Assessment of Cholinergic and Cognitive Function in Healthy Young Adults Using Pharmacologic ASL Perfusion MRI (S29.003)

Abstract

Objective: To examine the cholinergic system in vivo using pharmacologic arterial spin-labeling (ASL) perfusion MRI. Background In vivo imaging of cholinergic function has the potential of advancing our understanding of the important role it plays in cognition. Pharmacologic MRI, by examining changes in cerebral blood flow (CBF) following drug administration, can elucidate physiological effects with high anatomic resolution in vivo and thereby link the cognitive effects of cholinergic modulation to specific anatomical structures. Design/Methods: Healthy young adults participated in a randomized, placebo-controlled crossover study (n=15). Each underwent four pharmacologic conditions (placebo, mecamylamine, scopolamine, mecamylamine+scopolamine) on four separate days. ASL scans were obtained at the time of peak drug concentration, and cognitive performance was assessed with a neuropsychological battery. SPM was used to identify regions of significantly altered CBF in clusters of at least 1800 voxels. Cognitive performance was analyzed with repeated measures ANOVA. Results: With scopolamine, CBF was decreased bilaterally in thalamus, frontal cortex, and supplementary motor area and increased in occipital cortex, postcentral gyrus, insula, hippocampus, and superior temporal pole (corrected p-value Conclusions: These results confirm previous findings of decreased frontal and thalamic perfusion and cognitive deficits with scopolamine and reveal other areas implicated in cognition with cholinergically modulated blood flow, suggesting that ASL may be more sensitive to the perfusion changes under study. The cognitive impairments with cholinergic antagonism, including impaired attention and encoding, are consistent with disruption of the attention network (eg. frontal cortex, supplementary motor area, thalamus, basal ganglia). Likewise memory deficits could result from disruptions of known memory structures (eg. hippocampus) or decreased activity of inhibitory thalamic projections to cortical structures. Supported by: This project was funded by the American Federation for Aging Research Medical Student Training in Aging Research (MSTAR) Program, NIH/NIA grants T35AG038027, T32AG023480, K23AG031320, the Doris Duke Charitable Foundation Clinical Research Fellowship at Harvard Medical School, and the American Academy of Neurology Medical Student Summer Research Scholarship. Disclosure: Dr. Huang has nothing to disclose. Dr. Dai has nothing to disclose. Dr. Alsop has nothing to disclose. Dr. Waterston has nothing to disclose. Dr. Inouye has nothing to disclose. Dr. Fong has nothing to disclose.