- Email: [email protected]
DISTINCTIVE PATTERN OF CORTICAL THICKNESS AND WHITE MATTER INTEGRITY BETWEEN SPORADIC SVCI WITH AND WITHOUT NOTCH3 VARIANTS AND TYPICAL CADASIL
Poster Presentations: Sunday, July 16, 2017 P1-417
THE CLINICAL AND NEUROIMAGING CHARACTERISTICS OF POSTERIOR CORTICAL ATROPHY: A MULTIDISCIPLINARY APPROACH
Ji Sun Kim, Geum Bong Lee, Yun Jeong Hong, Kyung Won Park, Dong-A University College of Medicine, Busan, Republic of South Korea. Contact e-mail: [email protected] Background: Posterior cortical atrophy (PCA) is a rare progressive de-
mentia syndrome characterized by prominent impairment of visuospatial and high visual cortical sense. The main pathology findings of PCA are beta-amyloid plaques and neurofibrillary tangles, which are the same with the Alzheimer’s disease. The aim of this study is to investigate clinical and neuroimaging characteristics of PCA compared to early-onset Alzheimer’s dementia (EOAD) via multidisciplinary approaches. Methods: We retrospectively recruited patients diagnosed as PCA and early-onset Alzheimer’s disease (EOAD) matching age and sex from 2011 to 2016. The clinical symptoms and signs associated with parieto-occipital lobar function such as elements of Balint syndrome, Gerstmann syndrome, alexia, apraxia, and visuospatial dysfunction were evaluated. The cognitive functions were evaluated with comprehensive neuropsychological tests. Neuroimaging including MRI, SPECT or FDG-PET, and amyloid PET were performed to compare structural, functional and molecular neuroimaging findings including cortical atrophy, hypofunctional regions, and amyloid pathology on brain. We used Chi-square and Kruskal Wallis test for analysis, Mann-whitney U test for post hoc analysis using SPSS version 23. Results: Nine PCA cases and 11 EOAD cases were included. Clinically, the elements of Balint syndrome such as simultanagnosia, optic ataxia, oculomotor apraxia and the elements of Gerstmann syndrome such as left/right disorientation, dysgraphia and dyscalculia, as well as dressing apraxia, ideomotor apraxia, visual agnosia, spatial disorientation, and alexia were dominant in PCA group, satisfying clinical diagnostic criteria. On neuropsychological tests, digit span forward (p¼0.006) and Rey Figure copy test (p¼0.020) were more impaired in PCA than EOAD (p¼0.006). Verbal delayed recall was more impaired in EOAD compared with that in PCA (p¼0.031). Brain MRI showed higher of medial temporal lobe atrophy scores in EOAD (p¼0.014) although there was no difference on Generalized atrophy score (P¼0.540, p¼0.577) or Parietal atrophy score (p¼0.227). Functional imaging showed more parietooccipital hypofunction indicated in PCA (p¼0.008). However, amyloid PET showed equally positive in both groups. Conclusions: These findings suggest that the clinical features of PCA are well correlated with the prominent parieto-occipital hypoperfusions and relatively spared medial temporal lobe, while amyloid burden and deposition patterns did not show significant difference between PCA and EOAD. P1-418
DISTINCTIVE PATTERN OF CORTICAL THICKNESS AND WHITE MATTER INTEGRITY BETWEEN SPORADIC SVCI WITH AND WITHOUT NOTCH3 VARIANTS AND TYPICAL CADASIL
Ko Woon Kim1, Sang Won Seo1,2, 1Samsung Medical Center, Seoul, Republic of South Korea; 2Neuroscience Center, Samsung Medical Center, Seoul, Republic of South Korea. Contact e-mail: [email protected] Background: Although cerebral autosomal dominant arteriopathy with
subcortical infarcts and leukoencephalopathy (CADASIL) is thought to be a common form of hereditary subcortical vascular cognitive impairment (SVCI). In our previous study, a few sporadic SVCI pa-
P437
tients have NOTCH3 variants and there were no differences in clinical features between SVCI patients with and without NOTCH3 variants. However, there is lack of research on structure brain difference among SVCI with and without NOTCH3 variants, and typical CADASIL. The aim of our investigation is to compare cortical thickness and white matter integrity among 3 groups. Methods: SVCI patients with (n¼15) and without (n¼101) NOTCH3 variants patients who were clinically diagnosed and then genetically confirmed in our previous study were included in this study. Typical CADASIL patients (n¼11) who were clinically diagnosed and then genetically confirmed in our previous study were also included in this study. We compared white matter hyperintensities (WMH) frequency map, fractional anisotrophy (FA) and mean diffusivity (MD) map of diffusion tensor images (DTI) measure, and cortical thickness between three groups. Results: Spatial distribution of WMH showed that CADASIL group tended to have more WMH than either SVCI with or without NOTCH3 variants in the bilateral posterior temporal region. FA values in the juxtacortical white matter in the frontal and parietal lobes, the periventricular white matter, the temporal white matter and the anterior and posterior corpus callosum were significantly lower in typical CADASIL patients than in SVCI patients with or without NOTCH3 variants (w-score). MD values in the same regions were opposed to FA. Meanwhile, SVCI without NOTCH3 variants group showed decreased cortical thickness in the left inferior temporal, right anterior temporal, bilateral occipital, dorsolateral prefrontal, medial prefrontal cortex compared to typical CADASIL group. Conclusions: In this study, sporadic SVCI and CADASIL showed distinctive anatomic vulnerabilities of cortical and subcortical structures respectively, suggesting that sporadic SVCI and CADASIL possibly reflect different pathophysiologic mechanisms.
