- Email: [email protected]
The practical utility of amyloid and FDG-PET in an academic dementia center
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Saturday, July 13, 2013: Alzheimer’s Imaging Consortium Poster Presentations: IC-P
beta-amyloid deposition show further involvement of parietal cortex. Furthermore, the data suggest that cortical thickness mediates the impact of vascular risk and beta-amyloid on memory function.
Impact on treatment was more modest than on diagnosis and limited to Ab negative patients. IC-P-024
[18F] FLUTEMETAMOL PET IMAGING FOR BETAAMYLOID DEPOSITION ACROSS THE SPECTRUM OF ALZHEIMER’S DISEASE
Shizuo Hatashita, Hidetomo Yamasaki, Yutaka Suzuki, Kumiko Tanaka, Keita Taniguchi, Taichi Wakebe, Hideki Hayakawa, 1Shonan-Atsugi Hospital, Atsugi, Japan. Contact e-mail: [email protected]
Figure. Vertex-wise analyses corrected for age, cognitive status and multiple comparisons assessing the impact of vascular risk (FCRP) total score) and HDL cholesterol on cortical thickness. IC-P-023
THE PRACTICAL UTILITY OF AMYLOID AND FDG-PET IN AN ACADEMIC DEMENTIA CENTER
Pascual S anchez Juan1, Pia Ghosh2, Jayne Hagen3, Benno Gesierich3, Maya Henry3, Maria-Luisa Gorno-Tempini3, Bruce Miller3, William Jagust4, Gil Rabinovici3, 1University Hospital Marques de Valdecilla, Santander, Spain; 2UCSF Memory and Aging Center, San Francisco, California, United States; 3UCSF Memory and Aging Center, San Francisco, California, United States; 4University of California, Berkeley, Berkeley, California, United States. Contact e-mail: psanchez@ humv.es Background: We evaluated the impact of amyloid and FDG PET on clinical decision making in a heterogeneous population of cognitively impaired patients. Methods: We selected all patients with FDG and PIB PET and had at least one clinical evaluation before and after PET. We evaluated for change in primary diagnosis and change in treatment between the pre- and post-PET visit. The association of discordant PIB and FDG with changes in clinical management was assessed separately using chi-square and together applying logistic regression. Results: 140 cognitively impaired patients were included in the study (mean age 65.0 6 8.2, 46.% primary Ab diagnosis, 55.0% of new patients, mean MMSE 22.7 6 9.0, 41.0 % CDR<1). PIB and FDG PET agreed in classifying 83.6% of patients. Concordance with pre-scan diagnosis was 84.3% for PIB and 82.1% for FDG. The primary diagnosis was changed after PET in 13/140 patients (9.3%): 12/13 changes were concordant with PIB and 8/13 with FDG results. When examined independently, both discordant PIB and discordant FDG were associated with a change in diagnosis (p<0.0001). However, multivariate analysis revealed that changes in diagnosis were associated with discordant PIB (p¼0.00013) but not discordant FDG (p¼0.087) (LR additional covariates: clinical dilemmas pre -PET, gender, age at PET, baseline diagnosis, new patient (follow up before PET of less than 1 year) and CDR <1) 35% of patients had a change in AD therapy post-PET (initiating or discontinuing acetycholinesterase inhibitors or memantine). In the entire population changes in treatment were not associated with discordant PIB or discordant FDG (p>0.05 in LR model); however discordant PIB did affect treatment in of patients with non-Ab pre-PET diagnoses (p¼0.028), driven by the initiation of acetycholinesterase inhibitors in patients who were unexpectedly PIB-positive. Conclusions: Overall concordance of PET amyloid and FDG results with clinical diagnosis was high and changes in diagnosis were uncommon. Discordant PIB had a greater effect on diagnostic changes than discordant FDG.
