- Email: [email protected]
P1-238: The Australian biomarker, imaging and lifestyle study: Preliminary PiB results
Poster Presentations P1 P1-238
THE AUSTRALIAN BIOMARKER, IMAGING AND LIFESTYLE STUDY: PRELIMINARY PIB RESULTS
Kathryn A. Ellis1, Victor L. Villemagne2,3, David Ames4, Nat Lenzo5,6, Kerryn E. Pike2, Graeme O’Keefe2, Henri Tochon-Danguy2, Roger Price5,7, Gareth Jones2, Mira Rimajova5, Pierrick Bourgeat8, Parnesh Raniga8, Jurgen Fripp8, Oscar Acosta8, Olivier Salvado8, Ralph Martins6, Colin L. Masters3, Christopher C. Rowe2, 1University of Melbourne, Melbourne, VIC, Australia; 2Austin Hospital, Melbourne, VIC, Australia; 3The Mental Health Research Institute of Victoria, Melbourne, VIC, Australia; 4National Ageing Research Institute, Melbourne, VIC, Australia; 5WA PET Centre, Perth, WA, Australia; 6 Edith Cowan University, Perth, WA, Australia; 7Sir Charles Gairdner Hospital, Perth, WA, Australia; 8CSIRO ICT Centre, Brisbane, QLD, Australia. Contact e-mail: [email protected] Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing is a three-year prospective longitudinal study recruiting 1,000 volunteers from a cross-section of Australia’s elderly population for a cohort study. A quarter of the participants will undergo both PiB-PET and MRI. Recruitment started in January 2007. Methods: Participants comprise 5 equal-sized groups: 1) Healthy participants (HP) with no genetic predisposition to Alzheimer’s disease (AD); 2) HP with an ApoE4 allele; 3) HP with subjective memory complaint; 4) Mild Cognitive Impairment (MCI); and 5) early stage AD. All participants undergo a comprehensive neuropsychological examination, and blood is collected for biomarker analysis. MRI comprises 3D T1 MP-RAGE and T2 FSE. PiB PET images are acquired from 40-70 mins post-injection of 10 mCi of 11C-PiB and analyzed visually and with regional and global cortical SUVR using the cerebellar cortex as reference region. A previously derived and published SUVR cut-off value of 1.6 is used to define PiB scans as normal or abnormal. Results: To date 130 participants underwent baseline PiB-PET and MRI scans. Cortical PIB binding was markedly elevated in all AD subjects except one. MCI subjects presented either an “AD-like” (52%) or normal pattern. Cortical PiB binding was abnormal in 32% of HP (mean age 75.3 years) and the prevalence increased with age. Despite normal neuropsychological scores, the abnormal PiB HP performed worse on episodic memory tasks. Conclusions: The AIBL cohort will generate a large set of neuroimaging, neuropsychological and biomarker data to assess change over time in HP, MCI and AD. This will assist development of techniques for early detection of AD and provide a cohort suitable for targeted early intervention studies. P1-239
DIFFUSION TENSOR MRI FOR IDENTICATION OF MCI CONVERTERS: A PROSPECTIVE FOLLOW-UP STUDY
Marco Essig1, Johannes Schroeder2, Kira Lutz1, Bram Stieltjes1, 1 German Cancer Research Center, Heidelberg, Germany; 2University of Heidelberg, Deptartment of Psychiatry, Heidelberg, Germany. Contact e-mail: [email protected] Background: It is generally accepted that mild cognitive impairment (MCI) represents its preclinical stage, defined by slight but consistently verifiable deficits that do not allow diagnosis of dementia. In larger clinical studies, subjects with mild cognitive impairment are found to be at a high risk of developing AD, with conversion rates of ⬃50% over a 3-year time period.Several reports indicate that DTI and quantification of the fiber integrity may be a tool for early detection of MCI.Here, we present data of a longitudinal study on 33 patients with memory complaints (15 AD, 18 MCI) and 15 healthy aged matched controls. Methods: All included patients were clinically reexamined yearly and the MMSE-score was used to evaluate conversion to AD in the MCI group. The DTI-exam was performed on a 1.5T scanner.Using the aforementioned method for fiber quantification, we measured the FA at five different positions of the corpus callosum in a blinded reading session. Results: All patients in the MCI group had comparable initial MMSE scores (26-28) In this group, 10 patients showed conversion (⌬ MMSE⫽ -3,2 SD⫽1,1) and 8 patients did not show conversion (⌬ MMSE⫽0 SD⫽0.7). The
