The diagnostic potential of the olfactory stress test in Alzheimer's disease

Olfactory deficits are a common symptom of Alzheimer’s disease (AD) and have been investigated as a potential biomarker for the early detection of this condition. One limitation has been the ability of olfactory tests to differentiate olfactory impairment associated with AD from those seen in other neurological conditions. The Olfactory Stress Test (OST) utilises the University of Pennsylvania Smell Identification Test (UPSIT) to measure olfactory ability before and after intranasal administration of the anticholinergic drug atropine. Cholinergic deficits are a central feature in emerging AD, and a change in UPSIT score or atropine effect stands to represent a sensitive measure of incipient decline. In this study the OST was explored in participants with AD (n=10), Parkinson’s disease (PD; n=13), Vascular Cognitive Impairment (VCI; n=11) and cognitively unimpaired older adults (Controls; n=25). Each participant also underwent neuropsychological evaluation, volumetric imaging of the hippocampi and apolipoprotein E genotyping. The AD group demonstrated a greater atropine effect than the control group or PD group, and there was no difference evident between the control, PD, and VCI group. A significant correlation was found between the atropine effect and a non-memory composite neuropsychological score. The differential effect of atropine on olfactory performance in people with AD in comparison with controls and other neurological conditions points to a potential diagnostic advantage of the OST over standard tests of olfaction. However, the significant effect of gender and the variance in the atropine effect seen in each group, makes its utility as a diagnostic tool uncertain. Methodological issues remain and longitudinal studies are required to evaluate whether the OST can be used to detect preclinical AD with adequate specificity.