Impaired frontostriatal circuitry linked to cognitive defects in PD

By Eleanor McDermid

Reduced activation of the frontostriatal circuits may underlie the mild cognitive impairment (MCI) often seen in patients with early Parkinson's disease (PD), say researchers.

"The cognitive dysfunctions associated with Parkinson's disease are gaining clinical importance because of the relative success of therapeutic approaches in the treatment of motor symptoms, but knowledge of the neuropathology underlying cognitive impairment remains insufficient," comment Urban Ekman (Umeå University, Sweden) and colleagues.

Reduced frontostriatal activation has been previously noted in PD patients with impaired executive function relative to cognitively normal controls, but Ekman et al say their study is the first to show the effect in PD patients with MCI.

In all, 33 of the 77 PD patients in the study had MCI, 21 of whom had impairment in at least one executive function. But impairment in attention or working memory, or in episodic memory, was also common, with each affecting more than 20 patients, while seven had language problems and two had visuospatial impairment.

The PD patients and 24 age- and gender-matched controls underwent functional magnetic resonance imaging while undertaking a verbal two-back working memory task. This revealed significantly reduced recruitment of multiple brain areas in the patients relative to the controls, including the right dorsolateral prefrontal cortex, the bilateral primary and premotor cortices, and the bilateral striatal regions.

In whole-brain analysis of the PD patients, those with MCI had significantly reduced recruitment of the bilateral anterior cingulate cortex compared with those without, but the reverse was true for the right parahippocampus and right superior parietal cortex.

In region-of-interest analysis, patients with MCI had significant under-recruitment of the right dorsal caudate relative to those without, as well as less pronounced, but still significant, under-recruitment of the right dorsolateral prefrontal cortex.

The reduced recruitment of the bilateral striatal regions seen in PD patients was more marked in the subgroup with MCI, the team notes in The Lancet Neurology.

In a commentary accompanying the article, Oury Monchi (University of Montreal, Quebec, Canada) and A Jon Stoessl (University of British Columbia, Vancouver, Canada) remark that nonfrontal cognitive deficits are also reported in patients with early PD.

They say that further studies are needed "to assess the early presence of MCI segregated according to cognitive domain and their ability to predict dementia in Parkinson's disease, as are studies that attempt to tease out the role of dopamine and those changes that show activation of compensatory circuits."

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