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

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Preserved noradrenergic function in Parkinson's disease patients with rest tremor. / Kinnerup, Martin B; Sommerauer, Michael; Damholdt, Malene F; Schaldemose, Jeppe L; Ismail, Rola; Terkelsen, Astrid J; Stær, Kristian; Hansen, Allan; Fedorova, Tatyana D; Knudsen, Karoline; Skjærbæk, Casper; Borghammer, Per; Pavese, Nicola; Brooks, David J; Nahimi, Adjmal.

In: Neurobiology of Disease, Vol. 152, 105295, 05.2021.

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@article{adcf0effa4b64b7ba42268e07f084ccf,
title = "Preserved noradrenergic function in Parkinson's disease patients with rest tremor",
abstract = "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 11C-methylreboxetine(11C-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 11C-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) 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 11C-MeNER DVR compared to PDT- in LC and thalamus. The PDT+ mean LC DVR was similar to that of HC. PDT+ mean 11C-MeNER DVRs were significantly lower than HC in the dorsal raphe while the PDT- group showed significantly lower mean 11C-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.",
keywords = "C-MeNER, Noradrenaline transporter, Parkinson's disease, Positron emission tomography (PET), Tremor",
author = "Kinnerup, {Martin B} and Michael Sommerauer and Damholdt, {Malene F} and Schaldemose, {Jeppe L} and Rola Ismail and Terkelsen, {Astrid J} and Kristian St{\ae}r and Allan Hansen and Fedorova, {Tatyana D} and Karoline Knudsen and Casper Skj{\ae}rb{\ae}k and Per Borghammer and Nicola Pavese and Brooks, {David J} and Adjmal Nahimi",
note = "Copyright {\textcopyright} 2021. Published by Elsevier Inc.",
year = "2021",
month = may,
doi = "10.1016/j.nbd.2021.105295",
language = "English",
volume = "152",
journal = "Neurobiology of Disease",
issn = "0969-9961",
publisher = "Academic Press",

}

RIS

TY - JOUR

T1 - Preserved noradrenergic function in Parkinson's disease patients with rest tremor

AU - Kinnerup, Martin B

AU - Sommerauer, Michael

AU - Damholdt, Malene F

AU - Schaldemose, Jeppe L

AU - Ismail, Rola

AU - Terkelsen, Astrid J

AU - Stær, Kristian

AU - Hansen, Allan

AU - Fedorova, Tatyana D

AU - Knudsen, Karoline

AU - Skjærbæk, Casper

AU - Borghammer, Per

AU - Pavese, Nicola

AU - Brooks, David J

AU - Nahimi, Adjmal

N1 - Copyright © 2021. Published by Elsevier Inc.

PY - 2021/5

Y1 - 2021/5

N2 - 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 11C-methylreboxetine(11C-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 11C-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) 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 11C-MeNER DVR compared to PDT- in LC and thalamus. The PDT+ mean LC DVR was similar to that of HC. PDT+ mean 11C-MeNER DVRs were significantly lower than HC in the dorsal raphe while the PDT- group showed significantly lower mean 11C-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.

AB - 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 11C-methylreboxetine(11C-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 11C-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) 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 11C-MeNER DVR compared to PDT- in LC and thalamus. The PDT+ mean LC DVR was similar to that of HC. PDT+ mean 11C-MeNER DVRs were significantly lower than HC in the dorsal raphe while the PDT- group showed significantly lower mean 11C-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.

KW - C-MeNER

KW - Noradrenaline transporter

KW - Parkinson's disease

KW - Positron emission tomography (PET)

KW - Tremor

U2 - 10.1016/j.nbd.2021.105295

DO - 10.1016/j.nbd.2021.105295

M3 - Journal article

C2 - 33549722

VL - 152

JO - Neurobiology of Disease

JF - Neurobiology of Disease

SN - 0969-9961

M1 - 105295

ER -