- Email: [email protected]
Comparison of tract-based spatial statistics and ROI-based approach in analyzing the white matter integrity in the elderly
Alzheimer’s Imaging Consortium IC-P: Imaging Posters
power in determining normals from neurodegenerative cases and normals from AD cases. Change in volume does not necessarily help distinguish AD subjects from non-AD dementia cases. IC-P-020
SHAPE CHANGES IN THE CA3 AND DENTATE REGIONS OF THE HIPPOCAMPUS IN INDIVIDUALS WITH MILD COGNITIVE IMPAIRMENT
Michael A. Yassa, Samantha Rutledge, Craig E. L. Stark, University of California, Irvine, Irvine, CA, USA. Contact e-mail: [email protected] Background: Shape and volume changes in the subfields in the hippocampus have been reported in MCI patients and have been shown to predict whether or not patients decline. Previous studies that reported shape changes in the CA1 region of the hippocampus did not segment the individual subfields of the hippocampus, thus these deflections could indeed be due to shape changes in the deeper subfields. More recent reports suggest that there may be shape and volume changes in the CA3 and dentate gyrus (DG) regions of the hippocampus that may differentiate healthy adults from those early in the course of AD or in some cases in asymptomatic carriers of the ApoE e4 gene. We sought to investigate the detailed profile of volume and shape changes in MCI patients (all CDR 0.5) using the OASIS (Open Access Series of Imaging Studies) freely available data set. Methods: We used an alternative approach to previous studies by combining traditional grayscale data with manual segmentations of the subfields. In this technique, we manually segmented hippocampal subfields on each individual scan and used a region-of-interest based diffeomorphic alignment technique (ROI-ANTS) that we recently developed in order to quantify each subfield’s shape changes. The method uses information from grayscale images but weights the transformations based on ROI segmentations, resulting in optimum cross-participant overlap. Results: We found significant shape changes in the deeper subfields (CA3/DG) in MCI patients compared to age and gender matched controls, suggesting that this is one of the first hippocampal regions that deteriorates in the course of AD and that previously studies likely underestimated the extent to which it was involved due to an inherent bias in the alignment techniques. Conclusions: Using a robust diffeomorphic technique and precise anatomical segmentations, we find evidence for shape changes in the CA3/DG that may precede other hippocampal changes very early in the course of AD. This is consistent with animal studies suggesting that loss of synaptic input into the DG early in AD may result in shape changes in this region. This can potentially be a viable biomarker for predicting AD onset. IC-P-021
VASOGENIC EDEMA OF GREY MATTER (VEG), A SYNDROME WITH REVERSIBLE DIFFUSION WEIGHTED MRI CHANGES, DISTINCT FROM POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES) AND ANOXIC CEREBRAL ISCHEMIA
Anil K. Nair1, Jasmeet Singh2, Andrew Westwood3, Apar Gupta3, 1The Alzheimers Disease Center, Boston, MA, USA; 2Boston University, Boston, MA, USA; 3Boston Medical Center, Boston, MA, USA. Contact e-mail: [email protected]
S13
Background: Vasogenic edema of grey matter (VEG) is a distinct type of vasogenic edema (VE) spectrum and can be detected by early diffusion imaging and is important to differentiate from Posterior Reversible Encephalopathy Syndrome (PRES) and Anoxic Cerebral Ischemia. Methods: This is a case series describing a new subtype of vasogenic edema and comparing clinical and radiological presentations of three similar cases. Results: Diffusion changes disappeared in our VEG case by the second week without FLAIR changes but the aphasia persisted for 3 months with eventual recovery. Diffusion changes are not seen in the first week in PRES, with the FLAIR changes appearing in the second week. VEG and PRES may be distinct forms of vasogenic edema, affecting the grey matter or the white matter respectively with different clinical courses. Sequential diffusion images in the first week, in addition to FLAIR sequences may be used to identify and differentiate VEG from PRES and acute stroke or anoxic brain injury. The clinical and radiological syndrome of VEG requires further study. Conclusions: We describe VEG, a distinct clinical manifestation of the vasogenic edema spectrum. The clinical syndrome in our case was seizures and a prolonged aphasia reversing after 3 months, as opposed to the rapid reversal seen in PRES or the lack of reversal in anoxic brain injury. Good clinical suspicion and presence of asymmetric grey matter involvement on diffusion images in the first week may help making the diagnosis of VEG possible. In our case with VEG, the abnormalities seen on diffusion weighted images did not progress to corresponding changes in FLAIR or ADC maps and subsequently disappeared by day 10. In contrast, PRES had symmetric FLAIR changes in the first week, without changes in ADC images. VEG is distinct from cytotoxic edema as abnormalities on ADC maps do not occur. Recognizing this condition may allow early intensive treatment, possibly improving the clinical outcome.