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most pronounced difference in FA was found in the first third of the body of the CC.When splitting the MCI group in conversion vs no conversion, the converted group showed no significant difference in FA when compared with AD (F(1,23)⫽0,71, p⫽0.41) whereas the non converted group showed significantly higher FA values when compared to AD and no significant differences from healthy controls (F(1,21)⫽ 49,31, p⫽0. 00623). Conclusions: Using our DTI method, we were able to discern between healthy controls, MCI patients and AD patients. Moreover we found a significant drop in FA in the first 3rd of the body of the CC in patients with MCI before conversion to AD. This indicates that DTI of the CC can be used as a fast and reliable method for the evaluation of patients with early forms of AD. P1-240
RATES OF WHOLE BRAIN ATROPHY AND VENTRICULAR ENLARGEMENT: CORRELATIONS WITH COGNITIVE PERFORMANCE
Matthew C. Evans1, Josephine Barnes1, Shona L. Clegg1, Manja Lehmann1, Tessa Mellow1, Elizabeth McNaught1, Laila Ahsan1, Richard Boyes1, Tracey Pepple1, Jo Foster1, Casper Nielsen1, 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: Whole-brain and ventricular change using serial MR has been shown to be useful in assessing putative treatments in Alzheimer’s disease (AD). We aimed to correlate change in whole brain and ventricular volume with cognitive scores in AD, MCI and control subjects. Methods: Eighty-seven controls, 118 mild cognitive impairment (MCI) and 48 AD subjects were selected from the Alzheimer’s disease neuroimaging initiative (ADNI) cohort. Each subject underwent a volumetric T1-weighted MRI at baseline and 12 months. Whole brain was segmented on baseline scans with a semi-automated technique. Repeat brain regions were propagated from the baseline regions. Baseline and repeat scans were registered using a 9-degrees of freedom algorithm. Ventricles were segmented at both time points, also using a semi-automated technique. Brain and ventricular changes were measured using the Boundary Shift Integral (BBSI and VBSI respectively). The MMSE was also completed by every participant at both time points. Results: Whole-brain loss was significantly different between controls, MCI and AD (p⬍0.001); pair-wise comparisons showed the BBSI was lower in controls than in AD (p⬍0.001) and MCI (p⫽0.022); the AD group had a trend towards a higher brain atrophy rate than MCI (p⫽0.052). Ventricular enlargement was different between the three groups (p⬍0.001), with AD⬎MCI (p⬍0.001), AD⬎control (p⬍0.001) and MCI⬎control (p⬍0.001). Change in MMSE was also different between controls, MCI and AD (p⬍0.001), with AD⬎MCI (p⫽0.009) and AD⬎controls (p⬍0.001) (table). In both MCI and AD groups change in MMSE was associated with BBSI (MCI p⬍0.001, AD p⫽0.003) and VBSI (MCI p⬍0.001, AD p⫽0.001). Finally, the MCI group was divided into two groups: those with MMSE change⬍1, and MMSE change⬎or equal to 1. There was no significant interaction between BBSI and MMSE change in the MCI divisions (p⬎0.05), but there was a significant interaction between MMSE change and VBSI and MCI divisions (p⬍0.01), (Figure). Conclusions: Whole-brain atrophy rates and ventricular enlargement increased across subject groups with control⬍MCI⬍AD. This was also reflected in neuropsychology, with MMSE change increasing across groups control⬍MCI⬍AD. Some association was found between MMSE (change) and brain atrophy and ventricular enlargement in AD and MCI.
