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

Flavia Niccolini; Heather Wilson; Gennaro Pagano; Christopher Coello; Mitul A. Mehta; Graham E. Searle; Roger N. Gunn; Eugenii A. Rabiner; Thomas Foltynie; Marios Politis

doi:10.1212/WNL.0000000000004201

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

Flavia Niccolini, Heather Wilson, Gennaro Pagano, Christopher Coello, Mitul A. Mehta, Graham E. Searle, Roger N. Gunn, Eugenii A. Rabiner, Thomas Foltynie, Marios Politis^*

^*Corresponding author for this work

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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.

Original language	English
Pages (from-to)	586-593
Number of pages	8
Journal	Neurology
Volume	89
Issue number	6
Early online date	12 Jul 2017
DOIs	https://doi.org/10.1212/WNL.0000000000004201
Publication status	Published - 12 Jul 2017

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Journal Article

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title = "Loss of phosphodiesterase 4 in Parkinson disease: Relevance to cognitive deficits",

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.",

keywords = "Journal Article",

author = "Flavia Niccolini and Heather Wilson and Gennaro Pagano and Christopher Coello and Mehta, {Mitul A.} and Searle, {Graham E.} and Gunn, {Roger N.} and Rabiner, {Eugenii A.} and Thomas Foltynie and Marios Politis",

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year = "2017",

month = jul,

day = "12",

doi = "10.1212/WNL.0000000000004201",

language = "English",

volume = "89",

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TY - JOUR

T1 - Loss of phosphodiesterase 4 in Parkinson disease

T2 - Relevance to cognitive deficits

AU - Niccolini, Flavia

AU - Wilson, Heather

AU - Pagano, Gennaro

AU - Coello, Christopher

AU - Mehta, Mitul A.

AU - Searle, Graham E.

AU - Gunn, Roger N.

AU - Rabiner, Eugenii A.

AU - Foltynie, Thomas

AU - Politis, Marios

PY - 2017/7/12

Y1 - 2017/7/12

N2 - 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.

AB - 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.

KW - Journal Article

UR - http://www.scopus.com/inward/record.url?scp=85026918692&partnerID=8YFLogxK

U2 - 10.1212/WNL.0000000000004201

DO - 10.1212/WNL.0000000000004201

M3 - Article

C2 - 28701494

SN - 0028-3878

VL - 89

SP - 586

EP - 593

JO - Neurology

JF - Neurology

IS - 6

ER -

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

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