IC-P-022
COMPARISON OF TRACT-BASED SPATIAL STATISTICS AND ROI-BASED APPROACH IN ANALYZING THE WHITE MATTER INTEGRITY IN THE ELDERLY
Huali Wang1,2, Daniel Chang3, Jing Liao4, L. Tugan Muftuler3, Orhan Nalcioglu3, Huishu Yuan4, Min-Ying Su3, Xin Yu1,2, 1Peking University Institute of Mental Health, Beijing, China; 2Key Laboratory for Mental Health, Ministry of Health (Peking University), Beijing, China; 3Tu & Yuen Center for Functional Onco-Imaging, University of California, Irvine, CA, USA; 4Department of Radiology, Peking University Third Hospital, Beijing, China. Contact e-mail: [email protected] Background: The purpose of this study was to compare tract-based-spatialstatistics (TBSS) and ROI-based approach in examining the white matter integrity between AD, MCI, and normal control (NC) subjects who have no obvious WM lesions. Methods: Sixty subjects without obvious white matter lesions were selected from a total of 243 subjects by two neuroradiologists. DTI images were acquired with 64 encoding directions using a Siemens 3T MRI scanner. The demographic characteristics were matched among the 3 groups (AD: n ¼ 19; M/F ¼ 7/12, 75.3 6 5 years; MCI: n ¼ 18; M/F ¼ 9/9, 73.2 6 3.7 years; NC: n ¼ 23; M/F ¼ 7/16, 73.6 6 5.9). TBSS analysis was performed with the FSL software package from Oxford’s Analysis Group. With the ROI-based approach, fractional anisotropy (FA) was calculated as the standard deviation of eigenvalues from the mean eigenvalue normalized by square norm of eignvalues. Results: With TBSS analysis, no significant differences were found in white matter tracts when AD was compared with MCI and MCI was compared with NC. Relative to NC, AD subjects exhibited significant lower FA values in the neural tracts of corpus callosum body, particularly in its radiations of the forceps major and forceps minor, which are categorically anterior and posterior cingulate fibers, respectively (Fig.1). There were also significant FA differences in the inferior and superior longitudinal fasciculus (p < 0.02). The ROI-based approach showed that the MCI group had significantly lower FA values in parietal WM (p < 0.001) compared to NC; and the AD group had significantly lower FA values in parietal, temporal, frontal WM, parahippocampal and posterior cingulate fibers (p < 0.001 for all). Compared to MCI, the AD group had significantly lower FA values in parietal (p ¼ 0.005), temporal, frontal WM, and
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Alzheimer’s Imaging Consortium IC-P: Imaging Posters
IC-P-024
parahippocampal and posterior cingulate fibers (p < 0.001 for all). Conclusions: The results may suggest that although TBSS uses WM tract skeleton for spatial normalization, the difference in small areas may be lost. The ROI based analysis uses native image, and may be more sensitive to detect them; however, it is time consuming and not suitable for analyzing differences in the whole brain. More research is needed to improve the group comparison analysis for DTI.
