Abstract

Several recently developed biomarkers of Alzheimer disease (AD) are invasive, expensive, and difficult to obtain in most clinical settings. Olfactory identification test performance represents a noninvasive, inexpensive biomarker of AD that may have predictive accuracy comparable with neuroimaging measures and biomarkers assessed in cerebrospinal fluid. Neurofibrillary tangles in the olfactory bulb are among the earliest pathologic features of AD and are also seen in the projection pathways from the olfactory bulb to secondary olfactory brain regions, including the piriform and medial temporal cortex, orbitofrontal cortex, and other limbic regions. Odor identification impairment characterizes AD and predicts the clinical transition from mild cognitive impairment to AD in both clinical and community samples. Epidemiologic data indicate that in cognitively intact older adults, impairment in odor identification predicts cognitive decline but that episodic verbal memory impairment does not predict cognitive decline. Odor identification impairment has also been shown to predict mortality in older subjects with mortality risk increasing with greater severity of impairment in odor identification. The exact cause of this association is not known, but olfactory deficits may lead to an increase in accidents in the home, because of the inability to smell and taste food that is unsafe or not smelling a gas leak or fire, and this may increase mortality risk. Standardized tests of odor identification ability are widely available and may provide a useful tool to improve diagnostic and predictive accuracy for cognitive decline, AD, and mortality in older adults.

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