- Email: [email protected]
CORTICAL CEREBRAL MICROINFARCTS ON 3T MRI IN ALZHEIMER’S DISEASE AND MILD COGNITIVE IMPAIRMENT
P1378
Poster Presentations: Wednesday, July 19, 2017
cortical region to cerebellar standardized uptake value ratios (SUVRs) were measured. We compared regional SUVRs among groups according to Ab positivity and identified correlations between the regional SUVRs and performance in each cognitive function test. Results: Global SUVRs of F-18 Florbetaben and F-18 THK5351 PET images for SMI, MCI and AD were 1.1860.09/ 1.4560.27/1.4960.23 (p¼1.000) and 1.3560.11/1.4660.14/ 1.5760.16 (p¼0.002) for each. Ab (+/-) SMI/MCI/AD were 33/1, 28/32, and 7/21, respectively. Compared to Ab- SMI (1.3560.12), Ab+ MCI and AD showed higher global SUVRs (1.4660.14, 1.6060.13, p¼0.004), but not in Ab- MCI and AD groups (1.4160.13, 1.4160.18, p¼0.078). In Ab+ groups, SUVRs of parietal area which is known to be affected in later stage were highly correlated (R¼0.6w0.7) with CDR-SB, MMSE, visuospatial function and memory. In Ab- groups, SUVR of frontal area were correlated (R¼0.6) with visuospatial function. Conclusions: F-18 THK-5351 uptake was higher in Ab+ groups than in Ab- groups. The regional uptake of THK-5351 in the AD spectrum related to functional deterioration in different cognitive domain according to amyloid positivity. P4-254
WITHDRAWN
P4-255
CORTICAL CEREBRAL MICROINFARCTS ON 3T MRI IN ALZHEIMER’S DISEASE AND MILD COGNITIVE IMPAIRMENT
Nawaf Yassi1,2, Saima Hilal3, Yen Ying Lim2, Simon Salinas1, Hugo Kuijf4, Ying Xia5, Christopher Chen6, Olivier Salvado5, Christopher C. Rowe7,8, Patricia Desmond1, Colin L. Masters8,9,10, AIBL Research Group, 1Uiversity of Melbourne, Parkville, Australia; 2Florey Institute of Neuroscience an Mental Health, Parkville, Australia; 3National University of Singapore, Singapore, Singapore; 4University Medical Centre Utrecht, Utrecht, Netherlands; 5Commonwealth Scientific and Industrial Research Organisation, Brisbane, Australia; 6Yong Loo
Lin School of Medicine, National University of Singapore, Singapore, Singapore; 7Austin Health, Heidelberg, Australia; 8 AIBL Research Group, Perth and Melbourne, Australia; 9The University of Melbourne, Parkville, Australia; 10The Florey Institute of Neuroscience and Mental Health, Parkville, Australia. Contact e-mail: [email protected] Background: The prevalence of cortical cerebral microinfarcts (CMI)
on neuropathological studies of Alzheimer’s disease (AD) is reported at approximately 40%, and they are associated with cognitive impairment. Recent studies have validated the detection of CMI in vivo using both 7Tand 3T MRI. We aimed to investigate the prevalence of CMI in patients with AD, mild cognitive impairment (MCI) and healthy controls (HC) from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL), and to examine their association with vascular risk factors. Methods: Participants were chosen at random from the AIBL database. Baseline imaging and clinical data were assessed in this cross-sectional analysis. CMI were visually graded using 3T MRI by simultaneously viewing 1x1x1mm isotropic T1-weighted and Fluid Attenuated Inversion Recovery (FLAIR) images. They were defined on T1-weighted images as discrete punched out lesions <5mm in diameter and perpendicular to the cortical ribbon (see figure). They were either isointense or hyperintense on FLAIR. Results: Baseline images from 97 participants were evaluated (51 female, mean age 73.6 years). The underlying diagnosis was AD in 33%, MCI in 28.9% and HC in 38.1%. The distribution of age and vascular risk factors was similar across the diagnostic categories. Overall, the prevalence of CMI was 8.2%, with 62% of cases being multiple. Only 2.7% of HC had CMI, compared to 14.3% of MCI patients and 9.4% of AD patients, although these trends were non-significant. The presence of CMI was associated with a history of stroke (p¼0.014, Fisher’s exact), and cigarette smoking (p¼0.029, Chi-square). Conclusions: CMI are detectable in large AD cohorts using standard 3T MRI acquisitions. Our preliminary analysis has demonstrated trends regarding the prevalence of CMI in AD and MCI versus healthy controls as well as associations with vascular risk factors. Important future analyses will explore interactions between CMI and other cerebrovascular disease markers (e.g. lacunes,
Poster Presentations: Wednesday, July 19, 2017
P1379
white-matter hyperintensities), as well as amyloid burden, and longitudinal change in cognition.
