Progression of brain atrophy in the early stages of Parkinson's disease: a longitudinal tensor-based morphometry study in de novo patients without cognitive impairment

Abstract

The presence of brain atrophy and its progression in early Parkinson's disease (PD) are still a matter of debate, particularly in patients without cognitive impairment. The aim of this longitudinal study was to assess whether PD patients who remain cognitively intact develop progressive atrophic changes in the early stages of the disease. For this purpose, we employed high-resolution T1-weighted MR imaging to compare 22 drug-naïve de novo PD patients without cognitive impairment to 17 age-matched control subjects, both at baseline and at three-year follow-up. We used tensor-based morphometry to explore the presence of atrophic changes at baseline and to compute yearly atrophy rates, after which we performed voxel-wise group comparisons using threshold-free cluster enhancement. At baseline, we did not observe significant differences in regional atrophy in PD patients with respect to control subjects. In contrast, PD patients showed significantly higher yearly atrophy rates in the prefrontal cortex, anterior cingulum, caudate nucleus, and thalamus when compared to control subjects. Our results indicate that even cognitively preserved PD patients show progressive cortical and subcortical atrophic changes in regions related to cognitive functions and that these changes are already detectable in the early stages of the disease.

Keywords: TBM; brain atrophy; cognitive status; de novo PD; longitudinal study.

Figure 1

Top pane: Sample axial views of average WR maps in control subjects (a) and PD patients (b), where red indicates local atrophy and blue indicates local enlargement. Bottom pane: voxel‐wise corrected p‐value maps (threshold‐free cluster enhancement, TFCE) testing the null hypothesis of zero WR in control subjects (a) and PD patients (b) separately. Highlighted clusters indicate significant (p < 0.05) atrophic changes (i.e., WR significantly lower than zero) within the respective groups. All maps are overlayed on population‐specific template. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 2

Voxel‐wise corrected p‐value maps (threshold‐free cluster enhancement, TFCE), testing the null hypothesis of zero differences in WR between in PD patients and control subjects. Highlighted clusters indicate significantly (p < 0.05) more pronounced mean atrophy in PD patients when compared to control subjects (i.e., WR in PD patients significantly lower than WR in control subjects). All maps are overlayed on population‐specific template. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]