Donepezil Effects on Hippocampal and Prefrontal Functional Connectivity in Alzheimer's Disease: Preliminary Report

Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Journal of Alzheimer's disease: JAD (Impact Factor: 4.15). 08/2012; 31:S221-6. DOI: 10.3233/JAD-2012-120709
Source: PubMed


We used functional connectivity magnetic resonance imaging (fcMRI) to investigate changes in interhemispheric brain connectivity in 11 patients with mild Alzheimer's disease (AD) following eight weeks of treatment with the cholinesterase inhibitor donepezil. We examined functional connectivity between four homologous temporal, frontal, and occipital regions. These regions were selected to represent sites of AD neuropathology, sites of donepezil-related brain activation change in prior studies, and sites that are minimally affected by the pathologic changes of AD. Based on previous findings of selective, localized frontal responses to donepezil, we predicted that frontal connectivity would be most strongly impacted by treatment. Of the areas examined, we found that treatment had a significant effect only on functional connectivity between right and left dorsolateral prefrontal cortices. Implications for understanding the impact of donepezil treatment on brain functioning and behavior in patients with AD are discussed. This preliminary report suggests that fcMRI may provide a useful index of treatment outcome in diseases affecting brain connectivity. Future research should investigate these treatment-related changes in larger samples of patients and age-matched controls.

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    • "Given this difference in methods, the comparability of our results with those previously reported on brain regions that are positively influenced by cholinergic enhancement is limited, in particular as studies using seed-based analyses have reported heterogeneous observations dependent upon the seed region selected for analysis. For instance, Goveas and colleagues reported an increase of functional connectivity in a hippocampal functional connectivity network particularly in the precentral gyrus but also in the left Parahippocampus and in the right posterior cingulate cortex (Goveas et al., 2011), Li and colleagues demonstrated an increase in cortical regions similar to DMN nodes including the ventral anterior cingulate cortex, the right Precuneus, and the left parahippocampal gyrus among others (Li et al., 2012), and Zaidel and co-workers reported an increase of interhemispheric functional connectivity only between dorsolateral prefrontal cortices (Zaidel et al., 2012). Despite the limitations in comparability, the findings presented in the current work are in line with these previous reports with respect to AChEI induced effects on the posterior cingulate cortex, the Precuneus, and the medial aspect of the temporal lobe. "
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