Efficacy of memantine in preventing neurocognitive dysfunction induced by radiation therapy in patients with brain metastases: A systematic review of clinical trials.

PURPOSE: About 50%-90% of patients with brain metastases who receive radiation therapy experience cognitive impairment. This systematic review aims to gather credible sources of comprehensive information on the efficacy of memantine in preventing cognitive dysfunction. METHODS: A comprehensive review conducted in compliance with the PRISMA statement and systematic search was performed across five databases included PubMedⓇ, EmbaseⓇ, ScopusⓇ, Cochrane LibraryⓇ, and ClinicalTrial.gov.in from inception until November 2021. RESULTS: A total of four eligible studies were selected in this review that included 1,444 patients with brain metastases who received radiation therapy (Intervention group [n = 729] and control group [n = 715]). Overall, three of the four studies reported some improvement in neurocognitive function in at least one or more parameters such as recall and recognition (P = .39, P = .10 and P = .05), verbal fluency (P = .03 and P < .0001), complex attention (P = .59) executive function (P = .92) and normal appearing white matter (P = .01) following memantine therapy compared to control group. Further, two of the four studies reported an improvement in the patients' quality of life following memantine therapy compared to the control group, and there was no significant difference in the toxicity profile of the interventional compared to the control group as reported from two studies. CONCLUSION: This review embraces the comprehensive evidence that the use of memantine therapy in patients with brain metastases to prevent radiation-induced neurocognitive dysfunction has a modest and statistically significant beneficial impact in improving quality of life and preserving some neurocognitive function without any complications. Pending the completion of additional ongoing studies, one can argue that memantine is a reasonable treatment to consider in patients with brain metastases while they receive whole brain radiation therapy.

Preservation of cognitive function after brain irradiation.

OBJECTIVE: Approximately 50-90% of brain metastatic patients who receive radiation therapy (RT) exhibit cognitive decline which may affects the quality of life of cancer survivors. Hence preservation of cognitive functions in brain metastatic patients becomes important. This review aims to evaluates the pathology or mechanism of cognitive function impairment after brain irradiation and strategies available to preserve cognitive function after radiation therapy. DATA SOURCES: Published articles evaluating the pathology behind radiation induced cognitive impairment and strategies to resolve or preserve cognitive impairment were searched for in scientific databases (eg: PubMed, Scopus, Cochrane database, Google scholar) using keywords including memantine, brain metastases, radiation therapy, pathophysiology, pathogenesis, mechanism and prevention. DATA SUMMARY: Several hypotheses have been offered to explain the mechanism of radiation induced cognitive decline. Among them, vascular hypotheses play a significant role. Some pharmacological agents have been also tested in patients receiving radiotherapy, memantine was found beneficial based with the reference to existing data. CONCLUSION: Future studies are required to evaluate the impact of memantine in different types of radiation therapy procedures and its effects on quality of life of brain metastatic survivors.