Cortical Thinning and Cognitive Impairment in Parkinson's Disease without Dementia

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized clinically by motor dysfunction (bradykinesia, rigidity, tremor, and postural instability), and pathologically by the loss of dopaminergic neurons in the substantia nigra of the basal ganglia. Growing literature supports that cognitive deficits may also be present in PD, even in non-demented patients. Gray matter (GM) atrophy has been reported in PD and may be related to cognitive decline. This study investigated cortical thickness in non-demented PD subjects and elucidated its relationship to cognitive impairment using high-resolution T1-weighted brain MRI and comprehensive cognitive function scores from 71 non-demented PD and 48 control subjects matched for age, gender, and education. Cortical thickness was compared between groups using a flexible hierarchical multivariate Bayesian model, which accounts for correlations between brain regions. Correlation analyses were performed among brain areas and cognitive domains as well, which showed significant group differences in the PD population. Compared to Controls, PD subjects demonstrated significant age-adjusted cortical thinning predominantly in inferior and superior parietal areas and extended to superior frontal, superior temporal, and precuneus areas (posterior probability >0.9). Cortical thinning was also found in the left precentral and lateral occipital, and right postcentral, middle frontal, and fusiform regions (posterior probability >0.9). PD patients showed significantly reduced cognitive performance in executive function, including set shifting (p = 0.005) and spontaneous flexibility (p = 0.02), which were associated with the above cortical thinning regions (p < 0.05).

Fig. 1

Correlation between brain mean thickness and and age in PD and Controls. Each hemisphere data are plotted separately: (a) left hemisphere, (b) right hemisphere.

Fig. 2

Cortical thickness contrast between PD and Controls using Bayesian hierarchical model. Pr(PD0; (b) Right hemisphere with the posterior probability threshold level set at 0; (c) Left hemisphere with the posterior probability threshold level set at 0.9, i.e. Pr(PD0.9; (d) Right hemisphere with the posterior probability threshold level set at 0.9.

Fig. 3

Posterior median correlation estimates of inter-regional connectivity for the PD data set. Top row are median correlation matrices for both the PD and Controls in the left hemisphere, bottom row show median correlation for PD and Control in the right hemisphere.