- Email: [email protected]
Increased cerebral blood flow in cognitively normal older adults with amyloid
P582
Poster Presentations: P3
of other regions were particularly located in the temporo-parietal and PCC/ precuneus regions (out-going); while amyloid hubs that are being influenced by a high amount of regions across the brain were located in the lateral and medial frontal regions (in-coming) (see an example of an individual subject in Fig. 1,-B and 1-C). Conclusions: Although these findings are promising to understand the dynamical binding of PIB and network activity of the amyloid pathology in preclinical stages of AD, further work is needed in order to clarify the specific meaning of the temporo-spatial relationships between amyloid hubs.
tiple comparisons. Results: DMT2 was associated with greater decrease in FA among voxels covering 2cc of the WM. WM tracts most heavily implicated included the corpus callosum (CC) (3.9cc) and the cortico-spinal tract (2.2cc). Greater age was independently associated with greater decrease in FA in WM pathways covering 140cc of the WM, with CC (41.7cc) and uncinate fasciculus (3.5cc) heavily represented. Conclusions: This is one of very few studies of longitudinal DTI change in the elderly. DMT2 and age are independently associated with accelerated WM degeneration in areas whose integrity is known to be reduced in mild cognitive impairment and dementia. Future work should clarify the independent role of DMT2 in accelerating WM degeneration in the aging brain. P3-088
STAGING OF MICROSTRUCTURAL WHITE MATTER DAMAGE IN EARLY ALZHEIMER’S DISEASE
Lin Zhuang1, Perminder Sachdev1, Julian Trollor1, Simone Reppermund2, Nicole Kochan1, Henry Brodaty3, Wei Wen1, 1Centre for Healthy Brain Ageing, School of Psychiatry UNSW Medicine, Sydney, Australia, Randwick, Australia; 2Centre for Healthy Brain Ageing, School of Psychiatry UNSW Medicine, Sydney, Australia, Sydney NSW, Australia; 3 Dementia Collaborative Research Centre, Sydney, NSW, California, Australia. Contact e-mail: [email protected]
Figure 1.
P3-087
TYPE 2 DIABETES IS ASSOCIATED WITH ACCELERATED LONGITUDINAL WHITE MATTER DEGENERATION IN THE ELDERLY
Pauline Maillard1, Owen Carmichael2, Dan Mungas3, Bruce Reed4, Charles DeCarli5, 1UC Davis, Davis, California, United States; 2University of California, Davis, Davis, California, United States; 3UC Davis Alzheimer’s Disease Research Center, Sacramento, California, United States; 4UC Davis, Martinez, California, United States; 5University of California at Davis, Sacramento, California, United States. Contact e-mail: [email protected] Background: Recent research suggests that diabetes mellitus type II (DMT2) in the elderly may double risk for dementia and may be associated with subtle white matter injury on cerebral diffusion tensor imaging (DTI) scans. However, the time course of white matter change associated with DMT2 is not well understood. We used longitudinal DTI to determine whether DMT2 is associated with accelerated microstructural WM degeneration over time in a sample of 162 individuals from the University of California, Davis Alzheimer’s Disease Center. Methods: A set of 162 participants aged 74.7 6 7.6 years spanning normal cognition, mild cognitive impairment, and dementia (including 50 with DMT2) received a comprehensive clinical evaluation and brain DTI on two dates (mean interval (Dt): 3.6 years). DMT2 was not associated with white matter hyperintensity volume or summary measures of cognitive performance (p-values>0.1). Baseline and follow-up FA maps were calculated for each individual from DTI. Corresponding baseline and follow-up FA maps were aligned using linear and non-linear transformations, and subtracted to provide maps of individual FA change (DFA). Baseline FA maps were warped to a common DTI template, and associated transformation parameters were applied to DFA maps. This enabled voxel-based linear regressions with DMT2 and age as predictors of interest, DFA/Dt as the outcome of interest, and clinical diagnosis (normal, MCI, or dementia), baseline FA, education and gender as covariates. T maps for the effects of DMT2 and age were corrected for mul-
