Objective: To investigate associations between hyposmia (olfactory dysfunction) and affective symptom burden in PREDICT-PD participants.

Background: Anxiety, depression, and hyposmia are common non-motor features of Parkinson’s disease (PD) and may emerge during prodromal PD. While both hyposmia and affective symptoms are associated with increased PD risk, whether they co-occur as part of a broader prodromal non-motor phenotype remains incompletely characterised.

Method: PREDICT-PD is an ongoing cohort study collecting longitudinal data remotely from individuals at varying risk of PD. Cross-sectional analyses included participants without diagnosed PD at baseline. Anxiety and depressive symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS), with scores combined to reflect affective burden. Hyposmia was defined using the University of Pennsylvania Smell Identification Test (UPSIT) and a six-item validated smell test incorporated within the PREDICT-PD risk assessment framework. Group differences in affective symptom burden between individuals with and without hyposmia were examined. Multivariable linear regression models assessed associations between binary hyposmia and total anxiety and depressive symptom scores, adjusting for age and sex.

Results: A total of 3,988 participants were included (mean age 68.2 years [SD 5.8]; 59.4% female). In adjusted analyses controlling for age and sex, hyposmia was independently associated with higher overall affective symptom burden as measured by total HADS score (β = 0.69 [95% CI 0.23–1.16], p = 0.003). When anxiety and depressive symptoms were examined separately, hyposmia was significantly associated with greater depressive symptom severity (β = 0.47 [95% CI 0.23–0.70], p < 0.001). In contrast, hyposmia was not associated with anxiety symptom severity after adjustment for age and sex (β = 0.23 [95% CI −0.06 to 0.52], p = 0.12).

Conclusion: Hyposmia is associated with greater affective symptom burden in individuals at risk of PD, driven primarily by depressive symptoms. These findings suggest that depressive features may cluster with hyposmia as part of a non-motor prodromal phenotype. Characterisation of non-motor symptom clustering may support phenotypic stratification and future PD risk prediction.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/affective-symptom-burden-in-individuals-with-olfactory-dysfunction-in-the-predict-pd-cohort/