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[Abstract]

PURPOSE: Neurotoxic effects of brain irradiation include cognitive impairment in 50% to 90% of patients. Prior studies have suggested that donepezil, a neurotransmitter modulator, may improve cognitive function.

PATIENTS AND METHODS: A total of 198 adult brain tumor survivors ≥ 6 months after partial- or whole-brain irradiation were randomly assigned to receive a single daily dose (5 mg for 6 weeks, 10 mg for 18 weeks) of donepezil or placebo. A cognitive test battery assessing memory, attention, language, visuomotor, verbal fluency, and executive functions was administered before random assignment and at 12 and 24 weeks. A cognitive composite score (primary outcome) and individual cognitive domains were evaluated.

RESULTS: Of this mostly middle-age, married, non-Hispanic white sample, 66% had primary brain tumors, 27% had brain metastases, and 8% underwent prophylactic cranial irradiation. After 24 weeks of treatment, the composite scores did not differ significantly between groups (P = .48); however, significant differences favoring donepezil were observed for memory (recognition, P = .027; discrimination, P = .007) and motor speed and dexterity (P = .016). Significant interactions between pretreatment cognitive function and treatment were found for cognitive composite (P = .01), immediate recall (P = .05), delayed recall (P = .004), attention (P = .01), visuomotor skills (P = .02), and motor speed and dexterity (P < .001), with the benefits of donepezil greater for those who were more cognitively impaired before study treatment.

CONCLUSION: Treatment with donepezil did not significantly improve the overall composite score, but it did result in modest improvements in several cognitive functions, especially among patients with greater pretreatment impairments.

© 2015 by American Society of Clinical Oncology.

[Author information]

Rapp SR1, Case LD2, Peiffer A2, Naughton MM2, Chan MD2, Stieber VW2, Moore DF Jr2, Falchuk SC2, Piephoff JV2, Edenfield WJ2, Giguere JK2, Loghin ME2, Shaw EG2.​

1 Stephen R. Rapp, L. Doug Case, Ann Peiffer, Michelle M. Naughton, Michael D. Chan, and Edward G. Shaw, Wake Forest School of Medicine and Wake Forest Community Clinical Oncology Program Research Base; Volker W. Stieber, Novant Health System, Winston-Salem, NC; Dennis F. Moore Jr, Wichita Community Clinical Oncology Program, Wichita, KS; Steven C. Falchuk, Christiana Care Health Services, Newark, DE; James V. Piephoff, Mercy Hospital, St Louis, MO; William J. Edenfield and Jeffrey K. Giguere, Cancer Center of Carolinas, Greenville, SC; and Monica E. Loghin, University of Texas MD Anderson Cancer Center, Houston, TX. srapp@wakehealth.edu.

2 Stephen R. Rapp, L. Doug Case, Ann Peiffer, Michelle M. Naughton, Michael D. Chan, and Edward G. Shaw, Wake Forest School of Medicine and Wake Forest Community Clinical Oncology Program Research Base; Volker W. Stieber, Novant Health System, Winston-Salem, NC; Dennis F. Moore Jr, Wichita Community Clinical Oncology Program, Wichita, KS; Steven C. Falchuk, Christiana Care Health Services, Newark, DE; James V. Piephoff, Mercy Hospital, St Louis, MO; William J. Edenfield and Jeffrey K. Giguere, Cancer Center of Carolinas, Greenville, SC; and Monica E. Loghin, University of Texas MD Anderson Cancer Center, Houston, TX.