- Email: [email protected]
Cerebral blood flow measured by arterial spin labeling magnetic resonance imaging: Regional reductions in early stages of Alzheimer's disease and comparisons with brain volume loss
Poster Presentations: P3
P3-101
CEREBRAL BLOOD FLOW MEASURED BY ARTERIAL SPIN LABELING MAGNETIC RESONANCE IMAGING: REGIONAL REDUCTIONS IN EARLY STAGES OF ALZHEIMER’S DISEASE AND COMPARISONS WITH BRAIN VOLUME LOSS
Niklas Mattsson1, Duygu Tosun2, Philip Insel2, Norbert Schuff3, Clifford Jack4, Michael Weiner5, Adni Adni6, 1UCSF, San Francisco, California, United States and University of Gothenburg, Sweden; 2UCSF, San Francisco, California, United States; 3Center for Imaging of Neurodegenerative Diseases, San Francisco, California, United States; 4 Mayo Clinic, Rochester, Minnesota, United States; 5Center for Imaging of Neurodegenerative Diseases; VA Medical Center and UCSF, San Francisco, California, United States; 6ADNI, ANBDI, United States. Contact e-mail: [email protected] Background: Arterial spin labeling (ASL) magnetic resonance imaging (MRI) is a non-invasive method to measure cerebral blood flow (CBF). A few studies have used this in Alzheimer’s disease (AD), showing reduced perfusion in some regions, including precuneus and inferior parietal cortex. We used data from the Alzheimer’s Disease Neuroimaging Initative (ADNI) to determine the extent to which the pattern of regional CBF changes in AD diverges from the pattern of regional volumetric changes and also whether this varies from normal controls, to mild cognitive impairment (MCI) to AD dementia. Methods: Using 21 AD dementia, 40 late (L) MCI, 65 early MCI (EMCI), and 50 controls (NL), ASL images were processed to quantify CBF. FreeSurfer was used to compute volumes and CBF within anatomical Regions of Interest (ROIs). We first tested 14 pre-determined ROI (left and right posterior cingulate, precuneus, inferior parietal, entorhinal, hippocampus, and inferior and middle temporal cortex), and subsequently exploratory all 82 available ROI. AD, LMCI and EMCI were compared separately to NL, using linear regression. Results: Compared to CN, AD patients had significantly reduced CBF in 11/14 pre-specified ROI, including (ordered by effect size, d) left inferior parietal (d¼0.54), left inferior temporal (d¼0.44) and left middle temporal (d¼0.43) (corresponding structure d¼0.31, d¼0.62, d¼0.54). LMCI patients had reduced CBF in left inferior temporal cortex (d¼0.22; structure d¼0.22) and EMCI in left precuneus (d¼0.19; structure d¼0.10). In the exploratory analysis, AD patients had widespread CBF loss, particularly in the left hemisphere. In some areas these changes differed significantly from structural changes (including left cuneus, d CBF ¼0.36 [reduction], d structure ¼0.26 [increase], p difference ¼0.001). Smaller alterations were seen in LMCI and EMCI, but CBF changes still differed significantly from structural changes in some areas (in LMCI again including left cuneus, d CBF ¼0.17 [reduction], d structure
P589
¼0.16 [increase], p difference ¼0.015). CBF effect sizes were generally greater than structural in EMCI, while structural got more dominating in later stages (Figure). Conclusions: The findings indicate that CBF alterations carry complementary information to structural alterations in early AD, and support the view that measuring CBF with ASL MRI may provide information similar to that obtained with FDG PET. A direct comparison with FDG PET is underway.
P3-102
IS THE SEVERITY OF DILATED VIRCHOW-ROBIN SPACES ASSOCIATED WITH COGNITIVE FUNCTION?
