- Email: [email protected]
Language-variant Alzheimer's disease: Defining early clinical and imaging characteristics of logopenic progressive aphasia
Poster Presentations: P2 can differentiate Filipino subjects with AD from controls. Methods: This case-control study recruited subjects from the St. Luke’s Memory Center. All subjects signed informed consent to participate before undergoing standardized diagnostic assessment and neuropsychological testing. Diagnosis of AD was based on the NINCDS-ADRDA criteria (McKhann 1994). All underwent non-contrast brain magnetic resonance imaging studies which were performed on either 1.5T or 3.0 T Phillips scanners (specifically 1.5T Intera version 8.5.3, 3T Intera-Achieva version 1.5.4.5; and 1.5 and 3T Achieva release 2.6.3.5 2009-10-12) using a head coil and following the Alzheimer’s Disease Neuroimaging Initiative (ADNI) protocol. High resolution MRI images were analyzed using the NeuroQuantÒ. Results: Nineteen subjects participated. Mean age was 78.23 + 10.52 years but subjects with AD were older (82.10 + 9.75 vs. 73.87 + 10.39); subjects with AD had mild dementia with CDR 1.00 + 0.273. The left, right and total hippocampal volumes (in cubic centimeters) among controls were 3.73 + 0.534, 3.93 + 0.409 and 7.66 + 0.905 respectively and significantly bigger than the volumes of subjects with AD which were 2.61 + 0.721, 2.55 + 0.697 and 4.89 + 1.594 respectively. When compared to normative values, controls were all above 25 th percentile (mean 48.75+14.67) while subjects with AD were below 12 th percentile (mean 5.10+4.49). Conclusions: The NeuroQuantÒ automated volumetric MRI software can differentiate subjects with AD from controls. This is particularly helpful in very mild and presymptomatic AD, and in difficult cases where confounding factors preclude the correct diagnosis. P2-188
EFFECT OF A PHANTOM-BASED DISTORTION CORRECTION OF MRI FOR ASSESSMENT OF ALZHEIMER’S DISEASE USING A TENSOR-BASED MORPHMETRY APPROACH
Norihide Maikusa1, Motonobu Fujishima1, Noriko Chida2, Noriko Sato1, Hiroshi Matsuda1, Takeshi Iwatsubo3 Japanese Alzheimer’s Disease Neuroimaging Intitiative2, 1National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan; 2Research Association for Biotechnology, Minato-Ku, Tokyo, Japan; 3The University of Tokyo, Tokyo, Japan. Contact e-mail: [email protected] Background: Measures of brain atrophy can be providing valuable information on disease progression for patient with Alzheimer’s disease (AD). Tensor-based morphometry (TBM) can extract voxel-wise volume difference between each individual’s brain and standard template. However, geometric distortions in MRI decrease the accuracy and precision of TBM analysis. We had proposed a specific phantom based distortion correction method. In this study, we investigate effect of geometrical distortion correction about special distribution of voxel size changes in whole brain and anatomical region volume changes. Methods: Three-dimensional T1-weighted MPRAGE scans of 55 healthy volunteers were acquired at 38 clinical sites in Japan using 1.5 T scanners. These images were corrected for geometric distortion by our method. A TBM approach was applied to between uncorrected and distortion corrected brain images as a three-dimensional Jacobian determinant map. Jacobian determinant map obtained by registering source image to scans target image. The Jacobian determinant operator shows expansion (Jacobian >1) or contraction (Jacobian <1) at each voxel. We defined an uncorrected image as a target and a corrected image as a source image, respectively. We applied TBM approach to each individual image dataset and created a median Jacobian map in a study-specific template brain space. Subsequently, each brain image was segmented to subcortical volume of interest (VOI) in individual brain space by FreeSurfer software package. We measured median Jacobian values in 7 VOIs: temporal horn, hippocampus, entorhinal, fusiform, inferior temporal, middle temporal. Results: A median Jacobian map showed voxel expansion consistently at the whole brain surface except for the vertex. Median voxel size expansion or contraction, i.e. Jacobian determinant, showed +0.55 % for temporal horn, +0.80 % for hippocampus, +0.89 (%) for entorhinal, +1.11 % for fusiform, +1.38 % for inferior temporal and +1.74 % for middle temporal. These results have a tendency that volume sizes of all specific VOIs will be overestimated before distortion correction. Conclusions:
P423
We assessed effects of distortion correction via TBM approach. These results suggested that distortion correction affected mainly the whole brain surface except for the vertex, particularly VOIs specifically associated with AD progression. This fact indicates importance of distortion correction when assessing AD using TBM approach.
