Cognitive impairment in Parkinson's disease: the dual syndrome hypothesis

Neurodegener Dis. 2013;11(2):79-92. doi: 10.1159/000341998. Epub 2012 Oct 3.

Abstract

Research into the heterogeneous nature of cognitive impairment documented in patients with Parkinson's disease (PD) has focused on disentangling deficits that vary between individuals, evolve and respond differentially to pharmacological treatments, and relate differentially to PD dementia (PDD). We summarise studies conducted in our laboratory over the last 2 decades, outlining the incremental development of our hypotheses, the starting point for which is our early work on executive deficits mirroring fronto-striatal dysfunction. We present subsequent findings linking these deficits to a model of dopaminergic function that conforms to an inverted curvilinear function. We review studies that investigated the range of dopamine-independent attentional and visuospatial memory deficits seen in PD, demonstrating that abnormalities in these domains more accurately predict PDD. We conclude with an exposition of the dual syndrome hypothesis, which distinguishes between dopaminergically mediated fronto-striatal executive impairments and a dementia syndrome with distinctive prodromal visuospatial deficits in which cholinergic treatments offer some clinical benefits.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antiparkinson Agents / administration & dosage*
  • Antiparkinson Agents / adverse effects
  • Brain Chemistry / drug effects
  • Brain Chemistry / physiology
  • Cognition Disorders / chemically induced
  • Cognition Disorders / etiology*
  • Cognition Disorders / physiopathology*
  • Disruptive, Impulse Control, and Conduct Disorders / chemically induced
  • Disruptive, Impulse Control, and Conduct Disorders / etiology
  • Disruptive, Impulse Control, and Conduct Disorders / physiopathology
  • Executive Function / physiology*
  • Humans
  • Parkinson Disease / complications*
  • Parkinson Disease / physiopathology*

Substances

  • Antiparkinson Agents