Eun Hye Jeong1, Yong Joo Lee2, Jae-Hong Lee2, 1Asan Medical Center, University of Ulsan College of Medicine/Bundang Jesaeng General Hospital, Seoul/Seongnam, South Korea; 2Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. Contact e-mail: [email protected] Background: Virchow-Robin spaces (VRS) are perivascular spaces surrounding the perforating cerebral arteries or arterioles. The detection of dilated VRS (dVRS) is not uncommon in the normal brain and dVRS have been regarded as benign variants. However, there are accumulating evidences that dVRS are associated with MRI markers of small vessel disease and cognitive decline. We investigated whether the severity of dVRS would be associated with cognitive function by comparing the subjects with subjective memory impairment (SMI), mild cognitive impairment (MCI), and dementia. Also, we examined whether there were differences in the degree of correlation between dVRS and MRI markers of small vessel disease among three groups. Methods: In this retrospective study, a total of 225 patients were included: those with SMI (n ¼ 65), MCI (n ¼ 100), and dementia (n ¼ 60).We rated the severity of dVRS according to a three-level arbitrary scale in the slice containing the greatest number of dVRS in BG (dVRS-BG) and CS (dVRS-CS) separately. We also assessed baseline characteristics including vascular risk factors and MRI markers of small vessel disease such as white matter hyperintensities (WMH), lacunar infarcts and microbleeds. Results: A cumulative logit model revealed that the severity of cognitive dysfunction was associated with age, hypertension, diabetes mellitus, the severity of dVRS-BG, the severity of WMH and the presence of lacunar infarcts and microbleeds in univariate analysis. However, after adjusting for other confounding variables, the severity of dVRS-BG was not a significant discriminating factor among patients with SMI, MCI and dementia. Spearman’s correlation analysis showed a trend that the correlation between the severity of dVRS-BG and the severity of WMH became more prominent in patients with dementia than in those with MCI or SMI, and the same is true of the severity of dVRS-BG and the number of lacunar infarcts. Conclusions: The severity of dVRS was associated with cognitive dysfunction, which seemed to be confounded by other well-known risk factors. The correlation between dVRS-BG and small vessel disease markers was more significant in patients with MCI and dementia. These results suggest that dVRS may be considered another marker of small vessel disease and implicated in cognitive impairment. P3-103
RELATIONSHIP BETWEEN ANATOMY AND FUNCTIONAL CONNECTIVITY IN DEFAULT MODE NETWORK IN NORMAL AGING AND MILD ALZHEIMER’S DISEASE
Thaıs Hayata1, Felipe Bergo1, Brunno Campos2, Alexandre Franco1, Benito Damasceno3, Fernando Cendes1, Marcio Balthazar4, 1University of Campinas, Campinas, Brazil; 2Unicamp, Campinas, Brazil; 3Unicamp, Campinas, Brazil; 4Unicamp, Campinas, Brazil. Contact e-mail: thais. [email protected]
Figure. Differences in effect size between CBF and structure in EMCI versus NL (A), LMCI versus NL (B) and AD versus NL (C). Positive (red) means larger effect size for CBF.
Background: Alterations in default mode network (DMN) functional connectivity have been increasingly recognized in Alzheimer’s disease (AD). This functional connectivity network comprises a characteristic set of brain regions which are among the earliest to show abnormal amyloid deposition (a key pathological feature of AD), specially the posterior cingulate cortex
P3-101
CEREBRAL BLOOD FLOW MEASURED BY ARTERIAL SPIN LABELING MAGNETIC RESONANCE IMAGING: REGIONAL REDUCTIONS IN EARLY STAGES OF ALZHEIMER’S DISEASE AND COMPARISONS WITH BRAIN VOLUME LOSS
Niklas Mattsson1, Duygu Tosun2, Philip Insel2, Norbert Schuff3, Clifford Jack4, Michael Weiner5, Adni Adni6, 1UCSF, San Francisco, California, United States and University of Gothenburg, Sweden; 2UCSF, San Francisco, California, United States; 3Center for Imaging of Neurodegenerative Diseases, San Francisco, California, United States; 4 Mayo Clinic, Rochester, Minnesota, United States; 5Center for Imaging of Neurodegenerative Diseases; VA Medical Center and UCSF, San Francisco, California, United States; 6ADNI, ANBDI, United States. Contact e-mail: [email protected] Background: Arterial spin labeling (ASL) magnetic resonance imaging (MRI) is a non-invasive method to measure cerebral blood flow (CBF). A few studies have used this in Alzheimer’s disease (AD), showing reduced perfusion in some regions, including precuneus and inferior parietal cortex. We used data from the Alzheimer’s Disease Neuroimaging Initative (ADNI) to determine the extent to which the pattern of regional CBF changes in AD diverges from the pattern of regional volumetric changes and also whether this varies from normal controls, to mild cognitive impairment (MCI) to AD dementia. Methods: Using 21 AD dementia, 40 late (L) MCI, 65 early MCI (EMCI), and 50 controls (NL), ASL images were processed to quantify CBF. FreeSurfer was used to compute volumes and CBF within anatomical Regions of Interest (ROIs). We first tested 14 pre-determined ROI (left and right posterior cingulate, precuneus, inferior parietal, entorhinal, hippocampus, and inferior and middle temporal cortex), and subsequently exploratory all 82 available ROI. AD, LMCI and EMCI were compared separately to NL, using linear regression. Results: Compared to CN, AD patients had significantly reduced CBF in 11/14 pre-specified ROI, including (ordered by effect size, d) left inferior parietal (d¼0.54), left inferior temporal (d¼0.44) and left middle temporal (d¼0.43) (corresponding structure d¼0.31, d¼0.62, d¼0.54). LMCI patients had reduced CBF in left inferior temporal cortex (d¼0.22; structure d¼0.22) and EMCI in left precuneus (d¼0.19; structure d¼0.10). In the exploratory analysis, AD patients had widespread CBF loss, particularly in the left hemisphere. In some areas these changes differed significantly from structural changes (including left cuneus, d CBF ¼0.36 [reduction], d structure ¼0.26 [increase], p difference ¼0.001). Smaller alterations were seen in LMCI and EMCI, but CBF changes still differed significantly from structural changes in some areas (in LMCI again including left cuneus, d CBF ¼0.17 [reduction], d structure
P589
¼0.16 [increase], p difference ¼0.015). CBF effect sizes were generally greater than structural in EMCI, while structural got more dominating in later stages (Figure). Conclusions: The findings indicate that CBF alterations carry complementary information to structural alterations in early AD, and support the view that measuring CBF with ASL MRI may provide information similar to that obtained with FDG PET. A direct comparison with FDG PET is underway.
