Tohon, Ehine, Japan; 2 Ehime University Graduate School of Medicine, Tohon, Ehime, Japan; 3 Ehime University, Tohon, Ehime, Japan. Contact e-mail: mmogi@m.ehime-u.ac.jp Background: Angiotensin II type 2 (AT 2) receptor activation has been re- ported to play a role in the cognitive function, although its detailed mecha- nisms are not fully understood. Compound 21 (C21) has become available to use as a direct AT 2 receptor agonist. Therefore, we examined the possibility that direct AT 2 receptor stimulation by C21 could prevent cognitive decline associated with hypo-perfusion in the brain. Methods: We employed bilat- eral common carotid artery stenosis model (BCAS) in mice by micro coil technique as model of vascular dementia. The Morris water maze task was performed 6 weeks after BCAS operation. C21 (10 m g/kg/day) was ad- ministrated daily by intraperitoneal injection 1 week before BCAS until Morris water maze task.C erebral blood flow (CBF) was analyzed by laser speckle flowmetry and i nflammatory cytokine levels were assessed by quantitative RT-PCR. Total protein was prepared from hippocampus and cortex, and phosphorylation of NMDA receptor (Ty 1472) was determined by immunoblot analysis. Results: The mice showed a significant impair- ment of spatial learning activity after BCAS and this impairment was signif- icantly attenuated by C21 treatment without influencing blood pressure. Spatial learning ability was severely impaired in AT 2 receptor deficient mice and preventive effect of C21 on cognitive decline was not observed in this mouse strain. CBF in BCAS-treated group was significantly de- creased and this decrease was blunted by the treatment with C21. TNF- a and MCP-1 mRNA expressions were significantly increased after BCAS, but attenuated by treatment with C21. To further examine the role of direct stimulation of AT2 receptor in cognitive function, we focused on NMDA receptor, which would be influenced by AT 2 receptor activation. After BCAS, phosphorylation of NMDA receptor with water maze task was impaired and the administration of C21 attenuated the decrease in NMDA receptor phosphorylation in BCAS-treated mice. Conclusions: These findings indicate that direct AT 2 stimulation by C21 prevents ische- mic vascular dementia induced by hypoperfusion at least in part due to in- crease in CBF, reduction of inflammation and activation of NMDA receptor. This study principally could offer the possibility to use direct AT 2 receptor stimulation by C21 as a therapeutic tool. P4-055 QUANTITATIVE TRACTOGRAPHY OF FIBERS CROSSING WHITE MATTER HYPERINTENSITIES Angeles Garcia 1 , William Reginold 1 , Angela Luedke 1 , Angela Tam 2 , Jennifer Reginold 2 , Omar Islam 2 , Juan Fernandez 2 , 1 Queen’s University, Kingston, Ontario, Canada; 2 Queen’s University, Kingston, Ontario, Canada. Contact e-mail: ag16@queensu.ca Background: According to the disconnection hypothesis, disruption of fi- ber tracts leads to impaired cognition. White matter hyperintensities (WMH) in the brain could contribute to impaired cognition by disrupting the underling fiber tracts crossing the lesions (WMH-tracts). Using quanti- tative tractography we assess if the injury within the WMH extends along the entire length of WMH-tracts and correlates with increasing WMH bur- den, Alzheimer’s disease (AD) diagnosis, and impaired cognition. Methods: Diffusion tensor magnetic resonance imaging (MRI) and T2 Fluid Attenuated Inversion Recovery (FLAIR) 3T MRI was performed in 18 participants (10 healthy controls, 8 AD patients). Tracts from diffusion tensor MRI were assigned in Diffusion Toolkit by the Fiber Assignment by Continuous Tracking (FACT) method. Tractography data and co-regis- tered T2 FLAIR were quantitatively analyzed with TrackVis (www. trackvis.org). All fibers in the brain by tractography that crossed WMH le- sions on T2 FLAIR magnetic resonance imaging (MRI) scans were analysed for length, apparent diffusion coefficient (ADC) and fractional anisotropy (FA), and compared to all other fibers that did not cross WMH lesions (lesion-free fibers). The association between WMH-tract and lesion-tract diffusivity properties with WMH lesion volume, AD diagnosis, and Mon- treal Cognitive Assessment (MoCA) scores was assessed. Results: There was no significant difference in ADC of WMH-tracts and lesion-free tracts (WMH tracts: 