- Email: [email protected]
P2-273
S318
Poster P2:: Monday Posters
with lower integrity will have lower linear anisotropy which, in turn, should cause the streamtube generation algorithm to terminate prematurely resulting in shorter streamtubes and lower values of NTWL. Objective(s): To determine the relative contribution of interhemispheric vs. cingulum bundle fibers to psychomotor processing speed ability in the elderly using quantitative DTI tractography. Methods: DTI was obtained on 12 cognitively normal individuals 49 to 83 years old NTWL was calculated on three TOIs: interhemispheric fibers (IHF) passing through the corpus callosum and right and left cingulum bundles. Trail Making Test part A (TMT-A) was used to measure psychomotor processing speed. Multiple linear regression was used to test the association between TMT-A and NTWL in the three TOIs after accounting for age. Age was entered at step 1 and the TOI variables were entered at step 2. Results: Age accounted for 28% of the variance in TMT-A performance (p ⫽.079, trend). The NTWL metrics for the three TOIs accounted for an additional 41% of the variance at step 2 (p ⫽ .101, trend for F change). Examination of standardized beta weights for the individual TOIs showed that only NTWL in the right cingulum bundle was a significant predictor (beta ⫽ -.585, p ⫽ .044). Conclusions: After accounting for age, performance on TMT-A appears to be more closely related to the ultrastructural integrity of the right cingulum bundle than to the left cingulum bundle or to interhemispheric fibers. Although the results are limited by the small sample, they demonstrate the potential of quantitative DTI tractography for correlating cognitive functions with specific white matter pathways. P2-271
WHITE MATTER CHANGES INVOLVING CHOLINERGIC PATHWAYS CONTRIBUTE TO THE COGNITIVE DECLINE IN PATIENTS WITH ALZHEIMER DISEASE
Ae Young Lee, Soo Young Choi, Eun Hee Sohn, Jae Moon Kim, Chungnam University Hospital, Daejon, Republic of Korea. Contact e-mail: [email protected] Background: White matter hyperintensities (WMH) on MRI are commonly seen in the elderly and known to be a risk factor for cognitive decline and dementia. Objective(s): To know WMH specifically involving cholinergic pathways to contribute cognitive decline in Alzheimer disease (AD). Methods: Fifty patients with AD (25 patients with WMH, 25 patients without WMH) were enrolled. The severity of WMH was rated with three different visual rating scales (one is developed specifically for cholinergic pathway involvement and the others are conventional scales for WMH) from selected axial MRI images by 3 raters. Hippocampal atrophy was rated with a 4-point scale. All subjects underwent standardized neuropsychological testing, which encompasses attention, language, memory, visuospatial function, frontal lobe function, and mood. Results: WMH involving cholinergic pathways were related with cognitive decline in patients with AD and WMH rating scale specifically developed for cholinergic pathways involvement was more useful to assess WMH contributing cognitive impairment than conventional WMH rating scales in the demented. Conclusions: WMH involving cholinergic pathways might be responsible for cognitive decline in patients with AD. P2-272
THE ONSET OF STRUCTURAL CHANGE IN FAMILIAL ALZHEIMER’S DISEASE
Henrike Wolf1, Marc Tittgemeyer2, Thomas Wittwar3, Lars-Olof Wahlund1, 1Karolinska Institutet, Stockholm, Sweden; 2MaxPlanck-Institute of Human Cognitive and Brain Sciences, Leipzig, Germany; 3Dep. of Psychiatry, Memory Clinic, University of Leipzig, Leipzig, Germany. Contact e-mail: [email protected] Objective: To study early structural changes in familial Alzheimer’s disease based on cross-sectional and serial magnetic resonance (MR) examinations in three pedigrees with autosomal dominant mutations. Method: 64 high-resolution T1w MR from 35 family members of FAD pedigrees were acquired. Seventeen were mutation carriers (cases), 18 were non carriers (controls). Nine cases were asymptomatic (22 to 6 before expected
