Olfactory deficits a biomarker of Alzheimer’s disease?


REPORT FROM THE 67TH AMERICAN ACADEMY OF NEUROLOGY (AAN) ANNUAL MEETING – WASHINGTON DC, APRIL 18-25, 2015 – Impaired olfaction is a common observation in patients with mild cognitive impairment (MCI) and Alzheimer’s disease, and has been variously attributed to neurodegenerative changes of the olfactory bulb, amygdala, hippocampus or other structures (Thomann et al. J Alzheimers Dis 2009;17:213-21; Kjelvik et al. BMC Neurol 2014;14:168).

A cross-sectional study of patients with amnestic MCI, AD and healthy controls assessed olfaction with the University of Pennsylvania Smell Identification Test (UPSIT) (Hagemeier et al. AAN 2015; abstract P2.169). Magnetic resonance imaging volumetric analysis was then performed on deep grey-matter (DGM) structures; results were adjusted for age/sex and normalized to head size.

Right hippocampus volume was slightly smaller in MCI patients with impaired olfaction compared to those with normal olfaction. In contrast, volumes were significantly lower for the right amygdala, right and left thalamus, right globus pallidus and total DGM in AD patients.

Olfactory deficits often precede cognitive and memory impairment in MCI/AD, and a recent study found that impaired odour identification was superior to deficits in verbal episodic memory in predicting cognitive decline in AD patients (Devanand et al. Neurology 2015;84:182-189). As a result, impaired olfaction may be a useful biomarker for early progression (Vasavada et al. J Alzheimers Dis 2015;45:947-58).

Two new studies have examined the potential utility of impaired olfaction as a biomarker in AD. Olfactory deficits were consistently associated with neocortical and GM volume loss in a series of MCI/AD patients (Rafique et al. AAN 2015; abstract P2.171). However, further work is needed to determine the timing of olfactory deficits, cognitive impairment and cerebral atrophy. This has been examined in a preliminary study of 96 patients with amnestic MCI followed for 16 months (Amrutkar et al. AAN 2015; abstract P2.170). During the observation period, 36.4% of aMCI patients with impaired olfaction developed AD, compared to 17.3% of aMCI patients with intact olfaction. The ROC AUC for conversion to AD was 0.62, which the authors noted is comparable to CSF biomarkers such as beta-amyloid42, tau and p-tau. Thus, impaired olfaction may be an easily administered, low-cost tool for stratifying the risk of conversion from aMCI to AD.

Guest Reviewer: Dr. Daniel Selchen, Head of Neurology, St. Michael’s Hospital, Toronto, Canada

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