Baseline demographics.

Background
Olfactory dysfunction is a common non-motor symptom in Parkinson’s disease (PD). The objective was to evaluate the association between olfaction in PD with cross-sectional and longitudinal assessments of clinical variables and novel cerebrospinal fluid (CSF) markers.
Methods
Patients with PD and baseline olfactory function assessed using the Brief Smell Identification Test (B-SIT) were included from the BioFINDER-1 cohort. Clinical variables, CSF measures and disease status were assessed longitudinally for up to 11 years. CSF was analyzed using Roche Elecsys® NeuroToolKit, including biomarkers of neurodegeneration, glial activation, neuroinflammation and the core Alzheimer disease biomarkers.
Results
A total of 172 patients with PD were included, 63 with normal olfactory function and 109 with hyposmia. No differences were seen in clinical variables at baseline. Glial fibrillary acidic protein was the only CSF marker differing at baseline, being elevated in hyposmic patients with PD (12.25 ± 3.87 vs 10.46 ± 3.68, p = 0.001). At follow-up, olfactory function declined predominantly in patients with normal olfaction at baseline (β = −0.25 [−0.40 to −0.12], p = 0.001). Patients with PD with both olfactory dysfunction and amyloid-positivity (defined by the CSF Aβ42/Aβ40 ratio) declined faster in several cognitive and motor measures. Olfaction and amyloid-status were independently associated with increased risk of progressing to dementia (B-SIT score, HR = 0.77 [0.67–0.88] and amyloid-positivity, HR = 4.47 [2.30–8.67]).
Conclusions
Olfactory dysfunction and amyloid-positivity are independently associated with a higher rate of cognitive decline and progression to dementia in patients with PD. Novel CSF markers of neurodegeneration and glial-activity do not differ depending on olfactory status in PD.