IC-P-023
ASSOCIATIONS BETWEEN REGIONAL BRAIN ATROPHY, EXECUTIVE CONTROL, AND SACCADIC LATENCY IN PARKINSON’S DISEASE AND HEALTHY AGING
Robert Perneczky1,2, Boyd C. P. Gosh2, Laura Hughes2,3, Roger H. S. Carpenter4, Roger A. Barker2,5, James B. Rowe2,3, 1Department of Psychiatry and Psychotherapy, Technische Universita¨t Mu¨nchen, Mu¨nchen, Germany; 2Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom; 3Medical Research Council Cognition and Brain Sciences Unit, Cambridge, United Kingdom; 4The Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom; 5Cambridge Centre for Brain Repair, Cambridge, United Kingdom. Contact e-mail: [email protected] Background: Both sub-cortical and cortical brain regions related to saccadic control are affected by Parkinson’s disease pathology, and a relationship between saccade alterations and cognitive features of Parkinson’s disease has been suggested. The mechanisms of the neuronal decision process for saccades and the patterns of saccade latencies have been characterised by the LATER model. The analysis of individual latency distributions reveals important information about how neural decision is affected by disease or medication. Methods: We used a head-mounted saccadometer and LATER model to determine the latency parameters in 18 patients with Parkinson’s disease in relative dopaminergic ‘on’ and ‘off’ states and 17 agematched control subjects. We correlated latency parameters with tests of motor and cognitive function, and voxelwise cerebral grey matter volume (voxel based morphometry). Results: There were no significant differences in any of the latency parameters between controls and patients, whether in the ‘on or the ‘off’ state; or between the patients in the ‘on’ and the ‘off’ state. However, there was a negative correlation between letter fluency and the variability of saccade latency, whereas no correlation was found between overall motor function and any of the latency parameters. Voxelwise grey matter volume estimates correlated with the latency parameters in several brain areas in patients and controls (p < 0.05 FWE corrected for multiple comparisons). Shorter saccade latency positively correlated with grey matter volume in regions of the prefrontal cortex, the cerebellar vermis, and the fusiform gyrus. The variability of saccade latency negatively correlated with grey matter volume in the frontal eye fields in patients; in controls, there was a negative correlation between the variability of latency and grey matter volume of the frontal and parietal eye fields, the premotor cortex, and the lateral prefrontal cortex. Conclusions: The behavioural and imaging findings point to an association between saccade latency, executive function and the prefrontal cortex. Our findings also suggest that saccadic latency and variability are associated with atrophy within a known oculomotor network. Therefore, saccadometry may provide important information on the severity of executive dysfunction and at the same time offer a rapid and non-invasive correlate of focal brain atrophy in healthy ageing and neurodegeneration.
CORTICAL THINNING IN VERBAL, VISUAL, AND BOTH AMNESTIC TYPES OF MILD COGNITIVE IMPAIRMENT
Min-Jeong Kim1, Kiho Im2, Jong-Min Lee2, Aram Park3, Geon Ha Kim1, Jong Hun Kim1, Jee Hoon Roh1, Sang Won Seo1, Duk L. Na1, 1Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of; 2Department of Biomedical Engineering, Hanyang University, Seoul, Korea, Republic of; 3Department of Neurology, Hanyang University Hospital, Seoul, Korea, Republic of. Contact e-mail: kmjchh@ gmail.com Background: Mild cognitive impairment (MCI) refers to a clinical transitional state between the cognitive changes of aging and the earliest clinical features of dementia, and the amnestic form of MCI (aMCI) has been known to be more likely a precursor of clinical Alzheimer disease (AD) than nonamnestic MCI. For the diagnosis of aMCI, both verbal and visual memory tests have been used, though which test is better in predicting underlying pathological changes have not been determined. The aim of this study was to compare the degree of cortical thinning among three types of aMCI: with only verbal memory impairment (Verbal-aMCI), with only visual memory impairment (Visual-aMCI), and with both verbal and visual memory impairment (Both-aMCI). Methods: The cortical thickness across the entire brain was measured in 143 normal healthy subjects and 124 aMCI patients that consisted of 33 with Verbal-aMCI, 35 with Visual-aMCI, and 56 with Both-aMCI. Differences in the patterns of cortical thinning among the groups were assessed using ANCOVA