P4-256
STRUCTURAL INTEGRITY OF WHITE MATTER TRACTS IN PAPEZ CIRCUIT DURING THE COURSE OF ALZHEIMER’S DISEASE
Ram J. Bishnoi, Sandarsh Surya, W. Vaughn McCall, Augusta University, Augusta, GA, USA. Contact e-mail: [email protected] Background: Posterior cingulate region’s involvement in Alz-
heimer’s disease (AD) pathogenesis has brought back the focus to Papez circuit (PC) which could have significant implications for AD’s biomarker research. In addition to grey-matter regions, PC’s integrity is also dependent on white matter (WM) tracts connecting those regions. Delineating the microstructural changes within WM tracts of PC during preclinical and clinical stages of AD may improve our understanding of temporal dynamics during the course of AD and ability to predict future disease. Diffusion tensor imaging (DTI) estimated fractional anisotropy (FA) in the diffusion of water through brain tissue can be used to quantify white matter micro-structural integrity. Methods: In this exploratory study, we included 45 patients with AD, 98 patients with mild cognitive impairment (MCI) and 75 cognitively normal (CN) controls. Statistical significant difference in FA between groups as determined by one-way ANCOVA after controlling for covariates including age. Results: Between groups, significant differences in FA was observed in following regions: fornix, left (F(2,213)¼ 14.399, p¼.000) and right (F(2,213)¼12.897, p¼.000); stria terminalis, left (F(2,213)¼15.989, p¼.000) and right (F(2,213)¼8.823, p¼.000); cingulum (hippocampus), left (F(2,213)¼6.074, p¼.003) and right (F(2,213)¼5.989, p¼.003); cingulum, right (F(2,213)¼3.315, p¼.038); and, anterior corona radiata, left (F(2,213)¼5.133, p¼.007) and right (F(2,213)¼3.397, p¼.035). In pairwise comparisons after Bonferroni correction, patients with MCI showed significant FA reduction in fornix and stria terminalis, bilaterally than CN group. Patients with AD were associated with significant reduction in FA in fornix, stria terminalis, anterior corona radiate, right cingulum and right cingulum (hippocampus) compared to MCI patients. In comparison to CN, there was a widespread reduction of FA within PC in the AD group. Conclusions: To conclude, the disruption of WM integrity in MCI is limited to fornix and stria terminalis which connect medial temporal lobe structures (hippocampus and amygdala) to other PC structures. In AD, this disintegration is widespread within PC, also involving WM tracts also projecting to thalamic and cingulate regions. This pattern of WM alteration point towards systematic progression of AD pathology involving PC structures during the course of AD. The extent of involvement of PC can therefore be a marker of disease progression or therapeutic response.
P4-257
Figure 1a. Progression of volume loss in the vision subgroup at early stages. At every stage, areas in gray are normal and areas in red are abnormal, while areas in white have not been selected for analysis. We only show the first 9 stages here (out of 25). Occipital areas are the first to become abnormal in this subgroup, followed by superior parietal and middle temporal abnormalities.
Figure 1b. Positional variance diagram for the vision subgroup showing the uncertainty in the progression of volume loss (biomarkers on y axis) across different stages (positions on x axis). Each entry (x,y) represents the probability of region y becoming abnormal at position x in the sequence, ranging from 0 in white to 1 in black.
ANALYSIS OF THE HETEROGENEITY OF POSTERIOR CORTICAL ATROPHY: DATADRIVEN MODEL PREDICTS DISTINCT ATROPHY PATTERNS FOR THREE DIFFERENT COGNITIVE SUBGROUPS
Razvan Valentin Marinescu1, Silvia Primativo2, Alexandra L. Young3, Neil P. Oxtoby3, Nicholas C. Firth4, Arman Eshaghi3,5, Sara Garbarino3, Jorge M. Cardoso3, Keir Yong2, Nick C. Fox2,3,5, Manja Lehmann2,3,6, Timothy J. Shakespeare2, Sebastian J. Crutch2,3, Daniel C. Alexander1,
Figure 2a. Progression of volume loss in the space subgroup at early stages. The superior parietal area is the first to become abnormal. This group shows an early parietal (dorsal) pattern of atrophy, with inferior occipital and middle temporal involvement in later stages.
