Preserved Serotonin Transporter Availability in Parkinson Disease Measured with Either [11C]MADAM or [11C]DASB: A Study Including 2 Separate Cohorts of Nondepressed Patients.

Serotonin transporter (SERT) availability was assessed using 2 tracers, [11C]N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine ([11C]DASB) and [11C]N,N-dimethyl-2-(2-amino-4-fluoromethylphenylthio)benzylamine) ([11C]MADAM), in independent cohorts of patients and controls. This study aimed to independently confirm whether SERT remains intact in nondepressed individuals with early-stage Parkinson disease (PD), because the use of diverse methodologies could potentially yield disparate results.

Methods

Seventeen PD patients (5 women and 12 men; age, 64 ± 7 y; Unified Parkinson's Disease Rating Scale motor score, 23 ± 5; Beck Depression Inventory score, 5 ± 4) and 20 age- and sex-matched healthy controls underwent [11C]MADAM PET at Karolinska Institutet. Fifteen PD patients (5 women and 10 men; age, 59 ± 9 y; Unified Parkinson's Disease Rating Scale motor score, 15 ± 7; Beck Depression Inventory score, 4 ± 4) and 8 controls were examined with [11C]DASB PET at the University of British Columbia. PET scans were performed at both institutions using a high-resolution research tomograph. A simplified reference tissue model and Logan graphical analysis were used to calculate the regional nondisplaceable binding potential (BPND), using the cerebellum as the reference. Parametric BPND images were generated using wavelet-aided parametric imaging. MRI-defined volumes of interest included cortical and subcortical regions, as well as brain stem nuclei.

Results

There were no significant differences between controls and early-stage PD patients in either the [11C]DASB or the [11C]MADAM cohort, regardless of the analysis method. Group differences (Cohen d) in the [11C]DASB cohort ranged from 0.34 to 0.86 in brain stem nuclei, 0.09 to 0.61 in subcortical regions, and 0.28 to 0.70 in cortical regions. In the [11C]MADAM cohort, they ranged from 0.16 to 0.40, 0.19 to 0.55, and 0.32 to 0.61, respectively. Logan BPND highly correlated with simplified reference tissue model BPND for both tracers in each group (P < 0.001).

Conclusion

SERT availability is relatively preserved in nondepressed patients with PD. This study suggests that serotonergic degeneration is not a major feature of the disease in nondepressed patients with nonadvanced disease.