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Loss of phosphodiesterase 4 in Parkinson disease: Relevance to cognitive deficits

Niccolini, F; Wilson, H; Pagano, G; Coello, C; Mehta, MA; Searle, GE; Gunn, RN; ... Politis, M; + view all (2017) Loss of phosphodiesterase 4 in Parkinson disease: Relevance to cognitive deficits. Neurology , 89 (6) pp. 586-593. 10.1212/WNL.0000000000004201. Green open access

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Abstract

OBJECTIVE: To assess in vivo the expression of phosphodiesterase 4 (PDE4) and its relevance to cognitive symptoms in patients with Parkinson disease (PD) using [(11)C]rolipram PET. METHODS: We studied 12 levodopa-treated patients with PD with no concurrent diagnosis of mild cognitive impairment or dementia. Their data were compared with those from 12 healthy controls. All participants underwent neuropsychiatric and cognitive assessment using the Cambridge Neuropsychological Test Automated Battery. Parametric images of [(11)C]rolipram volume of distribution (VT) values were determined with the Logan plot. RESULTS: Patients with PD performed worse than healthy controls in cognitive examinations assessing psychomotor speed, episodic memory, and spatial working memory and executive function. Patients with PD showed reductions in [(11)C]rolipram VT compared to healthy controls, in the caudate (28%), thalamus (23%), hypothalamus (32%), and cortex (16%). Within thalamic subregions, [(11)C]rolipram VT values in patients with PD were decreased by 12%-32%, with most marked decreases observed in prefrontal and temporal thalamic nuclei, whereas motor nuclei were less affected. Within the cortex, [(11)C]rolipram VT values in patients with PD were decreased by 11%-20%, with most marked decreases observed in posterior dorsolateral frontal cortex, medial frontal cortex, and supplementary motor area, whereas orbitofrontal cortex was less affected. Worse performance in spatial working memory correlated with lower [(11)C]rolipram VT values in posterior dorsolateral frontal cortex, medial frontal cortex, supplementary motor area, precentral gyrus, caudate, and prefrontal thalamic nuclei. CONCLUSIONS: Our findings demonstrate loss of PDE4 expression in the striato-thalamo-cortical circuit, which is associated with deficits of spatial working memory in patients with PD.

Type: Article
Title: Loss of phosphodiesterase 4 in Parkinson disease: Relevance to cognitive deficits
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1212/WNL.0000000000004201
Publisher version: http://dx.doi.org/10.1212/WNL.0000000000004201
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: https://discovery-pp.ucl.ac.uk/id/eprint/1568060
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