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

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)
357 Downloads (Pure)

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 languageEnglish
Pages (from-to)586-593
Number of pages8
JournalNeurology
Volume89
Issue number6
Early online date12 Jul 2017
DOIs
Publication statusPublished - 12 Jul 2017

Keywords

  • Journal Article

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