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Different patterns of cortical atrophy in early- and late-onset Alzheimer's disease
P14
Alzheimer’s Imaging Consortium Posters: IC-P
DLB-likelihood was made according to the Third Report of the DLB Consortium Criteria, which considers the contribution of both AD and LB related pathologies. Antemortem structural magnetic resonance images were assessed for hippocampal and amygdaloid volume. Tissue densities of both structures were obtained to give age and head-size-adjusted Structural Abnormality iNDex (STAND) z-scores to examine calculated differences from neurologically normal controls. Pathologic burden of hyperphosphorylated neurofibrillary-tau, 6 -synuclein, and b-amyloid from both hippocampus and amygdala were quantitated. Results: pRBD was found in 19 high-likelihood DLB cases (BS 1-4), 8 intermediate-likelihood DLB cases (BS 5-6), and no low-likelihood DLB cases (BS 6). DLB cases who were pRBD-positive had a higher male-to-female ratio (P ¼ 0.005) and were younger at death than the pRBD-negative group (P ¼ 0.013). Hippocampal neurofibrillary-tau (P ¼ 0.049) and b-amyloid (P<0.001) burden was lower in pRBD-positive compared to pRBD-negative cases. Similarly, the amygdaloid neurofibrillary-tau (P ¼ 0.018) and b-amyloid burden (P ¼ 0.011) was lower in pRBD-positive compared to pRBD-negative cases. 6 -Synuclein burden did not differ among pRBDpositive and pRBD-negative cases in either structure. Hippocampal STAND z-scores were higher in pRBD-positive cases (P ¼ 0.055), suggesting there is a greater departure from normal hippocampal volume in pRBD-negative cases. Conclusions: In DLB,pRBD-positive cases are more likely to be male and have a younger death age. Presence of pRBD is associated with less severe AD pathology and AD-related hippocampal atrophy in patients with DLB. Our data suggests that AD is less likely to contribute to the dementia syndrome in DLB with RBD.
IC-P-009
DIFFERENT PATTERNS OF CORTICAL ATROPHY IN EARLY- AND LATE-ONSET ALZHEIMER’S DISEASE
Christiane M€ oller1, Hugo Vrenken1, Lize Jiskoot1, Adriaan Versteeg1, Frederik Barkhof1, Philip Scheltens1, Wiesje Van der Flier2, 1VU Medical Center, Amsterdam, Netherlands; 2VU University Medical Center, Amsterdam, Netherlands. Background: Alzheimer’s disease (AD) is typically regarded as a disease of old age, although it also occurs in younger patients, commonly referred to as early onset AD. This study aimed to assess patterns of cortical atrophy according to age of onset in a large sample of AD patients and controls with voxel-based morphometry (VBM). Methods: We included 344 subjects classified into late-onset AD (LOAD, 65 years; n ¼ 120; 72 years 6 5; 46% females; MMSE 21 6 5), early-onset AD (EOAD,<65 years, n ¼ 95; 60 years 6 4; 55% females; MMSE 20 6 6), older controls (OC; 65 years; n ¼ 32; 71 years 6 4; 50% females; MMSE 28 6 2) and younger controls (YC;<65 years; n ¼ 97; 58 years 6 4; 47% females; MMSE 28 6 2). Whole brain 3D T1-weighted magnetic resonance (MR) imaging was performed using a GE 3T scanner. Image preprocessing and VBM analyses were performed using SPM8 running under MATLAB 7.11. Groups were compared using two-sample t-tests with sex and total intracranial volume as covariates. In a second model we added ApolipoproteinE -E4 (ApoEE4) status and Mini-Mental State Examination (MMSE) as covariates. Correlations between atrophy and MMSE scores were assessed in each group. The threshold for statistical significance was set to P <0.05 using family wise error correction (FWE). Results: Compared to YC, EOAD patients showed widespread atrophy, particularly in the temporal lobe, parahippocampal gyrus, precuneus, posterior cingulate and in the inferior frontal cortex. LOAD patients showed a more specific pattern of atrophy, predominantly in the parahippocampal gyrus and in the right temporal lobe. Additional adjustment for MMSE and ApoE-E4 did not change these results essentially. Direct comparisons between LOAD and EOAD patients revealed more pronounced atrophy in the precuneus of EOAD patients, while we observed more severe atrophy in the parahippocampal gyrus and cerebellum of LOAD patients. Correlation analyses revealed that lower MMSE scores were related to more severe atrophy of the inferior temporal lobe in both EOAD (right and left) and LOAD (only left). Conclusions: Compared to age-matched controls, EOAD patients exhibited more diffuse
and widespread atrophy than LOAD patients. In a direct comparison, EOAD patients had more pronounced atrophy of the precuneus than patients with LOAD, despite their younger age.