Background: We had demonstrated that a diagnostic framework with a beta amyloid (Ab) deposition by [11C]-PIB PET allows for an earlier Alzheimer’s disease (AD) diagnosis. The PET amyloid imaging with a tracer of [18F]-labeled PIB derivate [18F]-Flutemetamol (FMM) have recently developed to be a novel technology of underlying AD pathology. The aim is to identify the Ab deposition by [18F]-FMM PET across the spectrum of AD. Methods: Twenty-eight patients with AD, 44 with mild cognitive impairment (MCI) and 32 subjects with healthy control (HC) were studied. All 104 subjects (age: 55-89 years) underwent 30-min static [18F]-FMM PET, acquired 85 min after injection (196.4 6 6.6 MBq), and cognitive test. [18F]-FMM scans were assessed visually with 3 blind readers as abnormal or normal cortical uptake. The standardized uptake value ratios (SUVR) were defined quantitatively in regions of interest defined on co-registered MRI (cerebellar gray as a reference region). Results: The visual assessments of [18F]-FMM scans had an increased uptake in 27 of 28 scans with AD and 4 of 32 scans with HC, corresponding to an overall sensitivity of 96.4% and a specificity of 87.7%. Inter-reader agreement was excellent (Kappa score¼0.84), and intra-reader agreement was 93.3%. Fourteen (31.8%) of 44 MCI scans showed an increased uptake of [18F]-FMM. The FMM SUVR of composite cortical regions in AD was significantly greater than in HC (1.84 6 0.27 vs 1.28 6 0.17, P<0.01). MCI patients had a bimodal distribution of SUVR. The FMM SUVR in 14 patients with [18F]-FMM positive MCI and 30 patients with negative MCI were 1.82 6 0.29 and 1.20 6 0.08, respectively. The regional FMM SUVR of all cortical regions in AD, except for medial temporal cortex, were significantly different from HC. Cortical FMM SUVR was significantly correlated negatively with MMSE scores (r¼0.62, P<0.01), and positively to CDR SB scores (r¼0.55, P<0.01) when all groups were analyzed. Conclusions: [18F]-Flutemetamol PET discriminates Alzheimer’s disease from healthy controls and facilitates integration of Ab imaging into clinical practice. The PET imaging with [18F]-Flutemetamol is a reliable biomarker of Ab deposition along the continuum from normal cognitive status to dementia of AD. IC-P-025
[18F]NAV4694 SHOWS HIGHER BINDING AND WIDER DYNAMIC RANGE COMPARED WITH [11C]PIB IN ALZHEIMER’S DISEASE POSTMORTEM TISSUE
Eduardo Zimmer1, Maxime Parent2, Antoine Leuzy3, Jared Rowley4, Laksanun Cheewakriengkrai3, Monica Shin3, Seqian Wang2, Marina Dauar2, Sara Mohades2, Esher Susanne Schirrmacher5, Jean-Paul Soucy5, Alexey Kostikov6, Marie-Christine Guiot7, Serge Gauthier8, Pedro Rosa-Neto9, 1McGill Center for Studies in Aging, Montreal, Quebec, Canada; 2McGill Center for Studies in Aging, Montreal, Quebec, Canada; 3McGill Centre for Studies in Aging, Montreal, Quebec, Canada; 4McGill University, Verdun, Quebec, Canada; 5McGill, Montreal, Quebec, Canada; 6McGill, Montreal, Quebec, Canada; 7McGill, Montreal, Quebec, Canada; 8Alzheimer Disease Research Unit, McGill Center for Studies in Aging, Montreal, Quebec, Canada; 9McGill University, Montreal, Quebec, Canada. Contact e-mail: [email protected] Background: [18 F]amyloid imaging agents have low dynamic range when compared with [11 C]PIB, the benchmark PET agent for quantifying brain amyloidosis. In this context, the new amyloid imaging agent [18 F] NAV4694 has been considered a promising amyloid agent. Here, we compare the binding and dynamic range of [11 C]PIB and [18 F]NAV4694 in AD post-mortem brains by means of in vitro autoradiography. Since [18 F]NAV4694 affinity (Kd ¼ 2.4 nM) is higher than [11 C]PIB (Kd ¼ 4.5
Saturday, July 13, 2013: Alzheimer’s Imaging Consortium Poster Presentations: IC-P
beta-amyloid deposition show further involvement of parietal cortex. Furthermore, the data suggest that cortical thickness mediates the impact of vascular risk and beta-amyloid on memory function.