P2-189
THE RELATIONSHIP BETWEEN HIPPOCAMPAL ATROPHY AND NEUROPATHOLOGY MARKERS: A 7T MRI STUDY
Sona Babakchanian1, Somme Johanne2, Hedieh Honarpisheh3, Kristy Hwang1, Kristina Biado1, Spencer Tung1, Andrew Frew1, Jeffry Alger4, Jonathan Wisco1, Stephen Schettler1, Chris Zarow5, Harry Vinters6, Paul Thompson1, Liana Apostolova1, 1UCLA, Los Angeles, California, United States; 2Alava University Hospital, Vitoria-Gasteiz, Spain; 3Yale University, New Haven, Connecticut, United States; 4UCLA, Los Angeles, California, United States; 5University of Southern California, Downey, California, United States; 6University of California, Los Angeles, Los Angeles, California, United States. Contact e-mail: sbabakchanian@ ucla.edu Background: Pathological examination of the brain is used to confirm Alzheimer’s disease (AD) diagnosis. In AD, the second earliest site where pathology occurs after the entorhinal cortex is the hippocampus. Hippocampal atrophy is the most established AD imaging biomarker. Methods: Temporal lobes of 10 deceased AD subjects and 5 deceased cognitively normal controls (NC) were obtained from the AD Research Center Brain Bank at the University of California, Los Angeles and scanned with a Bruker Biospec 7 Tesla MRI machine at the UCLA Brain Mapping Center. Hippocampal MRI scans were manually registered to the International Consortium for Brain Mapping template. Hippocampal structures were manually traced and converted into 3D mesh models. Radial distance maps and volumes were computed for each hippocampal structure. Temporal lobes were sectioned coronally in 5mm blocks, embedded in paraffin and cut into 6 mm slices, mounted, and stained for amyloid beta 40, tau, and Cresyl Violet. Aperio ScanScope Ò CS was used to scan the slides digitally at 20x. The CA1 hippocampal subfield was manually traced. To quantify disease burden in the CA1 subfield, in-house nuclear and positively immunostaining pixel algorithms were used to determine neuronal counts and amyloid beta 40 and tau burden. Results: We found significant correlations between amyloid beta 40 burden and hippocampal volume (r¼-0.55, p corrected ¼0.035) and mean hippocampal radial distance (r¼-0.58, p corrected ¼0.025). In addition, neuronal count per CA1 mm 2 was positively correlated with mean radial distance (r¼0.61, p corrected ¼0.016). Conclusions: As expected, our findings suggest that amyloid burden is inversely related to hippocampal volume and radial distance. Lower CA1 neuronal count also showed a significant association with hippocampal atrophy. The observed associations provide pathological confirmation of hippocampal morphometry as a valid biomarker for AD pathology.
P2-190
LANGUAGE-VARIANT ALZHEIMER’S DISEASE: DEFINING EARLY CLINICAL AND IMAGING CHARACTERISTICS OF LOGOPENIC PROGRESSIVE APHASIA
Kimiko Domoto-Reilly1, Amy Zoller1, Michael Brickhouse1, Daisy Sapolsky2, Brad Dickerson3, 1Massachusetts General Hospital, Charlestown, Massachusetts, United States; 2MGH, Charlestown, Massachusetts, United States; 3MGH/Harvard Medical School, Charlestown, Massachusetts, United States. Contact e-mail: [email protected] Background: The logopenic variant of Primary Progressive Aphasia, also known as Logopenic Progressive Aphasia (LPA), is often an atypical clinical presentation of Alzheimer’s disease (AD). With the anticipated emergence of novel therapeutics aimed at the earliest stages of AD pathobiology, the ability to identify individuals with an incipient progressive aphasia due to underlying AD pathology is increasingly urgent.
