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Objective: To elucidate possible mechanisms leading to neurodegeneration in patients with glucocerebrosidase ( GBA )–associated Parkinson disease (PD) using combined proton ( 1 H) and phosphorus ( 31 P) magnetic resonance spectroscopic imaging (MRSI) in vivo. Methods: 1 H and 1 H-decoupled 31 P MRSI was performed in 13 patients with PD with heterozygous GBA mutations (GBA-PD) and 19 age- and sex-matched healthy controls to investigate metabolite concentrations in the mesostriatal target regions of PD pathology. NAA as marker of neuronal integrity, choline and ethanolamine containing compounds as markers of membrane phospholipid metabolism, and energy metabolites (notably high-energy phosphates) were quantified. Results: Compared to controls, NAA was significantly reduced in the putamen ( p = 0.012) and in the midbrain of GBA-PD ( p = 0.05). The choline concentration obtained from 1 H MRSI was significantly decreased in the midbrain of GBA-PD ( p = 0.010). The phospholipid degradation product glycerophosphoethalonamine was increased in the putamen of GBA-PD ( p = 0.05). Changes of energy metabolism were not detected in any region of interest. Conclusion: The pattern of neurodegeneration in GBA -associated PD is more pronounced in the putamen than in the midbrain. Our MRSI findings suggest that the neurodegenerative process in GBA-PD is associated with alterations of membrane phospholipid metabolism which might be also involved in abnormal α-synuclein aggregation.

Objective: To evaluate whether there exists distinct characteristics in glucocerebrosidase ( GBA )–associated Parkinson disease (PD) with regard to motor and nonmotor symptoms as well as imaging characteristics assessed by transcranial sonography (TCS). Methods: Twenty patients with PD with heterozygous GBA mutations (N370S, L444P) (GBA-PD) in comparison to 20 patients with sporadic PD negative for GBA mutations (sPD) were included. We assessed motor impairment with the Unified Parkinson’s Disease Rating Scale–III. Nonmotor symptoms were evaluated using the Montreal Cognitive Assessment, Neuropsychiatric Inventory, revised form of the Beck Depression Inventory, Parkinson Disease Sleep Scale, Sniffin’ Sticks, and Unified Multiple System Atrophy Rating Scale items 9–12. TCS imaging was used to detect morphologic characteristics. Results: Patients with GBA-PD more often had a variety of nonmotor symptoms, namely dementia, neuropsychiatric disturbances, and autonomic dysfunction, and had more severe cases, than patients with sPD. They also demonstrated a higher prevalence of a reduced echogenicity of the brainstem raphe assessed by TCS. Conclusions: Especially nonmotor symptoms seem to be very common in GBA-PD. Further studies are needed to validate these observations in order to better understand the pathogenesis of GBA-PD and develop specific therapeutic concepts.