Article

Goveas JS, Xie C, Ward BD, Wu Z, Li W, Franczak M et al. Recovery of hippocampal network connectivity correlates with cognitive improvement in mild Alzheimer's disease patients treated with donepezil assessed by resting-state fMRI. J Magn Reson Imaging 34: 764-773

Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Journal of Magnetic Resonance Imaging (Impact Factor: 3.21). 10/2011; 34(4):764-73. DOI: 10.1002/jmri.22662
Source: PubMed

ABSTRACT

To identify the neural correlates of cognitive improvement in mild Alzheimer's disease (AD) subjects following 12 weeks of donepezil treatment.
Resting-state functional connectivity magnetic resonance imaging (R-fMRI) was used to measure the hippocampal functional connectivity (HFC) in 14 mild AD and 18 age-matched normal (CN) subjects. AD subjects were scanned at baseline and after donepezil treatment. CN subjects were scanned only at baseline as a reference to identify regions correlated or anticorrelated to the hippocampus. Before each scan, participants underwent cognitive, behavioral, and functional assessments.
After donepezil treatment, neural correlates of cognitive improvement measured by Mini-Mental State Examination scores were identified in the left parahippocampus, dorsolateral prefrontal cortex (DLPFC), and inferior frontal gyrus. Improvement in AD Assessment Scale-cognitive subscale scores correlated with the HFC changes in the left DLPFC and middle frontal gyrus. Stronger recovery in the network connectivity was associated with cognitive improvement.
R-fMRI may provide novel insights into the brain's responses to AD treatment in clinical pharmacological trials, and also may predict clinical response.

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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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    • "Reduced integrity in the default mode network is also associated with amyloid beta and tau pathology before the clinical onset of AD (Wang et al., 2013). Several pharmacological intervention studies have employed the resting-state connectivity as a biomarker for testing the efficacy of the treatment (Goveas et al., 2011; Lorenzi et al., 2011; Li et al., 2012) [see Hampel et al., 2011 for a related discussion]. Future cognitive training studies need to adopt a similar approach to test the effect of cognitive training on default-mode network. "
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    • "Furthermore, several fMRI studies reported markedly reduced functional connectivity in hippocampus-related memory networks in early-stage AD [15], [16] as well as mild cognitive impairment [17]–[19]. One recent resting-state fMRI study found stronger recovery of hippocampal functional connectivity after donepezil treatment in AD patients [20], which indicates there is some plasticity in hippocampal connectivity. Therefore, we selected the hippocampus as the region of interest to conduct functional connectivity analysis and to explore the effects of acupuncture. "
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