- Email: [email protected]
P2-006: Baseline data from a multi-centre, prospective longitudinal study of ageing in 1000 volunteers (the AIBL study)
Poster Presentations P2
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P2-006
BASELINE DATA FROM A MULTI-CENTRE, PROSPECTIVE LONGITUDINAL STUDY OF AGEING IN 1000 VOLUNTEERS (THE AIBL STUDY)
is clinically characterized by variable degrees of Balint and Gerstmann syndromes, visual agnosia and transcortical motor aphasia. We report a large series of PCA with a SPECT exam aimed at defining the specificity of the perfusion profile of PCA. Objectives: 1) To define the brain perfusion profile of PCA; 2) to compare the whole brain perfusion profile between PCA and that of typical Alzheimer’s disease (AD) and 3) to study the relationships between cognitive deficits and cerebral perfusion. Methods: Sixty-three subjects were included: 18 PCA patients; 18 AD patients (matched by the mean disease duration and by the MMSE score) and 27 age matched normal controls. Each patient underwent a neuropsychological evaluation and a SPECT (99mTc-ECD). The SPECT images were analyzed on the voxel scale with the SPM2 software (p ⫽ 0,05). Results: When compared to the AD group, the hypoperfusion in PCA patients was more extensive and severe especially in the visual associative cortex (precuneus, BA 18/19) and in the parietal associative cortex (BA 39/40). When compared to the control group, the perfusion profile of PCA group was characterized by: 1) a bilateral and symmetrical hypoperfusion in parieto-temporo-occipital cortex, with a maximal decrease in the associative parietal cortex (superior parietal lobule) and in the precuneus; 2) a bilateral and symmetrical hypoperfusion in dorsolateral frontal lobes from BA 6/8 (Frontal Eyes Field) to BA 9. 3). The perfusion analyze within the PCA group showed: 1) a more severe hypoperfusion in the right parieto-temporo-occipital cortex in the subgroup of patients with neglect (n ⫽ 10) than in the patients without neglect (n ⫽ 8); 2) a more severe hypoperfusion in the right associative occipital cortex in the patients with visual apraxia (n ⫽ 7) than in the patients without visual apraxia (n ⫽ 11). Conclusions: The SPECT is a valuable tool for PCA because it can help for distinguishing it from AD and for understanding the neurological foundations of the symptoms. P2-005
PET IMAGING OF AMYLOID-BETA IN ALZHEIMER’S DISEASE WITH 18F-AV-144
P. Murali Doraiswamy1, Stewart J. Edmunds1, Jeffrey Petrella1, Thomas Hawk1, Timothy Turkington1, Salvadore Neto-Borges1, Jeff Williamson2, Pradeep Garg2, Sudha Garg3, Abhinay Joshi4, Michael Pontecorvo4, Edward R. Coleman1, 1Duke University Medical Center, Durham, NC, USA; 2Wake Forest University, Wake Forest, NC, USA; 3Wake Forest University, Wake forest, NC, USA; 4Avid Radiopharmaceuticals, Philadelphia, PA, USA. Contact e-mail: [email protected] Background: The aims of this study were to characterize uptake and distribution of a novel 18F labeled PET agent that binds with high affinity to amyloid plaque in Alzheimer’s disease (AD) compared to normal controls (NC). A secondary aim was to examine initial correlations with clinical variables. Methods: Twenty-two research subjects, including 9 AD (MMSE 16-24) and 13 NC (MMSE 29-30) subjects, underwent 18F-AV-144 PET imaging at 4 centers. PET data were co-registered with segmented MRI data allowing ROI generated regional lobar cortical grey matter activity comparisons between AD subjects and controls. The procedure was well tolerated. Results: AD subjects demonstrated significantly greater 18F-AV-144 SUVRs in several regions (relative to cerebellum) such as frontal, precuneus and posterior cingulate, than NC. In AD subjects, 18F-AV-144 frontal/ cerebellum SUVR tended to increase with older age (r⫽0.53). Two younger NCs also showed elevated SUVRs. Precuneal/cerebellum SUVR showed trends to be inversely correlated with MMSE in AD (r⫽-0.26) and NCs (r⫽-0.19). Conclusions: Despite limitations of a small sample size, this novel PET amyloid binding agent differentiates AD from normal controls. These data will be discussed in relation to the further development of PET amyloid imaging agents.