IC-P-011
AMYLOID PET IMAGING USING AZD4694 AND UNUSUALLY BRIEF RADIOTRACER UPTAKE AND SCANNING PERIODS
Kewei Chen1, Jessica Langbaum1, Adam Fleisher1, Auttawut Roontiva1, Xiaofen Liu1, Pradeep Thiyyagura1, Dan Bandy1, Nicole Richter1, Laura Jakimovich1, Anita Prouty1, Zsolt Cselenyi2, Lars Farde3, Samantha Budd4, Eric Reiman1, 1Banner Alzheimer’s Institute, Phoenix, Arizona, United States; 2Astra Zeneca R&D, Karolinska Institute, Sodertalje, Sweden; 3Astra Zeneca R&D, Karolinska Institute, Sodertalje, Sweden; 4Astra Zeneca R&D, Sodertalje, Sweden. Background: AZD4694 is a second-generation [18F]-labeled amyloid PET ligand associated with relatively rapid uptake and equilibrium in brain and which appears to have relatively high specific-to-white matter binding. In this study, we compared the use of PET frames acquired at different times following radiotracer administration, roughly corresponding to the average time associated with peak specific binding in gray matter (i.e. maximal cerebral-to-cerebellar uptake difference), and with different durations. Methods: Dynamic 90-minute AZD4694 PET scans were performed in 10 patients with probable AD, 10 cognitively normal older adults, and 4 cognitively normal young adult APOE e 4 noncarriers. Preselected regions-of-interest and an automated brain mapping algorithm were each used to characterize and compare the ability of AZD4694 standard uptake value ratios (SUVRs) to distinguish the probable AD patients from the cognitively normal older and younger adults using 20-30 min, 20-25, 25-30, and 25-35 min frames. Results: PET frames from each of the selected intervals used in this study was able to distinguish the probable AD group from the older and younger controls groups (P<0.05) using either mean cortical SUVRs or brain maps. Voxel-wise analysis revealed a spatial pattern of amyloid deposition typically observed in patients with pAD. Conclusions: While larger studies are needed to compare the ability of different time intervals to distinguish subject groups with greater statistical power, AZD4694 could help characterize cerebral amyloid deposition with a radiotracer uptake period as brief as 20 min and an emission fame as brief as 5 min, a feature that may have practical advantages in certain settings.
IC-P-012
ADDED VALUE OF 11C-PIB-PET IMAGING IN THE DIAGNOSIS OF ALZHEIMER’S DISEASE
Kristian Frederiksen, Anne-Mette Hejl, Ian Law, Steen Hasselbalch, Gunhild Waldemar, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. Background: Cerebral beta-amyloid, a central component of the pathology in Alzheimers disease (AD), may be imaged using the PET ligand
Alzheimer’s Imaging Consortium Posters: IC-P
DLB-likelihood was made according to the Third Report of the DLB Consortium Criteria, which considers the contribution of both AD and LB related pathologies. Antemortem structural magnetic resonance images were assessed for hippocampal and amygdaloid volume. Tissue densities of both structures were obtained to give age and head-size-adjusted Structural Abnormality iNDex (STAND) z-scores to examine calculated differences from neurologically normal controls. Pathologic burden of hyperphosphorylated neurofibrillary-tau, 6 -synuclein, and b-amyloid from both hippocampus and amygdala were quantitated. Results: pRBD was found in 19 high-likelihood DLB cases (BS 1-4), 8 intermediate-likelihood DLB cases (BS 5-6), and no low-likelihood DLB cases (BS 6). DLB cases who were pRBD-positive had a higher male-to-female ratio (P ¼ 0.005) and were younger at death than the pRBD-negative group (P ¼ 0.013). Hippocampal neurofibrillary-tau (P ¼ 0.049) and b-amyloid (P<0.001) burden was lower in pRBD-positive compared to pRBD-negative cases. Similarly, the amygdaloid neurofibrillary-tau (P ¼ 0.018) and b-amyloid burden (P ¼ 0.011) was lower in pRBD-positive compared to pRBD-negative cases. 6 -Synuclein burden did not differ among pRBDpositive and pRBD-negative cases in either structure. Hippocampal STAND z-scores were higher in pRBD-positive cases (P ¼ 0.055), suggesting there is a greater departure from normal hippocampal volume in pRBD-negative cases. Conclusions: In DLB,pRBD-positive cases are more likely to be male and have a younger death age. Presence of pRBD is associated with less severe AD pathology and AD-related hippocampal atrophy in patients with DLB. Our data suggests that AD is less likely to contribute to the dementia syndrome in DLB with RBD.