P424
Poster Presentations: P2
We set out to identify the earliest clinical, psychometric, and imaging characteristics of LPA, and to characterize longitudinal clinical outcome. Methods: 9 patients were identified as meeting criteria for LPA, based on consensus between two neurologists and a speech pathologist. Clinical and psychometric characteristics were assessed at baseline and longitudinally. Quantitative MRI analysis was performed to measure regional cortical atrophy. Molecular markers of AD (CSF or PiB-PET) were assessed when available. Results: All patients were identified in early stage LPA (global CDR 0.5), with average follow up of 3.8 years. Quantitative speech and language assessment with our Progressive Aphasia Severity Scale (PASS) demonstrated a distinct initial profile, preserved over longitudinal assessment. Cortical thickness analysis demonstrated focal atrophy in the dominant temporoparietal junction, detectable at an individual level on quantitative MRI. 5 out of 7 subjects had molecular markers consistent with AD. All subjects are still alive, and thus pathologic confirmation is not yet available. Conclusions: It is possible to identify patients with the prototypical clinical phenotype of LPA at the clinical stage of mild cognitive impairment or very mild dementia. Initial disease progression is characterized by worsening language dysfunction, out of proportion to other cognitive domains, and with a profile distinct from other progressive aphasias. There is a signature cortical atrophy pattern in the dominant temporoparietal junction, also identifiable at the earliest clinical stages. These findings provide further support for the consistency of this clinico-anatomic phenotype and potential biomarkers for use in clinical trials. P2-191
CEREBRAL AMYLOID ANGIOPATHY IN A MULTICENTER COHORT OF PEOPLE WITH MCI AND ALZHEIMER’S DISEASE
Adeline Enderle1, Julia Salleron2, Christine Delmaire3, Audrey Gabelle4, Charlotte Cordonnier5, Frederic Blanc6, Florence Pasquier5, Olivier Hanon7, Stephanie Bombois5, 1University Lille Nord de France, UDSL, CHU Lille, Lille, France; 2Univ. Lille Nord de France, UDSL, CHU Lille, Lille, France; 3University Lille Nord de France, UDSL, CHU Lille, Lille Cedex, France; 4University Montpellier 1, CHU Montpellier, Montpellier, France; 5Univ. Lille Nord de France, UDSL, CHU Lille, Lille Cedex, France; 6University Hospital of Strasbourg, Strasbourg, France; 7 APHP, Paris, France. Contact e-mail: [email protected] Background: The well-known MRI correlates of cerebral amylo€ıd angiopathy (CAA) include brain microbleeds (BMB) and white matter changes. Cortical superficial siderosis has been recently recognized as CAA imaging correlates. The prevalence of this hemorrhagic lesion is unknown in Alzheimer disease (AD) patients. The objective was to describe the prevalence of the MRI correlates of CAA in a multicenter cohort of mild cognitive impairment (MCI) and AD patients. Methods: Consecutive amnestic MCI (a-MCI), non-amnestic MCI (na-MCI), and AD patients from 4 French memory centers (Paris, Strasbourg, Lille, Montpellier) were included. A 3 Tesla MRI with a standardized protocol was performed. White matter changes in the periventricular (PVH) and sub-cortical (WMH) regions were assessed using the Fazekas scale, BMB were assessed using the BOMBS scale, and cortical superficial siderosis (SH-CSS) was recorded, in the absence of validated scale. Results: 289 patients (mean age: 77.366.5 years) were included: 126 (43.6%) AD patients (mean MMSE: 22.163.6), 126 (43.6%) a-MCI patients (mean MMSE 26.462.5) and 37 (12.7%) na-MCI patients (mean MMSE 27.661.9), without significant differences between the 3 subgroups on age and gender. There was no significant difference between the 3 sub-groups of patients on vascular risk factors. Only 3 patients had no PVH and/or WMH, 111 (38.4%) patients had at least one BMB, 9 (3.1%) patients had at least one SH-CSS, without significant difference between the 3 sub-groups of patients. SH-CSS was significantly associated with PVH (p¼0.0062) and WMH (p¼0.0001), unlike BMB (p¼0.75). 112 (34%) patients had probable or possible CAA according to the modified Boston criteria with an equal repartition in the 3 sub-groups. Conclusions: CAA was highly prevalent in this AD and MCI multicenter cohort. CAA is a non-inclusion condition for amylo€ıd disease-modifier trials.
