The Impact of Motor Symptom Asymmetry on the Relationship Between Non-Motor Manifestations and Neurometabolic Profiles in Parkinson’s Disease

Parkinson's disease (PD) is characterized by asymmetric motor symptoms (MSs), which may influence non-motor symptoms (NMSs). This study investigated the relationship between NMSs and the neurometabolic profile of the substantia nigra (SN) and globus pallidus (GP) of patients with PD, examining how these associations vary according to MS asymmetry. Forty-three PD patients (20 with right-predominant motor symptoms-RPD, and 23 with left-predominant motor symptoms-LPD) and 20 healthy controls (HCs) underwent single-voxel proton magnetic resonance spectroscopy, along with comprehensive clinical assessments of MSs and NMSs. Compared with HCs, PD patients showed higher N-acetylaspartate (NAA) levels in the SN, lower myo-inositol (Ins) levels in both sides of the SN, and higher glutamate/glutamine (Glx) levels in the right GP. Choline (Cho) in the left GP was positively associated with cognitive performance. In LPD patients, compared with HCs, NAA levels were increased in the right SN, whereas Ins levels were reduced in both hemispheres. These patients reported higher anxiety and exhibited marked hemispheric asymmetry of SN NAA. In this group, higher NAA levels in the right SN were associated with fewer sleep disturbances, while Ins in the right GP was related to both cognitive function and NMS severity. RPD patients showed elevated Glx levels in the right GP compared with HCs, with no significant hemispheric differences in metabolite levels. Nevertheless, Cho in the right SN was positively associated with sleep disturbances. Overall, these findings suggest that motor asymmetry in PD influences the neurometabolic correlates of NMSs, revealing distinct metabolic-clinical profiles in RPD and LPD patients.