- Email: [email protected]
ADNI PiB Studies
Alzheimer’s & Dementia 5 (Suppl 1) (2009)
ABSTRACTS SATURDAY, JULY 11, 2009 ALZHEIMER’S IMAGING CONSORTIUM PRESENTATIONS PLENARY IC-PL IC-PL-01
WILL NEUROIMAGING HELP US UNDERSTAND ALZHEIMER’S DISEASE?
William Jagust, Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, USA. Contact e-mail: jagust@berkeley. edu Background: The amyloid hypothesis of AD is the leading theory of the cause and pathogenesis of the disease. Yet this hypothesis remains contentious partly because associations between beta-amyloid deposition and cognition are weak. While major insights have been gained from pathological and molecular approaches, it is only in vivo studies that provide the ability to relate biomarkers of pathology to cognition in close temporal proximity, and to evaluate the dynamics of longitudinal change and compensation. Imaging of beta amyloid and glucose metabolism with PET, hippocampal volume with MRI, and brain activation with functional MRI offer ways of analyzing both pathology and the brain’s response to this pathology. Methods: These studies support an evolving model whereby brain beta-amyloid deposition is an early and critical step in the initiation of a chain of events that involve neurofibrillary pathology and synaptic dysfunction that ultimately lead to dementia. Most interestingly, it appears that while beta-amyloid may play an inciting role, regional vulnerability to this downstream pathology may be more important in defining the nature and severity of cognitive impairment than the deposition of beta-amyloid itself. Results: Imaging studies have been crucial in supporting this model since they have demonstrated that biomarkers of downstream pathology - specifically hippocampal volume and glucose metabolism - are better correlated with cognition than are beta-amyloid measures. While there is evidence of regional vulnerability in terms of where beta-amyloid is deposited in the brain, there is also evidence of regional vulnerability in the brain’s response to betaamyloid since regions with similar beta-amyloid load are differentially affected. This regional vulnerability is expressed in abnormalities of specific structures and networks, but these are not identical in all affected individuals. In fact, response to beta-amyloid appears to be an important factor in the inter-individual vulnerability as individuals with similar beta-amyloid loads show differential cognitive impairment that is also reflected by downstream markers. Conclusions: This model also has important clinical implications, since biomarkers that reflect the severity and extent of this downstream pathology are likely to be important in the prediction of who will develop cognitive decline.
SATURDAY, JULY 11, 2009 ALZHEIMER’S IMAGING CONSORTIUM PRESENTATIONS SYMPOSIA IC-S1 AMYLOID IMAGING FINDINGS FROM MULTICENTER STUDIES IC-S1-01
ADNI PIB STUDIES
Chester A. Mathis, University of Pittsburgh, Pittsburgh, PA, USA. Contact e-mail: [email protected] Background: PIB PET imaging was added to the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study in 2007 to provide a publically accessible, imaging biomarker data base for use in clinical trials of anti-amyloid therapies as well as for other academic studies. Data on the ADNI site allow correlation of PIB status with other biomarkers such as CSF Abeta42, t-tau, and p-tau measured in the same subjects. Methods: As of February 2009, 103 baseline PIB PET studies from 12 ADNI sites had been collected and posted on the UCLA Laboratory of NeuroImaging (LONI) website after completion of requisite quality control and pre-processing steps by the University of Michigan, which included summing over 50-70 min post-injection, co-registration to Talaraich space, re-orientation along AC-PC axis, standardization to a uniform voxel size and resolution, and normalization to cerebellar grey matter. The ADNI LONI database included PIB PET studies in 19 controls (MMSE range 24 - 30, mean 29 6 1; Age: 78 6 5 yrs), 65 mild cognitive impairment (MCI) (MMSE range 20 - 30, 27 6 2; Age: 75 6 8 yrs), and 19 Alzheimer’s disease (AD) (MMSE range 15 - 26, 22 6 3; Age: 73 6 9 yrs) subjects. One year longitudinal PIB PET studies have been completed in 67 subjects (15 controls, 42 MCI, and 10 AD). CSF Abeta42 and tau measures were collected in 11 controls, 34 MCI, and 10 AD subjects. Results: Positive amyloid deposition (PIBþ) was defined when the average SUVR (standardized uptake value ratio in region relative to the cerebellum) of four regions (frontal, anterior cingulate, precuneus, parietal cortex) exceeded 1.50. With this cut-off value, a large percentage of the elderly control (47%) and MCI (71%) subjects were PIBþ, while 2 clinically diagnosed AD subjects were clearly PIB-. Dichotomous categorization of all subject groups showed substantial agreement (90%) between PIB PET and CSFAbeta42 measures and modest agreement (75%) between PIB PET and p-tau. Conclusions: Multisite PIB PET data have been successfully collected and analyzed. Comparison of PIB status with CSF measures in ADNI subjects provided substantial agreement with Abeta42 and lesser agreement with p-tau and t-tau.
IC-S1-02
AIBL (AUSTRALIAN IMAGING, BIOMARKERS AND LIFESTYLE) FLAGSHIP STUDY OF AGING
Victor L. Villemagne, Austin Hospital, Heidelberg, VIC, Australia. Contact e-mail: [email protected] IC-PL-02
DO THE BIOMARKER FINDINGS FIT THE HYPOTHESES?
Roger Nitsch, University of Zu¨rich, Zu¨rich, Switzerland. Contact e-mail: [email protected] Abstract not available.
Background: Phase I of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing, a three-year prospective longitudinal study recruiting 1,112 volunteers from a cross-section of Australia’s elderly population, concluded with more than a quarter of the participants undergoing PiB-PET scans. Methods: Two hundred and eighty-seven participants received PiB PET scans: 177 Healthy controls (HC); 57 Mild Cognitive Impairment (MCI) subjects; and 53 mild Alzheimer’s disease (AD) patients. HC
ABSTRACTS SATURDAY, JULY 11, 2009 ALZHEIMER’S IMAGING CONSORTIUM PRESENTATIONS PLENARY IC-PL IC-PL-01
WILL NEUROIMAGING HELP US UNDERSTAND ALZHEIMER’S DISEASE?