on a vertex-by-vertex basis, and the statistical maps of differences in cortical thickness among the groups were constructed using a surface model. Results: The Both-aMCI group showed more severe cortical thinning compared to other aMCI groups, particularly in the bilateral medial temporal regions. The Verbal-aMCI group showed cortical thinning in the areas of the left anterior temporal pole, which is similar to that in the Both-aMCI group despite the relatively less extent and severity in the Verbal-aMCI group. The Visual-aMCI group showed no significant cortical thinning when compared to the normal control group. Conclusions: Our results suggest that aMCI is on the spectrum from normal aging to AD in the order of Verbal- and Both-aMCI. Visual-aMCI might be composed with more heterogeneous status of disease than other types of aMCI. Thus, verbal memory tests will be more valuable than visual memory tests if a single type of memory test is used to diagnose aMCI. IC-P-025
CLASSIFICATION OF ADNI SUBJECTS BASED ON LONGITUDINAL ANALYSIS OF THE HIPPOCAMPAL FDG-PET SIGNAL
Katherine R. Gray1, Robin Wolz1, Rolf A. Heckemann1,2, Alexander Hammers1,2, Daniel Rueckert1, 1Imperial College London, London, United Kingdom; 2Fondation Neurodis, Lyon, France. Contact e-mail: [email protected] Background: As research continues to focus on the development of new treatments for Alzheimer’s disease (AD), and the selection of suitable subjects for clinical trials becomes increasingly important, the ability to reliably identify patients in the early or pre-symptomatic stages of the disease, and particularly those with amnestic mild cognitive impairment (aMCI), is desirable. The aim of this study is to classify subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), based on a regional analysis of their baseline and 12-month FDG-PET scans, as healthy controls (HC), or as having either aMCI or AD. Methods: Image data were obtained from 179 subjects (37 AD, 94 aMCI, 48 HC), whose baseline and 12-month FDG-PET scans were each re-aligned into the space of their corresponding baseline MRI, in which hippocampal masks were automatically generated for both timepoints. The signal intensity per cubic millimetre was determined in the hippocampus for both the baseline and 12-month FDG-PET scans, and the difference between the two calculated. Global variations in the cerebral metabolic rate of glucose between subjects were accounted for using the recently proposed ‘‘reference cluster’’ method, in which areas of apparent hypermetabolism between patients and controls (relatively unaffected by the disease) are extracted from the image data and used for normalisation.
power in determining normals from neurodegenerative cases and normals from AD cases. Change in volume does not necessarily help distinguish AD subjects from non-AD dementia cases. IC-P-020
SHAPE CHANGES IN THE CA3 AND DENTATE REGIONS OF THE HIPPOCAMPUS IN INDIVIDUALS WITH MILD COGNITIVE IMPAIRMENT
Michael A. Yassa, Samantha Rutledge, Craig E. L. Stark, University of California, Irvine, Irvine, CA, USA. Contact e-mail: [email protected] Background: Shape and volume changes in the subfields in the hippocampus have been reported in MCI patients and have been shown to predict whether or not patients decline. Previous studies that reported shape changes in the CA1 region of the hippocampus did not segment the individual subfields of the hippocampus, thus these deflections could indeed be due to shape changes in the deeper subfields. More recent reports suggest that there may be shape and volume changes in the CA3 and dentate gyrus (DG) regions of the hippocampus that may differentiate healthy adults from those early in the course of AD or in some cases in asymptomatic carriers of the ApoE e4 gene. We sought to investigate the detailed profile of volume and shape changes in MCI patients (all CDR 0.5) using the OASIS (Open Access Series of Imaging Studies) freely available data set. Methods: We used an alternative approach to previous studies by combining traditional grayscale data with manual segmentations of the subfields. In this technique, we manually segmented hippocampal subfields on each individual scan and used a region-of-interest based diffeomorphic alignment technique (ROI-ANTS) that we recently developed in order to quantify each subfield’s shape changes. The method uses information from grayscale images but weights the transformations based on ROI segmentations, resulting in optimum cross-participant overlap. Results: We found significant shape changes in the deeper subfields (CA3/DG) in MCI patients