Different brain spatial metabolic patterns characterizing different subtypes of multiple system atrophy

Multiple system atrophy (MSA) includes parkinsonian (MSA-P) and cerebellar (MSA-C) subtypes. This study characterizes the spatial pattern of brain metabolic PET for MSA subtypes and assesses their relationship to striatal dopamine transporter (DAT) loss, considering sex, age and disease duration. We studied 270 MSA patients using ¹⁸F-flurodeoxyglucose-PET and scaled subprofile modeling (SSM) to characterize subtype-specific disease-related metabolic patterns and ¹⁸F-fluoro-propyl-β-CIT-PET to quantify striatal DAT loss. SSM analysis characterized an MSA-P-related metabolic pattern (MSAPRP-Combined), which was created by linear combination of two principal components (PC) that differentiated MSA-P from 16 age-matched controls subsequently named as MSAPRP-PC1 and MSAPRP-PC2. For MSA-C-related pattern (MSACRP), only one PC (MSACRP-PC1) differentiated the MSA-C patients from the same healthy controls, therefore MSACRP-PC1 equaled to MSACRP. MSAPRP-Combined showed hypermetabolism in the pons, the posterior lobe of the cerebellum, the pallidum and in the sensorimotor cortex, and hypometabolism in the putamen, the vermis of the cerebellum, the lateral premotor cortex and the parieto-occipital association regions. MSACRP showed hypometabolism in the cerebellum and putamen. MSAPRP-PC1 was topographically more similar to MSAPRP-Combined while MSAPRP-PC2 was more similar to MSACRP. MSA-P had greater DAT loss than MSA-C and controls. In MSA-P, age correlated with MSAPRP-Combined and DAT binding, while disease duration correlated with DAT. For MSA-P females, MSAPRP-PC2 correlated with disease duration. In MSA-C, MSACRP correlated with disease duration and, in females, with age. These findings suggest that metabolic and dopaminergic relationships with disease progression may differ by sex and age in MSA subtypes.