Cerebral Imaging Markers of GBA and LRRK2 Related Parkinson’s Disease and Their First-Degree Unaffected Relatives
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Cerebral atrophy has been detected in patients with Parkinson’s disease (PD) both with and without dementia, however differentiation based on genetic status has thus far not yielded robust findings. We assessed cortical thickness and subcortical volumes in a cohort of PD patients and healthy controls carriers of the G2019S mutation in the LRRK2 gene and the common GBA mutations, in an attempt to determine whether genetic status influences structural indexes. Cortical thickness and subcortical volumes were computed and compared between six groups of participants; idiopathic PD, GBA-PD, LRRK2-PD, non-manifesting non-carriers (NMNC), GBA-non-manifesting carriers (NMC) and LRRK2-NMC utilizing the FreeSurfer software program. All participants were cognitively intact based on a computerized cognitive assessment battery. Fifty-seven idiopathic PD patients, 9 LRRK2-PD, 12 GBA-PD, 49 NMNC, 41 LRRK2-NMC and 14 GBA-NMC participated in this study. Lower volumes among patients with PD compared to unaffected participants were detected in bilateral hippocampus, nucleus accumbens, caudate, thalamus, putamen and amygdala and the right pallidum (p = 0.016). PD patients demonstrated lower cortical thickness indexes in a majority of regions assessed compared with non-manifesting participants. No differences in cortical thickness and subcortical volumes were detected within each of the groups of participants based on genetic status. Mutations in the GBA and LRRK2 genes are not important determinants of cortical thickness and subcortical volumes in both patients with PD and non-manifesting participants. PD is associated with a general reduction in cortical thickness and sub-cortical atrophy even in cognitively intact patients.
KeywordsCortical thickness Sub-cortical volumes Parkinson’s disease LRRK2 GBA
We would like to thank the MJFF for supporting this work. A special thanks to Dr. Moran Artzi for art assistance with the figure. This work has been made possible by the help of the MJFF.
Avner Thaler reports receiving funding for consulting from AbbVie pharmaceuticals. Tanya Gurevich reports receiving funding for travel and speaker honoraria from the National Parkinson Foundation, Solvay pharmaceuticals, TEVA, RAFA, Medtronic, Novartis, Medison, Allergan, GlaxoSmithKline, Perrigo and Intecpharma. Avi Orr-Urtreger reports receiving research support from the Israeli Science Foundation Legacy Heritage Fund, the Chief Scientist Department of Health, Israel, the ALS Association USA and the Kahn Foundation Israel. Nir Giladi reports serving on the advisory boards of Teva-Lundbeck, NeuroDerm, Intec Pharma and Chairing the Data monitoring safety committee of Teva LTD. Receiving funding for travel and honoraria from Teva-Lundbeck, UCB and NeuroDerm. Serving on the editorial board of the Journal of Parkinson’s Disease. Being a consultant for LTI, NeuroDerm and Intec Pharma. Receiving grants from the NPF, MJFF, Biogen. Anat Mirelman reports receiving funding from the Israeli Science Foundation, Israeli Ministry of Science and Technology, MJFF. Efrat Kliper, Inbal Maidan, Talia Herman, Keren Rosenberg-Katz, Noa Bregman, Tamara Shiner, and Jeffrey M Hausdorff have no funding.
Compliance with Ethical Standards
Conflict of interest
The paper has not been previously published and is not under review by another journal and no conflict of interest was identified among all authors.
The method section contains a statement that the local institute review board has approved this study and that each participant signed an informed consent form.
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