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Diffusion tensor imaging as a diagnostic tool for Alzheimer's disease
Alzheimer’s Imaging Consortium Posters: IC-P
P37
Conclusions: This reflects measuring FA in hippocampus is a sensitive method to determine early microstructural changes of brain. Diagnostic power of hippocampal FA value for AD and MCI in individual subject needs to be determined for future application as a new diagnostic biomarker.
IC-P-063
IC-P-062
DIFFUSION TENSOR IMAGING AS A DIAGNOSTIC TOOL FOR ALZHEIMER’S DISEASE 1
2
3
4
Dong Won Yang , Yun Jeong Hong , Bora Yoon , Il-Woo Han , SungChul Lim5, Yong Soo Shim6, Jee Young Kim5, 1Seoul St. Mary’s Hospital, Seoul, South Korea; 2Hyoja Geriatric Hospital, Yong-In, South Korea; 3 Konyang University, Daejeon, South Korea; 4Hyoja Geriatric Hospital, Yong-In, South Korea; 5Seoul St. Mary’s Hospital, Seoul, South Korea; 6 Bucheon St. Mary’s Hospital, Bucheon, South Korea. Background: Diffusion tensor imaging (DTI) can be used to assess the degradation of white matter tracts by measuring the fractional anisotropy (FA) and mean diffusivity (MD). Decreased FA and increased MD values of brain represents tissue damage in many neurodegenerative diseases. The aim of this study was to investigate the changes of microstructural integrity of the hippocampus and posterior cingulated (PC) in normal controls(NC), Mild Cognitive Impairment(MCI) and Alzheimer’s disease(AD) and to determine whether this method could be a reliable tool for early diagnosis of AD. Methods: We recruited 80 participants (34 NC, 13 MCI, and 33 AD). We included AD patients with Clinical Dementia Rating (CDR) scores of 0.5 and 1. The FA and MD values were measured with regions of interest (ROI) method in bilateral hippocampal head (HH) and PC. Clinical history, neurologic examination and neuropsychological assessment were conducted. Results: The FA and MD values in bilateral HH and PC of MCI and AD were significantly lower and higher than those of NC. No differences could be found in FA and MD values between MCI and AD. Correlation coefficient between CDR sum of box scores and FA was higher than that between CDR sum of box scores and MD in both HH and PC. FA in HH was the best single measure to detect early microstructural changes of AD. Table 1 Basic demographics & neuropsychological test results in each group
Age(yr) Sex (female) K-MMSE Education CDR score CDR -SOB
Healthy(A)
MCI(B)
AD(C)
P
Post Hoc
71.3 6 5.84 52.9% 28.5 6 1.26 9.7 6 6.17 0.0 0.0
71.1 6 5.56 76.9% 25.5 6 2.82 8.3 6 4.46 0.5 1.75 6 0.979
73.9 6 7.87 55.9% 19.3 6 4.49 8.0 6 4.99 0.89 6 0.370 5.25 6 2.569
0.210 0.299 0.000 0.404 0.000 0.000
A¼B¼C X2 A>B>C A¼B¼C C>B>A C>B>A
COGNITIVE TRAJECTORIES ASSOCIATED WITH BETA-AMYLOID DEPOSITION IN THE NONDEMENTED OLDEST-OLD
Beth Snitz1, Lisa Weissfeld1, Oscar Lopez1, Lewis Kuller1, Judith Saxton1, Dilrukshika Singhabahu1, William Klunk1, Julie Price1, Chester Mathis1, Ann Cohen1, Steven DeKosky2, 1University of Pittsburgh, Pittsburgh, Pennsylvania, United States; 2University of Virginia School of Medicine, Charlottesville, Virginia, United States. Background: A significant number of non-demented older adults show Alzheimer Disease-like beta-amyloid (Ab) plaques and neurofibrillary tangles at autopsy. This proportion increases with age, provoking questions about the clinical significance of Alzheimer pathology in an advanced age group. Here we examined whether a high prevalence (55%) of Ab deposition, as measured in vivo by Pittsburgh Compound B (PiB)-PET imaging in an oldest-old cohort is associated with cognitive decline 7-9 years before the scan, even in individuals remaining dementia-free into their 9th and 10th decades. Methods: 194 older adults (85.5 6 2.8 (SD) years, range 82 - 95 years) who completed and remained dementia-free at the conclusion of the Ginkgo Evaluation of Memory Study (GEMS) were recruited for a subsequent neuroimaging sub-study. PiB retention was measured using the standardized uptake value ratio (SUVr) summed over 50-70 minutes post-injection using