Impact on treatment was more modest than on diagnosis and limited to Ab negative patients. IC-P-024
[18F] FLUTEMETAMOL PET IMAGING FOR BETAAMYLOID DEPOSITION ACROSS THE SPECTRUM OF ALZHEIMER’S DISEASE
Shizuo Hatashita, Hidetomo Yamasaki, Yutaka Suzuki, Kumiko Tanaka, Keita Taniguchi, Taichi Wakebe, Hideki Hayakawa, 1Shonan-Atsugi Hospital, Atsugi, Japan. Contact e-mail: [email protected]
Figure. Vertex-wise analyses corrected for age, cognitive status and multiple comparisons assessing the impact of vascular risk (FCRP) total score) and HDL cholesterol on cortical thickness. IC-P-023
THE PRACTICAL UTILITY OF AMYLOID AND FDG-PET IN AN ACADEMIC DEMENTIA CENTER
Pascual S anchez Juan1, Pia Ghosh2, Jayne Hagen3, Benno Gesierich3, Maya Henry3, Maria-Luisa Gorno-Tempini3, Bruce Miller3, William Jagust4, Gil Rabinovici3, 1University Hospital Marques de Valdecilla, Santander, Spain; 2UCSF Memory and Aging Center, San Francisco, California, United States; 3UCSF Memory and Aging Center, San Francisco, California, United States; 4University of California, Berkeley, Berkeley, California, United States. Contact e-mail: psanchez@ humv.es Background: We evaluated the impact of amyloid and FDG PET on clinical decision making in a heterogeneous population of cognitively impaired patients. Methods: We selected all patients with FDG and PIB PET and had at least one clinical evaluation before and after PET. We evaluated for change in primary diagnosis and change in treatment between the pre- and post-PET visit. The association of discordant PIB and FDG with changes in clinical management was assessed separately using chi-square and together applying logistic regression. Results: 140 cognitively impaired patients were included in the study (mean age 65.0 6 8.2, 46.% primary Ab diagnosis, 55.0% of new patients, mean MMSE 22.7 6 9.0, 41.0 % CDR<1). PIB and FDG PET agreed in classifying 83.6% of patients. Concordance with pre-scan diagnosis was 84.3% for PIB and 82.1% for FDG. The primary diagnosis was changed after PET in 13/140 patients (9.3%): 12/13 changes were concordant with PIB and 8/13 with FDG results. When examined independently, both discordant PIB and discordant FDG were associated with a change in diagnosis (p<0.0001). However, multivariate analysis revealed that changes in diagnosis were associated with discordant PIB (p¼0.00013) but not discordant FDG (p¼0.087) (LR additional covariates: clinical dilemmas pre -PET, gender, age at PET, baseline diagnosis, new patient (follow up before PET of less than 1 year) and CDR <1) 35% of patients had a change in AD therapy post-PET (initiating or discontinuing acetycholinesterase inhibitors or memantine). In the entire population changes in treatment were not associated with discordant PIB or discordant FDG (p>0.05 in LR model); however discordant PIB did affect treatment in of patients with non-Ab pre-PET diagnoses (p¼0.028), driven by the initiation of acetycholinesterase inhibitors in patients who were unexpectedly PIB-positive. Conclusions: Overall concordance of PET amyloid and FDG results with clinical diagnosis was high and changes in diagnosis were uncommon. Discordant PIB had a greater effect on diagnostic changes than discordant FDG.