Background: Alzheimer’s disease (AD) is generally considered to be a disease of gray matter (GM). Cerebral GM loss develops in a stereotypical pattern, beginning in the medial temporal lobe before spreading to the association cortices, and then the rest of the brain. However, studies investigating the evolution of white matter (WM) changes in AD are still lacking. In this study, we used diffusion tensor imaging (DTI) fibre tractography to evaluate the microstructural integrity of limbic WM tracts: the fornix, the parahippocampal cingulum, the uncinate fasciculus, and two major cortico-cortical association fibre tracts: the inferior longitudinal fasciculus and superior longitudinal fasciculus, and one projection fibre: the corticospinal tract, at different stages of amnestic mild cognitive impairment (aMCI), a preclinical stage of AD. We aimed to identify the staging of WM tract degeneration in early AD. Methods: 155 cognitively normal subjects (CN), 39 early aMCI and 27 late aMCI subjects were involved in the current study. All participants were recruited from the Sydney Memory and Ageing Study (MAS), a population-based longitudinal study of non-demented older people aged 70-90 in the Eastern Suburbs of Sydney, Australia. 32 directional DTI scans were acquired on a Philips 3T MRI scanner. Probabilistic diffusion tensor tractography was performed to reconstruct the fibre tracts in vivo. Fractional anisotropy (FA), axial diffusivity (DA), and radial diffusivity (RD) were then extracted along the reconstructed fibre tracts. Automated measurement of hippocampal volume was performed using the FIRST program. Results: Early aMCI had significantly higher RD and AxD values of the fornix than that of controls. No significant group difference in the hippocampal volume was found between early aMCI and controls. Late aMCI showed lower FA values in the left fornix, while RD and AxD values were significantly greater in the fornix, uncinate fasciculus, and parahippocampal cingulum, when compared with controls. In addition, hippocampal volumes were significantly smaller in late aMCI than in controls. Conclusions: These results suggest that the use of microstructural WM measures by DTI can provide a more sensitive and earlier detection of brain structural changes in early AD than conventional GM volumetric measures. P3-089
INCREASED CEREBRAL BLOOD FLOW IN COGNITIVELY NORMAL OLDER ADULTS WITH AMYLOID
Aaron Schultz1, Donald McLaren2, Jasmeer Chhatwal1, Karleyton Evans1, Keith Johnson3, Reisa Sperling4, 1Massachusetts General Hospital, Charlestown, Massachusetts, United States; 2Massachusetts General Hospital, Harvard Medical School, Bedford VA Medical Center, Charlestown, Massachusetts, United States; 3Massachusetts General Hospital, Boston, Massachusetts, United States; 4Brigham and Women’s Hospital, Boston, Massachusetts, United States. Contact e-mail: mclaren@ nmr.mgh.harvard.edu
Poster Presentations: P3
Figure 1.
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CBF using pASL. Methods: 84 CN participants (CDR¼0) in the Harvard Aging Brain Study had a pASL scan that passed quality control, a PiBPET scan, and APOE genotyping. pASL images were motion corrected and entered into the UPenn ASL Toolbox to compute CBF maps. The CBF maps were then normalized to MNI space and additionally smoothed (Fig 1). Mean cortical (mc) DVR PiB values were obtained from the PiBPET scans. Regional CBF from fcMRI networks derived using a factor analysis were analyzed with general linear models with PiB status (mcPiB+ defined as mcPiB>1.4), APOE genotype (ε 3/ε 3 vs ε 3/ε 4), age and their interactions as predictors. Forward and backward model selection methods were used to select the final model for each region. Results: Amyloid positive CN had significantly higher CBF in the DMN (p¼0.0315, Fig 2,), lateral visual network (p¼0.045), medial visual network (p¼0.011), and dorsal attention network (p¼0.002). Significant decreases with age were found in the both visual networks (p<0.001) and the dorsal attention network (p¼0.002). Interestingly, we found that ε 4 carriers had greater age-related decreases in the DMN (p¼0.008, Fig 3) and association network (p¼0.007). Conclusions: Consistent with reports from longitudinal studies, we found that amyloid burden is associated with increased cerebral blood flow cross-sectionally in our sample. The amyloid-related increases might represent the brains response to initial stages of neuronal damage. Furthermore, the increased age-related decline in ε4 carriers extends previous work comparing young and old ε 4 carriers. These results support the potential of CBF as a biomarker to detect early functional change in the DMN, specifically related to amyloid deposition. P3-090
STRATEGIC BRAIN AREAS FOR COGNITIVE DECLINE IN SUBCORTICAL VASCULAR COGNITIVE IMPAIRMENT: A DIFFUSIONTENSOR IMAGING AND PET STUDY
Min-Jeong Kim1, Kyoung-Min Lee2, Young-Don Son3, Hyeon-Ae Jeon4, Sejin Yoo5, Young-Bo Kim3, Zang-Hee Cho3, 1Department of Neurology, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, South Korea; 2Seoul National University Hospital, Seoul, South Korea; 3Neuroscience Research Institute, Gachon Medical School, Incheon, South Korea; 4Department of Neuropsychology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; 5Interdisciplinary Program in Cognitive Science, Seoul National University, Seoul, South Korea. Contact e-mail: [email protected] Figure 2.