More than a third of patients of our cohort would not have access to these treatments. P2-192
HIPPOCAMPAL SUBFIELDS SEGMENTATION USING AUTOMATED METHOD IN PEOPLE WITH ALZHEIMER’S DISEASE
Wangyoun Won, Changtae Hahn, The Catholic University of Korea, Seoul, South Korea. Contact e-mail: [email protected] Background: Although a few automated hippocampal subfields segmentation methods were developed, there was no study of the effects of diagnosis of Alzheimer’s disease (AD) on the hippocampal subfield volume in vivo MRI. The aim of this study was to investigate hippocampal subfield volume difference between drug naive AD subjects and healthy elderly controls using automated hippocampal subfields segmentation technique. Methods: Thirty one drug naive subjects with AD and 33 group-matched healthy control subjects underwent 3T MRI scanning, and hippocampal subfield volume were measured and compared between the groups. Results: Subjects with AD had significantly smaller volumes of the presubiculum, the subiculum, the cornu ammonis (CA) 2-3 and the CA4-dentate gyrus(DG) compared with the healthy subjects (uncorrected, p<0.001). In addition, we also found significant positive correlations between the presubiculum and the subicular volumes and the MMSE-K and the CERAD-K verbal delayed recall scores in the AD group. Conclusions: We are unaware of previous imaging studies of automated hippocampal subfields segmentation in AD. These structural changes in the hippocampal presubiculum, subiculum and CA2-3 might be at the core of underlying neurobiological mechanisms of hippocampal dysfunction and their relevance to verbal delayed recall impairments in AD.
P2-193
A REFINED CORTICAL SIGNATURE OF ALZHEIMER’S DISEASE
Liang Wang1, Lindsay Ercole1, Tyler Blazey2, Tammie Benzinger2, Jason Hassenstab3, John Morris4, Beau Ances5, 1Washington University in St. Louis, St Louis, Missouri, United States; 2Washington University in St Louis, St. Louis, Missouri, United States; 3Washington University in St Louis, St Louis, Missouri, United States; 4Washington University, St. Louis, Missouri, United States; 5Washington University School of Medicine, St. Louis, Missouri, United States. Contact e-mail: [email protected] Background: Postmortem studies have identified certain brain areas that are selectively vulnerable to AD pathology. MRI assessment of differences in brain structure between cognitively normal (CN) individuals and symptomatic AD patients has defined the topographies of brain areas affected by AD. However, since roughly 30% of CN individuals harbor AD pathology, and since some clinically defined AD individuals may instead have non-AD pathology, originally defined topographies may need to be refined. Methods: A cohort of CN (Clinical Dementia Rating (CDR) 0; N¼106) and symptomatic AD (CDR 0.5/1; N¼64) participants was selected from longitudinal studies of aging and AD at the Knight Alzheimer’s Disease Research Center at Washington University in St. Louis (Table 1). All participants were assessed using amyloid b (Ab) imaging with Pittsburgh Compound B (PiB), cerebrospinal fluid (CSF)Ab 42, tau and phosphorylated tau 181 (ptau 181), and brain MRI scanning. Each participant was classified as negative or
Table 1 Participant demographics
N Mean age (SD), years * Mean Education (SD), years * Sex, % Male SD: standard deviation *p < 0.05.
Cognitively normal
AD
106 71.84 (5.02) 15.35 (2.61) 47.2
64 74.81 (5.10) 14.44 (2.82) 48.4
EFFECT OF A PHANTOM-BASED DISTORTION CORRECTION OF MRI FOR ASSESSMENT OF ALZHEIMER’S DISEASE USING A TENSOR-BASED MORPHMETRY APPROACH
Norihide Maikusa1, Motonobu Fujishima1, Noriko Chida2, Noriko Sato1, Hiroshi Matsuda1, Takeshi Iwatsubo3 Japanese Alzheimer’s Disease Neuroimaging Intitiative2, 1National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan; 2Research Association for Biotechnology, Minato-Ku, Tokyo, Japan; 3The University of Tokyo, Tokyo, Japan. Contact e-mail: [email protected] Background: Measures of brain atrophy can be providing valuable information on disease progression for patient with Alzheimer’s disease (AD). Tensor-based morphometry (TBM) can extract voxel-wise volume difference between each individual’s brain and standard template. However, geometric distortions in MRI decrease the accuracy and precision of TBM analysis. We had proposed a specific phantom based distortion correction method. In this study, we investigate effect of geometrical distortion correction about special distribution of voxel size changes in whole brain and anatomical region volume