IC-P-009
DIFFERENT PATTERNS OF CORTICAL ATROPHY IN EARLY- AND LATE-ONSET ALZHEIMER’S DISEASE
Christiane M€ oller1, Hugo Vrenken1, Lize Jiskoot1, Adriaan Versteeg1, Frederik Barkhof1, Philip Scheltens1, Wiesje Van der Flier2, 1VU Medical Center, Amsterdam, Netherlands; 2VU University Medical Center, Amsterdam, Netherlands. Background: Alzheimer’s disease (AD) is typically regarded as a disease of old age, although it also occurs in younger patients, commonly referred to as early onset AD. This study aimed to assess patterns of cortical atrophy according to age of onset in a large sample of AD patients and controls with voxel-based morphometry (VBM). Methods: We included 344 subjects classified into late-onset AD (LOAD, 65 years; n ¼ 120; 72 years 6 5; 46% females; MMSE 21 6 5), early-onset AD (EOAD,<65 years, n ¼ 95; 60 years 6 4; 55% females; MMSE 20 6 6), older controls (OC; 65 years; n ¼ 32; 71 years 6 4; 50% females; MMSE 28 6 2) and younger controls (YC;<65 years; n ¼ 97; 58 years 6 4; 47% females; MMSE 28 6 2). Whole brain 3D T1-weighted magnetic resonance (MR) imaging was performed using a GE 3T scanner. Image preprocessing and VBM analyses were performed using SPM8 running under MATLAB 7.11. Groups were compared using two-sample t-tests with sex and total intracranial volume as covariates. In a second model we added ApolipoproteinE -E4 (ApoEE4) status and Mini-Mental State Examination (MMSE) as covariates. Correlations between atrophy and MMSE scores were assessed in each group. The threshold for statistical significance was set to P <0.05 using family wise error correction (FWE). Results: Compared to YC, EOAD patients showed widespread atrophy, particularly in the temporal lobe, parahippocampal gyrus, precuneus, posterior cingulate and in the inferior frontal cortex. LOAD patients showed a more specific pattern of atrophy, predominantly in the parahippocampal gyrus and in the right temporal lobe. Additional adjustment for MMSE and ApoE-E4 did not change these results essentially. Direct comparisons between LOAD and EOAD patients revealed more pronounced atrophy in the precuneus of EOAD patients, while we observed more severe atrophy in the parahippocampal gyrus and cerebellum of LOAD patients. Correlation analyses revealed that lower MMSE scores were related to more severe atrophy of the inferior temporal lobe in both EOAD (right and left) and LOAD (only left). Conclusions: Compared to age-matched controls, EOAD patients exhibited more diffuse
and widespread atrophy than LOAD patients. In a direct comparison, EOAD patients had more pronounced atrophy of the precuneus than patients with LOAD, despite their younger age.
IC-P-011
AMYLOID PET IMAGING USING AZD4694 AND UNUSUALLY BRIEF RADIOTRACER UPTAKE AND SCANNING PERIODS
Kewei Chen1, Jessica Langbaum1, Adam Fleisher1, Auttawut Roontiva1, Xiaofen Liu1, Pradeep Thiyyagura1, Dan Bandy1, Nicole Richter1, Laura Jakimovich1, Anita Prouty1, Zsolt Cselenyi2, Lars Farde3, Samantha Budd4, Eric Reiman1, 1Banner Alzheimer’s Institute, Phoenix, Arizona, United States; 2Astra Zeneca R&D, Karolinska Institute, Sodertalje, Sweden; 3Astra Zeneca R&D, Karolinska Institute, Sodertalje, Sweden; 4Astra Zeneca R&D, Sodertalje, Sweden. Background: AZD4694 is a second-generation [18F]-labeled amyloid PET ligand associated with relatively rapid uptake and equilibrium in brain and which appears to have relatively high specific-to-white matter binding. In this study, we compared the use of PET frames acquired at different times following radiotracer administration, roughly corresponding to the average time associated with peak specific binding in gray matter (i.e. maximal cerebral-to-cerebellar uptake difference), and with different durations. Methods: Dynamic 90-minute AZD4694 PET scans were performed in 10 patients with probable AD, 10 cognitively normal older adults, and 4 cognitively normal young adult APOE e 4 noncarriers. Preselected regions-of-interest and an automated brain mapping algorithm were each used to characterize and compare the ability of AZD4694 standard uptake value ratios (SUVRs) to distinguish the probable AD patients from the cognitively normal older and younger adults using 20-30 min, 20-25, 25-30, and 25-35 min frames. Results: PET frames from each of the selected intervals used in this study was able to distinguish the probable AD group from the older and younger controls groups (P<0.05) using either mean cortical SUVRs or brain maps. Voxel-wise analysis revealed a spatial pattern of amyloid deposition typically observed in patients with pAD. Conclusions: While larger studies are needed to compare the ability of different time intervals to distinguish subject groups with greater statistical power, AZD4694 could help characterize cerebral amyloid deposition with a radiotracer uptake period as brief as 20 min and an emission fame as brief as 5 min, a feature that may have practical advantages in certain settings.
IC-P-012
ADDED VALUE OF 11C-PIB-PET IMAGING IN THE DIAGNOSIS OF ALZHEIMER’S DISEASE
Kristian Frederiksen, Anne-Mette Hejl, Ian Law, Steen Hasselbalch, Gunhild Waldemar, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. Background: Cerebral beta-amyloid, a central component of the pathology in Alzheimers disease (AD), may be imaged using the PET ligand