P2-441 DECREASED BINDING OF [ 11 C] DONEPEZIL AS SHOWN BY PET CORRELATED WITH CLINICAL EFFECT OF DONEPEZIL ADMINISTRATION IN ALZHEIMER’S DISEASE: THE OSAKI-TAJIRI PROJECT (4) Masashi Kasuya 1,2 , Hiroyasu Ishikawa 1 , Nobuyuki Okamura 3 , Motohisa Kato 3 , Yumi Sasaki 1 , Eriko Nakata 1 , Yoichi Ishikawa 4 , Yoshihito Funaki 4 , Naofumi Tanaka 1 , Ren Iwata 4 , Kazuhiko Yanai 3 , Kenichi Meguro 1 , 1 Department of Geriatric Behavioral Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan; 2 Miyagi University, Miyagi, Japan; 3 Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan; 4 Cyclotron RI Center, Tohoku University, Sendai, Japan. Contact e-mail: kasuya-mi@umin.ac.jp Background: Donepezil hydrochloride exhibits selective inhibition of acetyl- cholinesterase (AChE) and has widely been used for Alzheimer’s disease (AD). Positron emission tomography (PET) with the 5- 11 C-methoxy donepezil ([ 11 C] donepezil) can visualize the distribution of donepezil in human brain. We previously reported that AD patients exhibited about 2030% reductions of donepezil binding in neocortex and hippocampus compared with normal subjects. We herein evaluated longitudinal changes by orally administered donepezil with clinical effects. Methods: Patients: Seven patients with prob- able AD (NINCDS-ADRDA) were studied. After the first PET study, 5 mg of donepezil was orally administered. After 6 months, they received the second PET study. Informed consent was received from family members of all patients. PET: After i.v. administration of 79 mCi of [ 11 C] donepezil, a dynamic scan was performed for 60 min. Arterialized venous blood samples were obtained from a hand vein for assessing blood RI activity. Standard uptake value images were obtained by normalizing tissue concentration by injected dose and body mass. Circular region of interest was put to evaluate regional distributions of the cerebellum, striatum, thalamus, frontal, temporal, parietal, occipital, anterior and posterior cingulate, and hippocampus. The distribution volume (DV), the ratio of the concentration in tissue to that in plasma at equilibrium, was calculated by Logan’s graphical analysis. The reduction rate was calculated by (PET1-PET2)/PET1*100.Clinical effects: The Mini-Mental State Examination (MMSE) was used for assessing global cognitive function, the Cognitive Abilities Screening Instrument (CASI) was used for evaluate nine domains such as recent memory, orientation, the frontal domains (attention, list-generating fluency concentration/mental manipula- tion). Results: The overall mean reduction rate by donepezil was 33.2%, with no remarkable regional difference. Four patients showed clinical improvement after donepezil administration with the increase of CASI domains attention and orientation. The MMSE scores increased in the 2 patients. The four ‘responders’ showed significantly higher DV values at baseline and greater reduction rate (p0.05). Conclusions: The PET with the [ 11 C] donepezil method can demonstrate possible responders for oral administration of done- pezil in AD patients. P2-442 FLUOXETINE STIMULATES PROLIFERATION AND DIFFERENTIATION OF FETAL NEURAL STEM CELLS Jeong-a Kim, Keun-A Chang, Yoo-Hun Suh, Seoul National University, College of Medicine, Seoul, Republic of Korea. Contact e-mail: moooo1329@hanmail.net Background: Recent studies have proposed that chronic treatment with anti- depressants increases neurogenesis in the adult hippocampus. This increase in the production of new neurons may be required for the behavioral effects of antidepressants. However, the effect of antidepressants does not define well in fetal neural stem cells. Methods: Fetal neural stem cells are derived from the fetal cerebral cortex of a 67-weeks-old pregnant (13 days) C57BL/6 mice. In the present study, we examined the in vitro effects of antidepressant, the serotonin transporter inhibitor ‘fluoxetine’ on the survival, proliferation, and differentiation in fetal neural stem cells. Results: Results here show fluox- etine’s role in the proliferation and neural differentiation of fetal neural stem cells (NSCs) based on its degree of