Kathryn A. Ellis1, Christopher C. Rowe2, Colin L. Masters3, Ralph N. Martins4,5, Peter Hudson6, Andrew Milner7, Lindsay Bevege7, Greg Savage8, David Ames9, 1Academic Unit for Psychiatry of Old Age, Department of Psychiatry, University of Melbourne, Melbourne, Australia; 2Department of Nuclear Medicine, Centre for PET, Austin Health, Melbourne, Australia; 3Mental Health Research Institute & Centre for Neurosciences, University of Melbourne, Melbourne, Australia; 4Centre of Excellence for Alzheimer’s Disease Research and Care, & the Sir James McCusker Alzheimer’s Disease Research Unit, Edith Cowan University, Joondalup, Australia; 5Hollywood Private Hospital, Nedlands, Australia; 6CSIRO P-Health Flagship, Melbourne, Australia; 7Neurosciences Australia, Melbourne, Australia; 8Macquarie Centre for Cognitive Science (MACCS) Macquarie University, Sydney, Australia; 9National Ageing Research Institute, Melbourne, Australia. Contact e-mail: [email protected] Background: The Australian Imaging Biomarkers and Lifestyle Flagship Study of Ageing (AIBL) is a prospective, longitudinal study of neuroimaging, biomarkers, clinical and neuropsychological measures, and lifestyle patterns in a cohort of 1000 volunteers comprised of patients with Alzheimer’s disease (AD), Mild Cognitive Impairment (MCI) and healthy volunteers. The AIBL study aims to improve understanding of the pathogenesis, early diagnosis and clinical course of AD. It was launched in November 2006 and by May 2008 comprehensive baseline data collection will be complete. Methods: The cohort consists of 1000 volunteers (minimum age 60 years), recruited in equal proportions from five population groups; 1) early AD (CDR 0.5 or 1), 2) MCI, 3) ApoE ⑀4⫹ healthy volunteers, 4) ApoE ⑀4- healthy volunteers, and 5) subjective memory complainers. At baseline, each volunteer completes the International Physical Activity Questionnaire, a Food Frequency Questionnaire, a comprehensive clinical and neuropsychology battery, and provides an 80ml blood sample for clinical pathology, biomarker analysis and storage in liquid nitrogen. In addition, 250 of the cohort (25% from each group) receive a [C-11]PIB PET scan as a measure of in vivo amyloid and a MRI scan. Baseline characteristics of the five population groups will be ascertained using cross-sectional analysis of measures of memory and learning (CVLT-II, logical memory), attention (digit symbol), language (COWAT and BNT), spatial ability (Rey Figure) and executive function (Stroop), coupled with clinical outcome measures, clinical pathology results (including levels of folate, homocysteine, B12, glucose, testosterone), lifestyle measures, and neuroimaging findings. Results: To end January 2008, complete baseline data has been collected from 814 volunteers. Current demographic characteristics demonstrate a well balanced cohort. The mean age of volunteers is 71.8 years (healthy volunteers 71.0 years, AD 75.7 years, MCI 76.3 years). Gender distribution is also balanced with 55% female overal, 55% in the AD group and 49% female in the MCI subgroup. Conclusions: The AIBL study is the largest study of its kind undertaken in Australia. Cross sectional analysis of baseline data from this large cohort will provide valuable information on the links between cognition, brain amyloid burden, structural brain changes, biomarkers, diet and lifestyle. P2-007
AUTOMATING THE BSI BRAIN ATROPHY RATE CALCULATION: COMPARISON OF USING AUTOMATED AND SEMI-AUTOMATED BRAIN REGIONS
Matthew C. Evans1, Casper Nielsen1, Abdel Douiri1, Josephine Barnes1, Shona L. Clegg1, Manja Lehmann1, Tessa Mellow1, Elizabeth McNaught1, Laila Ahsan1, Richard Boyes1, Tracey Pepple1, Jo Foster1, Martin N. Rossor1,2, Nick C. Fox1, 1Dementia Research Centre, University College London, London, United Kingdom; 2Faculty of Medicine, Imperial College of Science, Engineering and Medicine, London, United Kingdom. Contact e-mail: [email protected] Background: Alzheimer’s disease (AD) is characterised by a decline in cognitive function, and an increase in brain atrophy, the rate of which can be
