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

NEUROBIOLOGY OF DISEASE

卷:152

Article

Kinnerup, Martin B.^1,2  Sommerauer, Michael^1,2,3,4  Damholdt, Malene F.^1,2,5  Schaldemose, Jeppe L.^1,2  Ismail, Rola^1,2  Terkelsen, Astrid J.⁶  Staer, Kristian^1,2  Hansen, Allan^1,2  Fedorova, Tatyana D.^1,2  Knudsen, Karoline^1,2  Skjaerbaek, Casper^1,2  Borghammer, Per^1,2  Pavese, Nicola^1,2,7  Brooks, David J.^1,2,7,8  Nahimi, Adjmal^1,2,9 

[1] Aarhus Univ Hosp, Dept Nucl Med, DK-8200 Aarhus N, Denmark

[2] Aarhus Univ Hosp, PET Ctr, DK-8200 Aarhus N, Denmark

[3] Univ Cologne, Univ Hosp Cologne, Dept Neurol, D-50937 Cologne, Germany

[4] Univ Cologne, Fac Med, D-50937 Cologne, Germany

[5] Aarhus Univ, Dept Psychol & Behav Sci, DK-8000 Aarhus, Denmark

[6] Aarhus Univ Hosp, Dept Neurol, DK-8200 Aarhus N, Denmark

[7] Newcastle Univ, Translat & Clin Res Inst, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[8] Imperial Coll London, Dept Brain Sci, London SW7 2AZ, England

[9] Univ Sjukhuset, Restorat Parkinson Unit, Dept Neurol, S-22184 Lund, Sweden

关键词: Parkinson's disease;    Tremor;    C-11-MeNER;    Positron emission tomography (PET);    Noradrenaline transporter;   

DOI  :  10.1016/j.nbd.2021.105295

来源: Elsevier

【 摘 要 】

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 (PDT+) or without (PDT-) rest tremor had C-11-methylreboxetine(C-11-MeNER) positron emission tomography (PET) to test the hypothesis that noradrenaline terminal function was relatively preserved in PDT+ compared to PDT-. Methods: Sixty-five PD patients and 28 healthy controls (HC) were scanned with C-11-MeNER PET. Patients were categorized as PDT+ if subscores in UPDRS-III item 3 or MDS-UPDRS-III item 17 was >= 2; remaining were categorized as PDT-. Simplified reference tissue model 2 distribution volume ratios (DVR) for C-11-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. Results: Tremor positive PD patients had a significantly higher mean C-11-MeNER DVR compared to PDT- in LC and thalamus. The PDT+ mean LC DVR was similar to that of HC. PDT+ mean C-11-MeNER DVRs were significantly lower than HC in the dorsal raphe while the PDT- group showed significantly lower mean C-11-MeNER DVR across all regions compared to HC. Conclusion: 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 PDT+ in LC and thalamus. The greater loss of noradrenergic transporters in PDT- in LC and thalamus compared with PDT+ is in line with earlier in-vitro studies and could potentially contribute to their tremor negative phenotype.