Poster Presentations: Wednesday, July 19, 2017
cortical region to cerebellar standardized uptake value ratios (SUVRs) were measured. We compared regional SUVRs among groups according to Ab positivity and identified correlations between the regional SUVRs and performance in each cognitive function test. Results: Global SUVRs of F-18 Florbetaben and F-18 THK5351 PET images for SMI, MCI and AD were 1.1860.09/ 1.4560.27/1.4960.23 (p¼1.000) and 1.3560.11/1.4660.14/ 1.5760.16 (p¼0.002) for each. Ab (+/-) SMI/MCI/AD were 33/1, 28/32, and 7/21, respectively. Compared to Ab- SMI (1.3560.12), Ab+ MCI and AD showed higher global SUVRs (1.4660.14, 1.6060.13, p¼0.004), but not in Ab- MCI and AD groups (1.4160.13, 1.4160.18, p¼0.078). In Ab+ groups, SUVRs of parietal area which is known to be affected in later stage were highly correlated (R¼0.6w0.7) with CDR-SB, MMSE, visuospatial function and memory. In Ab- groups, SUVR of frontal area were correlated (R¼0.6) with visuospatial function. Conclusions: F-18 THK-5351 uptake was higher in Ab+ groups than in Ab- groups. The regional uptake of THK-5351 in the AD spectrum related to functional deterioration in different cognitive domain according to amyloid positivity. P4-254
WITHDRAWN
P4-255
CORTICAL CEREBRAL MICROINFARCTS ON 3T MRI IN ALZHEIMER’S DISEASE AND MILD COGNITIVE IMPAIRMENT
Nawaf Yassi1,2, Saima Hilal3, Yen Ying Lim2, Simon Salinas1, Hugo Kuijf4, Ying Xia5, Christopher Chen6, Olivier Salvado5, Christopher C. Rowe7,8, Patricia Desmond1, Colin L. Masters8,9,10, AIBL Research Group, 1Uiversity of Melbourne, Parkville, Australia; 2Florey Institute of Neuroscience an Mental Health, Parkville, Australia; 3National University of Singapore, Singapore, Singapore; 4University Medical Centre Utrecht, Utrecht, Netherlands; 5Commonwealth Scientific and Industrial Research Organisation, Brisbane, Australia; 6Yong Loo
Lin School of Medicine, National University of Singapore, Singapore, Singapore; 7Austin Health, Heidelberg, Australia; 8 AIBL Research Group, Perth and Melbourne, Australia; 9The University of Melbourne, Parkville, Australia; 10The Florey Institute of Neuroscience and Mental Health, Parkville, Australia. Contact e-mail: [email protected] Background: The prevalence of cortical cerebral microinfarcts (CMI)
on neuropathological studies of Alzheimer’s disease (AD) is reported at approximately 40%, and they are associated with cognitive impairment. Recent studies have validated the detection of CMI in vivo using both 7Tand 3T MRI. We aimed to investigate the prevalence of CMI in patients with AD, mild cognitive impairment (MCI) and healthy controls (HC) from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL), and to examine their association with vascular risk factors. Methods: Participants were chosen at random from the AIBL database. Baseline imaging and clinical data were assessed in this cross-sectional analysis. CMI were visually graded using 3T MRI by simultaneously viewing 1x1x1mm isotropic T1-weighted and Fluid Attenuated Inversion Recovery (FLAIR) images. They were defined on T1-weighted images as discrete punched out lesions <5mm in diameter and perpendicular to the cortical ribbon (see figure). They were either isointense or hyperintense on FLAIR. Results: Baseline images from 97 participants were evaluated (51 female, mean age 73.6 years). The underlying diagnosis was AD in 33%, MCI in 28.9% and HC in 38.1%. The distribution of age and vascular risk factors was similar across the diagnostic categories. Overall, the prevalence of CMI was 8.2%, with 62% of cases being multiple. Only 2.7% of HC had CMI, compared to 14.3% of MCI patients and 9.4% of AD patients, although these trends were non-significant. The presence of CMI was associated with a history of stroke (p¼0.014, Fisher’s exact), and cigarette smoking (p¼0.029, Chi-square). Conclusions: CMI are detectable in large AD cohorts using standard 3T MRI acquisitions. Our preliminary analysis has demonstrated trends regarding the prevalence of CMI in AD and MCI versus healthy controls as well as associations with vascular risk factors. Important future analyses will explore interactions between CMI and other cerebrovascular disease markers (e.g. lacunes,
Poster Presentations: Wednesday, July 19, 2017
P1379
white-matter hyperintensities), as well as amyloid burden, and longitudinal change in cognition.
