Neuropsychology Review, Vol. 6, No. 2, 1996 Increased Regional Cerebral Glucose Metabolism and Semantic Memory Performance in Alzheimer's Disease: A Pilot Double Blind Transdermal Nicotine Positron Emission Tomography Study Randolph W. Parks, 1,3 Robert E. Becker, 1 Robert F. Rippey, 1 David G. Gilbert, 1 Jane R. Matthews, 1 Esperanza Kabatay, 1 Carter S. Young, 2 Cathy Vohs, 2 Valerie Danz, 2 Patricia Keim, 2 G. Todd Collins, 2 Steven S. Zigler, 2 and Paul G. Urycki 2 Nicotinic receptor dysfunction and impaired semantic memory occur early in Alzheimer's disease patients (AD). Previous research implied that nicotine's ability to enhance alertness, arousal, and cognition in a number of nonclinical popula- tions was a function of its ability to stimulate CNS nicotinic cholinergic receptors. In this study it was hypothesized that transdermal administration of nicotine would increase both regional cerebral glucose metabolism (rCMRglc) and semantic mem- ory (as assessed by verbal fluency). Two mild AD and two elderty controls under- went positron emission tomography scanning during a double blind nicotinic agonist verbal fluency challenge procedure, rCMRglc increases occurred in both AD patients, but not controls. In the two AD patients, verbal fluency scores in- creased by an average of 17%. One elderly control's verbal fluency increased, and the other decreased. These findings suggest that nicotine's effect on metabolism and verbal fluency is due to its ability to stimulate the cholinergic system. KEY WORDS: Alzheimer's disease; transdermal nicotine; positron emission tomography; cholinergic stimulation; semantic memory; verbal fluency. 1Departments of Psychiatry and Psychology, Southern Illinois University School of Medicine, Springfield a/ad Carbondale, Illinois 62794-1412. 2Departments of Nuclear Medicine and PET Imaging, Downstate Clinical Positron Emission Tomography Center, Methodist Medical Center, Peoria, Illinois. 3Requests for reprints should be sent to Randolph W. Parks, Ph.D., Psy.D., Department of Psychiatry, Southern Illinois University School of Medicine, P. O. Box 19230, Springfield, Illinois 62794-1412. Electronic mail may be sent to rparks@siumed.edu. 61 1040-7308/96/II6130-0061509.50/0 9 1996 Plenum Publishing Corporation