Nils Schröter

Background Multiple system atrophy (MSA) clinically manifests with either predominant nigrostriatal or cerebellopontine degeneration. This corresponds to two different phenotypes, one with predominant Parkinson's symptoms (MSA‐P [multiple system atrophy‐parkinsonian subtype]) and one with predominant cerebellar deficits (MSA‐C [multiple system atrophy‐cerebellar subtype]). Both nigrostriatal and cerebellar degeneration can lead to impaired dexterity, which is a frequent cause of disability in MSA. Objective The aim was to disentangle the contribution of nigrostriatal and cerebellar degeneration to impaired dexterity in both subtypes of MSA. Methods We thus investigated nigrostriatal and cerebellopontine integrity using diffusion microstructure imaging in 47 patients with MSA‐P and 17 patients with MSA‐C compared to 31 healthy controls (HC). Dexterity was assessed using the 9‐Hole Peg Board (9HPB) performance. Results Nigrostriatal degeneration, represented by the loss of cells and neurites, leading to a larger free‐fluid compartment, was present in MSA‐P and MSA‐C when compared to HCs. Whereas no intergroup differences were observed between the MSAs in the substantia nigra, MSA‐P showed more pronounced putaminal degeneration than MSA‐C. In contrast, a cerebellopontine axonal degeneration was observed in MSA‐P and MSA‐C, with stronger effects in MSA‐C. Interestingly, the degeneration of cerebellopontine fibers is associated with impaired dexterity in both subtypes, whereas no association was observed with nigrostriatal degeneration. Conclusion Cerebellar dysfunction contributes to impaired dexterity not only in MSA‐C but also in MSA‐P and may be a promising biomarker for disease staging. In contrast, no significant association was observed with nigrostriatal dysfunction. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background Cognitive deficits considerably contribute to the patient's burden in Parkinson's disease (PD). While cognitive decline is linked to neuronal dysfunction, the additional role of white matter lesions (WML) is discussed controversially. Objective To investigate the influence of WML, in comparison to neuronal dysfunction, on cognitive deficits in PD. Methods We prospectively recruited patients with PD who underwent neuropsychological assessment using the Mattis Dementia Rating Scale 2 (DRS‐2) or Parkinson Neuropsychometric Dementia Assessment (PANDA) and both MRI and PET with [ 18 F]fluorodeoxyglucose (FDG). WML‐load and PD cognition‐related covariance pattern (PDCP) as a measure of neuronal dysfunction were read out. Relationship between cognitive performance and rank‐transformed WML was analyzed with linear regression, controlling for the patients’ age. PDCP subject scores were investigated likewise and in a second step adjusting for age and WML load. Results Inclusion criteria were met by 76 patients with a mean (± SD) age of 63.5 ± 9.0 years and disease duration of 10.7 ± 5.4 years. Neuropsychological testing revealed front executive and parietal deficits and a median DRS‐2 score of 137 (range 119–144)/144 and PANDA score of 22 (range 3–30)/30. No association between WML and cognition was observed, whereas PDCP subject scores showed a trend‐level negative correlation with the DRS‐2 ( P = 0.060) as well as a negative correlation with PANDA ( P = 0.049) which persisted also after additional correction for WML ( P = 0.039). Conclusion The present study indicates that microangiopathic WML do not have a relevant impact on neurocognitive performance in PD whereas neuronal dysfunction does.