compared to age and gender matched controls, suggesting that this is one of the first hippocampal regions that deteriorates in the course of AD and that previously studies likely underestimated the extent to which it was involved due to an inherent bias in the alignment techniques. Conclusions: Using a robust diffeomorphic technique and precise anatomical segmentations, we find evidence for shape changes in the CA3/DG that may precede other hippocampal changes very early in the course of AD. This is consistent with animal studies suggesting that loss of synaptic input into the DG early in AD may result in shape changes in this region. This can potentially be a viable biomarker for predicting AD onset. IC-P-021
VASOGENIC EDEMA OF GREY MATTER (VEG), A SYNDROME WITH REVERSIBLE DIFFUSION WEIGHTED MRI CHANGES, DISTINCT FROM POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES) AND ANOXIC CEREBRAL ISCHEMIA
Anil K. Nair1, Jasmeet Singh2, Andrew Westwood3, Apar Gupta3, 1The Alzheimers Disease Center, Boston, MA, USA; 2Boston University, Boston, MA, USA; 3Boston Medical Center, Boston, MA, USA. Contact e-mail: [email protected]
S13
Background: Vasogenic edema of grey matter (VEG) is a distinct type of vasogenic edema (VE) spectrum and can be detected by early diffusion imaging and is important to differentiate from Posterior Reversible Encephalopathy Syndrome (PRES) and Anoxic Cerebral Ischemia. Methods: This is a case series describing a new subtype of vasogenic edema and comparing clinical and radiological presentations of three similar cases. Results: Diffusion changes disappeared in our VEG case by the second week without FLAIR changes but the aphasia persisted for 3 months with eventual recovery. Diffusion changes are not seen in the first week in PRES, with the FLAIR changes appearing in the second week. VEG and PRES may be distinct forms of vasogenic edema, affecting the grey matter or the white matter respectively with different clinical courses. Sequential diffusion images in the first week, in addition to FLAIR sequences may be used to identify and differentiate VEG from PRES and acute stroke or anoxic brain injury. The clinical and radiological syndrome of VEG requires further study. Conclusions: We describe VEG, a distinct clinical manifestation of the vasogenic edema spectrum. The clinical syndrome in our case was seizures and a prolonged aphasia reversing after 3 months, as opposed to the rapid reversal seen in PRES or the lack of reversal in anoxic brain injury. Good clinical suspicion and presence of asymmetric grey matter involvement on diffusion images in the first week may help making the diagnosis of VEG possible. In our case with VEG, the abnormalities seen on diffusion weighted images did not progress to corresponding changes in FLAIR or ADC maps and subsequently disappeared by day 10. In contrast, PRES had symmetric FLAIR changes in the first week, without changes in ADC images. VEG is distinct from cytotoxic edema as abnormalities on ADC maps do not occur. Recognizing this condition may allow early intensive treatment, possibly improving the clinical outcome.
IC-P-022
COMPARISON OF TRACT-BASED SPATIAL STATISTICS AND ROI-BASED APPROACH IN ANALYZING THE WHITE MATTER INTEGRITY IN THE ELDERLY
Huali Wang1,2, Daniel Chang3, Jing Liao4, L. Tugan Muftuler3, Orhan Nalcioglu3, Huishu Yuan4, Min-Ying Su3, Xin Yu1,2, 1Peking University Institute of Mental Health, Beijing, China; 2Key Laboratory for Mental Health, Ministry of Health (Peking University), Beijing, China; 3Tu & Yuen Center for Functional Onco-Imaging, University of California, Irvine, CA, USA; 4Department of Radiology, Peking University Third Hospital, Beijing, China. Contact e-mail: [email protected] Background: The purpose of this study was to compare tract-based-spatialstatistics (TBSS) and ROI-based approach in examining the white matter integrity between AD, MCI, and normal control (NC) subjects who have no obvious WM lesions. Methods: Sixty subjects without obvious white matter lesions were selected from a total of 243 subjects by two neuroradiologists. DTI images were acquired with 64 encoding directions using a Siemens 3T MRI scanner. The demographic characteristics were matched among the 3 groups (AD: n ¼ 19; M/F ¼ 7/12, 75.3 6 5 years; MCI: n ¼ 18; M/F ¼ 9/9, 73.2 6 3.7 years; NC: n ¼ 23; M/F ¼ 7/16, 73.6 6 5.9). TBSS analysis was performed with the FSL software package from Oxford’s Analysis Group. With the ROI-based approach, fractional anisotropy (FA) was calculated as the standard deviation of eigenvalues from the mean eigenvalue normalized by square norm of eignvalues. Results: With TBSS analysis, no significant differences were found in white matter tracts when AD was compared with MCI and MCI was compared with NC. Relative to NC, AD subjects exhibited significant lower FA values in the neural tracts of corpus callosum body, particularly in its radiations of the forceps major and forceps minor, which are categorically anterior and posterior cingulate fibers, respectively (Fig.1). There were also significant FA differences in the inferior and superior longitudinal fasciculus (p < 0.02). The ROI-based approach showed that the MCI group had significantly lower FA values in parietal WM (p < 0.001) compared to NC; and the AD group had significantly lower FA values in parietal, temporal, frontal WM, parahippocampal and posterior cingulate fibers (p < 0.001 for all). Compared to MCI, the AD group had significantly lower FA values in parietal (p ¼ 0.005), temporal, frontal WM, and
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Alzheimer’s Imaging Consortium IC-P: Imaging Posters
IC-P-024
parahippocampal and posterior cingulate fibers (p < 0.001 for all). Conclusions: The results may suggest that although TBSS uses WM tract skeleton for spatial normalization, the difference in small areas may be lost. The ROI based analysis uses native image, and may be more sensitive to detect them; however, it is time consuming and not suitable for analyzing differences in the whole brain. More research is needed to improve the group comparison analysis for DTI.
IC-P-023
ASSOCIATIONS BETWEEN REGIONAL BRAIN ATROPHY, EXECUTIVE CONTROL, AND SACCADIC LATENCY IN PARKINSON’S DISEASE AND HEALTHY AGING
Robert Perneczky1,2, Boyd C. P. Gosh2, Laura Hughes2,3, Roger H. S. Carpenter4, Roger A. Barker2,5, James B. Rowe2,3, 1Department of Psychiatry and Psychotherapy, Technische Universita¨t Mu¨nchen, Mu¨nchen, Germany; 2Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom; 3Medical Research Council Cognition and Brain Sciences Unit, Cambridge, United Kingdom; 4The Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom; 5Cambridge Centre for Brain Repair, Cambridge, United Kingdom. Contact e-mail: [email protected] Background: Both sub-cortical and cortical brain regions related to saccadic control are affected by Parkinson’s disease pathology, and a relationship between saccade alterations and cognitive features of Parkinson’s disease has been suggested. The mechanisms of the neuronal decision process for saccades and the patterns of saccade latencies have been characterised by the LATER model. The analysis of individual latency distributions reveals important information about how neural decision is affected by disease or medication. Methods: We used a head-mounted saccadometer and LATER model to determine the latency parameters in 18 patients with Parkinson’s disease in relative dopaminergic ‘on’ and ‘off’ states and 17 agematched control subjects. We correlated latency parameters with tests of motor and cognitive function, and voxelwise cerebral grey matter volume (voxel based morphometry). Results: There were no significant differences in any of the latency parameters between controls and patients, whether in the ‘on or the ‘off’ state; or between the patients in the ‘on’ and the ‘off’ state. However, there was a negative correlation between letter fluency and the variability of saccade latency, whereas no correlation was found between overall motor function and any of the latency parameters. Voxelwise grey matter volume estimates correlated with the latency parameters in several brain areas in patients and controls (p < 0.05 FWE corrected for multiple comparisons). Shorter saccade latency positively correlated with grey matter volume in regions of the prefrontal cortex, the cerebellar vermis, and the fusiform gyrus. The variability of saccade latency negatively correlated with grey matter volume in the frontal eye fields in patients; in controls, there was a negative correlation between the variability of latency and grey matter volume of the frontal and parietal eye fields, the premotor cortex, and the lateral prefrontal cortex. Conclusions: The behavioural and imaging findings point to an association between saccade latency, executive function and the prefrontal cortex. Our findings also suggest that saccadic latency and variability are associated with atrophy within a known oculomotor network. Therefore, saccadometry may provide important information on the severity of executive dysfunction and at the same time offer a rapid and non-invasive correlate of focal brain atrophy in healthy ageing and neurodegeneration.
CORTICAL THINNING IN VERBAL, VISUAL, AND BOTH AMNESTIC TYPES OF MILD COGNITIVE IMPAIRMENT
Min-Jeong Kim1, Kiho Im2, Jong-Min Lee2, Aram Park3, Geon Ha Kim1, Jong Hun Kim1, Jee Hoon Roh1, Sang Won Seo1, Duk L. Na1, 1Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of; 2Department of Biomedical Engineering, Hanyang University, Seoul, Korea, Republic of; 3Department of Neurology, Hanyang University Hospital, Seoul, Korea, Republic of. Contact e-mail: kmjchh@ gmail.com Background: Mild cognitive impairment (MCI) refers to a clinical transitional state between the cognitive changes of aging and the earliest clinical features of dementia, and the amnestic form of MCI (aMCI) has been known to be more likely a precursor of clinical Alzheimer disease (AD) than nonamnestic MCI. For the diagnosis of aMCI, both verbal and visual memory tests have been used, though which test is better in predicting underlying pathological changes have not been determined. The aim of this study was to compare the degree of cortical thinning among three types of aMCI: with only verbal memory impairment (Verbal-aMCI), with only visual memory impairment (Visual-aMCI), and with both verbal and visual memory impairment (Both-aMCI). Methods: The cortical thickness across the entire brain was measured in 143 normal healthy subjects and 124 aMCI patients that consisted of 33 with Verbal-aMCI, 35 with Visual-aMCI, and 56 with Both-aMCI. Differences in the patterns of cortical thinning among the groups were assessed using ANCOVA on a vertex-by-vertex basis, and the statistical maps of differences in cortical thickness among the groups were constructed using a surface model. Results: The Both-aMCI group showed more severe cortical thinning compared to other aMCI groups, particularly in the bilateral medial temporal regions. The Verbal-aMCI group showed cortical thinning in the areas of the left anterior temporal pole, which is similar to that in the Both-aMCI group despite the relatively less extent and severity in the Verbal-aMCI group. The Visual-aMCI group showed no significant cortical thinning when compared to the normal control group. Conclusions: Our results suggest that aMCI is on the spectrum from normal aging to AD in the order of Verbal- and Both-aMCI. Visual-aMCI might be composed with more heterogeneous status of disease than other types of aMCI. Thus, verbal memory tests will be more valuable than visual memory tests if a single type of memory test is used to diagnose aMCI. IC-P-025
CLASSIFICATION OF ADNI SUBJECTS BASED ON LONGITUDINAL ANALYSIS OF THE HIPPOCAMPAL FDG-PET SIGNAL
Katherine R. Gray1, Robin Wolz1, Rolf A. Heckemann1,2, Alexander Hammers1,2, Daniel Rueckert1, 1Imperial College London, London, United Kingdom; 2Fondation Neurodis, Lyon, France. Contact e-mail: [email protected] Background: As research continues to focus on the development of new treatments for Alzheimer’s disease (AD), and the selection of suitable subjects for clinical trials becomes increasingly important, the ability to reliably identify patients in the early or pre-symptomatic stages of the disease, and particularly those with amnestic mild cognitive impairment (aMCI), is desirable. The aim of this study is to classify subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), based on a regional analysis of their baseline and 12-month FDG-PET scans, as healthy controls (HC), or as having either aMCI or AD. Methods: Image data were obtained from 179 subjects (37 AD, 94 aMCI, 48 HC), whose baseline and 12-month FDG-PET scans were each re-aligned into the space of their corresponding baseline MRI, in which hippocampal masks were automatically generated for both timepoints. The signal intensity per cubic millimetre was determined in the hippocampus for both the baseline and 12-month FDG-PET scans, and the difference between the two calculated. Global variations in the cerebral metabolic rate of glucose between subjects were accounted for using the recently proposed ‘‘reference cluster’’ method, in which areas of apparent hypermetabolism between patients and controls (relatively unaffected by the disease) are extracted from the image data and used for normalisation.