Progressive loss of raphe nuclei serotonin transporter in early Parkinson's disease: A longitudinal 123 I-FP-CIT SPECT study

Background: Serotonergic raphe nuclei dysfunction has been documented in Parkinson's disease, both in pathological and neuroimaging studies, and has been associated with scores of tremor and non-motor symptoms. However, no in vivo longitudinal investigations have been conducted to assess the rate of decline of raphe serotonin transporter availability in the early stages of the disease. Objective: To measure the rate of decline of raphe serotonin transporter availability over a two-year interval in patients with recently diagnosed disease and its association with non-motor symptoms over time. Methods: Baseline and two-year follow-up 123 ioflupane-fluoropropyl-carbomethoxy-3-beta-4-iodo-phenyltropane ( 123 I-FP-CIT) SPECT scans of 173 early Parkinson's disease patients enrolled in the Parkinson's Progressive Markers Initiative were analysed and non-motor symptoms scores recorded. Results: A 16.6 ± 20.9% (mean ± SD) reduction in raphe serotonin transporter availability was found from baseline to two-year follow-up in the entire cohort. No differences in progression were found between tremor dominant and postural instability/gait difficulty phenotypes. At follow-up 34.1% of patients showed a moderate-to-severe reduction of raphe serotonin transporter availability with respect to the controls’ mean. We did not find any significant correlation between raphe serotonin transporter availability and scores of depression, excessive daytime sleepiness and REM sleep behaviour disorder. Conclusion: 123 I-FP-CIT SPECT was able to measure longitudinal reductions in raphe serotonin transporter availability in the early phases of Parkinson's disease. About four years after diagnosis, raphe serotonin transporter availability was significantly reduced in more than one third of the population, but does not appear to be correlated to non-motor symptoms at this stage.