Abstract
This minireview discusses our current understanding of the olfactory dysfunction that is frequently observed in sporadic and familial forms of Parkinson's disease and parkinsonian syndromes. We review the salient characteristics of olfactory dysfunction in these conditions, discussing its prevalence and characteristics, how neuronal processes and circuits are altered in Parkinson's disease, and what is assessed by clinically used measures of olfactory function. We highlight how studies of monogenic Parkinson's disease and investigations in ethnically diverse populations have contributed to understanding the mechanisms underlying olfactory dysfunction. Furthermore, we discuss how imaging and system-level approaches have been used to understand the pathogenesis of olfactory dysfunction. We discuss the challenging, remaining gaps in understanding the basis of olfactory dysfunction in neurodegeneration. We propose that insights could be obtained by following longitudinal cohorts with familial forms of Parkinson's disease using a combination of approaches: a multifaceted longitudinal assessment of olfactory function during disease progression is essential to identify not only how dysfunction arises, but also to address its relationship to motor and non-motor Parkinson's disease symptoms. An assessment of cohorts having monogenic forms of Parkinson's disease, available within the Genetic Epidemiology of Parkinson's Disease (GEoPD), as well as other international consortia, will have heuristic value in addressing the complexity of olfactory dysfunction in the context of the neurodegenerative process. This will inform our understanding of Parkinson's disease as a multisystem disorder and facilitate the more effective use of olfactory dysfunction assessment in identifying prodromal Parkinson's disease and understanding disease progression.
Highlights
Since Ansari and Johnson [1] first reported that olfactory dysfunction (OD) occurs in Parkinson’s disease (PD), OD has been evaluated using tests of odor identification, odor discrimination, odor-threshold detection and electrophysiology [2,3,4]
Because OD is prominent in PD [16, 17] and its onset may signal prodromal PD, Olfactory Dysfunction in Parkinson’s Disease it is important to understand how and when OD arises, the mechanisms underlying its association with PD progression, and identify interventions for OD
Cross-sectional studies revealed that OD occurs in sporadic PD prior to the initiation of dopaminergic therapy [reviews: [3, 4, 18,19,20]]
Summary
Since Ansari and Johnson [1] first reported that olfactory dysfunction (OD) occurs in Parkinson’s disease (PD), OD has been evaluated using tests of odor identification, odor discrimination, odor-threshold detection and electrophysiology [2,3,4]. Variable OD is seen in all studies of sporadic PD and those monogenic PD forms resembling sporadic PD (SNCA, GBA, LRRK2), including at motor-symptom onset.
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