onset of symptoms, EOoS). Serial scans (2-5) were available from 22 subjects (11 mutation carriers), spanning up to10 years observation time. A precise anatomical protocol was used for manual hippocampal outlining, enabling 3D reconstructions of the hippocampus. This was accompanied by unbiased methods to segment brain compartments and to quantify and visualize structural change over time. Results: Cross-sectional analyses imply that pronounced HcV loss (approximating 25%) occurs in the few years over which first symptoms develop. In some asymptomatic mutation carriers, accelerated HcV loss of up to 6% per annum was observed as early as 20 years before EOoS. Conclusions: A single HcV measurement seems unsuitable to detect AD in asymptomatic subjects, due to the high interindividual variation in HcV. However, accellerated Hc atrophy appears to be present many years before first symptoms develop. Serial measurements could be useful to detect AD in presymptomatic stages. P2-273
PET-IMAGING OF AMYLOID DEPOSITIONS AND ASTROCYTOSIS IN SEVERE AD AND HISTOPATHOLOGICAL CORRELATIONS IN ONE PATIENT
Henry W. Engler1,2, Ulla M. Louhija2, Irina Savitcheva2, Tommie Olofsson2, Hannu Kalimo2, Lars Lannfelt2, Bengt R. Långstro¨m1. 1Uppsala Imanet AB, Uppsala, Sweden; 2Uppsala University Hospital, Uppsala, Sweden. Contact e-mail: [email protected] Backgound: In a study performed at Uppsala University PET Centre, reactive astrocytosis and neuronal dysfunction was observed in the brain of patients with Creutzfeldt-Jakob’s disease (CJD) using PET and combining 11 C-deuteriumdeprenyl (DED) and FDG. In another recent study, amyloid depositions and hypometabolic changes were found in the brain of AD patients using PET with N-methyl[11C]2-(4⬘methylaminophenyl) -6-hydroxy-benzothiazole (PIB) and FDG.2 The mechanism of PIB binding to amyloid is yet unclear, while the binding of DED to monoamine oxidase-B has been demonstrated to increase in reactive astrocytes. Objective: To study the relations between amyloid depositions and reactive astrocytosis in AD patients. Methods: 10 patients with the clinical diagnosis of severe AD (MMSE approx: 15), were examined with PET using PIB and DED. Results: The preliminary results indicate a correlation between high amyloid deposition and increased DED uptake in the frontoparietal cortex of some patients. However, a mismatch was observed between the PIB retention (low) and the DED uptake (high) in the medial temporal areas. Furthermore, one of these patients died shortly after the PET-examination. The diagnosis “Lewy body disease of neocortical type” was established at autopsy. Alzheimer disease changes were also found. In the medial temporal region, the histopathological findings indicated slight astrocytosis surrounding neuritic plaques. PIB did not show retention in this region, whereas the astrocytosis surrounding the plaques was detected by DED. We intend to classify the subtype of plaques present in the autopsied brain to gain a better understanding of the relation between PIB deposition and DED uptake. Conclusions: It seems that DED can contribute to the diagnostic accuracy by indicating reactive astrocytosis surrounding neuritic plaques in places without PIB retention. Our findings suggest the value of multitracer protocols to improve the accuracy in the differential diagnoses. Like the pathologist using the microscope and different dyes, we will need the PET technology and a combination of “staining” tracers to detect in vivo patterns expressing the complex pathological changes in neurodegeneration. P2-274
FDDNP-PET BINDING DIFFERENTIATES MCI FROM DEMENTIA AND INCREASES WITH CLINICAL PROGRESSION
Gary W. Small1, Vladimir Kepe2, Linda M. Ercoli2, Prabha Siddarth2, Harry V. Vinters2, N. Satyamurthy2, S.C. Huang2, Michael E. Phelps2, Jorge R. Barrio2, 1UCLA, Los Angeles, CA, USA; 2UCLA, Los Angeles, USA. Contact e-mail: [email protected]
