- Email: [email protected]
Quantitative tractography of fibers crossing white matter hyperintensities
P722
Poster Presentations: P4
Tohon, Ehine, Japan; 2Ehime University Graduate School of Medicine, Tohon, Ehime, Japan; 3Ehime University, Tohon, Ehime, Japan. Contact e-mail: [email protected] Background: Angiotensin II type 2 (AT 2) receptor activation has been reported to play a role in the cognitive function, although its detailed mechanisms 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 bilateral 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 administrated 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 impairment of spatial learning activity after BCAS and this impairment was significantly 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 decreased and this decrease was blunted by the treatment with C21. TNFa 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 ischemic vascular dementia induced by hypoperfusion at least in part due to increase 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 Garcia1, William Reginold1, Angela Luedke1, Angela Tam2, Jennifer Reginold2, Omar Islam2, Juan Fernandez2, 1Queen’s University, Kingston, Ontario, Canada; 2Queen’s University, Kingston, Ontario, Canada. Contact e-mail: [email protected] Background: According to the disconnection hypothesis, disruption of fiber 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 quantitative tractography we assess if the injury within the WMH extends along the entire length of WMH-tracts and correlates with increasing WMH burden, 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-registered T2 FLAIR were quantitatively analyzed with TrackVis (www. trackvis.org). All fibers in the brain by tractography that crossed WMH lesions 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 Montreal 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 decreased FA (p¼0.01). There was no difference between controls and AD patients 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 Karadas1, Hakan Gul2, Serdar Firtina1, 1Erzincan Military Hospital, Erzincan, Turkey; 2Kartal Education and Treatment Hospital, Istanbul/ Turkey, Istanbul, Turkey. Contact e-mail: [email protected] 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 cerebrospinal 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 significant higher than group 2’s levels. Grup 2’s blood IL-6 levels were statistically significant higher than group 1’s levels. Other parameters had no difference between two groups. Conclusions: The results of the study suggest that inflammatory process has an important role when we evaluate the two groups according to biological basics. We detected that CSF amyloid 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 TRANSFERASEINHIBITOR IN PARKINSON’S DISEASE ASSOCIATED WITH DEMENTIA
Dushin Jeong1, In-Uk Song2, Jaehoon Joung3, Sung-Woo Chung4, Yong-An Chung2, Hakjae Roh5, 1Department of Neurology College of Medicine Soonchunhyang University, Asan, South Korea; 2College of Medicine, The Catholic University of Korea, Incheon, South Korea; 3College of Medicine, Soonchunhyang University, Gumi, South Korea; 4Neuroscience Center, Incheon St. Mary’s Hospital, Incheon, South Korea; 5SCH University Seoul Hospital, Seoul, South Korea. Contact e-mail: [email protected] 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-Omethyl 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 neurological 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 arranging this study, higher hcy levels in PDD than PDwoD but there was no significant 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
Tohon, Ehine, Japan; 2Ehime University Graduate School of Medicine, Tohon, Ehime, Japan; 3Ehime University, Tohon, Ehime, Japan. Contact e-mail: [email protected] Background: Angiotensin II type 2 (AT 2) receptor activation has been reported to play a role in the cognitive function, although its detailed mechanisms 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 bilateral 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 administrated 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 impairment of spatial learning activity after BCAS and this impairment was significantly 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 decreased and this decrease was blunted by the treatment with C21. TNFa 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 ischemic vascular dementia induced by hypoperfusion at least in part due to increase 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 Garcia1, William Reginold1, Angela Luedke1, Angela Tam2, Jennifer Reginold2, Omar Islam2, Juan Fernandez2, 1Queen’s University, Kingston, Ontario, Canada; 2Queen’s University, Kingston, Ontario, Canada. Contact e-mail: [email protected] Background: According to the disconnection hypothesis, disruption of fiber 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 quantitative tractography we assess if the injury within the WMH extends along the entire length of WMH-tracts and correlates with increasing WMH burden, 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-registered T2 FLAIR were quantitatively analyzed with TrackVis (www. trackvis.org). All fibers in the brain by tractography that crossed WMH lesions 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 Montreal 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 decreased FA (p¼0.01). There was no difference between controls and AD patients 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 Karadas1, Hakan Gul2, Serdar Firtina1, 1Erzincan Military Hospital, Erzincan, Turkey; 2Kartal Education and Treatment Hospital, Istanbul/ Turkey, Istanbul, Turkey. Contact e-mail: [email protected] 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 cerebrospinal 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 significant higher than group 2’s levels. Grup 2’s blood IL-6 levels were statistically significant higher than group 1’s levels. Other parameters had no difference between two groups. Conclusions: The results of the study suggest that inflammatory process has an important role when we evaluate the two groups according to biological basics. We detected that CSF amyloid 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 TRANSFERASEINHIBITOR IN PARKINSON’S DISEASE ASSOCIATED WITH DEMENTIA
Dushin Jeong1, In-Uk Song2, Jaehoon Joung3, Sung-Woo Chung4, Yong-An Chung2, Hakjae Roh5, 1Department of Neurology College of Medicine Soonchunhyang University, Asan, South Korea; 2College of Medicine, The Catholic University of Korea, Incheon, South Korea; 3College of Medicine, Soonchunhyang University, Gumi, South Korea; 4Neuroscience Center, Incheon St. Mary’s Hospital, Incheon, South Korea; 5SCH University Seoul Hospital, Seoul, South Korea. Contact e-mail: [email protected] 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-Omethyl 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 neurological 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 arranging this study, higher hcy levels in PDD than PDwoD but there was no significant difference between PDwoD and healthy controls. In regarding to effect of COMT inhibitor, no correlation was found in hcy levels of two