Cerebral Imaging Markers of GBA and LRRK2 Related Parkinson’s Disease and Their First-Degree Unaffected Relatives

Avner Thaler, Efrat Kliper, Inbal Maidan, Talia Herman, Keren Rosenberg-Katz, Noa Bregman, Tanya Gurevich, Tamara Shiner, Jeffrey M. Hausdorff, Avi Orr-Urtreger, Nir Giladi, Anat Mirelman

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1029-1036
Number of pages8
JournalBrain Topography
Volume31
Issue number6
DOIs
StatePublished - 1 Nov 2018
Externally publishedYes

Keywords

  • Cortical thickness
  • GBA
  • LRRK2
  • Parkinson’s disease
  • Sub-cortical volumes

ASJC Scopus subject areas

  • Anatomy
  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology

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