concentration. Nano M level of fluoxetine stimulated proliferation of NSCs and increased the number of Tuj1 positive cells, suggesting a role in activation of neuronal differentiation. Conclusions: The results suggest that treatment of fluoxetine will be useful in stem cells differentiation. Although this study should be further described possible mech- anisms by which antidepressant, the serotonin trasporter can affect neural stem cell function, our contributions will be using to study and aid in stem cell trasplantation studies to found a cell-based therapeutic system for neurode- generative disease. P2-443 CHANGES IN VITAMIN E PRESCRIBING PRACTICES FOR ALZHEIMER’S DISEASE PATIENTS Laura N. Kirk, Michael Kuskowski, Maurice Dysken, GRECC, VA Medical Center/University of Minnesota, Minneapolis, MN, USA. Contact e-mail: lauranelsonkirk@yahoo.com Background: In 1997 Sano et al. demonstrated the effectiveness of 2,000 IU/day of vitamin E in slowing clinical progression in patients with moderately severe Alzheimer’s disease. Subsequent clincial guidelines recommended the use of vitamin E based not only on efficacy but also on a side-effect profile showing no significant differences in serious adverse events compared to placebo. In 2005, Miller et al. published a vitamin E meta-analysis in 19 clinical trials and concluded that a dosage of 400 IU/day or greater was associated with increased all-cause mortality. Also in 2005, an extension of the Heart Outcomes Prevention Evaluation, known as the HOPE-TOO trial, showed an association between vitamin E and increased risk of heart failure. To assess the impact of these published studies on vitamin E prescribing practices, we surveyed members of the American Association of Geriatric Psychiatry (AAGP). Methods: Between October 23rd and November 21st, 2006, we mailed surveys to 1,626 AAGP members with prescribing privileges. This 3-item questionnaire assessed vitamin E prescribing practices before and after January, 2005. Results: A total of 582 completed surveys were returned for a response rate of 35%. Nearly 60% of respondents reported changing their vitamin E prescribing practice after January 2005. Prior to January, 2005, 37% reported prescribing vitamin E according to guidelines published by the Amer- ican Psychiatric Association (2,000 IU/day for moderately severe Alzheimer patients). A total of 57% reported prescribing vitamin E but not in strict adherence to the APA guidelines. A total of 7% did not prescribe vitamin E. At the time of the survey, 4% of these respondents were following APA guidelines, 38% were prescribing vitamin E but not strictly adhering to the guidelines, and 58% were not prescribing vitamin E. These percentage changes were highly significant (McNemar Test, p  .001). Conclusions: The findings from this survey suggest that the publication of the Miller et al. and the HOPE-TOO studies resulted in a significant change in the way geriatric psychiatrists prescribe vitamin E to Alzheimer patients. These findings have implications for the care and treatment of patients with Alzheimer disease. P2-444 A NOVEL POTENT HISTAMINE H3 RECEPTOR ANTAGONIST PRODUCES DISCRETE CHANGES IN BRAIN ACTIVITY DURING LEARNING AND EPISODIC MEMORY: IMPLICATIONS FOR COGNITIVE ENHANCEMENT Robert Y. Lai 1 , Sarah Gregory 2 , D. Hall 2 , G. Kenny 2 , Alejandro Caceres 2 , Vincenzo Libri 1 , Steve C. R. Williams 2 , Fernando O. Zelaya 2 , Mitul A. Mehta 2 , 1 GlaxoSmithKline R&D, Harlow, United Kingdom; 2 Institute of Psychiatry, King’s College, London, United Kingdom. Contact e-mail: eboxmartin@yahoo.com Background: Histamine is a neurotransmitter which may modulate cognitive processes, e.g. memory and learning 1 . Histaminergic neurons in the posterior hypothalamus project widely throughout the cerebral cortex 1 and regulates the activity of other neurotransmitters via pre-synaptic H3 receptors. 1 Rodent studies have shown cognitive enhancement using H3 antagonists. 2 This mech- anism may offer therapeutic applications in the treatment of age-related de- mentia. Objective To investigate effects of a H3 antagonist (GSK189254) on T503 Poster Presentations P2: