Session Information
Date: Wednesday, September 25, 2019
Session Title: Neuroimaging
Session Time: 1:15pm-2:45pm
Location: Les Muses Terrace, Level 3
Objective: We aimed to assess the associations between Phosphodiesterase 10A (PDE10A) expression in the executive striatum and cognitive performance in vivo, using [11C]IMA107 PET and diffusion tensor imaging in Parkinson’s patients.
Background: PhosphPDE10A regulates cAMP/PKA-CREB signalling, modulating the tonic inhibitory output of indirect and direct pathway neurons on thalamocortical circuits. Preclinical studies have demonstrated PDE10A-associated cognitive changes. Therefore, PDE10A dysregulation in Parkinson’s disease (PD) could potentially contribute to cognitive impairment.
Method: We studied 41 PD patients, 17 early de novo and 24 moderate-advanced levodopa-treated, with no concurrent formal diagnosis of mild cognitive impairment or dementia. Their data was compared with that of 22 healthy controls. Parametric images of [11C]IMA107 non-displaceable binding potential (BPND) values were calculated using the simplified reference tissue model with the cerebellum as nonspecific binding reference tissue. Probabilistic tractography was performed on subjects’ diffusion data, functionally parcellating the striatum by cortical connectivity.
Results: Functional-based parcellations of the striatum revealed lower mean [11C]IMA107 BPND in executive striatum (P=0.008) in PD compared to healthy controls. Middle-advanced levodopa-treated Parkinson’s patients showed greater reduction in the executive striatum mean [11C]IMA107 BPND values compared to de novo PD. Worse performance in visual memory and new learning, assessed with paired associated learning test, correlated with lower [11C]IMA107 BPND values in connectivity-based executive striatum (r=0.450, P=0.024) in Parkinson’s patients.
Conclusion: Our findings demonstrate that loss of PDE10A expression in the executive striatum is associated with visual memory deficits in Parkinson’s patients. This could reflect increased indirect-pathway inhibition of striatal-cortical signalling to cognitive regions. This abstract was also submitted for presentation at the 2019 European Academy of Neurology conference.
To cite this abstract in AMA style:
Z. Chappell, G. Pagano, H. Wilson, F. Niccolini, R. Gunn, E. Rabiner, T. Foltynie, M. Politis. Phosphodiesterase 10A and cognition in Parkinson’s disease [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/phosphodiesterase-10a-and-cognition-in-parkinsons-disease/. Accessed May 18, 2025.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/phosphodiesterase-10a-and-cognition-in-parkinsons-disease/