William Jagust, Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, USA. Contact e-mail: jagust@berkeley. edu Background: The amyloid hypothesis of AD is the leading theory of the cause and pathogenesis of the disease. Yet this hypothesis remains contentious partly because associations between beta-amyloid deposition and cognition are weak. While major insights have been gained from pathological and molecular approaches, it is only in vivo studies that provide the ability to relate biomarkers of pathology to cognition in close temporal proximity, and to evaluate the dynamics of longitudinal change and compensation. Imaging of beta amyloid and glucose metabolism with PET, hippocampal volume with MRI, and brain activation with functional MRI offer ways of analyzing both pathology and the brain’s response to this pathology. Methods: These studies support an evolving model whereby brain beta-amyloid deposition is an early and critical step in the initiation of a chain of events that involve neurofibrillary pathology and synaptic dysfunction that ultimately lead to dementia. Most interestingly, it appears that while beta-amyloid may play an inciting role, regional vulnerability to this downstream pathology may be more important in defining the nature and severity of cognitive impairment than the deposition of beta-amyloid itself. Results: Imaging studies have been crucial in supporting this model since they have demonstrated that biomarkers of downstream pathology - specifically hippocampal volume and glucose metabolism - are better correlated with cognition than are beta-amyloid measures. While there is evidence of regional vulnerability in terms of where beta-amyloid is deposited in the brain, there is also evidence of regional vulnerability in the brain’s response to betaamyloid since regions with similar beta-amyloid load are differentially affected. This regional vulnerability is expressed in abnormalities of specific structures and networks, but these are not identical in all affected individuals. In fact, response to beta-amyloid appears to be an important factor in the inter-individual vulnerability as individuals with similar beta-amyloid loads show differential cognitive impairment that is also reflected by downstream markers. Conclusions: This model also has important clinical implications, since biomarkers that reflect the severity and extent of this downstream pathology are likely to be important in the prediction of who will develop cognitive decline.
SATURDAY, JULY 11, 2009 ALZHEIMER’S IMAGING CONSORTIUM PRESENTATIONS SYMPOSIA IC-S1 AMYLOID IMAGING FINDINGS FROM MULTICENTER STUDIES IC-S1-01
ADNI PIB STUDIES
Chester A. Mathis, University of Pittsburgh, Pittsburgh, PA, USA. Contact e-mail: [email protected] Background: PIB PET imaging was added to the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study in 2007 to provide a publically accessible, imaging biomarker data base for use in clinical trials of anti-amyloid therapies as well as for other academic studies. Data on the ADNI site allow correlation of PIB status with other biomarkers such as CSF Abeta42, t-tau, and p-tau measured in the same subjects. Methods: As of February 2009, 103 baseline PIB PET studies from 12 ADNI sites had been collected and posted on the UCLA Laboratory of NeuroImaging (LONI) website after completion of requisite quality control and pre-processing steps by the University of Michigan, which included summing over 50-70 min post-injection, co-registration to Talaraich space, re-orientation along AC-PC axis, standardization to a uniform voxel size and resolution, and normalization to cerebellar grey matter. The ADNI LONI database included PIB PET studies in 19 controls (MMSE range 24 - 30, mean 29 6 1; Age: 78 6 5 yrs), 65 mild cognitive impairment (MCI) (MMSE range 20 - 30, 27 6 2; Age: 75 6 8 yrs), and 19 Alzheimer’s disease (AD) (MMSE range 15 - 26, 22 6 3; Age: 73 6 9 yrs) subjects. One year longitudinal PIB PET studies have been completed in 67 subjects (15 controls, 42 MCI, and 10 AD). CSF Abeta42 and tau measures were collected in 11 controls, 34 MCI, and 10 AD subjects. Results: Positive amyloid deposition (PIBþ) was defined when the average SUVR (standardized uptake value ratio in region relative to the cerebellum) of four regions (frontal, anterior cingulate, precuneus, parietal cortex) exceeded 1.50. With this cut-off value, a large percentage of the elderly control (47%) and MCI (71%) subjects were PIBþ, while 2 clinically diagnosed AD subjects were clearly PIB-. Dichotomous categorization of all subject groups showed substantial agreement (90%) between PIB PET and CSFAbeta42 measures and modest agreement (75%) between PIB PET and p-tau. Conclusions: Multisite PIB PET data have been successfully collected and analyzed. Comparison of PIB status with CSF measures in ADNI subjects provided substantial agreement with Abeta42 and lesser agreement with p-tau and t-tau.
IC-S1-02
AIBL (AUSTRALIAN IMAGING, BIOMARKERS AND LIFESTYLE) FLAGSHIP STUDY OF AGING
Victor L. Villemagne, Austin Hospital, Heidelberg, VIC, Australia. Contact e-mail: [email protected] IC-PL-02
DO THE BIOMARKER FINDINGS FIT THE HYPOTHESES?
Roger Nitsch, University of Zu¨rich, Zu¨rich, Switzerland. Contact e-mail: [email protected] Abstract not available.
Background: Phase I of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing, a three-year prospective longitudinal study recruiting 1,112 volunteers from a cross-section of Australia’s elderly population, concluded with more than a quarter of the participants undergoing PiB-PET scans. Methods: Two hundred and eighty-seven participants received PiB PET scans: 177 Healthy controls (HC); 57 Mild Cognitive Impairment (MCI) subjects; and 53 mild Alzheimer’s disease (AD) patients. HC