Rivastigmine is associated with restoration of left frontal brain activity in Parkinson's disease

Abstract

The objective of this study was to investigate how acetylcholinesterase inhibitor (ChEI) treatment affects brain function in Parkinson's disease (PD). Twelve patients with PD and either dementia or mild cognitive impairment underwent task-free functional magnetic resonance imaging before and after 3 months of ChEI treatment and were compared with 15 age- and sex-matched neurologically healthy controls. Regional spontaneous brain activity was measured using the fractional amplitude of low-frequency fluctuations. At baseline, patients showed reduced spontaneous brain activity in regions important for motor control (eg, caudate, supplementary motor area, precentral gyrus, thalamus), attention and executive functions (eg, lateral prefrontal cortex), and episodic memory (eg, precuneus, angular gyrus, hippocampus). After treatment, the patients showed a similar but less extensive pattern of reduced spontaneous brain activity relative to controls. Spontaneous brain activity deficits in the left premotor cortex, inferior frontal gyrus, and supplementary motor area were restored such that the activity was increased posttreatment compared with baseline and was no longer different from controls. Treatment-related increases in left premotor and inferior frontal cortex spontaneous brain activity correlated with parallel reaction time improvement on a test of controlled attention. PD patients with cognitive impairment show numerous regions of decreased spontaneous brain function compared with controls, and rivastigmine is associated with performance-related normalization in the left frontal cortex function.

Keywords: acetylcholine; acetylcholinesterase inhibitors; attention; executive control; magnetic resonance imaging functional.

© 2013 International Parkinson and Movement Disorder Society.

Figures

Figure 1

Patients with PD show distributed reductions compared to controls in brain activity as measured by fALFF at both baseline (red) and post-treatment (blue); the overlap is shown in purple. Results are generated with a joint height-extent threshold (p

Figure 2

A. Regions where PD patients showed greater fALFF at post-treatment compared to baseline. B. Bar graphs depict mean fALLF*100 with standard errors bars for each cluster by group. At baseline, the PD patients differed in mean fALLF in each cluster from post-treatment and from the NCs; the PD patients post-treatment did not differ from controls. C. The increase in local functional activity (mean falff*100) in the left precentral/inferior frontal gyri (PCG/IFG) cluster correlates significantly with improvement on the Continuous Performance Test (CPT). No other correlations with cognitive change scores were significant, including the correlation between this cluster and change on the Montreal Cognitive Assessment (MoCA) or the correlations between improvement in the left supplementary motor (SMA) cluster and change on the CPT or MoCA. Negative scores on the CPT Change indicate faster median reaction times (milliseconds) after treatment, and positive scores on the MoCA Change indicate higher MoCA scores after treatment.