changes. Methods: Three-dimensional T1-weighted MPRAGE scans of 55 healthy volunteers were acquired at 38 clinical sites in Japan using 1.5 T scanners. These images were corrected for geometric distortion by our method. A TBM approach was applied to between uncorrected and distortion corrected brain images as a three-dimensional Jacobian determinant map. Jacobian determinant map obtained by registering source image to scans target image. The Jacobian determinant operator shows expansion (Jacobian >1) or contraction (Jacobian <1) at each voxel. We defined an uncorrected image as a target and a corrected image as a source image, respectively. We applied TBM approach to each individual image dataset and created a median Jacobian map in a study-specific template brain space. Subsequently, each brain image was segmented to subcortical volume of interest (VOI) in individual brain space by FreeSurfer software package. We measured median Jacobian values in 7 VOIs: temporal horn, hippocampus, entorhinal, fusiform, inferior temporal, middle temporal. Results: A median Jacobian map showed voxel expansion consistently at the whole brain surface except for the vertex. Median voxel size expansion or contraction, i.e. Jacobian determinant, showed +0.55 % for temporal horn, +0.80 % for hippocampus, +0.89 (%) for entorhinal, +1.11 % for fusiform, +1.38 % for inferior temporal and +1.74 % for middle temporal. These results have a tendency that volume sizes of all specific VOIs will be overestimated before distortion correction. Conclusions:
P423
We assessed effects of distortion correction via TBM approach. These results suggested that distortion correction affected mainly the whole brain surface except for the vertex, particularly VOIs specifically associated with AD progression. This fact indicates importance of distortion correction when assessing AD using TBM approach.
P2-189
THE RELATIONSHIP BETWEEN HIPPOCAMPAL ATROPHY AND NEUROPATHOLOGY MARKERS: A 7T MRI STUDY
Sona Babakchanian1, Somme Johanne2, Hedieh Honarpisheh3, Kristy Hwang1, Kristina Biado1, Spencer Tung1, Andrew Frew1, Jeffry Alger4, Jonathan Wisco1, Stephen Schettler1, Chris Zarow5, Harry Vinters6, Paul Thompson1, Liana Apostolova1, 1UCLA, Los Angeles, California, United States; 2Alava University Hospital, Vitoria-Gasteiz, Spain; 3Yale University, New Haven, Connecticut, United States; 4UCLA, Los Angeles, California, United States; 5University of Southern California, Downey, California, United States; 6University of California, Los Angeles, Los Angeles, California, United States. Contact e-mail: sbabakchanian@ ucla.edu Background: Pathological examination of the brain is used to confirm Alzheimer’s disease (AD) diagnosis. In AD, the second earliest site where pathology occurs after the entorhinal cortex is the hippocampus. Hippocampal atrophy is the most established AD imaging biomarker. Methods: Temporal lobes of 10 deceased AD subjects and 5 deceased cognitively normal controls (NC) were obtained from the AD Research Center Brain Bank at the University of California, Los Angeles and scanned with a Bruker Biospec 7 Tesla MRI machine at the UCLA Brain Mapping Center. Hippocampal MRI scans were manually registered to the International Consortium for Brain Mapping template. Hippocampal structures were manually traced and converted into 3D mesh models. Radial distance maps and volumes were computed for each hippocampal structure. Temporal lobes were sectioned coronally in 5mm blocks, embedded in paraffin and cut into 6 mm slices, mounted, and stained for amyloid beta 40, tau, and Cresyl Violet. Aperio ScanScope Ò CS was used to scan the slides digitally at 20x. The CA1 hippocampal subfield was manually traced. To quantify disease burden in the CA1 subfield, in-house nuclear and positively immunostaining pixel algorithms were used to determine neuronal counts and amyloid beta 40 and tau burden. Results: We found significant correlations between amyloid beta 40 burden and hippocampal volume (r¼-0.55, p corrected ¼0.035) and mean hippocampal radial distance (r¼-0.58, p corrected ¼0.025). In addition, neuronal count per CA1 mm 2 was positively correlated with mean radial distance (r¼0.61, p corrected ¼0.016). Conclusions: As expected, our findings suggest that amyloid burden is inversely related to hippocampal volume and radial distance. Lower CA1 neuronal count also showed a significant association with hippocampal atrophy. The observed associations provide pathological confirmation of hippocampal morphometry as a valid biomarker for AD pathology.