T367
P2-006
BASELINE DATA FROM A MULTI-CENTRE, PROSPECTIVE LONGITUDINAL STUDY OF AGEING IN 1000 VOLUNTEERS (THE AIBL STUDY)
is clinically characterized by variable degrees of Balint and Gerstmann syndromes, visual agnosia and transcortical motor aphasia. We report a large series of PCA with a SPECT exam aimed at defining the specificity of the perfusion profile of PCA. Objectives: 1) To define the brain perfusion profile of PCA; 2) to compare the whole brain perfusion profile between PCA and that of typical Alzheimer’s disease (AD) and 3) to study the relationships between cognitive deficits and cerebral perfusion. Methods: Sixty-three subjects were included: 18 PCA patients; 18 AD patients (matched by the mean disease duration and by the MMSE score) and 27 age matched normal controls. Each patient underwent a neuropsychological evaluation and a SPECT (99mTc-ECD). The SPECT images were analyzed on the voxel scale with the SPM2 software (p ⫽ 0,05). Results: When compared to the AD group, the hypoperfusion in PCA patients was more extensive and severe especially in the visual associative cortex (precuneus, BA 18/19) and in the parietal associative cortex (BA 39/40). When compared to the control group, the perfusion profile of PCA group was characterized by: 1) a bilateral and symmetrical hypoperfusion in parieto-temporo-occipital cortex, with a maximal decrease in the associative parietal cortex (superior parietal lobule) and in the precuneus; 2) a bilateral and symmetrical hypoperfusion in dorsolateral frontal lobes from BA 6/8 (Frontal Eyes Field) to BA 9. 3). The perfusion analyze within the PCA group showed: 1) a more severe hypoperfusion in the right parieto-temporo-occipital cortex in the subgroup of patients with neglect (n ⫽ 10) than in the patients without neglect (n ⫽ 8); 2) a more severe hypoperfusion in the right associative occipital cortex in the patients with visual apraxia (n ⫽ 7) than in the patients without visual apraxia (n ⫽ 11). Conclusions: The SPECT is a valuable tool for PCA because it can help for distinguishing it from AD and for understanding the neurological foundations of the symptoms. P2-005
PET IMAGING OF AMYLOID-BETA IN ALZHEIMER’S DISEASE WITH 18F-AV-144
P. Murali Doraiswamy1, Stewart J. Edmunds1, Jeffrey Petrella1, Thomas Hawk1, Timothy Turkington1, Salvadore Neto-Borges1, Jeff Williamson2, Pradeep Garg2, Sudha Garg3, Abhinay Joshi4, Michael Pontecorvo4, Edward R. Coleman1, 1Duke University Medical Center, Durham, NC, USA; 2Wake Forest University, Wake Forest, NC, USA; 3Wake Forest University, Wake forest, NC, USA; 4Avid Radiopharmaceuticals, Philadelphia, PA, USA. Contact e-mail: [email protected] Background: The aims of this study were to characterize uptake and distribution of a novel 18F labeled PET agent that binds with high affinity to amyloid plaque in Alzheimer’s disease (AD) compared to normal controls (NC). A secondary aim was to examine initial correlations with clinical variables. Methods: Twenty-two research subjects, including 9 AD (MMSE 16-24) and 13 NC (MMSE 29-30) subjects, underwent 18F-AV-144 PET imaging at 4 centers. PET data were co-registered with segmented MRI data allowing ROI generated regional lobar cortical grey matter activity comparisons between AD subjects and controls. The procedure was well tolerated. Results: AD subjects demonstrated significantly greater 18F-AV-144 SUVRs in several regions (relative to cerebellum) such as frontal, precuneus and posterior cingulate, than NC. In AD subjects, 18F-AV-144 frontal/ cerebellum SUVR tended to increase with older age (r⫽0.53). Two younger NCs also showed elevated SUVRs. Precuneal/cerebellum SUVR showed trends to be inversely correlated with MMSE in AD (r⫽-0.26) and NCs (r⫽-0.19). Conclusions: Despite limitations of a small sample size, this novel PET amyloid binding agent differentiates AD from normal controls. These data will be discussed in relation to the further development of PET amyloid imaging agents.