P4-256
STRUCTURAL INTEGRITY OF WHITE MATTER TRACTS IN PAPEZ CIRCUIT DURING THE COURSE OF ALZHEIMER’S DISEASE
Ram J. Bishnoi, Sandarsh Surya, W. Vaughn McCall, Augusta University, Augusta, GA, USA. Contact e-mail: [email protected] Background: Posterior cingulate region’s involvement in Alz-
heimer’s disease (AD) pathogenesis has brought back the focus to Papez circuit (PC) which could have significant implications for AD’s biomarker research. In addition to grey-matter regions, PC’s integrity is also dependent on white matter (WM) tracts connecting those regions. Delineating the microstructural changes within WM tracts of PC during preclinical and clinical stages of AD may improve our understanding of temporal dynamics during the course of AD and ability to predict future disease. Diffusion tensor imaging (DTI) estimated fractional anisotropy (FA) in the diffusion of water through brain tissue can be used to quantify white matter micro-structural integrity. Methods: In this exploratory study, we included 45 patients with AD, 98 patients with mild cognitive impairment (MCI) and 75 cognitively normal (CN) controls. Statistical significant difference in FA between groups as determined by one-way ANCOVA after controlling for covariates including age. Results: Between groups, significant differences in FA was observed in following regions: fornix, left (F(2,213)¼ 14.399, p¼.000) and right (F(2,213)¼12.897, p¼.000); stria terminalis, left (F(2,213)¼15.989, p¼.000) and right (F(2,213)¼8.823, p¼.000); cingulum (hippocampus), left (F(2,213)¼6.074, p¼.003) and right (F(2,213)¼5.989, p¼.003); cingulum, right (F(2,213)¼3.315, p¼.038); and, anterior corona radiata, left (F(2,213)¼5.133, p¼.007) and right (F(2,213)¼3.397, p¼.035). In pairwise comparisons after Bonferroni correction, patients with MCI showed significant FA reduction in fornix and stria terminalis, bilaterally than CN group. Patients with AD were associated with significant reduction in FA in fornix, stria terminalis, anterior corona radiate, right cingulum and right cingulum (hippocampus) compared to MCI patients. In comparison to CN, there was a widespread reduction of FA within PC in the AD group. Conclusions: To conclude, the disruption of WM integrity in MCI is limited to fornix and stria terminalis which connect medial temporal lobe structures (hippocampus and amygdala) to other PC structures. In AD, this disintegration is widespread within PC, also involving WM tracts also projecting to thalamic and cingulate regions. This pattern of WM alteration point towards systematic progression of AD pathology involving PC structures during the course of AD. The extent of involvement of PC can therefore be a marker of disease progression or therapeutic response.
P4-257
Figure 1a. Progression of volume loss in the vision subgroup at early stages. At every stage, areas in gray are normal and areas in red are abnormal, while areas in white have not been selected for analysis. We only show the first 9 stages here (out of 25). Occipital areas are the first to become abnormal in this subgroup, followed by superior parietal and middle temporal abnormalities.
Figure 1b. Positional variance diagram for the vision subgroup showing the uncertainty in the progression of volume loss (biomarkers on y axis) across different stages (positions on x axis). Each entry (x,y) represents the probability of region y becoming abnormal at position x in the sequence, ranging from 0 in white to 1 in black.
ANALYSIS OF THE HETEROGENEITY OF POSTERIOR CORTICAL ATROPHY: DATADRIVEN MODEL PREDICTS DISTINCT ATROPHY PATTERNS FOR THREE DIFFERENT COGNITIVE SUBGROUPS
Razvan Valentin Marinescu1, Silvia Primativo2, Alexandra L. Young3, Neil P. Oxtoby3, Nicholas C. Firth4, Arman Eshaghi3,5, Sara Garbarino3, Jorge M. Cardoso3, Keir Yong2, Nick C. Fox2,3,5, Manja Lehmann2,3,6, Timothy J. Shakespeare2, Sebastian J. Crutch2,3, Daniel C. Alexander1,
Figure 2a. Progression of volume loss in the space subgroup at early stages. The superior parietal area is the first to become abnormal. This group shows an early parietal (dorsal) pattern of atrophy, with inferior occipital and middle temporal involvement in later stages.