Patterns of cortical thinning in nondemented Parkinson's disease patients

Abstract

Background: Clinical variability in the Parkinson's disease phenotype suggests the existence of disease subtypes. We investigated whether distinct anatomical patterns of atrophy can be identified in Parkinson's disease using a hypothesis-free, data-driven approach based on cortical thickness data.

Methods: T1-weighted 3-tesla MRI and a comprehensive neuropsychological assessment were performed in a sample of 88 nondemented Parkinson's disease patients and 31 healthy controls. We performed a hierarchical cluster analysis of imaging data using Ward's linkage method. A general linear model with cortical thickness data was used to compare clustering groups.

Results: We observed 3 patterns of cortical thinning in patients when compared with healthy controls. Pattern 1 (n = 30, 34.09%) consisted of cortical atrophy in bilateral precentral gyrus, inferior and superior parietal lobules, cuneus, posterior cingulate, and parahippocampal gyrus. These patients showed worse cognitive performance when compared with controls and the other 2 patterns. Pattern 2 (n = 29, 32.95%) consisted of cortical atrophy involving occipital and frontal as well as superior parietal areas and included patients with younger age at onset. Finally, in pattern 3 (n = 29, 32.95%), there was no detectable cortical thinning. Patients in the 3 patterns did not differ in disease duration, motor severity, dopaminergic medication doses, or presence of mild cognitive impairment.

Conclusions: Three cortical atrophy subtypes were identified in nondemented Parkinson's disease patients: (1) parieto-temporal pattern of atrophy with worse cognitive performance, (2) occipital and frontal cortical atrophy and younger disease onset, and (3) patients without detectable cortical atrophy. These findings may help identify prognosis markers in Parkinson's disease. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Keywords: Parkinson disease; cluster analysis; cortical atrophy; magnetic resonance imaging; neuropsychology.

Figure 1

Dendrogram of PD patients clustered according to vertex‐by‐vertex information of cortical thickness. The distance along the y axis represents the similarity between clusters so that the shorter the distance, the greater the similarity. Numbers on the horizontal axis represent the 88 PD patients included in the cluster analysis. P1, Pattern 1; P2, Pattern 2; P3, Pattern 3. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Figure 2

Cortical atrophy patterns at 3‐cluster level. a: Color maps indicate significant thinning when compared with healthy controls. b: Color maps indicate significant differences in thickness between the 3 patterns. Results were corrected by Monte Carlo simulation. HC, healthy controls. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Figure 3

Neuropsychological profile at the 3‐cluster level. Neuropsychological profiles for healthy controls in green, pattern 1 in blue, pattern 2 in red, and pattern 3 in purple. Data are presented as z scores. Lower z scores indicate worse performance. BNT, Boston Naming Test; JLO, Judgment of Line Orientation Test; RAVLT total, Rey Auditory Verbal Learning Test total; RAVLT recall, Rey Auditory Verbal Learning Test recall after 30 minutes; SDMT, Symbol Digits Modalities Test; TMTA, Trail Making Test Part A; TMTB, Trail Making Test Part B; TMTA minus B, Trail Making Test A minus B; VFD, Visual Form Discrimination Test. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]