The neurobiological basis of cognitive impairment in Parkinson's disease

Glenda M. Halliday, James B. Leverenz, Jay S. Schneider, Charles Howard Adler

Research output: Contribution to journalArticle

139 Citations (Scopus)

Abstract

The recent formalization of clinical criteria for Parkinson's disease with dementia (PDD) codifies many studies on this topic, including those assessing biological correlates. These studies show that the emergence of PDD occurs on the background of severe dopamine deficits with, the main pathological drivers of cognitive decline being a synergistic effect between alpha-synuclein and Alzheimer's disease pathology. The presence of these pathologies correlates with a marked loss of limbic and cortically projecting dopamine, noradrenaline, serotonin, and acetylcholine neurons, although the exact timing of these relationships remains to be determined. Genetic factors, such as triplications in the α-synuclein gene, lead to a clear increased risk of PDD, whereas others, such as parkin mutations, are associated with a reduced risk of PDD. The very recent formalization of clinical criteria for PD with mild cognitive impairment (PD-MCI) allows only speculation on its biological and genetic bases. Critical assessment of animal models shows that chronic low-dose MPTP treatment in primates recapitulates PD-MCI over time, enhancing the current biological concept of PD-MCI as having enhanced dopamine deficiency in frontostriatal pathways as well as involvement of other neurotransmitter systems. Data from other animal models support multiple transmitter involvement in cognitive impairment in PD. Whereas dopamine dysfunction has been highlighted because of its obvious role in PD, the role of the other neurotransmitter systems, neurodegenerative pathologies, and genetic factors in PD-MCI remains to be fully elucidated.

Original languageEnglish (US)
Pages (from-to)634-650
Number of pages17
JournalMovement Disorders
Volume29
Issue number5
DOIs
StatePublished - Apr 15 2014

Fingerprint

Parkinson Disease
Dementia
Dopamine
Pathology
Neurotransmitter Agents
Animal Models
Synucleins
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
alpha-Synuclein
Primates
Acetylcholine
Cognitive Dysfunction
Serotonin
Norepinephrine
Alzheimer Disease
Neurons
Mutation
Genes

Keywords

  • Genetic risk
  • Neuropathology
  • Neurotransmitters
  • Parkinson's disease dementia
  • Preclinical models

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Medicine(all)

Cite this

The neurobiological basis of cognitive impairment in Parkinson's disease. / Halliday, Glenda M.; Leverenz, James B.; Schneider, Jay S.; Adler, Charles Howard.

In: Movement Disorders, Vol. 29, No. 5, 15.04.2014, p. 634-650.

Research output: Contribution to journalArticle

Halliday, Glenda M. ; Leverenz, James B. ; Schneider, Jay S. ; Adler, Charles Howard. / The neurobiological basis of cognitive impairment in Parkinson's disease. In: Movement Disorders. 2014 ; Vol. 29, No. 5. pp. 634-650.
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