Kathryn A. Ellis1, Christopher C. Rowe2, Colin L. Masters3, Ralph N. Martins4,5, Peter Hudson6, Andrew Milner7, Lindsay Bevege7, Greg Savage8, David Ames9, 1Academic Unit for Psychiatry of Old Age, Department of Psychiatry, University of Melbourne, Melbourne, Australia; 2Department of Nuclear Medicine, Centre for PET, Austin Health, Melbourne, Australia; 3Mental Health Research Institute & Centre for Neurosciences, University of Melbourne, Melbourne, Australia; 4Centre of Excellence for Alzheimer’s Disease Research and Care, & the Sir James McCusker Alzheimer’s Disease Research Unit, Edith Cowan University, Joondalup, Australia; 5Hollywood Private Hospital, Nedlands, Australia; 6CSIRO P-Health Flagship, Melbourne, Australia; 7Neurosciences Australia, Melbourne, Australia; 8Macquarie Centre for Cognitive Science (MACCS) Macquarie University, Sydney, Australia; 9National Ageing Research Institute, Melbourne, Australia. Contact e-mail: [email protected] Background: The Australian Imaging Biomarkers and Lifestyle Flagship Study of Ageing (AIBL) is a prospective, longitudinal study of neuroimaging, biomarkers, clinical and neuropsychological measures, and lifestyle patterns in a cohort of 1000 volunteers comprised of patients with Alzheimer’s disease (AD), Mild Cognitive Impairment (MCI) and healthy volunteers. The AIBL study aims to improve understanding of the pathogenesis, early diagnosis and clinical course of AD. It was launched in November 2006 and by May 2008 comprehensive baseline data collection will be complete. Methods: The cohort consists of 1000 volunteers (minimum age 60 years), recruited in equal proportions from five population groups; 1) early AD (CDR 0.5 or 1), 2) MCI, 3) ApoE ⑀4⫹ healthy volunteers, 4) ApoE ⑀4- healthy volunteers, and 5) subjective memory complainers. At baseline, each volunteer completes the International Physical Activity Questionnaire, a Food Frequency Questionnaire, a comprehensive clinical and neuropsychology battery, and provides an 80ml blood sample for clinical pathology, biomarker analysis and storage in liquid nitrogen. In addition, 250 of the cohort (25% from each group) receive a [C-11]PIB PET scan as a measure of in vivo amyloid and a MRI scan. Baseline characteristics of the five population groups will be ascertained using cross-sectional analysis of measures of memory and learning (CVLT-II, logical memory), attention (digit symbol), language (COWAT and BNT), spatial ability (Rey Figure) and executive function (Stroop), coupled with clinical outcome measures, clinical pathology results (including levels of folate, homocysteine, B12, glucose, testosterone), lifestyle measures, and neuroimaging findings. Results: To end January 2008, complete baseline data has been collected from 814 volunteers. Current demographic characteristics demonstrate a well balanced cohort. The mean age of volunteers is 71.8 years (healthy volunteers 71.0 years, AD 75.7 years, MCI 76.3 years). Gender distribution is also balanced with 55% female overal, 55% in the AD group and 49% female in the MCI subgroup. Conclusions: The AIBL study is the largest study of its kind undertaken in Australia. Cross sectional analysis of baseline data from this large cohort will provide valuable information on the links between cognition, brain amyloid burden, structural brain changes, biomarkers, diet and lifestyle. P2-007
AUTOMATING THE BSI BRAIN ATROPHY RATE CALCULATION: COMPARISON OF USING AUTOMATED AND SEMI-AUTOMATED BRAIN REGIONS
Matthew C. Evans1, Casper Nielsen1, Abdel Douiri1, Josephine Barnes1, Shona L. Clegg1, Manja Lehmann1, Tessa Mellow1, Elizabeth McNaught1, Laila Ahsan1, Richard Boyes1, Tracey Pepple1, Jo Foster1, Martin N. Rossor1,2, Nick C. Fox1, 1Dementia Research Centre, University College London, London, United Kingdom; 2Faculty of Medicine, Imperial College of Science, Engineering and Medicine, London, United Kingdom. Contact e-mail: [email protected] Background: Alzheimer’s disease (AD) is characterised by a decline in cognitive function, and an increase in brain atrophy, the rate of which can be