P2-190
LANGUAGE-VARIANT ALZHEIMER’S DISEASE: DEFINING EARLY CLINICAL AND IMAGING CHARACTERISTICS OF LOGOPENIC PROGRESSIVE APHASIA
Kimiko Domoto-Reilly1, Amy Zoller1, Michael Brickhouse1, Daisy Sapolsky2, Brad Dickerson3, 1Massachusetts General Hospital, Charlestown, Massachusetts, United States; 2MGH, Charlestown, Massachusetts, United States; 3MGH/Harvard Medical School, Charlestown, Massachusetts, United States. Contact e-mail: [email protected] Background: The logopenic variant of Primary Progressive Aphasia, also known as Logopenic Progressive Aphasia (LPA), is often an atypical clinical presentation of Alzheimer’s disease (AD). With the anticipated emergence of novel therapeutics aimed at the earliest stages of AD pathobiology, the ability to identify individuals with an incipient progressive aphasia due to underlying AD pathology is increasingly urgent.
P424
Poster Presentations: P2
We set out to identify the earliest clinical, psychometric, and imaging characteristics of LPA, and to characterize longitudinal clinical outcome. Methods: 9 patients were identified as meeting criteria for LPA, based on consensus between two neurologists and a speech pathologist. Clinical and psychometric characteristics were assessed at baseline and longitudinally. Quantitative MRI analysis was performed to measure regional cortical atrophy. Molecular markers of AD (CSF or PiB-PET) were assessed when available. Results: All patients were identified in early stage LPA (global CDR 0.5), with average follow up of 3.8 years. Quantitative speech and language assessment with our Progressive Aphasia Severity Scale (PASS) demonstrated a distinct initial profile, preserved over longitudinal assessment. Cortical thickness analysis demonstrated focal atrophy in the dominant temporoparietal junction, detectable at an individual level on quantitative MRI. 5 out of 7 subjects had molecular markers consistent with AD. All subjects are still alive, and thus pathologic confirmation is not yet available. Conclusions: It is possible to identify patients with the prototypical clinical phenotype of LPA at the clinical stage of mild cognitive impairment or very mild dementia. Initial disease progression is characterized by worsening language dysfunction, out of proportion to other cognitive domains, and with a profile distinct from other progressive aphasias. There is a signature cortical atrophy pattern in the dominant temporoparietal junction, also identifiable at the earliest clinical stages. These findings provide further support for the consistency of this clinico-anatomic phenotype and potential biomarkers for use in clinical trials. P2-191
CEREBRAL AMYLOID ANGIOPATHY IN A MULTICENTER COHORT OF PEOPLE WITH MCI AND ALZHEIMER’S DISEASE
Adeline Enderle1, Julia Salleron2, Christine Delmaire3, Audrey Gabelle4, Charlotte Cordonnier5, Frederic Blanc6, Florence Pasquier5, Olivier Hanon7, Stephanie Bombois5, 1University Lille Nord de France, UDSL, CHU Lille, Lille, France; 2Univ. Lille Nord de France, UDSL, CHU Lille, Lille, France; 3University Lille Nord de France, UDSL, CHU Lille, Lille Cedex, France; 4University Montpellier 1, CHU Montpellier, Montpellier, France; 5Univ. Lille Nord de France, UDSL, CHU Lille, Lille Cedex, France; 6University Hospital of Strasbourg, Strasbourg, France; 7 APHP, Paris, France. Contact e-mail: [email protected] Background: The well-known MRI correlates of cerebral amylo€ıd angiopathy (CAA) include brain microbleeds (BMB) and white matter changes. Cortical superficial siderosis has been recently recognized as CAA imaging correlates. The prevalence of this hemorrhagic lesion is unknown in Alzheimer disease (AD) patients. The objective was to describe the prevalence of the MRI correlates of CAA in a multicenter cohort of mild cognitive impairment (MCI) and AD patients. Methods: Consecutive amnestic MCI (a-MCI), non-amnestic MCI (na-MCI), and AD patients from 4 French memory centers (Paris, Strasbourg, Lille, Montpellier) were included. A 3 Tesla MRI with a standardized protocol was performed. White matter changes in the periventricular (PVH) and sub-cortical (WMH) regions were assessed using the Fazekas scale, BMB were assessed using the BOMBS scale, and cortical superficial siderosis (SH-CSS) was recorded, in the absence of validated scale. Results: 289 patients (mean age: 77.366.5 years) were included: 126 (43.6%) AD patients (mean MMSE: 22.163.6), 126 (43.6%) a-MCI patients (mean MMSE 26.462.5) and 37 (12.7%) na-MCI patients (mean MMSE 27.661.9), without significant differences between the 3 subgroups on age and gender. There was no significant difference between the 3 sub-groups of patients on vascular risk factors. Only 3 patients had no PVH and/or WMH, 111 (38.4%) patients had at least one BMB, 9 (3.1%) patients had at least one SH-CSS, without significant difference between the 3 sub-groups of patients. SH-CSS was significantly associated with PVH (p¼0.0062) and WMH (p¼0.0001), unlike BMB (p¼0.75). 112 (34%) patients had probable or possible CAA according to the modified Boston criteria with an equal repartition in the 3 sub-groups. Conclusions: CAA was highly prevalent in this AD and MCI multicenter cohort. CAA is a non-inclusion condition for amylo€ıd disease-modifier trials.