Poster P2:: Monday Posters
with lower integrity will have lower linear anisotropy which, in turn, should cause the streamtube generation algorithm to terminate prematurely resulting in shorter streamtubes and lower values of NTWL. Objective(s): To determine the relative contribution of interhemispheric vs. cingulum bundle fibers to psychomotor processing speed ability in the elderly using quantitative DTI tractography. Methods: DTI was obtained on 12 cognitively normal individuals 49 to 83 years old NTWL was calculated on three TOIs: interhemispheric fibers (IHF) passing through the corpus callosum and right and left cingulum bundles. Trail Making Test part A (TMT-A) was used to measure psychomotor processing speed. Multiple linear regression was used to test the association between TMT-A and NTWL in the three TOIs after accounting for age. Age was entered at step 1 and the TOI variables were entered at step 2. Results: Age accounted for 28% of the variance in TMT-A performance (p ⫽.079, trend). The NTWL metrics for the three TOIs accounted for an additional 41% of the variance at step 2 (p ⫽ .101, trend for F change). Examination of standardized beta weights for the individual TOIs showed that only NTWL in the right cingulum bundle was a significant predictor (beta ⫽ -.585, p ⫽ .044). Conclusions: After accounting for age, performance on TMT-A appears to be more closely related to the ultrastructural integrity of the right cingulum bundle than to the left cingulum bundle or to interhemispheric fibers. Although the results are limited by the small sample, they demonstrate the potential of quantitative DTI tractography for correlating cognitive functions with specific white matter pathways. P2-271
WHITE MATTER CHANGES INVOLVING CHOLINERGIC PATHWAYS CONTRIBUTE TO THE COGNITIVE DECLINE IN PATIENTS WITH ALZHEIMER DISEASE
Ae Young Lee, Soo Young Choi, Eun Hee Sohn, Jae Moon Kim, Chungnam University Hospital, Daejon, Republic of Korea. Contact e-mail: [email protected] Background: White matter hyperintensities (WMH) on MRI are commonly seen in the elderly and known to be a risk factor for cognitive decline and dementia. Objective(s): To know WMH specifically involving cholinergic pathways to contribute cognitive decline in Alzheimer disease (AD). Methods: Fifty patients with AD (25 patients with WMH, 25 patients without WMH) were enrolled. The severity of WMH was rated with three different visual rating scales (one is developed specifically for cholinergic pathway involvement and the others are conventional scales for WMH) from selected axial MRI images by 3 raters. Hippocampal atrophy was rated with a 4-point scale. All subjects underwent standardized neuropsychological testing, which encompasses attention, language, memory, visuospatial function, frontal lobe function, and mood. Results: WMH involving cholinergic pathways were related with cognitive decline in patients with AD and WMH rating scale specifically developed for cholinergic pathways involvement was more useful to assess WMH contributing cognitive impairment than conventional WMH rating scales in the demented. Conclusions: WMH involving cholinergic pathways might be responsible for cognitive decline in patients with AD. P2-272
THE ONSET OF STRUCTURAL CHANGE IN FAMILIAL ALZHEIMER’S DISEASE
Henrike Wolf1, Marc Tittgemeyer2, Thomas Wittwar3, Lars-Olof Wahlund1, 1Karolinska Institutet, Stockholm, Sweden; 2MaxPlanck-Institute of Human Cognitive and Brain Sciences, Leipzig, Germany; 3Dep. of Psychiatry, Memory Clinic, University of Leipzig, Leipzig, Germany. Contact e-mail: [email protected] Objective: To study early structural changes in familial Alzheimer’s disease based on cross-sectional and serial magnetic resonance (MR) examinations in three pedigrees with autosomal dominant mutations. Method: 64 high-resolution T1w MR from 35 family members of FAD pedigrees were acquired. Seventeen were mutation carriers (cases), 18 were non carriers (controls). Nine cases were asymptomatic (22 to 6 before expected
