Interacting neurodegenerative changes promote Parkinson’s cognitive decline

By Eleanor McDermid, Senior medwireNews Reporter

Research indicates that neurodegeneration in the cholinergic system in the brain is a major contributor to cognitive decline in patients with Parkinson’s disease (PD).

Cholinergic denervation typically occurred in patients who had significant caudate nucleus dopaminergic denervation, however, and damage to the two systems had multiplicative effects on cognitive performance.

“Our data provide a good rationale for improved cholinergic augmentation therapy in patients with PD with cognitive symptoms”, write Nicolaas Bohnen (University of Michigan, Ann Arbor, USA) and co-workers in JAMA Neurology.

The team found that caudate nucleus dopaminergic denervation was common in 143 patients with PD (average disease duration 6 years), at 70%. Even among patients who had a global cognitive z score above –0.5, indicating minimal or no cognitive impairment, 51% had dopaminergic denervation.

The prevalence did rise significantly with declining cognition, but the pattern was somewhat variable, at rates of 73%, 50%, 100% and 71% in patients with z scores of –0.5 to –1.0, –1.0 to –1.5, –1.5 to –2.0 and–2.0 or less, respectively.

Cortical cholinergic denervation was less prevalent, affecting 32% of the cohort, but its relationship with cognitive decline was stronger, with the rate rising from 25% of patients with a cognition z score higher than –0.5 to 86% of those with a score below –2.0. Thalamic cholinergic denervation was present in about a sixth of the cohort, but was not associated with cognitive performance.

Caudate nucleus dopaminergic denervation was present in 87% of patients who had cortical cholinergic denervation, and the proportion of patients with denervation in both systems rose from 15% of those with the least impaired to 71% of those with the most impaired cognition.

On multiple regression analysis, dopaminergic and cholinergic denervation were each significantly associated with cognitive impairment, and there was also a significant interaction effect, such that the effect of the two combined was greater than their additive effects. This was the case for executive function and attention, as well as for global cognition. Denervation in both systems also significantly influenced verbal learning, but their effect was not interactive.

The researchers say that attempts to correlate damage to a single neurochemical system with distinct cognitive deficits “are undoubtedly too simplistic.”

They conclude: “Our findings support more complex pathophysiological models of interacting dopaminergic and cholinergic degenerative changes producing cognitive dysfunctions in PD.”

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