Structural and metabolic correlates of neuropsychological profiles in multiple system atrophy and Parkinson's disease

Dorothee Kübler, Christopher Kobylecki, Kathryn R. McDonald, José M. Anton-Rodriguez, Karl Herholz, Stephen F. Carter, Rainer Hinz, Jennifer C. Thompson, Bassam Al-Fatly, Alexander Gerhard

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Background: Despite increased recognition of cognitive impairment in Multiple System Atrophy (MSA), its neuroanatomical correlates are not well defined. We aimed to explore cognitive profiles in MSA with predominant parkinsonism (MSA-P) and Parkinson's disease (PD) and their relationship to frontostriatal structural and metabolic changes. Methods: Detailed clinical and neuropsychological evaluation was performed together with diffusion tensor imaging (DTI) and [ 18F]-fluoro-deoxyglucose positron emission tomography ([ 18F]-FDG-PET) in patients with MSA-P (n = 11) and PD (n = 11). We compared clinical and neuropsychological data to healthy controls (n = 9) and correlated neuropsychological data with imaging findings in MSA-P and PD. Results: Patients with MSA-P showed deficits in executive function (Trail Making Test B-A) and scored higher in measures of depression and anxiety compared to those with PD and healthy controls. Widespread frontostriatal white matter tract reduction in fractional anisotropy was seen in MSA-P and PD compared to an imaging control group. Stroop Test interference performance correlated with [ 18F]-FDG uptake in the bilateral dorsolateral prefrontal cortex (DLPFC) and with white matter integrity between the striatum and left inferior frontal gyrus (IFG) in PD. Trail Making Test performance correlated with corticostriatal white matter integrity along tracts from the bilateral IFG in MSA-P and from the right DLPFC in both groups. Conclusion: Executive dysfunction was more prominent in patients with MSA-P compared to PD. DLPFC metabolism and frontostriatal white matter integrity seem to be a driver of executive function in PD, whereas alterations in corticostriatal white matter integrity may contribute more to executive dysfunction in MSA-P.

Original languageEnglish
Article number105277
JournalParkinsonism & Related Disorders
Early online date2 Jan 2023
Publication statusPublished - 1 Feb 2023


  • Cognition
  • Diffusion tensor imaging
  • Multiple system atrophy
  • Parkinson's disease
  • [ F]-FDG PET


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