Dementia risk in Parkinson's disease is associated with interhemispheric connectivity loss and determined by regional gene expression.

摘要: Parkinson's dementia is a common and devastating part of disease. Whilst timing severity vary, in often preceded by visual dysfunction. White matter changes, representing axonal loss, occur early the disease process. Clarifying which white connections are affected with dysfunction why specific vulnerable will provide important mechanistic insights. Here, we use diffusion tractography 100 patients (33 low performers) 34 controls to identify patterns connectivity loss We examine relationship between regional transcription using Allen Institute for Brain Science transcriptome atlas. show that interhemispheric preferentially performers. Interhemispheric connection was associated downweighted genes related smoothened signalling pathway (enriched glutamatergic neurons) upweighted metabolic genes. Risk but not Alzheimer's or Dementia Lewy bodies were over-represented loss. Our findings suggest selective vulnerability at highest risk (those dysfunction), where differences gene expression dysfunction, affecting longer higher burden, drive