- Email: [email protected]
Clinical and MRI correlates of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
S420
Poster Presentations P2
ERC. In aMCI studies, ERC volume loss appears more important that HC volume loss. The variability of measurements between aMCI and LLD studies raises the important issue of comparability. Future volumetric studies could benefit from using standardized segmentation protocols. No volumetric studies focusing on aMCI subjects with concomitant depression were found, and hence are needed in order to validate our interpretations.
P2-360
SEVERE MRI HIPPOCAMPAL ATROPHY DISTINGUISHES HIPPOCAMPAL SCLEROSIS FROM ALZHEIMER’S DISEASE AND OTHER NEUROPATHOLOGIC DISORDERS
Chris Zarow1, Ling Zheng1, Helena C. Chui1, Lon R. White2, 1University of Southern California, Los Angeles, CA, USA; 2Pacific Health Research Institute, Honolulu, HI, USA. Contact e-mail: [email protected] Background: Hippocampal sclerosis (HS) in the elderly describes a condition of severe neuron loss with gliosis in the CA1 sector and subiculum of the hippocampus. Patients with HS are usually clinically diagnosed with Alzheimer disease (AD), since AD is also associated with prominent hippocampal atrophy and severe amnesia. In this study, the area under receiver operating characteristic (ROC) curve, sensitivity, specificity, and positive likelihood ratio (PLR) were used to assess the ability of premortem MRI hippocampal volumes to predict postmortem confirmed HS. Methods: 1.5 Tesla MRIs were acquired from 22 HS and 89 non-HS (n ¼ 59 total AD) subjects from the Aging Brain program project and 11 HS and 80 non-HS subjects (n ¼ 35 total AD) from the Honolulu Asia Aging Study (HAAS). When more than one MRI was available for analysis, the MRI closest to death was selected. Hippocampal volumes were determined using a semi-automated high dimensional brain-warping algorithm (Medtronic Surgical Navigation Technologies, Louisville, CO). Hippocampal volumes were normalized to percent of intracranial volume, and normalized by norms in Aging Brain and HAAS independently to create z-scores. ROC curves were created for each sample as a plot of a test’s false-positive rate (1 - specificity) versus its true-positive rate (sensitivity). PLR is a measure of how much the odds of the condition increase when a test is positive. In general, PLR of 5-10 indicates a moderate increase while PLR >10 is a large increase. Results: ROC curves created from the Aging Brain PPG subjects show that severe hippocampal atrophy (z-scores < -2.67) distinguish HS from non-HS cases. The area under the ROC curve (AUC) was 0.85. Using a cut-off of z ¼ -2.67, standardized hippocampal volume showed 59% sensitivity, 88.8% specificity, and 5.3 PLR. For HAAS sample, the AUC was 0.96. The threshold of z ¼ -2.67 yielded 72.7% sensitivity, 96.3% specificity, and 19.6 PLR. Conclusions: Exceptionally severe hippocampal volume loss has excellent specificity (>90%) for excluding cases without HS and is an important contribution to clinical diagnosis. Lesser sensitivity (59% to 73%) reflects overlap between HS and AD for cases with moderate hippocampal atrophy and underscores continued need for alternate biomarkers to improve sensitivity.