P1-419
PET-GUIDED MR SPECTROSCOPY REVEALS DISTINCT RELATIONS BETWEEN BRAIN METABOLITES, AMYLOID AND HYPOMETABOLISM IN ALZHEIMER’S DISEASE
Nasim Sheikh-Bahaei1, S. Ahmad Sajjadi2, Roido Manavaki1, Mary McLean3, Jonathan H. Gillard1, John T. O’Brien1, 1University of Cambridge, Cambridge, United Kingdom; 2University of California, Irvine, Irvine, CA, USA; 3Cancer Research UK, Cambridge, United Kingdom. Contact e-mail: [email protected] Background: There is limited understanding of the role of brain me-
tabolites in Alzheimer’s disease (AD) and their correlation with other pathological changes. In this study, we used PET-guided MR spectroscopy (MRS) to measure the level of brain metabolites in areas of amyloid (Ab) deposition and hypometabolism in AD. We hypothesized that the patterns of change in some of brain metabolites are correlated with the underlying pathology. Methods: Cases with diagnoses of early AD (n¼11), Mild Cognitive Impairment (MCI) (n¼10), and healthy control (HC)(n¼8) underwent 11 C- Pittsburg compound B-(PiB) and 18 F-fluorodeoxyglucose(FDG)-PET followed by 3T MRI and MRS. After co-registration of PET on T1W images, MRS voxels were placed on two areas each of maximum Ab deposition and minimum metabolism. Corresponding regions of interest (ROI) were selected in HC. The ratios of total N-acetyl (tNA) group, myoinositol (mI), Choline (Chol), and Glutamate plus Glutamine (Glx) over Creatine (Cr) were measured in each ROI and compared between groups. Results: Compared to representative normal regions, the mean of tNA/Cr was significantly lower in areas of hypometabolism (p-value <0.001) and high Ab deposition (p-value<0.0001). A regression
THE CLINICAL AND NEUROIMAGING CHARACTERISTICS OF POSTERIOR CORTICAL ATROPHY: A MULTIDISCIPLINARY APPROACH
Ji Sun Kim, Geum Bong Lee, Yun Jeong Hong, Kyung Won Park, Dong-A University College of Medicine, Busan, Republic of South Korea. Contact e-mail: [email protected] Background: Posterior cortical atrophy (PCA) is a rare progressive de-
mentia syndrome characterized by prominent impairment of visuospatial and high visual cortical sense. The main pathology findings of PCA are beta-amyloid plaques and neurofibrillary tangles, which are the same with the Alzheimer’s disease. The aim of this study is to investigate clinical and neuroimaging characteristics of PCA compared to early-onset Alzheimer’s dementia (EOAD) via multidisciplinary approaches. Methods: We retrospectively recruited patients diagnosed as PCA and early-onset Alzheimer’s disease (EOAD) matching age and sex from 2011 to 2016. The clinical symptoms and signs associated with parieto-occipital lobar function such as elements of Balint syndrome, Gerstmann syndrome, alexia, apraxia, and visuospatial dysfunction were evaluated. The cognitive functions were evaluated with comprehensive neuropsychological tests. Neuroimaging including MRI, SPECT or FDG-PET, and amyloid PET were performed to compare structural, functional and molecular neuroimaging findings including cortical atrophy, hypofunctional regions, and amyloid pathology on brain. We used Chi-square and Kruskal Wallis test for analysis, Mann-whitney U test for post hoc analysis using SPSS version 23. Results: Nine PCA cases and 11 EOAD cases were included. Clinically, the elements of Balint syndrome such as simultanagnosia, optic ataxia, oculomotor apraxia and the elements of Gerstmann syndrome such as left/right disorientation, dysgraphia and dyscalculia, as well as dressing apraxia, ideomotor apraxia, visual agnosia, spatial disorientation, and alexia were dominant in PCA group, satisfying clinical diagnostic criteria. On neuropsychological tests, digit span forward (p¼0.006) and Rey Figure copy test (p¼0.020) were more impaired in PCA than EOAD (p¼0.006). Verbal delayed recall was more impaired in EOAD compared with that in PCA (p¼0.031). Brain MRI showed higher of medial temporal lobe atrophy scores in EOAD (p¼0.014) although there was no difference on Generalized atrophy score (P¼0.540, p¼0.577) or Parietal atrophy score (p¼0.227). Functional imaging showed more parietooccipital hypofunction indicated in PCA (p¼0.008). However, amyloid PET showed equally positive in both groups. Conclusions: These findings suggest that the clinical features of PCA are well correlated with the prominent parieto-occipital hypoperfusions and relatively spared medial temporal lobe, while amyloid burden and deposition patterns did not show significant difference between PCA and EOAD. P1-418
