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

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.

Disparate effects of training on brain activation in Parkinson disease.

OBJECTIVE: To compare the effects of 2 forms of exercise, i.e., a 6-week trial of treadmill training with virtual reality (TT + VR) that targets motor and cognitive aspects of safe ambulation and a 6-week trial of treadmill training alone (TT), on brain activation in patients with Parkinson disease (PD). METHODS: As part of a randomized controlled trial, patients were randomly assigned to 6 weeks of TT (n = 17, mean age 71.5 ± 1.5 years, disease duration 11.6 ± 1.6 years; 70% men) or TT + VR (n = 17, mean age 71.2 ± 1.7 years, disease duration 7.9 ± 1.4 years; 65% men). A previously validated fMRI imagery paradigm assessed changes in neural activation pretraining and post-training. Participants imagined themselves walking in 2 virtual scenes projected in the fMRI: (1) a clear path and (2) a path with virtual obstacles. Whole brain and region of interest analyses were performed. RESULTS: Brain activation patterns were similar between training arms before the interventions. After training, participants in the TT + VR arm had lower activation than the TT arm in Brodmann area 10 and the inferior frontal gyrus (cluster level familywise error-corrected [FWEcorr] p < 0.012), while the TT arm had lower activation than TT + VR in the cerebellum and middle temporal gyrus (cluster level FWEcorr p < 0.001). Changes in fall frequency and brain activation were correlated in the TT + VR arm. CONCLUSIONS: Exercise modifies brain activation patterns in patients with PD in a mode-specific manner. Motor-cognitive training decreased the reliance on frontal regions, which apparently resulted in improved function, perhaps reflecting increased brain efficiency.