More than a third of patients of our cohort would not have access to these treatments. P2-192
HIPPOCAMPAL SUBFIELDS SEGMENTATION USING AUTOMATED METHOD IN PEOPLE WITH ALZHEIMER’S DISEASE
Wangyoun Won, Changtae Hahn, The Catholic University of Korea, Seoul, South Korea. Contact e-mail: [email protected] Background: Although a few automated hippocampal subfields segmentation methods were developed, there was no study of the effects of diagnosis of Alzheimer’s disease (AD) on the hippocampal subfield volume in vivo MRI. The aim of this study was to investigate hippocampal subfield volume difference between drug naive AD subjects and healthy elderly controls using automated hippocampal subfields segmentation technique. Methods: Thirty one drug naive subjects with AD and 33 group-matched healthy control subjects underwent 3T MRI scanning, and hippocampal subfield volume were measured and compared between the groups. Results: Subjects with AD had significantly smaller volumes of the presubiculum, the subiculum, the cornu ammonis (CA) 2-3 and the CA4-dentate gyrus(DG) compared with the healthy subjects (uncorrected, p<0.001). In addition, we also found significant positive correlations between the presubiculum and the subicular volumes and the MMSE-K and the CERAD-K verbal delayed recall scores in the AD group. Conclusions: We are unaware of previous imaging studies of automated hippocampal subfields segmentation in AD. These structural changes in the hippocampal presubiculum, subiculum and CA2-3 might be at the core of underlying neurobiological mechanisms of hippocampal dysfunction and their relevance to verbal delayed recall impairments in AD.
P2-193
A REFINED CORTICAL SIGNATURE OF ALZHEIMER’S DISEASE
Liang Wang1, Lindsay Ercole1, Tyler Blazey2, Tammie Benzinger2, Jason Hassenstab3, John Morris4, Beau Ances5, 1Washington University in St. Louis, St Louis, Missouri, United States; 2Washington University in St Louis, St. Louis, Missouri, United States; 3Washington University in St Louis, St Louis, Missouri, United States; 4Washington University, St. Louis, Missouri, United States; 5Washington University School of Medicine, St. Louis, Missouri, United States. Contact e-mail: [email protected] Background: Postmortem studies have identified certain brain areas that are selectively vulnerable to AD pathology. MRI assessment of differences in brain structure between cognitively normal (CN) individuals and symptomatic AD patients has defined the topographies of brain areas affected by AD. However, since roughly 30% of CN individuals harbor AD pathology, and since some clinically defined AD individuals may instead have non-AD pathology, originally defined topographies may need to be refined. Methods: A cohort of CN (Clinical Dementia Rating (CDR) 0; N¼106) and symptomatic AD (CDR 0.5/1; N¼64) participants was selected from longitudinal studies of aging and AD at the Knight Alzheimer’s Disease Research Center at Washington University in St. Louis (Table 1). All participants were assessed using amyloid b (Ab) imaging with Pittsburgh Compound B (PiB), cerebrospinal fluid (CSF)Ab 42, tau and phosphorylated tau 181 (ptau 181), and brain MRI scanning. Each participant was classified as negative or
Table 1 Participant demographics
N Mean age (SD), years * Mean Education (SD), years * Sex, % Male SD: standard deviation *p < 0.05.
Cognitively normal
AD
106 71.84 (5.02) 15.35 (2.61) 47.2
64 74.81 (5.10) 14.44 (2.82) 48.4