Figure 3.
Background: Substantial work in preclinical Alzheimer’s disease (AD) has been focused on understanding the relationships between amyloid, cognition, atrophy and neural activity; however, there have been limited investigations of cerebral blood flow (CBF) to date. Recently, CBF, as measured with pulsed arterial spinning labeling (pASL), has been shown to be a reliable marker of blood flow in cognitively normal older adults (CN) and may have potential as an early AD biomarker. The objective of the present study is to a ssess the effect of amyloid burden, APOE ε4 carrier status and age on
Background: Subcortical vascular cognitive impairment is known to be caused by subcortical ischemic changes that are presented as white matter hyperintensities, lacunar infarcts, and microbleeds on MRI. However, the specific brain area which is critical for clinical cognitive decline has not been revealed yet in subcortical vascular cognitive impairment. Here we aimed to investigate the difference of affected brain areas between those with and without clinical cognitive impairment in patients having subcortical ischemic changes on conventional MRI by using diffusion tensor imaging (DTI) and [18F]-Fluorodeoxygucose (FDG)-PET. Methods: 17 patients with both of subcortical vascular ischemic changes and clinical cognitive impairment, 12 patients with subcortical vascular changes but without cognitive impairment, and 10 normal healthy subjects underwent DTI and FDG-PET. Frational anisotropy (FA) of whole brain areas was compared among the groups by using tract-based spatial statistics. Cortical glucose metabolism was also compared among the groups by using 3-dimensional MRI-PET co-registration and spatial normalization. The statistical maps for significantly different areas were constructed. Results: Those with both subcortical ischemia and cognitive impairment showed significantly decreased FA value in the periventricular white matters including the superior longitudinal fasciculus, the inferior longitudinal fasciculus, and the corpus callosum compared to those without cognitive impairment. Those with cognitive impairment also showed significant cortical hypometabolism in the bilateral dorsal and ventral inferior frontal, the left dorsal inferior temporal areas compared to those without cognitive impairment. Comparison between normal control subjects and those with subcortical ischemia showed significant difference in more extensive and non-specific areas: white matter tracts including both
Poster Presentations: P3
of other regions were particularly located in the temporo-parietal and PCC/ precuneus regions (out-going); while amyloid hubs that are being influenced by a high amount of regions across the brain were located in the lateral and medial frontal regions (in-coming) (see an example of an individual subject in Fig. 1,-B and 1-C). Conclusions: Although these findings are promising to understand the dynamical binding of PIB and network activity of the amyloid pathology in preclinical stages of AD, further work is needed in order to clarify the specific meaning of the temporo-spatial relationships between amyloid hubs.
tiple comparisons. Results: DMT2 was associated with greater decrease in FA among voxels covering 2cc of the WM. WM tracts most heavily implicated included the corpus callosum (CC) (3.9cc) and the cortico-spinal tract (2.2cc). Greater age was independently associated with greater decrease in FA in WM pathways covering 140cc of the WM, with CC (41.7cc) and uncinate fasciculus (3.5cc) heavily represented. Conclusions: This is one of very few studies of longitudinal DTI change in the elderly. DMT2 and age are independently associated with accelerated WM degeneration in areas whose integrity is known to be reduced in mild cognitive impairment and dementia. Future work should clarify the independent role of DMT2 in accelerating WM degeneration in the aging brain. P3-088
STAGING OF MICROSTRUCTURAL WHITE MATTER DAMAGE IN EARLY ALZHEIMER’S DISEASE
Lin Zhuang1, Perminder Sachdev1, Julian Trollor1, Simone Reppermund2, Nicole Kochan1, Henry Brodaty3, Wei Wen1, 1Centre for Healthy Brain Ageing, School of Psychiatry UNSW Medicine, Sydney, Australia, Randwick, Australia; 2Centre for Healthy Brain Ageing, School of Psychiatry UNSW Medicine, Sydney, Australia, Sydney NSW, Australia; 3 Dementia Collaborative Research Centre, Sydney, NSW, California, Australia. Contact e-mail: [email protected]
Figure 1.