onset of symptoms, EOoS). Serial scans (2-5) were available from 22 subjects (11 mutation carriers), spanning up to10 years observation time. A precise anatomical protocol was used for manual hippocampal outlining, enabling 3D reconstructions of the hippocampus. This was accompanied by unbiased methods to segment brain compartments and to quantify and visualize structural change over time. Results: Cross-sectional analyses imply that pronounced HcV loss (approximating 25%) occurs in the few years over which first symptoms develop. In some asymptomatic mutation carriers, accelerated HcV loss of up to 6% per annum was observed as early as 20 years before EOoS. Conclusions: A single HcV measurement seems unsuitable to detect AD in asymptomatic subjects, due to the high interindividual variation in HcV. However, accellerated Hc atrophy appears to be present many years before first symptoms develop. Serial measurements could be useful to detect AD in presymptomatic stages. P2-273
PET-IMAGING OF AMYLOID DEPOSITIONS AND ASTROCYTOSIS IN SEVERE AD AND HISTOPATHOLOGICAL CORRELATIONS IN ONE PATIENT
Henry W. Engler1,2, Ulla M. Louhija2, Irina Savitcheva2, Tommie Olofsson2, Hannu Kalimo2, Lars Lannfelt2, Bengt R. Långstro¨m1. 1Uppsala Imanet AB, Uppsala, Sweden; 2Uppsala University Hospital, Uppsala, Sweden. Contact e-mail: [email protected] Backgound: In a study performed at Uppsala University PET Centre, reactive astrocytosis and neuronal dysfunction was observed in the brain of patients with Creutzfeldt-Jakob’s disease (CJD) using PET and combining 11 C-deuteriumdeprenyl (DED) and FDG. In another recent study, amyloid depositions and hypometabolic changes were found in the brain of AD patients using PET with N-methyl[11C]2-(4⬘methylaminophenyl) -6-hydroxy-benzothiazole (PIB) and FDG.2 The mechanism of PIB binding to amyloid is yet unclear, while the binding of DED to monoamine oxidase-B has been demonstrated to increase in reactive astrocytes. Objective: To study the relations between amyloid depositions and reactive astrocytosis in AD patients. Methods: 10 patients with the clinical diagnosis of severe AD (MMSE approx: 15), were examined with PET using PIB and DED. Results: The preliminary results indicate a correlation between high amyloid deposition and increased DED uptake in the frontoparietal cortex of some patients. However, a mismatch was observed between the PIB retention (low) and the DED uptake (high) in the medial temporal areas. Furthermore, one of these patients died shortly after the PET-examination. The diagnosis “Lewy body disease of neocortical type” was established at autopsy. Alzheimer disease changes were also found. In the medial temporal region, the histopathological findings indicated slight astrocytosis surrounding neuritic plaques. PIB did not show retention in this region, whereas the astrocytosis surrounding the plaques was detected by DED. We intend to classify the subtype of plaques present in the autopsied brain to gain a better understanding of the relation between PIB deposition and DED uptake. Conclusions: It seems that DED can contribute to the diagnostic accuracy by indicating reactive astrocytosis surrounding neuritic plaques in places without PIB retention. Our findings suggest the value of multitracer protocols to improve the accuracy in the differential diagnoses. Like the pathologist using the microscope and different dyes, we will need the PET technology and a combination of “staining” tracers to detect in vivo patterns expressing the complex pathological changes in neurodegeneration. P2-274
FDDNP-PET BINDING DIFFERENTIATES MCI FROM DEMENTIA AND INCREASES WITH CLINICAL PROGRESSION
Gary W. Small1, Vladimir Kepe2, Linda M. Ercoli2, Prabha Siddarth2, Harry V. Vinters2, N. Satyamurthy2, S.C. Huang2, Michael E. Phelps2, Jorge R. Barrio2, 1UCLA, Los Angeles, CA, USA; 2UCLA, Los Angeles, USA. Contact e-mail: [email protected]