P3-102
IS THE SEVERITY OF DILATED VIRCHOW-ROBIN SPACES ASSOCIATED WITH COGNITIVE FUNCTION?
Eun Hye Jeong1, Yong Joo Lee2, Jae-Hong Lee2, 1Asan Medical Center, University of Ulsan College of Medicine/Bundang Jesaeng General Hospital, Seoul/Seongnam, South Korea; 2Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. Contact e-mail: [email protected] Background: Virchow-Robin spaces (VRS) are perivascular spaces surrounding the perforating cerebral arteries or arterioles. The detection of dilated VRS (dVRS) is not uncommon in the normal brain and dVRS have been regarded as benign variants. However, there are accumulating evidences that dVRS are associated with MRI markers of small vessel disease and cognitive decline. We investigated whether the severity of dVRS would be associated with cognitive function by comparing the subjects with subjective memory impairment (SMI), mild cognitive impairment (MCI), and dementia. Also, we examined whether there were differences in the degree of correlation between dVRS and MRI markers of small vessel disease among three groups. Methods: In this retrospective study, a total of 225 patients were included: those with SMI (n ¼ 65), MCI (n ¼ 100), and dementia (n ¼ 60).We rated the severity of dVRS according to a three-level arbitrary scale in the slice containing the greatest number of dVRS in BG (dVRS-BG) and CS (dVRS-CS) separately. We also assessed baseline characteristics including vascular risk factors and MRI markers of small vessel disease such as white matter hyperintensities (WMH), lacunar infarcts and microbleeds. Results: A cumulative logit model revealed that the severity of cognitive dysfunction was associated with age, hypertension, diabetes mellitus, the severity of dVRS-BG, the severity of WMH and the presence of lacunar infarcts and microbleeds in univariate analysis. However, after adjusting for other confounding variables, the severity of dVRS-BG was not a significant discriminating factor among patients with SMI, MCI and dementia. Spearman’s correlation analysis showed a trend that the correlation between the severity of dVRS-BG and the severity of WMH became more prominent in patients with dementia than in those with MCI or SMI, and the same is true of the severity of dVRS-BG and the number of lacunar infarcts. Conclusions: The severity of dVRS was associated with cognitive dysfunction, which seemed to be confounded by other well-known risk factors. The correlation between dVRS-BG and small vessel disease markers was more significant in patients with MCI and dementia. These results suggest that dVRS may be considered another marker of small vessel disease and implicated in cognitive impairment. P3-103
RELATIONSHIP BETWEEN ANATOMY AND FUNCTIONAL CONNECTIVITY IN DEFAULT MODE NETWORK IN NORMAL AGING AND MILD ALZHEIMER’S DISEASE
Thaıs Hayata1, Felipe Bergo1, Brunno Campos2, Alexandre Franco1, Benito Damasceno3, Fernando Cendes1, Marcio Balthazar4, 1University of Campinas, Campinas, Brazil; 2Unicamp, Campinas, Brazil; 3Unicamp, Campinas, Brazil; 4Unicamp, Campinas, Brazil. Contact e-mail: thais. [email protected]
Figure. Differences in effect size between CBF and structure in EMCI versus NL (A), LMCI versus NL (B) and AD versus NL (C). Positive (red) means larger effect size for CBF.
Background: Alterations in default mode network (DMN) functional connectivity have been increasingly recognized in Alzheimer’s disease (AD). This functional connectivity network comprises a characteristic set of brain regions which are among the earliest to show abnormal amyloid deposition (a key pathological feature of AD), specially the posterior cingulate cortex