Functional imaging of hippocampal dysfunction among persons with Alzheimer’s disease: a proof-of-concept study

Abstract

David B Arciniegas1,2, Jason R Tregellas1,3, Donald C Rojas1, Burlleen Hewitt1, C Alan Anderson1,2,41Neurobehavioral Disorders Program, Department of Psychiatry, 2Behavioral Neurology Section, University of Colorado Denver, Aurora, CO, USA; 3Research Service, 4Neurology Service, Denver Veterans Affairs Medical Denver, Denver, CO, USAAbstract: Cholinergic deficits are an early and functionally significant manifestation of Alzheimer’s disease (AD). These deficits contribute to impairment of hippocampally mediated information processing, including declarative memory impairments and abnormal auditory sensory gating. A functional imaging technique that facilitates identification of changes in cholinergically dependent hippocampal information processing would be of considerable use in the study and clinical evaluation of persons with this condition. Techniques that interrogate hippocampal function passively, ie, in a manner requiring no cognitive effort or novel task learning during the neuroimaging procedure, would also be especially useful in this cognitively impaired population. The functional magnetic resonance imaging sensory gating paradigm developed at the University of Colorado, CO, USA, is a functional neuroimaging technique that possesses both of these characteristics. We developed a demonstration project using this paradigm in which we passively interrogated hippocampal function in two subjects with probable AD of mild severity. Imaging data were quick and easy in these subjects and served usefully as an initial demonstration of the feasibility of using this neuroimaging method in this population. Preliminary analyses of the data obtained from these subjects identified abnormal blood oxygen level-dependent responses when compared with four healthy comparators, and the pattern of these responses was consistent with impaired function of the auditory sensory gating network. The strengths and limitations of this neuroimaging paradigm and the additional issues that require investigation in order to continue its development into a research and clinical technique for use in this population are discussed.Keywords: Alzheimer’s disease, hippocampus, acetylcholine, functional magnetic resonance imaging