MCI in Parkinson’s Linked to Frontostriatal Dysfunction

Parkinson’s disease patients with mild cognitive impairment have dysfunctional circuitry in brain networks involving the right dorsal caudate nucleus and the bilateral anterior cingulate cortex, compared with unaffected Parkinson’s patients, according to a prospective cohort study.

“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,” wrote first author Urban Ekman and his colleagues at Umeå University, Sweden.

The investigators looked at all patients in the Umeå University catchment area who were newly diagnosed with idiopathic Parkinson’s disease between Jan. 1, 2004, and April 30, 2009, in what they called the first study to evaluate mild cognitive impairment with functional MRI (fMRI) (Lancet Neurol. 2012;11:679-87).

In total, 77 Parkinson’s patients were included in the analysis (60% male, mean age 68 years); they were compared with 24 controls (50% male, mean age 68 years).

All patients were drug naive for dopaminergic medication. Patients were excluded from the study if they had dementia, major depression, or if they answered fewer than 55% of questions in the working memory task correctly.

Mild cognitive impairment (MCI) was diagnosed according to Movement Disorder Society criteria (Mov. Disord. 2012;27:349-56). In short, participants were tested in several cognitive domains: executive function, attention and working memory, episodic memory, language, and visuospatial function. Participants who scored 1.5 standard deviations or more below the mean for at least two domains were diagnosed with MCI.

Mr. Ekman and his colleagues found that 33 (43%) of the 77 Parkinson’s patients had MCI, according to the criteria. Thirty were included in the analysis after three patients were excluded because their impairment was primarily visuospatial or language contingent.

The researchers then conducted a verbal “two-back” working memory task while patients and controls underwent fMRI scans. Upon hearing a series of nouns, patients were asked to respond “yes” when the word matched the one presented two items earlier, and “no” when it was different, using MRI-compatible keypads.

On this test, in general, patients with Parkinson’s had fewer correct answers than did controls (P = .024), and patients with Parkinson’s and MCI had fewer correct answers compared with both controls (P = .02) and Parkinson’s patients without MCI (P = .04).

“Compared with controls, patients with Parkinson’s disease had significant underrecruitment of the right dorsolateral prefrontal cortex, the bilateral primary and premotor cortices, the occipital cortex, and the cerebellum when undertaking the two-back task,” the authors wrote regarding the fMRI results.

Moreover, “A lower BOLD [blood-oxygen-level-dependent] signal was noted for the Parkinson’s disease group in bilateral striatal regions compared with the control group,” they added.

The authors then looked at Parkinson’s patients with and without MCI in a whole-brain analysis.

They found that “the anterior cingulate cortex region was significantly recruited in both control individuals and patients with Parkinson’s disease without MCI [P less than .001], but weakly and nonsignificantly recruited in patients with Parkinson’s disease with MCI.”

Finally, in region of interest analysis, “there was underrecruitment of the right dorsal caudate in patients with Parkinson’s disease with MCI compared with those without MCI [P = .005],” wrote the authors.

Indeed, a plot of the effect revealed a “stepwise” response, “such that the right caudate response was maximum in control individuals, intermediate in patients with Parkinson’s disease without MCI, and lowest and nonsignificant in those with Parkinson’s disease and MCI,” they wrote.

In seeking to verify that these results were due to cognition and were not motor related, the researchers compared groups matched according to motor scores.

“The results persisted” in the right caudate and anterior cingulate cortex, they wrote.

The authors declared that they had no conflicts of interest. The study was funded by nonprofit organizations, including the Swedish Medical Research Council and the Swedish Parkinson Foundation.

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