P3-087
TYPE 2 DIABETES IS ASSOCIATED WITH ACCELERATED LONGITUDINAL WHITE MATTER DEGENERATION IN THE ELDERLY
Pauline Maillard1, Owen Carmichael2, Dan Mungas3, Bruce Reed4, Charles DeCarli5, 1UC Davis, Davis, California, United States; 2University of California, Davis, Davis, California, United States; 3UC Davis Alzheimer’s Disease Research Center, Sacramento, California, United States; 4UC Davis, Martinez, California, United States; 5University of California at Davis, Sacramento, California, United States. Contact e-mail: [email protected] Background: Recent research suggests that diabetes mellitus type II (DMT2) in the elderly may double risk for dementia and may be associated with subtle white matter injury on cerebral diffusion tensor imaging (DTI) scans. However, the time course of white matter change associated with DMT2 is not well understood. We used longitudinal DTI to determine whether DMT2 is associated with accelerated microstructural WM degeneration over time in a sample of 162 individuals from the University of California, Davis Alzheimer’s Disease Center. Methods: A set of 162 participants aged 74.7 6 7.6 years spanning normal cognition, mild cognitive impairment, and dementia (including 50 with DMT2) received a comprehensive clinical evaluation and brain DTI on two dates (mean interval (Dt): 3.6 years). DMT2 was not associated with white matter hyperintensity volume or summary measures of cognitive performance (p-values>0.1). Baseline and follow-up FA maps were calculated for each individual from DTI. Corresponding baseline and follow-up FA maps were aligned using linear and non-linear transformations, and subtracted to provide maps of individual FA change (DFA). Baseline FA maps were warped to a common DTI template, and associated transformation parameters were applied to DFA maps. This enabled voxel-based linear regressions with DMT2 and age as predictors of interest, DFA/Dt as the outcome of interest, and clinical diagnosis (normal, MCI, or dementia), baseline FA, education and gender as covariates. T maps for the effects of DMT2 and age were corrected for mul-
Background: Alzheimer’s disease (AD) is generally considered to be a disease of gray matter (GM). Cerebral GM loss develops in a stereotypical pattern, beginning in the medial temporal lobe before spreading to the association cortices, and then the rest of the brain. However, studies investigating the evolution of white matter (WM) changes in AD are still lacking. In this study, we used diffusion tensor imaging (DTI) fibre tractography to evaluate the microstructural integrity of limbic WM tracts: the fornix, the parahippocampal cingulum, the uncinate fasciculus, and two major cortico-cortical association fibre tracts: the inferior longitudinal fasciculus and superior longitudinal fasciculus, and one projection fibre: the corticospinal tract, at different stages of amnestic mild cognitive impairment (aMCI), a preclinical stage of AD. We aimed to identify the staging of WM tract degeneration in early AD. Methods: 155 cognitively normal subjects (CN), 39 early aMCI and 27 late aMCI subjects were involved in the current study. All participants were recruited from the Sydney Memory and Ageing Study (MAS), a population-based longitudinal study of non-demented older people aged 70-90 in the Eastern Suburbs of Sydney, Australia. 32 directional DTI scans were acquired on a Philips 3T MRI scanner. Probabilistic diffusion tensor tractography was performed to reconstruct the fibre tracts in vivo. Fractional anisotropy (FA), axial diffusivity (DA), and radial diffusivity (RD) were then extracted along the reconstructed fibre tracts. Automated measurement of hippocampal volume was performed using the FIRST program. Results: Early aMCI had significantly higher RD and AxD values of the fornix than that of controls. No significant group difference in the hippocampal volume was found between early aMCI and controls. Late aMCI showed lower FA values in the left fornix, while RD and AxD values were significantly greater in the fornix, uncinate fasciculus, and parahippocampal cingulum, when compared with controls. In addition, hippocampal volumes were significantly smaller in late aMCI than in controls. Conclusions: These results suggest that the use of microstructural WM measures by DTI can provide a more sensitive and earlier detection of brain structural changes in early AD than conventional GM volumetric measures. P3-089
INCREASED CEREBRAL BLOOD FLOW IN COGNITIVELY NORMAL OLDER ADULTS WITH AMYLOID
Aaron Schultz1, Donald McLaren2, Jasmeer Chhatwal1, Karleyton Evans1, Keith Johnson3, Reisa Sperling4, 1Massachusetts General Hospital, Charlestown, Massachusetts, United States; 2Massachusetts General Hospital, Harvard Medical School, Bedford VA Medical Center, Charlestown, Massachusetts, United States; 3Massachusetts General Hospital, Boston, Massachusetts, United States; 4Brigham and Women’s Hospital, Boston, Massachusetts, United States. Contact e-mail: mclaren@ nmr.mgh.harvard.edu
Poster Presentations: P3
Figure 1.