Background: We had demonstrated that a diagnostic framework with a beta amyloid (Ab) deposition by [11C]-PIB PET allows for an earlier Alzheimer’s disease (AD) diagnosis. The PET amyloid imaging with a tracer of [18F]-labeled PIB derivate [18F]-Flutemetamol (FMM) have recently developed to be a novel technology of underlying AD pathology. The aim is to identify the Ab deposition by [18F]-FMM PET across the spectrum of AD. Methods: Twenty-eight patients with AD, 44 with mild cognitive impairment (MCI) and 32 subjects with healthy control (HC) were studied. All 104 subjects (age: 55-89 years) underwent 30-min static [18F]-FMM PET, acquired 85 min after injection (196.4 6 6.6 MBq), and cognitive test. [18F]-FMM scans were assessed visually with 3 blind readers as abnormal or normal cortical uptake. The standardized uptake value ratios (SUVR) were defined quantitatively in regions of interest defined on co-registered MRI (cerebellar gray as a reference region). Results: The visual assessments of [18F]-FMM scans had an increased uptake in 27 of 28 scans with AD and 4 of 32 scans with HC, corresponding to an overall sensitivity of 96.4% and a specificity of 87.7%. Inter-reader agreement was excellent (Kappa score¼0.84), and intra-reader agreement was 93.3%. Fourteen (31.8%) of 44 MCI scans showed an increased uptake of [18F]-FMM. The FMM SUVR of composite cortical regions in AD was significantly greater than in HC (1.84 6 0.27 vs 1.28 6 0.17, P<0.01). MCI patients had a bimodal distribution of SUVR. The FMM SUVR in 14 patients with [18F]-FMM positive MCI and 30 patients with negative MCI were 1.82 6 0.29 and 1.20 6 0.08, respectively. The regional FMM SUVR of all cortical regions in AD, except for medial temporal cortex, were significantly different from HC. Cortical FMM SUVR was significantly correlated negatively with MMSE scores (r¼0.62, P<0.01), and positively to CDR SB scores (r¼0.55, P<0.01) when all groups were analyzed. Conclusions: [18F]-Flutemetamol PET discriminates Alzheimer’s disease from healthy controls and facilitates integration of Ab imaging into clinical practice. The PET imaging with [18F]-Flutemetamol is a reliable biomarker of Ab deposition along the continuum from normal cognitive status to dementia of AD. IC-P-025
[18F]NAV4694 SHOWS HIGHER BINDING AND WIDER DYNAMIC RANGE COMPARED WITH [11C]PIB IN ALZHEIMER’S DISEASE POSTMORTEM TISSUE
Eduardo Zimmer1, Maxime Parent2, Antoine Leuzy3, Jared Rowley4, Laksanun Cheewakriengkrai3, Monica Shin3, Seqian Wang2, Marina Dauar2, Sara Mohades2, Esher Susanne Schirrmacher5, Jean-Paul Soucy5, Alexey Kostikov6, Marie-Christine Guiot7, Serge Gauthier8, Pedro Rosa-Neto9, 1McGill Center for Studies in Aging, Montreal, Quebec, Canada; 2McGill Center for Studies in Aging, Montreal, Quebec, Canada; 3McGill Centre for Studies in Aging, Montreal, Quebec, Canada; 4McGill University, Verdun, Quebec, Canada; 5McGill, Montreal, Quebec, Canada; 6McGill, Montreal, Quebec, Canada; 7McGill, Montreal, Quebec, Canada; 8Alzheimer Disease Research Unit, McGill Center for Studies in Aging, Montreal, Quebec, Canada; 9McGill University, Montreal, Quebec, Canada. Contact e-mail: [email protected] Background: [18 F]amyloid imaging agents have low dynamic range when compared with [11 C]PIB, the benchmark PET agent for quantifying brain amyloidosis. In this context, the new amyloid imaging agent [18 F] NAV4694 has been considered a promising amyloid agent. Here, we compare the binding and dynamic range of [11 C]PIB and [18 F]NAV4694 in AD post-mortem brains by means of in vitro autoradiography. Since [18 F]NAV4694 affinity (Kd ¼ 2.4 nM) is higher than [11 C]PIB (Kd ¼ 4.5