Clinical and Dopamine Depletion Patterns in Hyposmia- and Dysautonomia-Dominant Parkinson's Disease

Background: Olfactory or autonomic dysfunction is one of the earliest prodromal symptoms of Parkinson's disease (PD). It has not been investigated whether PD patients have different phenotypes depending on the presence of these prodromal symptoms. Objective: To investigate whether hyposmia-dominant and dysautonomia-dominant patients with early PD have different clinical manifestations and nigrostriatal degeneration. Methods: This cross-sectional study recruited 168 drug-naive PD patients and 34 control subjects. PD patients were classified as patients without hyposmia and dysautonomia (PD-H+D, n = 51), hyposmia dominant patients (PD H+D, n = 36), dysautonomia-dominant patients (PD-H-D+, n = 33), and patients with hyposmia and dysautonomia (PD-H+D+, n = 48). We then compared the baseline clinical characteristics, striatal specific to non-specific binding ratio (SNBR), neuropsychological performance, and neuropsychiatric symptoms among the groups. Results: The PD-H+D- group had a lower SNBR in the ventral striatum (p = 0.013), a greater asymmetric index of striatal SNBRs, and higher prevalence of apathy (p = 0.021) than the PD-H-D+ group. The PD-H-D+ group had older age at onset (p = 0.043) and a higher prevalence of REM sleep behavior disorder (p = 0.041) than the PD-H+D- group. The PD-H+D+ group had higher motor deficits, lower cognitive function, and lower SNBRs in all striatal subregions than the PD-H-D- group. Decreased SNBRs in the anterior caudate, posterior caudate, and ventral striatum were associated with the presence of apathy. Conclusion: The present study suggests that hyposmia-dominant and dysautonomia-dominant PD have different clinical characteristics and patterns of striatal dopamine depletion.