0.000960.0001, lesion-free tracts: 0.000960.0001, p¼1). With increasing WMH lesion load there was decreasing FA in lesion-free tracts (correlation coefficient or cc: -0.66, p¼0.002) while there was no change in the FA (cc: -0.34, p¼0.17) and ADC (cc: -0.4, p¼0.09) of WMH-tracts. Compared to controls, patients with AD diagnosis had de- creased FA (p¼0.01). There was no difference between controls and AD pa- tients in WMH-tracts. MoCA scores correlated with elevated FA (cc: 0.72, p<0.0001) and reduced ADC (cc: -0.68, p¼0.001) of lesion-free tracts. For WMH-tracts there was no correlation between FA (cc: 0.10, p¼0.69) and ADC (cc: -0.23, p¼0.35) with MoCA scores. Conclusions: WMH lesions do not appear to disrupt the integrity of coincident tracts or "disconnect" them to produce cognitive decline. The integrity of the larger population of lesion-free tracts has stronger associations with cognitive function than the few tracts that cross WMH lesions. P4-056 PRO- AND ANTI-INFLAMMATORY CYTOKINES IN ALZHEIMER’S DISEASE AND VASCULAR DEMENTIA Omer Karadas 1 , Hakan Gul 2 , Serdar Firtina 1 , 1 Erzincan Military Hospital, Erzincan, Turkey; 2 Kartal Education and Treatment Hospital, Istanbul/ Turkey, Istanbul, Turkey. Contact e-mail: leventgul2003@yahoo.com Background: A chronic inflammatory process has been implicated in the neuropathology of Alzheimer’s disease (AD) and vascular dementia (VAD). The current knowledge shows that circulating serum and plasma biomarkers of AD and VAD are linked to inflammatory reactions. We have demonstrated the presence of certain inflammatory cytokines in the ce- rebrospinal fluid (CSF) and blood of AD and VAD patients. Methods: Blood and CSF analysis were made in 15 AD (group1) and 15 VAD (group2) patients. Blood and CSF glutathionon (GSH), protein carbonile (PCO) and b-Amyloid 1-40 (amyloid) studies were made in both groups; blood TNF-a, interleukin-1b and interleukin-6 studies were also made. Results: 8 men, 7 women were included in group1 and 7 men, 8 women were included in group2. The mean age of patients in group1 and group 2 was 70,20 and 71,26, respectively. Group 1’s CSF amyloid levels were statistically signif- icant higher than group 2’s levels. Grup 2’s blood IL-6 levels were statisti- cally significant higher than group 1’s levels. Other parameters had no difference between two groups. Conclusions: The results of the study sug- gest that inflammatory process has an important role when we evaluate the two groups according to biological basics. We detected that CSF amy- loid has an important role in AD while blood IL-6 has an important role in VAD. P4-057 THERE IS NO PREVENTIVE ROLE OF CATECHOL-O-METHYL TRANSFERASE- INHIBITOR IN PARKINSON’S DISEASE ASSOCIATED WITH DEMENTIA Dushin Jeong 1 , In-Uk Song 2 , Jaehoon Joung 3 , Sung-Woo Chung 4 , Yong-An Chung 2 , Hakjae Roh 5 , 1 Department of Neurology College of Medicine Soonchunhyang University, Asan, South Korea; 2 College of Medicine, The Catholic University of Korea, Incheon, South Korea; 3 College of Medicine, Soonchunhyang University, Gumi, South Korea; 4 Neuroscience Center, Incheon St. Mary’s Hospital, Incheon, South Korea; 5 SCH University Seoul Hospital, Seoul, South Korea. Contact e-mail: Jbrain@schmc.ac.kr Background: Elevated homocysteine (hcy) levels may be associated with dementia which is a frequent non-motor symptom of Parkinson’s disease (PD). The hcy levels in PD treated with levodopa is thought to be elevated for increasing synthesis from the metabolism of levodopa by catechol-O- methyl transferase (COMT). It is thought that COMT-inhibitor may reduce elevated hcy levels. Therefore, the goal of this study is to be establishing the effect of COMT-inhibitor on PD with dementia. Methods: 40 PD without dementia (PDwoD) and 40 PD with dementia (PDD) were compared with 50 controls. All subjects were performed neuropsychological test and neu- rological examination. The hcy levels were measured. And we evaluated to relate with hcy levels and dementia scale in two groups (levodopa-alone treated and levodopa plus COMT inhibitor treated). Results: When arrang- ing this study, higher hcy levels in PDD than PDwoD but there was no sig- nificant difference between PDwoD and healthy controls. In regarding to effect of COMT inhibitor, no correlation was found in hcy levels of two Poster Presentations: P4 P722