P2-361
DIFFERENTIAL VULNERABILITY OF HIPPOCAMPAL SUBREGIONS IN FRONTOTEMPORAL LOBAR DEGENERATION
Olof E. Lindberg1, Mark Walterfaing2, Dennis Velakoulis3, Jeffrey C. L. Looi4, Bram Zandbelt5, Yi Zhang1, Nikolai V. Malykhin6, LarsOlof Wahlund1, 1NVS, Stockholm, Sweden; 2Melbourne Neuropsychiatry Centre, Melbourne, Australia; 3Melbourne Neuropsychiatry Centre, M, Australia; 4RESCENA, Academic Unit of Psychological Medicine, Canberra, Australia; 5Rudolf Magnus Institute of Neuroscience, Utrecht, New Zealand; 6Department of Psychiatry, University of Alberta, Walter MacKenzie Centre, 8440-112 Street, Edmonton, AB, Canada. Contact e-mail: olof. [email protected] Background: Atrophy in the hippocampus is present in patients suffering from frontotemporal lobar degeneration (FTLD), and may be different in the subtypes of FTLD: progressive nonfluent aphasia (PNFA), semantic dementia (SD) and behavioral variant frontotemporal dementia (FTD). The
hippocampus may be anatomically subdivided into a head, body and tail; each of which may show differential atrophy in subtypes of FTLD. As FTLD patients generally display more atrophy in anterior parts of affected brain regions we hypothesized that the head of hippocampus would be a better discriminator between patients and controls than the total hippocampal volume. Methods: We investigated the atrophic pattern of the hippocampus in 13 SD, 8 PNFA and 12 FTD patients compared with 16 age and sex matched controls. The head, body and tail of hippocampus was manually segmented on MRI scans using a previously validated protocol. All volumetric data was analyzed as ratio between volume of region divided by intracranial volume. Results: The head of hippocampus showed the greatest atrophy and was also a discriminator between the FTLD subtypes. Thus the left head (HL) of hippocampus showed greater atrophy in all the FTLD subtypes than controls (p < 0,01). HL also showed greater atrophy in SD than in FTD (p < 0,01) and PNFA (p ¼ 0,03). The right head of hippocampus (HR) showed greater atrophy in FTD and SD than controls (p < 0,01); and SD showed more atrophy than PNFA (p ¼ 0,04). The left and right body of hippocampus was significantly atrophic in all the FTLD subtypes compared with controls (p < 0,01 in SD and FTD and p < 0,05 in PNFA). However, no differences between FTLD subtypes were found for the body. No differences between FTLD subtypes and controls were found in the tail of the hippocampus tail. Conclusions: Different patterns of atrophy of the hippocampal head may be a significant contributor to clinical differences in FTLD subtypes.
P2-362
CLINICAL AND MRI CORRELATES OF CEREBRAL AUTOSOMAL DOMINANT ARTERIOPATHY WITH SUBCORTICAL INFARCTS AND LEUKOENCEPHALOPATHY
Jung Seok Lee1, Jay Chol Choi1, Sa-Yoon Kang1, Ji-Hoon Kang1, Hae Ri Na2, SangYun Kim3, 1Jeju National University College of Medicine, Jeju, Korea; 2Bobath Memorial Hospital, Seongnam, Korea; 3Seoul National University Bundang Hospital, Seongnam, Korea. Contact e-mail: [email protected] Background: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited microangiopathy caused by mutations in the Notch3 gene on chromosome 19 and is characterized by recurrent ischemic stroke, migraine, and vascular dementia. Recent studies have shown the association between neuroimaging measures and cognitive dysfunction. We investigate clinical and MRI correlates in CADASIL patients. Methods: We studied forty CADASIL patients with prospective protocol. The diagnosis of CADASIL was confirmed by identification of mutation of the Notch3 gene in all patients. MRI analysis included semi-quantification of WMH volume, number of lacunar infarcts, number of cerebral microbleeds, and the ratio of brain volume to intracranial cavity volume (brain parenchymal fraction). All patients underwent a detailed neuropsychological testing, including executive function tests, and degree of disability. Results: Cognitive impairment including executive dysfunction was associated with increase in number of lacunar infarcts and brain atrophy. In contrast, WMH volume and number of cerebral microbleeds were not associated with cognitive dysfunction after adjustment for age and sex. Degree of disability was only associated with number of lacunar infarcts. Conclusions: Our findings suggest that severity of lacunar infarction and brain atrophy may play important role in executive dysfunction as well as global cognitive dysfunction in CADASIL.
P2-363
CLINICAL-NEUROIMAGING CHARACTERISTICS IN MILD COGNITIVE IMPAIRMENT WITH AND WITHOUT PARKINSON’S DISEASE
Phil Hyu Lee, Ji E Lee, Young H Sohn, Yonsei University College of Medicine, Seoul, Korea. Contact e-mail: [email protected] Background: In this study, with a hypothesis that different pathologies contribute to MCI in PD and non-PD patients, we investigate the clinical and
Poster Presentations P2
ERC. In aMCI studies, ERC volume loss appears more important that HC volume loss. The variability of measurements between aMCI and LLD studies raises the important issue of comparability. Future volumetric studies could benefit from using standardized segmentation protocols. No volumetric studies focusing on aMCI subjects with concomitant depression were found, and hence are needed in order to validate our interpretations.