THE AUSTRALIAN BIOMARKER, IMAGING AND LIFESTYLE STUDY: PRELIMINARY PIB RESULTS
Kathryn A. Ellis1, Victor L. Villemagne2,3, David Ames4, Nat Lenzo5,6, Kerryn E. Pike2, Graeme O’Keefe2, Henri Tochon-Danguy2, Roger Price5,7, Gareth Jones2, Mira Rimajova5, Pierrick Bourgeat8, Parnesh Raniga8, Jurgen Fripp8, Oscar Acosta8, Olivier Salvado8, Ralph Martins6, Colin L. Masters3, Christopher C. Rowe2, 1University of Melbourne, Melbourne, VIC, Australia; 2Austin Hospital, Melbourne, VIC, Australia; 3The Mental Health Research Institute of Victoria, Melbourne, VIC, Australia; 4National Ageing Research Institute, Melbourne, VIC, Australia; 5WA PET Centre, Perth, WA, Australia; 6 Edith Cowan University, Perth, WA, Australia; 7Sir Charles Gairdner Hospital, Perth, WA, Australia; 8CSIRO ICT Centre, Brisbane, QLD, Australia. Contact e-mail: [email protected] Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing is a three-year prospective longitudinal study recruiting 1,000 volunteers from a cross-section of Australia’s elderly population for a cohort study. A quarter of the participants will undergo both PiB-PET and MRI. Recruitment started in January 2007. Methods: Participants comprise 5 equal-sized groups: 1) Healthy participants (HP) with no genetic predisposition to Alzheimer’s disease (AD); 2) HP with an ApoE4 allele; 3) HP with subjective memory complaint; 4) Mild Cognitive Impairment (MCI); and 5) early stage AD. All participants undergo a comprehensive neuropsychological examination, and blood is collected for biomarker analysis. MRI comprises 3D T1 MP-RAGE and T2 FSE. PiB PET images are acquired from 40-70 mins post-injection of 10 mCi of 11C-PiB and analyzed visually and with regional and global cortical SUVR using the cerebellar cortex as reference region. A previously derived and published SUVR cut-off value of 1.6 is used to define PiB scans as normal or abnormal. Results: To date 130 participants underwent baseline PiB-PET and MRI scans. Cortical PIB binding was markedly elevated in all AD subjects except one. MCI subjects presented either an “AD-like” (52%) or normal pattern. Cortical PiB binding was abnormal in 32% of HP (mean age 75.3 years) and the prevalence increased with age. Despite normal neuropsychological scores, the abnormal PiB HP performed worse on episodic memory tasks. Conclusions: The AIBL cohort will generate a large set of neuroimaging, neuropsychological and biomarker data to assess change over time in HP, MCI and AD. This will assist development of techniques for early detection of AD and provide a cohort suitable for targeted early intervention studies. P1-239
DIFFUSION TENSOR MRI FOR IDENTICATION OF MCI CONVERTERS: A PROSPECTIVE FOLLOW-UP STUDY
Marco Essig1, Johannes Schroeder2, Kira Lutz1, Bram Stieltjes1, 1 German Cancer Research Center, Heidelberg, Germany; 2University of Heidelberg, Deptartment of Psychiatry, Heidelberg, Germany. Contact e-mail: [email protected] Background: It is generally accepted that mild cognitive impairment (MCI) represents its preclinical stage, defined by slight but consistently verifiable deficits that do not allow diagnosis of dementia. In larger clinical studies, subjects with mild cognitive impairment are found to be at a high risk of developing AD, with conversion rates of ⬃50% over a 3-year time period.Several reports indicate that DTI and quantification of the fiber integrity may be a tool for early detection of MCI.Here, we present data of a longitudinal study on 33 patients with memory complaints (15 AD, 18 MCI) and 15 healthy aged matched controls. Methods: All included patients were clinically reexamined yearly and the MMSE-score was used to evaluate conversion to AD in the MCI group. The DTI-exam was performed on a 1.5T scanner.Using the aforementioned method for fiber quantification, we measured the FA at five different positions of the corpus callosum in a blinded reading session. Results: All patients in the MCI group had comparable initial MMSE scores (26-28) In this group, 10 patients showed conversion (⌬ MMSE⫽ -3,2 SD⫽1,1) and 8 patients did not show conversion (⌬ MMSE⫽0 SD⫽0.7). The
