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Smell Identification Test as a Treatment Response Marker in Patients With Alzheimer Disease Receiving Donepezil

Velayudhan, Latha DNB (Psychiatry)*†; Lovestone, Simon PhD*†

Journal of Clinical Psychopharmacology: August 2009 - Volume 29 - Issue 4 - p 387-390
doi: 10.1097/JCP.0b013e3181aba5a5
Brief Reports

Background: Olfactory dysfunction, impaired odor identification in particular, is known to occur in Alzheimer disease (AD). The entorhinal cortex and the olfactory bulb, critical areas for olfactory function, are rich in acetylcholine, the neurotransmitter implicated in AD pathology and treatment. In view of the common anatomical substrate, we aimed to determine whether performance on an olfaction test can be used as a clinical marker for monitoring the efficacy of donepezil in elderly people with AD.

Methods: Twenty-five participants with mild to moderate AD, planned for donepezil treatment, were recruited from mental health services for older adults in this open-labeled study. Assessments before commencing donepezil included Mini-Mental State Examination, Neuropsychiatric Inventory, Bristol Activities of Daily Living, and the University of Pennsylvania Smell Identification Test. After 3 months of treatment, the primary outcome measure, the Clinician Interview Based Impression of Change plus caregiver input (CIBIC-plus), was completed, and the baseline assessments were repeated.

Results: Eighteen patients continued to receive donepezil at follow-up. The CIBIC-plus outcome correlated with changes in University of Pennsylvania Smell Identification Test and Bristol Activities of Daily Living scores from the baseline (r = 0.7, P < 0.01). In addition, it was the change in smell identification function after treatment that best predicted CIBIC-plus outcome (P < 0.05) on ordinal regression analysis.

Conclusions: Smell identification function could be useful as a clinical measure to assess treatment response with donepezil in AD. This is a nonblind uncontrolled study, and the outcome indicates the need for a controlled study.

From the *Institute of Psychiatry, King's College London; and †South London and Maudsley NHS Foundation Trust, London, United Kingdom.

Received December 3, 2008; accepted after revision April 24, 2009.

Reprints: Latha Velayudhan, DNB (Psychiatry), Section of Old Age Psychiatry, Institute of Psychiatry, King's College London, PO Box 70, De Crespigny Park, London SE5 8AF, United Kingdom (e-mail:

This work was supported by the National Institute for Health Research Specialist Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and the Institute of Psychiatry, King's College London and the Medical Research Council Centre for Neurodegeneration Research at King's College London.

© 2009 Lippincott Williams & Wilkins, Inc.