MRI as an imaging marker for disease progression in regional subcortical grey matter nuclei of patients with Parkinson’s disease

Abstract

Background: Parkinson’s disease (PD) is a chronic neurodegenerative disease affecting approximately 1% of the global population. It is well established that there is significant cell death in the substantia nigra (SN) in PD; however, the progression of atrophy in other regional subcortical grey matter nuclei remains to be explored. PD is not purely a motor disease, but a syndrome with a prodromal stage, followed by overt motor and non-motor symptoms. Of the non-motor symptoms, cognitive impairment and eventual dementia are considered to be the most prevalent and devastating. There is an urgent need for an imaging marker of PD progression to help develop a better understanding of the transition through the stages of cognitive impairment which would help optimise treatment, planning and also aid in research with a more quantitative interpretation of the pathological cascade. Aims: To investigate the volume and shape of key subcortical structures in Parkinson’s disease using MRI. Specifically, to evaluate the relationship between subcortical structure and (1) cognitive decline in PD, (2) laterality of motor symptom onset, and (3) atrophy over time. Methods: 181 PD participants representative of a full spectrum of cognitive status and 49 healthy controls were followed up every two years, for up to 10 years, with comprehensive neuropsychological testing and 3T MRI at each time point. Subcortical volumes were calculated using FreeSurfer; Bayesian regression models assessed the relationship with cognitive impairment and progression over time. Differences in the shapes of subcortical structures across cognitive subgroups, as well as association with global cognitive ability and motor impairments, were investigated using FSL FIRST. Results: At cross-section, the PD group exhibited smaller volumes across most subcortical structures, with little evidence of a relationship with laterality of symptom onset. Only the thalamus and putamen showed a robust association with cognitive ability. Subcortical shape analysis showed progressive contraction with advancing cognitive decline. The thalamus displayed the most widespread, global contraction when associated with cognitive decline. Bilateral contraction in both putamen was also seen. The majority of subcortical structures exhibited significant change in volume over time in controls. While iii the PD group generally showed accelerated loss of tissue relative to controls, none of the investigated structures reached statistical significance. Conclusions: A differential effect within the thalamus (increased volume in PD-N, greatest loss over time, association between shape differences and cognitive ability) justifies further investigation into this interesting structure. Considering shape change in addition to gross volumes reveals more specific information in subtle localised shape change associated with progressing cognitive decline than when considering volume alone in the thalamus, putamen and pallidum. Including additional MRI metrics (i.e., perfusion, diffusion, and quantitative susceptibility mapping) along with volume and shape metrics may provide a more complete picture of the process of cognitive decline in PD in the future.