Olfaction in Parkin-associated Parkinson disease

Impairment of olfactory function is commonly seen in neurodegenerative diseases such as Parkinson disease (PD), Alzheimer disease, and Huntington disease, but also occurs during normal aging. Therefore, it is not too surprising that in sporadic PD (SPD), olfactory impairment can appear both before and after the onset of motor dysfunction. Nonetheless, in PD, the severity of the olfactory impairment seems to correlate with the severity of motor symptoms, although not in a linear fashion.

Interestingly, olfactory dysfunction in PD is independent of disease stage and disease duration but is dependent on disease subtype—it is more severe in the rigidity-bradykinesia–predominant form than in the tremor-predominant form of PD.^1,2 Olfactory dysfunction is also independent of dopaminergic therapy, suggesting that deficits in other neurotransmitter systems contribute to olfactory dysfunction. Indeed, neuropathologic studies of the olfactory system in PD reveal that even though there is significant neuronal loss, dopaminergic neurons in the olfactory bulb are not affected by the neurodegenerative process and do not exhibit Lewy bodies (LB).³ Somewhat surprisingly, one study reported an increase in the numbers of dopaminergic neurons in patients with PD compared to controls.⁴

Given the extensive interactions of the olfactory system with its environment, early hypotheses to explain olfactory system dysfunction in neurodegenerative disease in general, …