P2-360
SEVERE MRI HIPPOCAMPAL ATROPHY DISTINGUISHES HIPPOCAMPAL SCLEROSIS FROM ALZHEIMER’S DISEASE AND OTHER NEUROPATHOLOGIC DISORDERS
Chris Zarow1, Ling Zheng1, Helena C. Chui1, Lon R. White2, 1University of Southern California, Los Angeles, CA, USA; 2Pacific Health Research Institute, Honolulu, HI, USA. Contact e-mail: [email protected] Background: Hippocampal sclerosis (HS) in the elderly describes a condition of severe neuron loss with gliosis in the CA1 sector and subiculum of the hippocampus. Patients with HS are usually clinically diagnosed with Alzheimer disease (AD), since AD is also associated with prominent hippocampal atrophy and severe amnesia. In this study, the area under receiver operating characteristic (ROC) curve, sensitivity, specificity, and positive likelihood ratio (PLR) were used to assess the ability of premortem MRI hippocampal volumes to predict postmortem confirmed HS. Methods: 1.5 Tesla MRIs were acquired from 22 HS and 89 non-HS (n ¼ 59 total AD) subjects from the Aging Brain program project and 11 HS and 80 non-HS subjects (n ¼ 35 total AD) from the Honolulu Asia Aging Study (HAAS). When more than one MRI was available for analysis, the MRI closest to death was selected. Hippocampal volumes were determined using a semi-automated high dimensional brain-warping algorithm (Medtronic Surgical Navigation Technologies, Louisville, CO). Hippocampal volumes were normalized to percent of intracranial volume, and normalized by norms in Aging Brain and HAAS independently to create z-scores. ROC curves were created for each sample as a plot of a test’s false-positive rate (1 - specificity) versus its true-positive rate (sensitivity). PLR is a measure of how much the odds of the condition increase when a test is positive. In general, PLR of 5-10 indicates a moderate increase while PLR >10 is a large increase. Results: ROC curves created from the Aging Brain PPG subjects show that severe hippocampal atrophy (z-scores < -2.67) distinguish HS from non-HS cases. The area under the ROC curve (AUC) was 0.85. Using a cut-off of z ¼ -2.67, standardized hippocampal volume showed 59% sensitivity, 88.8% specificity, and 5.3 PLR. For HAAS sample, the AUC was 0.96. The threshold of z ¼ -2.67 yielded 72.7% sensitivity, 96.3% specificity, and 19.6 PLR. Conclusions: Exceptionally severe hippocampal volume loss has excellent specificity (>90%) for excluding cases without HS and is an important contribution to clinical diagnosis. Lesser sensitivity (59% to 73%) reflects overlap between HS and AD for cases with moderate hippocampal atrophy and underscores continued need for alternate biomarkers to improve sensitivity.
