Olfactory Dysfunction in the Elderly: Basic Circuitry and Alterations with Normal Aging and Alzheimer's Disease

Abstract

Preclinical detection of Alzheimer disease is critical to determining at-risk individuals in order to improve patient and caregiver planning for their futures and to identify individuals likely to benefit from treatment as advances in therapeutics develop over time. Identification of olfactory dysfunction at the preclinical and early stages of the disease is a potentially useful method to accomplish these goals. We first review basic olfactory circuitry. We then evaluate the evidence of pathophysiological change in the olfactory processing pathways during aging and Alzheimer disease in both human and animal models. We also review olfactory behavioral studies during these processes in both types of models. In doing so, we suggest hypotheses about the localization and mechanisms of olfactory dysfunction and identify important avenues for future work.

Keywords: Alzheimer disease; Olfaction; aging; amyloid plaque; early detection; entorhinal cortex; hippocampus; mild cognitive impairment; neurofibrillary tangle; olfactory bulb; olfactory epithelium; orbitofrontal cortex; piriform cortex; tau.

Figure 1

Diagram of the Olfactory Pathway. From Benarroch EE, “Olfactory system: Functional organization and involvement in neurodegenerative disease,” Neurology, Volume 75(12): 1104–1109, with permission from Wolters Kluwer Health.