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Noradrenergic deficits in Parkinson's disease: Relations to cognitive and cortical oscillatory activity declines

Publikation: Forskning - peer reviewKonferenceabstrakt i tidsskrift

A. Nahimi, M. Sommerauer, K. Ostergaard, M. B. Kinnerup, M. Winterdahl, R. Krogbaek, J. Jacobsen, A. Schacht, P. Borghammer, M. F. Damholdt, B. Johnsen, A. Gjedde

Objectives: In vitro studies suggest that noradrenergic projections from locus coeruleus to subcortical and cortical brain structures, e.g., thalamus, undergo severe neurodegeneration in Parkinson’s disease (PD). Loss of noradrenergic projections may alter oscillatory activity that in turn may be associated with cognitive decline. To test this hypothesis of the origin of cognitive decline in this disease, we used positron emission tomography (PET) to quantify the density of noradrenergic projections in groups of PD patients and healthy controls (HC), in combination with neuropsychological assessment and recording of quantitative electroencephalography (qEEG).

Methods: Following administration of 11C-MeNER, the positron-emitting form of a selective noradrenaline reuptake transporter antagonist, 17 non-demented PD patients and 10 HC underwent 90–120 minutes' dynamic PET. The caudate was established as the reference region in datasets with arterial blood samples. The binding potential of 11C-MeNER relative to non-displaceable tracer (BPND) was estimated with the simplified reference tissue model 2 (SRTM2), correlated to cognitive function in four domains, and to changes of cortical oscillatory activities measured with qEEG.

Results: Global 11C-MeNER BPND values were reduced numerically in the PD group, with regionally significant declines in the thalamus, hypothalamus, and nucleus ruber. Tremor was associated with attenuated decline of tracer binding. The value of thalamic 11C-MeNER BPND was associated with cognitive performance, independent of premorbid cognitive function or disease. PD patients had significant slowing of qEEG, e.g., the background alpha rhythm, but only EEG reactivity upon eye opening correlated with thalamic 11C-MeNER BPND in PD patients.

Conclusion: This is the first direct quantification of noradrenergic denervation in vivo in PD patients. In agreement with predictions from in vitro studies, we discovered a global decline of noradrenergic projections in the brains of PD patients in vivo. Noradrenergic degeneration in PD may explain perturbed cognition associated with the reduced cortical oscillatory activity.
OriginalsprogEngelsk
TidsskriftJournal of Cerebral Blood Flow and Metabolism
Vol/bind37
TidsskriftsnummerS1
Sider (fra-til)310-310
ISSN0271-678X
DOI
StatusUdgivet - apr. 2017

ID: 182544640