Objective: To investigate whether olfactory function predicts disease progression in progressive supranuclear palsy (PSP).

Background: Olfactory function is under-investigated in PSP. Emerging evidence from clinico-neuropathological studies suggests that mild olfactory impairment occurs in some patients with PSP. However, the clinical significance of olfactory dysfunction, especially its association with disease progression in PSP, remains largely unexplored.

Method: We included 244 PSP patients (145 PSP-RS, 82 PSP-subcortical, and 17 PSP-cortical) who underwent the Sniffin’ Sticks Smell Test-12 (SSST-12) from the Progressive Supranuclear Palsy Neuroimage Initiative (PSPNI). Olfactory dysfunction was defined by age-related cut-offs: <10, <7, <6, and <5 for ages 41–50, 51–69, 70–79, and ≥80 years, respectively. Survival and progression to loss of independence were analyzed using the Kaplan-Meier curve and Cox proportional hazards models. In a longitudinal subset (n=117; mean 2.9 visits over a median of 2.4 years), linear mixed-effects models examined associations between baseline olfaction and PSP Rating Scale (PSPRS) trajectories.

Results: At baseline, patients with olfactory dysfunction (n=134, 54.9%) had higher PSPRS total, history, mentation, ocular motor, and limb motor scores (all P<0.05). Olfactory dysfunction was associated with a higher risk of death or loss of independence (log-rank test, P<0.001). After adjusting for age at onset, disease duration, sex, education, and Mini-Mental State Examination (MMSE), the SSST-12 score remained an independent prognosticator (P=0.016). Longitudinally, the olfactory dysfunction group (n=60, 51.3%) exhibited faster worsening in PSPRS total (P=0.012), history (P=0.018), and gait/midline (P=0.001) scores. SSST-12 scores similarly predicted more rapid progression in these domains (all P<0.01), whereas baseline MMSE failed to predict PSPRS changes (all P>0.05). These associations remained stable after excluding patients with baseline MMSE < 24 and adjusting for phenotype-by-time interactions.

Conclusion: Olfactory dysfunction independently predicts poorer survival and faster disease progression in PSP. Olfactory assessment may serve as a convenient tool for prognostic stratification and patient selection in clinical trials.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/olfactory-function-as-a-biomarker-of-disease-progression-in-progressive-supranuclear-palsy/