P2-361
DIFFERENTIAL VULNERABILITY OF HIPPOCAMPAL SUBREGIONS IN FRONTOTEMPORAL LOBAR DEGENERATION
Olof E. Lindberg1, Mark Walterfaing2, Dennis Velakoulis3, Jeffrey C. L. Looi4, Bram Zandbelt5, Yi Zhang1, Nikolai V. Malykhin6, LarsOlof Wahlund1, 1NVS, Stockholm, Sweden; 2Melbourne Neuropsychiatry Centre, Melbourne, Australia; 3Melbourne Neuropsychiatry Centre, M, Australia; 4RESCENA, Academic Unit of Psychological Medicine, Canberra, Australia; 5Rudolf Magnus Institute of Neuroscience, Utrecht, New Zealand; 6Department of Psychiatry, University of Alberta, Walter MacKenzie Centre, 8440-112 Street, Edmonton, AB, Canada. Contact e-mail: olof. [email protected] Background: Atrophy in the hippocampus is present in patients suffering from frontotemporal lobar degeneration (FTLD), and may be different in the subtypes of FTLD: progressive nonfluent aphasia (PNFA), semantic dementia (SD) and behavioral variant frontotemporal dementia (FTD). The
hippocampus may be anatomically subdivided into a head, body and tail; each of which may show differential atrophy in subtypes of FTLD. As FTLD patients generally display more atrophy in anterior parts of affected brain regions we hypothesized that the head of hippocampus would be a better discriminator between patients and controls than the total hippocampal volume. Methods: We investigated the atrophic pattern of the hippocampus in 13 SD, 8 PNFA and 12 FTD patients compared with 16 age and sex matched controls. The head, body and tail of hippocampus was manually segmented on MRI scans using a previously validated protocol. All volumetric data was analyzed as ratio between volume of region divided by intracranial volume. Results: The head of hippocampus showed the greatest atrophy and was also a discriminator between the FTLD subtypes. Thus the left head (HL) of hippocampus showed greater atrophy in all the FTLD subtypes than controls (p < 0,01). HL also showed greater atrophy in SD than in FTD (p < 0,01) and PNFA (p ¼ 0,03). The right head of hippocampus (HR) showed greater atrophy in FTD and SD than controls (p < 0,01); and SD showed more atrophy than PNFA (p ¼ 0,04). The left and right body of hippocampus was significantly atrophic in all the FTLD subtypes compared with controls (p < 0,01 in SD and FTD and p < 0,05 in PNFA). However, no differences between FTLD subtypes were found for the body. No differences between FTLD subtypes and controls were found in the tail of the hippocampus tail. Conclusions: Different patterns of atrophy of the hippocampal head may be a significant contributor to clinical differences in FTLD subtypes.
P2-362
CLINICAL AND MRI CORRELATES OF CEREBRAL AUTOSOMAL DOMINANT ARTERIOPATHY WITH SUBCORTICAL INFARCTS AND LEUKOENCEPHALOPATHY
Jung Seok Lee1, Jay Chol Choi1, Sa-Yoon Kang1, Ji-Hoon Kang1, Hae Ri Na2, SangYun Kim3, 1Jeju National University College of Medicine, Jeju, Korea; 2Bobath Memorial Hospital, Seongnam, Korea; 3Seoul National University Bundang Hospital, Seongnam, Korea. Contact e-mail: [email protected] Background: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited microangiopathy caused by mutations in the Notch3 gene on chromosome 19 and is characterized by recurrent ischemic stroke, migraine, and vascular dementia. Recent studies have shown the association between neuroimaging measures and cognitive dysfunction. We investigate clinical and MRI correlates in CADASIL patients. Methods: We studied forty CADASIL patients with prospective protocol. The diagnosis of CADASIL was confirmed by identification of mutation of the Notch3 gene in all patients. MRI analysis included semi-quantification of WMH volume, number of lacunar infarcts, number of cerebral microbleeds, and the ratio of brain volume to intracranial cavity volume (brain parenchymal fraction). All patients underwent a detailed neuropsychological testing, including executive function tests, and degree of disability. Results: Cognitive impairment including executive dysfunction was associated with increase in number of lacunar infarcts and brain atrophy. In contrast, WMH volume and number of cerebral microbleeds were not associated with cognitive dysfunction after adjustment for age and sex. Degree of disability was only associated with number of lacunar infarcts. Conclusions: Our findings suggest that severity of lacunar infarction and brain atrophy may play important role in executive dysfunction as well as global cognitive dysfunction in CADASIL.
P2-363
CLINICAL-NEUROIMAGING CHARACTERISTICS IN MILD COGNITIVE IMPAIRMENT WITH AND WITHOUT PARKINSON’S DISEASE
Phil Hyu Lee, Ji E Lee, Young H Sohn, Yonsei University College of Medicine, Seoul, Korea. Contact e-mail: [email protected] Background: In this study, with a hypothesis that different pathologies contribute to MCI in PD and non-PD patients, we investigate the clinical and