Preserved noradrenergic function in Parkinson's disease patients with rest tremor

Noradrenergic neurotransmission may play an important role in tremor modulation through its innervation of key structures of the central tremor circuits. Here, Parkinson's disease (PD) patients with (PD^T+) or without (PD^T-) rest tremor had ¹¹C-methylreboxetine(¹¹C-MeNER) positron emission tomography (PET) to test the hypothesis that noradrenaline terminal function was relatively preserved in PD^T+ compared to PD^T-.

Sixty-five PD patients and 28 healthy controls (HC) were scanned with ¹¹C-MeNER PET. Patients were categorized as PD^T+ if subscores in UPDRS-III item 3 or MDS-UPDRS-III item 17 was ≥2; remaining were categorized as PD^T-. Simplified reference tissue model 2 distribution volume ratios (DVR) for ¹¹C-MeNER were calculated for thalamus, dorsal and median raphe, locus coeruleus (LC) and red nucleus using time activity curves (TACs) obtained from volumes of interest (VOI). Data were statistically interrogated with a general linear mixed model using 'region', and 'group' as factors and the interaction of 'region x group' was examined.

Tremor positive PD patients had a significantly higher mean ¹¹C-MeNER DVR compared to PD^T- in LC and thalamus. The PD^T+ mean LC DVR was similar to that of HC. PD^T+ mean ¹¹C-MeNER DVRs were significantly lower than HC in the dorsal raphe while the PD^T- group showed significantly lower mean ¹¹C-MeNER DVR across all regions compared to HC.

While both PD ^T+ and PD ^T- groups showed a significant loss of noradrenaline terminal function compared to controls, noradrenergic neurons were relatively preserved in PD^T+ in LC and thalamus. The greater loss of noradrenergic transporters in PD^T- in LC and thalamus compared with PD^T+ is in line with earlier in-vitro studies and could potentially contribute to their tremor negative phenotype.