Anatomical correlates of apathy and impulsivity co-occurrence in early Parkinson's disease

Abstract

Background: Although apathy and impulse control disorders (ICDs) are considered to represent opposite extremes of a continuum of motivated behavior (i.e., hypo- and hyperdopaminergic behaviors), they may also co-occur in Parkinson's disease (PD).

Objectives: We aimed to explore the co-occurrence of ICDs and apathy and its neural correlates analyzing gray matter (GM) changes in early untreated PD patients. Moreover, we aimed to investigate the possible longitudinal relationship between ICDs and apathy and their putative impact on cognition during the first five years of PD.

Methods: We used the Parkinson's Progression Markers Initiative (PPMI) database to identify the co-occurrence of apathy and ICDs in 423 early drug-naïve PD patients at baseline and at 5-year follow-up. Baseline MRI volumes and gray matter changes were analyzed between groups using voxel-based morphometry. Multi-level models assessed the longitudinal relationship (across five years) between apathy and ICDs and cognitive functioning.

Results: At baseline, co-occurrence of apathy and ICDs was observed in 23 patients (5.4%). This finding was related to anatomical GM reduction along the cortical regions involved in the limbic circuit and cognitive control systems. Longitudinal analyses indicated that apathy and ICDs were related to each other as well as to the combined use of levodopa and dopamine agonists. Worse apathetic and ICDs states were associated with poorer executive functions.

Conclusions: Apathy and ICDs are joint non-exclusive neuropsychiatric disorders also in the early stages of PD and their co-occurrence was associated with GM decrease in several cortical regions of the limbic circuit and cognitive control systems.

Keywords: Addiction; Apathy; Impulse control disorders; Impulsivity; Neuropsychiatry; Parkinson’s disease.

Fig. 1

Percentages of groups distribution according to the presence of apathy (PD + A), PD + ICD (PD + ICD), patients with the co-occurrence of apathy and PD + ICD (PD + ICD + A) and PD without ICD and apathy (PD). Frequencies for each PD + ICD sub-type were described for all the patients reporting PD + ICD and for the PD + ICD + A group. Note that the sum of the percentages of specific ICDs may exceed 100% due to comorbidities

Fig. 2

Whole-brain focal differences in gray matter for the co-occurrence of PD + ICD + A. Imaging results reveal significantly reduced GM density for: A the co-occurrence of apathy and ICD (PD + ICD + A), B PD + A, and, C PD + ICD compared to baseline PD without ICD and apathy (PD). Each group was compared independently through nonparametric random effects analysis as shown in the three panels. No significant increases in GM density were found for the PD neuropsychiatric groups compared to PD; FWE corrected at p = 0.05

Fig. 3

Post-hoc comparisons reveal significant changes in cortical areas within the neuropsychiatric PD groups. A Comparison between PD + ICD vs PD + A; B Comparisons between PD + ICD vs PD + ICD + A; C Comparisons between PD + A vs PD + ICD + A. All contrast were evaluated using FWE corrected at p < 0.05 and extent threshold of 100 voxels. Increased GM density in hot and reduced in cold colors