cerebellum as reference region. A global cortical cutoff of 1.57 SUVr was used to define Ab-negative and Ab-positive PiB status. We examined the relationship between PiB status determined in 2009 and cognitive performance on an extensive neuropsychological test battery completed at entry to GEMS 7-9 years prior to neuroimaging. We also longitudinally examined cognition over annual GEMS evaluations using linear mixed models. Results: At GEMS baseline (entered the study between 2000-2002), participants who were Ab-positive in 2009 (n ¼ 107; 55.2%) had lower performance on the Stroop test (P <0.01), Raven’s Progressive Matrices (P ¼ 0.05) with trend level difference for Block Design (P ¼ 0.07), adjusting for age, education, sex and race. Longitudinal analyses showed significant slope differences for immediate and delayed recall of the Rey-Osterrieth figure, semantic fluency, and Trail Making Test parts A & B, indicating greater performance decline for Ab-positive relative to Ab-negative participants (p’s<0.05). Conclusions: Highly prevalent Ab deposition in oldest-older adults is associated with cognitive decline in visual memory, semantic fluency and psychomotor speed over 7-9 years prior to imaging. Mean differences in non-memory domains, primarily executive functions, between
Table 2 Mean FA and MD results in each group
FA Lt.HB Rt.HB Lt.PC Rt.PC MD Lt.HB Rt.HB Lt.PC Rt.PC
Normal (a)
MCI(b)
AD(c)
P value post-hoc
0.143 6 0.0170 0.150 6 0.0165 0.243 6 0.0297 0.235 6 0.0263
0.097 6 0.0158 0.095 6 0.0120 0.203 6 0.0311 0.197 6 0.0263
0.084 6 0.0112 0.090 6 0.0101 0.188 6 0.0293 0.178 6 0.0279
0.000 0.000 0.000 0.000
a>b ¼ c a>b ¼ c a>b ¼ c a>b ¼ c
0.843 6 0.0712 0.828 6 0.0714 0.716 6 0.0633 0.700 6 0.0751
0.962 6 0.0584 1.024 6 0.0926 0.796 6 0.0939 0.835 6 0.0880
1.164 6 0.2126 1.108 6 0.1536 0.795 6 0.0760 0.776 6 0.0610
0.000 0.000 0.000 0.000
c>b>a b ¼ c>a b ¼ c>a b ¼ c>a
Figure. Mean performance on semantic fluency (+/- S.E.) over a span of 7-9 (mean 7.6) years up to the time of neuroimaging, showing greater decline in the Ab-positive (n ¼ 107) compared to Ab-negative group (n ¼ 87).
P37
Conclusions: This reflects measuring FA in hippocampus is a sensitive method to determine early microstructural changes of brain. Diagnostic power of hippocampal FA value for AD and MCI in individual subject needs to be determined for future application as a new diagnostic biomarker.
IC-P-063
IC-P-062
DIFFUSION TENSOR IMAGING AS A DIAGNOSTIC TOOL FOR ALZHEIMER’S DISEASE 1
2
3
4
Dong Won Yang , Yun Jeong Hong , Bora Yoon , Il-Woo Han , SungChul Lim5, Yong Soo Shim6, Jee Young Kim5, 1Seoul St. Mary’s Hospital, Seoul, South Korea; 2Hyoja Geriatric Hospital, Yong-In, South Korea; 3 Konyang University, Daejeon, South Korea; 4Hyoja Geriatric Hospital, Yong-In, South Korea; 5Seoul St. Mary’s Hospital, Seoul, South Korea; 6 Bucheon St. Mary’s Hospital, Bucheon, South Korea. Background: Diffusion tensor imaging (DTI) can be used to assess the degradation of white matter tracts by measuring the fractional anisotropy (FA) and mean diffusivity (MD). Decreased FA and increased MD values of brain represents tissue damage in many neurodegenerative diseases. The aim of this study was to investigate the changes of microstructural integrity of the hippocampus and posterior cingulated (PC) in normal controls(NC), Mild Cognitive Impairment(MCI) and Alzheimer’s disease(AD) and to determine whether this method could be a reliable tool for early diagnosis of AD. Methods: We recruited 80 participants (34 NC, 13 MCI, and 33 AD). We included AD patients with Clinical Dementia Rating (CDR) scores of 0.5 and 1. The FA and MD values were measured with regions of interest (ROI) method in bilateral hippocampal head (HH) and PC. Clinical history, neurologic examination and neuropsychological assessment were conducted. Results: The FA and MD values in bilateral HH and PC of MCI and AD were significantly lower and higher than those of NC. No differences could be found in FA and MD values between MCI and AD. Correlation coefficient between CDR sum of box scores and FA was higher than that between CDR sum of box scores and MD in both HH and PC. FA in HH was the best single measure to detect early microstructural changes of AD. Table 1 Basic demographics & neuropsychological test results in each group
