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Non-demented Parkinson’s disease patients with apathy show decreased grey matter volume in key executive and reward-related nodes

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Abstract

Apathy is a common but poorly understood neuropsychiatric disturbance in Parkinson’s disease (PD). In a recent study using event-related brain potentials we demonstrated impaired reward processing and compromised mesocortico-limbic pathways in PD patients with clinical symptoms of apathy. Here we aimed to further investigate the involvement of reward circuits in apathetic PD patients by assessing potential differences in brain structure. Using structural magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) we quantified grey matter volume (GMV) in a sample of 18 non-demented and non-depressed PD patients with apathy, and 18 matched non-apathetic patients. Both groups were equivalent in terms of sociodemographic characteristics, disease stage, cognitive performance and L-Dopa equivalent daily dose. Apathetic patients showed significant GMV loss in cortical and subcortical brain structures. Various clusters of cortical GMV decrease were found in the parietal, lateral prefrontal cortex, and orbitofrontal cortex (OFC). The second largest cluster of GMV loss was located in the left nucleus accumbens (NAcc), a subcortical structure that is a key node of the human reward circuit. Isolated apathy in our sample is explained by the combined GMV loss in regions involved in executive functions, and cortical and subcortical structures of the mesolimbic reward pathway. The correlations observed between apathy and cognition suggests apathy as a marker of more widespread brain degeneration even in a sample of non-demented PD patients.

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Acknowledgments

The work of Frederic Sampedro is supported by a Spanish Government FPU doctoral grant.

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Authors and Affiliations

  1. Department of Neurology, Movement Disorders Unit, Hospital de la Santa Creu i Sant Pau Sant Antoni M. Claret 167, Universitat Autònoma de Barcelona, 08025, Barcelona, Spain

    Saul Martinez-Horta, Javier Pagonabarraga, Ramón Fernandez-Bobadilla, Juan Marin-Lahoz & Jaime Kulisevsky

  2. Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain

    Saul Martinez-Horta, Javier Pagonabarraga, Ramón Fernandez-Bobadilla, Juan Marin-Lahoz, Jordi Riba & Jaime Kulisevsky

  3. Centro Investigación Biomedica en Red-Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain

    Saul Martinez-Horta, Javier Pagonabarraga, Ramón Fernandez-Bobadilla, Juan Marin-Lahoz & Jaime Kulisevsky

  4. Faculty of Medicine, Autonomous University of Barcelona, Barcelona, Spain

    Frederic Sampedro & Jaime Kulisevsky

  5. Universitat Oberta de Catalunya (UOC), Barcelona, Spain

    Ramón Fernandez-Bobadilla & Jaime Kulisevsky

  6. Human Neuropsychopharmacology Group IIB-Sant Pau, Barcelona, Spain

    Jordi Riba

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  1. Saul Martinez-Horta
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  2. Frederic Sampedro
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  3. Javier Pagonabarraga
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  4. Ramón Fernandez-Bobadilla
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  5. Juan Marin-Lahoz
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  6. Jordi Riba
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  7. Jaime Kulisevsky
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Correspondence to Jaime Kulisevsky.

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Financial disclosures

Saul Martinez-Horta, Frederic Sampedro, Ramon Fernandez-Bobadilla and Juan Marin-Lahoz declare that they have no conflict of interest.

Javier Pagonabarraga: Has received honoraria for lecturing or consultation from Boehringer Ingelheim, UCB, Allergan, Ipsen, and Lundbeck.

Jaime Kulisevsky: Has received honoraria for lecturing or consultation from the Michael J Fox Foundation, Merck Serono, AbbVie, Boehringer Ingelheim, UCB, Zambon, MSD, Italfarmaco, General Electric, and Lundbeck.

Informed consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, and the applicable revisions at the time of the investigation. Informed consent was obtained from all patients for being included in the study.

Conflict of interest

All the authors report no conflict of interest.

Funding sources

This study was partially funded by public research grants from CIBERNED (Fundación CIEN, Instituto de Salud Carlos III, Spain). The work of Frederic Sampedro is supported by a Spanish Government FPU doctoral grant.

Additional information

Saul Martinez-Horta and Frederic Sampedro are contributed equally to this work

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Figure shows a more bilateral distribution of GMV loss when less strict criteria is applied (p < 0.01). (GIF 352 kb)

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Martinez-Horta, S., Sampedro, F., Pagonabarraga, J. et al. Non-demented Parkinson’s disease patients with apathy show decreased grey matter volume in key executive and reward-related nodes. Brain Imaging and Behavior 11, 1334–1342 (2017). https://doi.org/10.1007/s11682-016-9607-5

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