Hetrogeneous pathologies associated with dementia in Parkinsonism share a prion-like spreading mechanism

Abstract

Cognitive alterations accompany or follow motor disorders in subjects with Parkinsonism. The canonical phenotype of the Parkinson’s disease Dementia (PD-D) or Lewy Body Dementia (LBD) includes deficit of attention, executive and visuospatial functions, and presents often with apathy, hallucinations, delusions, excessive daytime sleepiness, or sleep disorders. However, the clinical expression may overlap with other neurodegenerative diseases associated with cognitive disorders. Thus, while clinicians rely on phenomenological patterns to infer the disease causing the cognitive impairment, the inference is weakened by the heterogeneous clinical expression of the disease. In addition, recent post-mortem studies seem to undermine the supposed pathology-phenotype coherence, making it more and more unreliable the diagnosis based on symptoms. The lack of coherence between phenotype and pathology may support the speculation about a common mechanism underlying the progression of the disease. While it is very likely that a distinct, specific causal event determines the disease itself, the progression might well follow common patterns. A number of observations suggest that progressive diseases, which cause cognitive impairment, share a prion-like mechanism. A seeding process is supposed to account for the spreading of the lesion.