Age(yr) Sex (female) K-MMSE Education CDR score CDR -SOB
Healthy(A)
MCI(B)
AD(C)
P
Post Hoc
71.3 6 5.84 52.9% 28.5 6 1.26 9.7 6 6.17 0.0 0.0
71.1 6 5.56 76.9% 25.5 6 2.82 8.3 6 4.46 0.5 1.75 6 0.979
73.9 6 7.87 55.9% 19.3 6 4.49 8.0 6 4.99 0.89 6 0.370 5.25 6 2.569
0.210 0.299 0.000 0.404 0.000 0.000
A¼B¼C X2 A>B>C A¼B¼C C>B>A C>B>A
COGNITIVE TRAJECTORIES ASSOCIATED WITH BETA-AMYLOID DEPOSITION IN THE NONDEMENTED OLDEST-OLD
Beth Snitz1, Lisa Weissfeld1, Oscar Lopez1, Lewis Kuller1, Judith Saxton1, Dilrukshika Singhabahu1, William Klunk1, Julie Price1, Chester Mathis1, Ann Cohen1, Steven DeKosky2, 1University of Pittsburgh, Pittsburgh, Pennsylvania, United States; 2University of Virginia School of Medicine, Charlottesville, Virginia, United States. Background: A significant number of non-demented older adults show Alzheimer Disease-like beta-amyloid (Ab) plaques and neurofibrillary tangles at autopsy. This proportion increases with age, provoking questions about the clinical significance of Alzheimer pathology in an advanced age group. Here we examined whether a high prevalence (55%) of Ab deposition, as measured in vivo by Pittsburgh Compound B (PiB)-PET imaging in an oldest-old cohort is associated with cognitive decline 7-9 years before the scan, even in individuals remaining dementia-free into their 9th and 10th decades. Methods: 194 older adults (85.5 6 2.8 (SD) years, range 82 - 95 years) who completed and remained dementia-free at the conclusion of the Ginkgo Evaluation of Memory Study (GEMS) were recruited for a subsequent neuroimaging sub-study. PiB retention was measured using the standardized uptake value ratio (SUVr) summed over 50-70 minutes post-injection using cerebellum as reference region. A global cortical cutoff of 1.57 SUVr was used to define Ab-negative and Ab-positive PiB status. We examined the relationship between PiB status determined in 2009 and cognitive performance on an extensive neuropsychological test battery completed at entry to GEMS 7-9 years prior to neuroimaging. We also longitudinally examined cognition over annual GEMS evaluations using linear mixed models. Results: At GEMS baseline (entered the study between 2000-2002), participants who were Ab-positive in 2009 (n ¼ 107; 55.2%) had lower performance on the Stroop test (P <0.01), Raven’s Progressive Matrices (P ¼ 0.05) with trend level difference for Block Design (P ¼ 0.07), adjusting for age, education, sex and race. Longitudinal analyses showed significant slope differences for immediate and delayed recall of the Rey-Osterrieth figure, semantic fluency, and Trail Making Test parts A & B, indicating greater performance decline for Ab-positive relative to Ab-negative participants (p’s<0.05). Conclusions: Highly prevalent Ab deposition in oldest-older adults is associated with cognitive decline in visual memory, semantic fluency and psychomotor speed over 7-9 years prior to imaging. Mean differences in non-memory domains, primarily executive functions, between
Table 2 Mean FA and MD results in each group
FA Lt.HB Rt.HB Lt.PC Rt.PC MD Lt.HB Rt.HB Lt.PC Rt.PC
Normal (a)
MCI(b)
AD(c)
P value post-hoc
0.143 6 0.0170 0.150 6 0.0165 0.243 6 0.0297 0.235 6 0.0263
0.097 6 0.0158 0.095 6 0.0120 0.203 6 0.0311 0.197 6 0.0263
0.084 6 0.0112 0.090 6 0.0101 0.188 6 0.0293 0.178 6 0.0279
0.000 0.000 0.000 0.000
a>b ¼ c a>b ¼ c a>b ¼ c a>b ¼ c
0.843 6 0.0712 0.828 6 0.0714 0.716 6 0.0633 0.700 6 0.0751
0.962 6 0.0584 1.024 6 0.0926 0.796 6 0.0939 0.835 6 0.0880
1.164 6 0.2126 1.108 6 0.1536 0.795 6 0.0760 0.776 6 0.0610
0.000 0.000 0.000 0.000
c>b>a b ¼ c>a b ¼ c>a b ¼ c>a
Figure. Mean performance on semantic fluency (+/- S.E.) over a span of 7-9 (mean 7.6) years up to the time of neuroimaging, showing greater decline in the Ab-positive (n ¼ 107) compared to Ab-negative group (n ¼ 87).