Cortical asymmetry in Parkinson's disease: early susceptibility of the left hemisphere

Abstract

Background and purpose: Clinically, Parkinson's disease (PD) presents with asymmetric motor symptoms. The left nigrostriatal system appears more susceptible to early degeneration than the right, and a left-lateralized pattern of early neuropathological changes is also described in several neurodegenerative conditions, including Alzheimer's disease, frontotemporal dementia, and Huntington's disease. In this study, we evaluated hemispheric differences in estimated rates of atrophy in a large, well-characterized cohort of PD patients.

Methods: Our cohort included 205 PD patients who underwent clinical assessments and T1-weighted brain MRI's. Patients were classified into Early (n = 109) and Late stage (n = 96) based on disease duration, defined as greater than or less than 10 years of motor symptoms. Cortical thickness was determined using FreeSurfer, and a bootstrapped linear regression model was used to estimate differences in rates of atrophy between Early and Late patients.

Results: Our results show that patients classified as Early stage exhibit a greater estimated rate of cortical atrophy in left frontal regions, especially the left insula and olfactory sulcus. This pattern was replicated in left-handed patients, and was not influenced by the degree of motor symptom asymmetry (i.e., left-sided predominant motor symptoms). Patients classified as Late stage exhibited greater atrophy in the bilateral occipital, and right hemisphere-predominant cortical areas.

Conclusions: We show that cortical degeneration in PD differs between cerebral hemispheres, and findings suggest a pattern of early left, and late right hemisphere with posterior cortical atrophy. Further investigation is warranted to elucidate the underlying mechanisms of this asymmetry and pathologic implications.

Keywords: MRI; Parkinson's disease; cortex; left hemisphere; neurodegeneration.

Figure 1

Illustrative rates of cortical thinning (mm/year) in the Early and Late Groups. In the Early stage group, the left insula (−0.072 mm/year) and medial olfactory sulcus (−0.063 mm/year) show high rates of atrophy, while the left orbitofrontal region (−0.022 mm/year) shows a slower rate of −0.022 mm/year. After the first decade, all cortical regions, especially the posterior regions, begin to atrophy much faster compared to the early stages

Figure 2

Regions with significant differences in the rates of atrophy between Early and Late stages of PD, [(rate of Late stage) – (rate of Early stage)]. In (A), right hemisphere regions are shown in light gray and left hemisphere regions are shown in dark gray. In (B–E), the solid lines represent the linear regression and the dashed lines represent the confidence intervals. (A) Rate differences of cortical thinning in the right (light gray) and left (dark gray) medial olfactory sulcus, insula, and the sup. occipital and calcarine cortex. Note that faster rates in early stages represent a negative value. (B, D) Cortical atrophy in the left medial olfactory sulcus is significantly faster in the first 10 years of PD. (C, E) Rates of atrophy in the left superior occipital region are more rapid after the first 10 years

Figure 3

Cortical thickness in the medial olfactory sulcus in left‐handed patients. Early in the disease course, there is a significant correlation between disease duration and cortical thickness in the left hemisphere but not the right. The same relationship was found in right‐handed patients as well (Fig. S1)