Donepezil effects on hippocampal and prefrontal functional connectivity in Alzheimer's disease: preliminary report.
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.
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ABSTRACT: Introduction: Donepezil is a highly selective acetylcholinesterase inhibitor and one of the only four drugs currently approved for treatment of Alzheimer's dementia. Providing high bioavailability and a very long half-time, donepezil is regarded as effective and well tolerable in Alzheimer's disease patients, even in difficult clinical conditions such as hepatic or renal impairment. It moderately improves cognitive and global functioning scores in patients with mild to moderate Alzheimer's disease over the course of 6 - 12 months, with open-label extension studies suggesting effects of even longer duration. Areas covered: We summarized relevant pharmacokinetic, pharmacodynamic, clinical trial and neuroimaging data of donepezil. A literature search was performed in the PubMed database; articles published until October 2013 have been considered for this review. Moreover, references from original work and reviews have been searched for further relevant literature. Expert opinion: Donepezil is one of the most frequently prescribed anti-dementia drugs. The recent additional approval of the 23 mg formulation will expand its use in patients with moderate to severe Alzheimer's disease. After numerous Phase III study failures of novel disease-modifying drugs for Alzheimer's disease, donepezil is likely going to stay a first-line therapeutic option in Alzheimer's disease in the upcoming years.Expert Opinion on Drug Metabolism & Toxicology 04/2014; DOI:10.1517/17425255.2014.915028 · 2.93 Impact Factor
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ABSTRACT: The resting brain exhibits continuous intrinsic activity, which is correlated between groups of regions forming resting state networks. Evaluating resting connectivity is a popular approach for studying brain diseases. Several hundred studies are now available that address integrity of resting connectivity in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI), as well as preclinical at-risk subjects. Most studies focus on the default mode network, a system of specific brain areas showing strong connected resting activity that attenuates during goal-directed behavior. The extent of intrinsic brain activity tends to be strongly correlated with cognitive processes and is specifically disrupted in AD and MCI patients and at-risk subjects, with changes seeming to evolve during the transition between the disease stages. In this study, we review the current findings in default mode network and other resting state network studies in AD and MCI patients and at-risk subjects as assessed by resting state functional magnetic resonance imaging.Current Neurology and Neuroscience Reports 10/2014; 14(10):491. DOI:10.1007/s11910-014-0491-3 · 3.67 Impact Factor