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Cognitive effects of donepezil therapy in patients with brain tumors: a pilot study

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Abstract

Cognitive dysfunction is prevalent among brain tumor patients treated with radiotherapy (RT) and chemotherapy. However, there are no approved pharmacological interventions for cognitive dysfunction in cancer patients. The goal of this pilot study was to examine the efficacy of donepezil, an acetylcholinesterase inhibitor used to treat Alzheimer’s disease, in improving cognitive functions in brain tumor patients previously treated with RT + chemotherapy or chemotherapy alone. Fifteen patients with a brain tumor received a single daily dose of donepezil for 24 weeks (5 mg for 4 weeks, then 10 mg for 20 weeks). Patients completed cognitive evaluations prior to initiating therapy (baseline), and about 12 weeks (mid-study) and 24 weeks (end-of-study) subsequent to initiation of donepezil therapy. The results of linear mixed models analysis, controlling for each patient’s baseline cognitive test score, showed a significant post-baseline improvement in attention (WAIS-III digit span forward; p = 0.037), graphomotor speed (WAIS-III digit symbol; p = 0.035) and visual memory (BVMT-R-delay; p = 0.025). There was also an improvement in self-reported quality of life (FACT-Br, social well-being subscale; p = 0.01). The findings of this pilot study suggest that treatment with donepezil may improve some aspects of cognitive functions and quality of life in brain tumor patients. Similar findings were reported in two prior trials of donepezil in brain tumor survivors.

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Funding

This work was supported the Society of Memorial Sloan Kettering Cancer Center, and by core grant P30 CA008748 from the National Cancer Institute.

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Authors and Affiliations

  1. Department of Neurology, Weill Cornell Medical College, New York, NY, USA

    Denise D. Correa, Maria Kryza-Lacombe & Lisa M. DeAngelis

  2. Department of Epidemiology and Biostatistics, Weill Cornell Medical College, New York, NY, USA

    Raymond E. Baser

  3. Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA

    Kathryn Beal

  4. Department of Neurology & Neuroscience, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, 1275 York Avenue, New York, NY, 10021, USA

    Denise D. Correa & Lisa M. DeAngelis

Authors
  1. Denise D. Correa
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  2. Maria Kryza-Lacombe
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  3. Raymond E. Baser
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  4. Kathryn Beal
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  5. Lisa M. DeAngelis
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Correspondence to Denise D. Correa.

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Conflict of Interest

Dr. Correa serves on the Editorial Board of Neuro-Oncology Practice and on the Neurotoxicity Advisory Board for Juno Therapeutics. Mr. Baser reports no disclosures, Ms. Kryza-Lacombe reports no disclosures, Dr. Kathryn Beal reports no disclosures,.Dr. DeAngelis serves on the Editorial Board of Neurology, Journal of Neuro-Oncology, Neuro-Oncology, Neuro-Oncology Practice, and The British Medical Journal. She serves on the Neurotoxicity Advisory Board for Juno Therapeutics. She serves as a Mentor for CTSC KL2 Scholar Award, KL2TR000458; A Pilot Trial of Enoxaprin vs. Aspirin in Patient with Cancer and Stroke.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Correa, D.D., Kryza-Lacombe, M., Baser, R.E. et al. Cognitive effects of donepezil therapy in patients with brain tumors: a pilot study. J Neurooncol 127, 313–319 (2016). https://doi.org/10.1007/s11060-015-2035-3

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  • DOI: https://doi.org/10.1007/s11060-015-2035-3

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