Olfaction in Parkinson's disease and related disorders

Abstract

Olfactory dysfunction is an early ‘pre-clinical’ sign of Parkinson's disease (PD). The present review is a comprehensive and up-to-date assessment of such dysfunction in PD and related disorders. The olfactory bulb is implicated in the dysfunction, since only those syndromes with olfactory bulb pathology exhibit significant smell loss. The role of dopamine in the production of olfactory system pathology is enigmatic, as overexpression of dopaminergic cells within the bulb's glomerular layer is a common feature of PD and most animal models of PD. Damage to cholinergic, serotonergic, and noradrenergic systems is likely involved, since such damage is most marked in those diseases with the most smell loss. When compromised, these systems, which regulate microglial activity, can influence the induction of localized brain inflammation, oxidative damage, and cytosolic disruption of cellular processes. In monogenetic forms of PD, olfactory dysfunction is rarely observed in asymptomatic gene carriers, but is present in many of those that exhibit the motor phenotype. This suggests that such gene-related influences on olfaction, when present, take time to develop and depend upon additional factors, such as those from aging, other genes, formation of α-synuclein- and tau-related pathology,or lowered thresholds to oxidative stress from toxic insults. The limited data available suggest that the physiological determinants of the early changes in PD-related olfactory function are likely multifactorial and may include the same determinants as those responsible for a number of other non-motor symptoms of PD, such as dysautonomia and sleep disturbances.

Optimizing odor identification testing as quick and accurate diagnostic tool for Parkinson's disease

“…Part B of the table: Preferred cutoffs of predictive scores were determined by Youden's index in the discovery cohort and, in a subgroup analysis, did not differ between sexes. SS‐8 = subscore of the eight best‐discriminating odors (licorice, anise, mint, cinnamon, banana, pineapple, rose, and coffee).aResults represent means ± standard deviation; P values calculated using Mann‐Whitney's U test.b P value calculated using chi‐square test.cAdditional lower cutoffs were applied in the distinction versus DDs because a mildly decreased sense of smell had been reported in MSA, PSP, and ET patients2, 5 and our model was established in a comparison of PD patients with HCs (discovery cohort).MMSE, Mini–Mental State Examination; NA, not applicable.…”

“…Olfactory deficits affect 75% to 90% of patients with Parkinson's disease (PD), and olfactory testing may also represent a sensitive screening test for individuals at risk of developing PD,1, 2, 3, 4 whereas olfactory function is normal or only mildly impaired in other forms of degenerative parkinsonism or essential tremor (ET) 2, 5. Olfactory testing has recently been incorporated in the newly established International Parkinson and Movement Disorder Society criteria for PD6 and prodromal PD 7…”

“…To test for olfactory performance in PD, most studies have focused on odor identification using the disposable University of Pennsylvania Smell Identification Test (UPSIT) or the reusable Sniffin' Sticks test battery assessing olfactory threshold and odor discrimination in addition to odor identification 2, 8. Both tests are time‐consuming, and olfactory testing is rarely performed in clinical routine.…”

Improved diagnosis of Parkinson's disease from a detailed olfactory phenotype

“…Previous studies have shown that clinically diagnosed PD is associated with olfactory dysfunction, most using the now common University of Pennsylvania Smell Identification Test (UPSIT) multiple choice test 6, 9. Such testing is critical for assessing olfactory dysfunction, since self‐report can be unreliable 10.…”

“…Such testing is critical for assessing olfactory dysfunction, since self‐report can be unreliable 10. However, the only information typically retained from an UPSIT test – the total score – may be a crude measure for guiding diagnosis; while the mean total score of the PD subpopulation is lower than in healthy subjects,9 the sensitivity and specificity of the total score in distinguishing PD from non‐PD‐related olfactory deficits may not be high enough, or early enough in disease progression, to be clinically valuable 11. But what if the pattern of olfactory decline due to PD differs from that due to other age‐related pathologies or to normal aging?…”