DISTINCTIVE PATTERN OF CORTICAL THICKNESS AND WHITE MATTER INTEGRITY BETWEEN SPORADIC SVCI WITH AND WITHOUT NOTCH3 VARIANTS AND TYPICAL CADASIL
Ko Woon Kim1, Sang Won Seo1,2, 1Samsung Medical Center, Seoul, Republic of South Korea; 2Neuroscience Center, Samsung Medical Center, Seoul, Republic of South Korea. Contact e-mail: [email protected] Background: Although cerebral autosomal dominant arteriopathy with
subcortical infarcts and leukoencephalopathy (CADASIL) is thought to be a common form of hereditary subcortical vascular cognitive impairment (SVCI). In our previous study, a few sporadic SVCI pa-
P437
tients have NOTCH3 variants and there were no differences in clinical features between SVCI patients with and without NOTCH3 variants. However, there is lack of research on structure brain difference among SVCI with and without NOTCH3 variants, and typical CADASIL. The aim of our investigation is to compare cortical thickness and white matter integrity among 3 groups. Methods: SVCI patients with (n¼15) and without (n¼101) NOTCH3 variants patients who were clinically diagnosed and then genetically confirmed in our previous study were included in this study. Typical CADASIL patients (n¼11) who were clinically diagnosed and then genetically confirmed in our previous study were also included in this study. We compared white matter hyperintensities (WMH) frequency map, fractional anisotrophy (FA) and mean diffusivity (MD) map of diffusion tensor images (DTI) measure, and cortical thickness between three groups. Results: Spatial distribution of WMH showed that CADASIL group tended to have more WMH than either SVCI with or without NOTCH3 variants in the bilateral posterior temporal region. FA values in the juxtacortical white matter in the frontal and parietal lobes, the periventricular white matter, the temporal white matter and the anterior and posterior corpus callosum were significantly lower in typical CADASIL patients than in SVCI patients with or without NOTCH3 variants (w-score). MD values in the same regions were opposed to FA. Meanwhile, SVCI without NOTCH3 variants group showed decreased cortical thickness in the left inferior temporal, right anterior temporal, bilateral occipital, dorsolateral prefrontal, medial prefrontal cortex compared to typical CADASIL group. Conclusions: In this study, sporadic SVCI and CADASIL showed distinctive anatomic vulnerabilities of cortical and subcortical structures respectively, suggesting that sporadic SVCI and CADASIL possibly reflect different pathophysiologic mechanisms.
P1-419
PET-GUIDED MR SPECTROSCOPY REVEALS DISTINCT RELATIONS BETWEEN BRAIN METABOLITES, AMYLOID AND HYPOMETABOLISM IN ALZHEIMER’S DISEASE
Nasim Sheikh-Bahaei1, S. Ahmad Sajjadi2, Roido Manavaki1, Mary McLean3, Jonathan H. Gillard1, John T. O’Brien1, 1University of Cambridge, Cambridge, United Kingdom; 2University of California, Irvine, Irvine, CA, USA; 3Cancer Research UK, Cambridge, United Kingdom. Contact e-mail: [email protected] Background: There is limited understanding of the role of brain me-
tabolites in Alzheimer’s disease (AD) and their correlation with other pathological changes. In this study, we used PET-guided MR spectroscopy (MRS) to measure the level of brain metabolites in areas of amyloid (Ab) deposition and hypometabolism in AD. We hypothesized that the patterns of change in some of brain metabolites are correlated with the underlying pathology. Methods: Cases with diagnoses of early AD (n¼11), Mild Cognitive Impairment (MCI) (n¼10), and healthy control (HC)(n¼8) underwent 11 C- Pittsburg compound B-(PiB) and 18 F-fluorodeoxyglucose(FDG)-PET followed by 3T MRI and MRS. After co-registration of PET on T1W images, MRS voxels were placed on two areas each of maximum Ab deposition and minimum metabolism. Corresponding regions of interest (ROI) were selected in HC. The ratios of total N-acetyl (tNA) group, myoinositol (mI), Choline (Chol), and Glutamate plus Glutamine (Glx) over Creatine (Cr) were measured in each ROI and compared between groups. Results: Compared to representative normal regions, the mean of tNA/Cr was significantly lower in areas of hypometabolism (p-value <0.001) and high Ab deposition (p-value<0.0001). A regression