T283
most pronounced difference in FA was found in the first third of the body of the CC.When splitting the MCI group in conversion vs no conversion, the converted group showed no significant difference in FA when compared with AD (F(1,23)⫽0,71, p⫽0.41) whereas the non converted group showed significantly higher FA values when compared to AD and no significant differences from healthy controls (F(1,21)⫽ 49,31, p⫽0. 00623). Conclusions: Using our DTI method, we were able to discern between healthy controls, MCI patients and AD patients. Moreover we found a significant drop in FA in the first 3rd of the body of the CC in patients with MCI before conversion to AD. This indicates that DTI of the CC can be used as a fast and reliable method for the evaluation of patients with early forms of AD. P1-240
RATES OF WHOLE BRAIN ATROPHY AND VENTRICULAR ENLARGEMENT: CORRELATIONS WITH COGNITIVE PERFORMANCE
Matthew C. Evans1, Josephine Barnes1, Shona L. Clegg1, Manja Lehmann1, Tessa Mellow1, Elizabeth McNaught1, Laila Ahsan1, Richard Boyes1, Tracey Pepple1, Jo Foster1, Casper Nielsen1, 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: Whole-brain and ventricular change using serial MR has been shown to be useful in assessing putative treatments in Alzheimer’s disease (AD). We aimed to correlate change in whole brain and ventricular volume with cognitive scores in AD, MCI and control subjects. Methods: Eighty-seven controls, 118 mild cognitive impairment (MCI) and 48 AD subjects were selected from the Alzheimer’s disease neuroimaging initiative (ADNI) cohort. Each subject underwent a volumetric T1-weighted MRI at baseline and 12 months. Whole brain was segmented on baseline scans with a semi-automated technique. Repeat brain regions were propagated from the baseline regions. Baseline and repeat scans were registered using a 9-degrees of freedom algorithm. Ventricles were segmented at both time points, also using a semi-automated technique. Brain and ventricular changes were measured using the Boundary Shift Integral (BBSI and VBSI respectively). The MMSE was also completed by every participant at both time points. Results: Whole-brain loss was significantly different between controls, MCI and AD (p⬍0.001); pair-wise comparisons showed the BBSI was lower in controls than in AD (p⬍0.001) and MCI (p⫽0.022); the AD group had a trend towards a higher brain atrophy rate than MCI (p⫽0.052). Ventricular enlargement was different between the three groups (p⬍0.001), with AD⬎MCI (p⬍0.001), AD⬎control (p⬍0.001) and MCI⬎control (p⬍0.001). Change in MMSE was also different between controls, MCI and AD (p⬍0.001), with AD⬎MCI (p⫽0.009) and AD⬎controls (p⬍0.001) (table). In both MCI and AD groups change in MMSE was associated with BBSI (MCI p⬍0.001, AD p⫽0.003) and VBSI (MCI p⬍0.001, AD p⫽0.001). Finally, the MCI group was divided into two groups: those with MMSE change⬍1, and MMSE change⬎or equal to 1. There was no significant interaction between BBSI and MMSE change in the MCI divisions (p⬎0.05), but there was a significant interaction between MMSE change and VBSI and MCI divisions (p⬍0.01), (Figure). Conclusions: Whole-brain atrophy rates and ventricular enlargement increased across subject groups with control⬍MCI⬍AD. This was also reflected in neuropsychology, with MMSE change increasing across groups control⬍MCI⬍AD. Some association was found between MMSE (change) and brain atrophy and ventricular enlargement in AD and MCI.