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

Issue title: Predictive Biomarkers for Alzheimer's Disease using State-of-the-Art Brain Imaging Techniques

Guest editors: Pravat K. Mandal

Article type: Research Article

Authors: Zaidel, Liam^b | Allen, Greg^{a; *} | Cullum, C. Munro^{b; c} | Briggs, Richard W.^{d; e} | Hynan, Linda S.^{f; b} | Weiner, Myron F.^{b; c} | McColl, Roderick^d | Gopinath, Kaundinya S.^{d; e} | McDonald, Elizabeth^e | Rubin, Craig D.^e

Affiliations: [a] Department of Educational Psychology, The University of Texas at Austin, Austin, TX, USA | [b] Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA | [c] Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA | [d] Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA | [e] Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA | [f] Department of Clinical Sciences (Biostatistics), University of Texas Southwestern Medical Center, Dallas, TX, USA

Correspondence: [*] Correspondence to: Greg Allen, PhD, Department of Educational Psychology, The University of Texas at Austin, 1 University Station, D5800, Austin, TX 78712-0383, USA. Tel.: +1 512 471 0218; Fax: +1 512 475 7641; E-mail: gallen@austin.utexas.edu.

Abstract: 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.

Keywords: Alzheimer's disease, donepezil, dorsolateral prefrontal cortex, functional connectivity, hippocampus, magnetic resonance imaging

DOI: 10.3233/JAD-2012-120709

Journal: Journal of Alzheimer's Disease, vol. 31, no. s3, pp. S221-S226, 2012