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CBF using pASL. Methods: 84 CN participants (CDR¼0) in the Harvard Aging Brain Study had a pASL scan that passed quality control, a PiBPET scan, and APOE genotyping. pASL images were motion corrected and entered into the UPenn ASL Toolbox to compute CBF maps. The CBF maps were then normalized to MNI space and additionally smoothed (Fig 1). Mean cortical (mc) DVR PiB values were obtained from the PiBPET scans. Regional CBF from fcMRI networks derived using a factor analysis were analyzed with general linear models with PiB status (mcPiB+ defined as mcPiB>1.4), APOE genotype (ε 3/ε 3 vs ε 3/ε 4), age and their interactions as predictors. Forward and backward model selection methods were used to select the final model for each region. Results: Amyloid positive CN had significantly higher CBF in the DMN (p¼0.0315, Fig 2,), lateral visual network (p¼0.045), medial visual network (p¼0.011), and dorsal attention network (p¼0.002). Significant decreases with age were found in the both visual networks (p<0.001) and the dorsal attention network (p¼0.002). Interestingly, we found that ε 4 carriers had greater age-related decreases in the DMN (p¼0.008, Fig 3) and association network (p¼0.007). Conclusions: Consistent with reports from longitudinal studies, we found that amyloid burden is associated with increased cerebral blood flow cross-sectionally in our sample. The amyloid-related increases might represent the brains response to initial stages of neuronal damage. Furthermore, the increased age-related decline in ε4 carriers extends previous work comparing young and old ε 4 carriers. These results support the potential of CBF as a biomarker to detect early functional change in the DMN, specifically related to amyloid deposition. P3-090
STRATEGIC BRAIN AREAS FOR COGNITIVE DECLINE IN SUBCORTICAL VASCULAR COGNITIVE IMPAIRMENT: A DIFFUSIONTENSOR IMAGING AND PET STUDY
Min-Jeong Kim1, Kyoung-Min Lee2, Young-Don Son3, Hyeon-Ae Jeon4, Sejin Yoo5, Young-Bo Kim3, Zang-Hee Cho3, 1Department of Neurology, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, South Korea; 2Seoul National University Hospital, Seoul, South Korea; 3Neuroscience Research Institute, Gachon Medical School, Incheon, South Korea; 4Department of Neuropsychology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; 5Interdisciplinary Program in Cognitive Science, Seoul National University, Seoul, South Korea. Contact e-mail: [email protected] Figure 2.
Figure 3.
Background: Substantial work in preclinical Alzheimer’s disease (AD) has been focused on understanding the relationships between amyloid, cognition, atrophy and neural activity; however, there have been limited investigations of cerebral blood flow (CBF) to date. Recently, CBF, as measured with pulsed arterial spinning labeling (pASL), has been shown to be a reliable marker of blood flow in cognitively normal older adults (CN) and may have potential as an early AD biomarker. The objective of the present study is to a ssess the effect of amyloid burden, APOE ε4 carrier status and age on
Background: Subcortical vascular cognitive impairment is known to be caused by subcortical ischemic changes that are presented as white matter hyperintensities, lacunar infarcts, and microbleeds on MRI. However, the specific brain area which is critical for clinical cognitive decline has not been revealed yet in subcortical vascular cognitive impairment. Here we aimed to investigate the difference of affected brain areas between those with and without clinical cognitive impairment in patients having subcortical ischemic changes on conventional MRI by using diffusion tensor imaging (DTI) and [18F]-Fluorodeoxygucose (FDG)-PET. Methods: 17 patients with both of subcortical vascular ischemic changes and clinical cognitive impairment, 12 patients with subcortical vascular changes but without cognitive impairment, and 10 normal healthy subjects underwent DTI and FDG-PET. Frational anisotropy (FA) of whole brain areas was compared among the groups by using tract-based spatial statistics. Cortical glucose metabolism was also compared among the groups by using 3-dimensional MRI-PET co-registration and spatial normalization. The statistical maps for significantly different areas were constructed. Results: Those with both subcortical ischemia and cognitive impairment showed significantly decreased FA value in the periventricular white matters including the superior longitudinal fasciculus, the inferior longitudinal fasciculus, and the corpus callosum compared to those without cognitive impairment. Those with cognitive impairment also showed significant cortical hypometabolism in the bilateral dorsal and ventral inferior frontal, the left dorsal inferior temporal areas compared to those without cognitive impairment. Comparison between normal control subjects and those with subcortical ischemia showed significant difference in more extensive and non-specific areas: white matter tracts including both