- Email: [email protected]
Cerebral amyloid angiopathy in a multicenter cohort of people with MCI and Alzheimer's disease
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
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