Cognitive Deficits in Parkinson's Disease Are Associated with Neuronal Dysfunction and Not White Matter Lesions

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.