cardiac tissues with clinical correlation in deceased patients with COVID-19. METHODS: We obtained pulmonary and cardiac tissues from 30 deceased patients with COVID-19 in Tehran, Iran, from January to May 2021. Sampling was performed through a percutaneous needle biopsy. After slide preparation, two expert pathologists studied them. We assessed the correlation between clinical and pathological data by Fisher's exact test. RESULTS: The mean age of the patients was 73.8±13.4 years, and the male-to-female ratio was 23/7. The most common underlying disease was hypertension (HTN) in 25 patients (83%). Fifty-five tissue samples were achieved, including 28 pulmonary and 27 cardiac samples. Our results showed that all patients (100%) developed diffuse alveolar damage (DAD), and 26 (93%) developed hyaline membrane formation. The most common phase of DAD was the exudative-proliferative phase in 16 (57.1%). Three cardiac samples (11%) revealed myocarditis, and seven (26%) showed cardiomyocyte hypertrophy. In univariate analysis using Fischer's exact test, myocarditis had significant relationships with C-reactive protein (CRP) levels higher than 80 mg/dL (P=0.008) and elevated cardiac troponin levels higher than two-fold (P=0.01). CONCLUSION: COVID-19 can affect the major vital organs. However, only myocarditis had a significant relationship with the circulating levels of inflammatory factors.

Donepezil Beyond Alzheimer's Disease? A Narrative Review of Therapeutic Potentials of Donepezil in Different Diseases.

Donepezil hydrochloride is an acetylcholine esterase inhibitor studied and approved to treat Alzheimer's disease (AD). However, this drug can have positive therapeutic potential in treating different conditions, including various neurodegenerative disorders such as other types of dementia, multiple sclerosis, Parkinson's disease, psychiatric and mood disorders, and even infectious diseases. Hence, this study reviewed the therapeutic potential of this drug in treating Alzheimer's and other diseases by reviewing the articles from databases including Web of Science, Scopus, PubMed, Cochrane, and Science Direct. It was shown that donepezil could affect the pathophysiology of these diseases via mechanisms such as increasing the concentration of acetylcholine, modulating local and systemic inflammatory processes, affecting acetylcholine receptors like nicotinic and muscarinic receptors, and activating various cellular signaling via receptors like sigma-1 receptors. Despite many therapeutic potentials, this drug has not yet been approved for treating non-Alzheimer's diseases, and more comprehensive studies are needed.