Abstract
Identification of both the initial and the sustained clinical benefits achieved with symptomatic treatments for Alzheimer disease (AD) is a challenge. This commentary addresses a report by Wattmo et al. on 3-year follow-up of a cohort of patients with AD who were treated with donepezil. The investigators developed predictive regression models that can accurately calculate group mean Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Mini-Mental State Examination (MMSE) scores. They determined that patients with mild to moderate AD have a mean 5–7-month cognitive improvement with donepezil treatment, with greater benefit in more-advanced disease. While these results are encouraging, this study has important limitations. Although the predictive models work well for determining group means, the authors note that they do not predict individual patient responses, which vary greatly. Additionally, the study had a drop-out rate of 62%, which might elicit survivorship bias and overestimation of treatment benefit. We remind clinicians that small improvements in cognition matter most when a concurrent measurable benefit is seen in daily function.
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Acknowledgements
The authors gratefully acknowledge the assistance of Dr Itthipol Tawankanjanachot for sourcing the references for this paper, and the support of the Ralph Fisher and Alzheimer Society of British Columbia Endowed Professorship in Alzheimer's Research.
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HH Feldman has received grant or research support from Pfizer, Eisai, Janssen, Lilly, AstraZeneca, Myriad, the NIH, the Canadian Institutes of Health Research, Alzheimer Society of Canada, and the Michael Smith Foundation for Health Research, has acted as a consultant for Pfizer, Eisai, Novartis, Janssen, Servier, Myriad, Targacept, Lundbeck, AstraZeneca and Wyeth, and has been involved in CME programs for Pfizer, Eisai, Janssen, Novartis, Forest and AstraZeneca. C Jacova declared no competing interests.
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Feldman, H., Jacova, C. Predicting response to acetylcholinesterase inhibitor treatment in Alzheimer disease: has the time come?. Nat Rev Neurol 5, 128–129 (2009). https://doi.org/10.1038/ncpneuro1007
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DOI: https://doi.org/10.1038/ncpneuro1007