- Email: [email protected]
Retinal imaging in early-onset Alzheimer’s disease
Poster Presentations: P2
(Beta¼-0.296, P¼0.142). WCTh positively correlated with WRD in PiB(+) ADCI (Beta¼0.387, P¼0.002), PiB(-) (Beta¼0.779, P<0.001) and PiB (+) SVCI (Beta¼0.880, P<0.001). However, their correlation is weaker in PiB(+) ADCI than in PiB (-) (P value ¼ 0.009) and PiB(+) SVCI (P value ¼ 0.016). Furthermore, there were interactive effects of WAD & WRD on WCTh in PiB(+) SVCI group. sCCA showed that in PiB (+) ADCI, cortical thinning pattern related to WAD were quite different from that related to WRD while two cortical thinning patterns were quite similar in PiB(+) SVCI. Conclusions: Our findings suggested that in PiB(+) ADCI, axonal degeneration rather than myelin break down contributed to cortical thinning while in SVCI, axonal degeneration and myelin breakdown correlated each other, and independently for PiB(-) SVCI or synergistically for PiB(+) SVCI affected cortical thickness.
P2-143
PREDICTION OF ALZHEIMER’S DISEASE PATHOPHYSIOLOGY BASED ON CORTICAL THICKNESS PATTERNS
Jihye Hwang1, Chan Mi Kim1, Seun Jeon2, Jong Min Lee2, Yun Jeong Hong1, Jee Hoon Roh1, Jae-Hong Lee1 Alzheimer’s Disease Neuroimaging Initiative, 1Asan Medical Center, Seoul, South Korea; 2 Hanyang University, Seoul, South Korea. Contact e-mail: laura110@ naver.com Background: Neuropathologically defined subtypes of Alzheimer’s
Disease (AD) have represented distinctive atrophy patterns and clinical characteristics in patients with AD. Cortical thickness based clustering of AD patients represented comparable results with autopsy findings culminating into 3 atrophy patterns: medial temporal (MT); diffuse (D); and parietal dominant (P) subtypes. It is not assessed, however, whether the new clustering method based on cortical thickness can reflect pathophysiologic changes in AD. Methods: A total of 77 AD subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) 2 dataset who completed 3T MRI, 18F-Fludeoxyglucose (FDG)-PET, 18F-Florbetapir-PET, and cerebrospinal fluid (CSF) study were enrolled for analyses. After obtaining cortical thickness using a CLASP algorithm, a hierarchical agglomerative cluster analysis was performed using a Ward’s clustering linkage to classify AD patients. FDG and Florbetabir PET data were compared among the groups using region of interest based analyses after controlling for age, gender, education, and intracranial volume. Differences in neuropsychological tests and CSF levels of amyloid-beta (Ab) and tau were assessed among the groups. Results: Cortical thickness-based clustering methods demonstarated three patterns of cortical thinning in AD patients: MT subtype (19.5%), D subtype (55.8%), and P (24.7%) subtype. Patients in the P subtype (67.567.4 years) were younger than MT (74.867.9) and D (76.166.6) subtypes (p¼0.0002). Patients in the P subtype represented more glucose hypometabolism in the left inferior parietal, right superior parietal, and left middle occipital cortices, which matches well with regions with cortical atrophy. Patients in the MT subtype revealed more glucose hypometabolism in left hippocampus and bilateral frontal cortices compared to the other 2 subtypes. Patients in the P subtype represented marked Ab accumulation in most of brain regions, including superior, middle, inferior frontal cortices, superior, inferior parietal cortices, and precuneus measured by florbetapir-PET. Neuropsychological test results and levels of CSF revealed no difference among the groups. Conclusions: The findings that the P subtype represented more glucose hypometabolism and more accumulation of Ab than the
P541
other groups and that the MT subtype had more glucose hypometabolism in compatible brain regions including the hippocampus indicates cortical thickness patterns can reflect pathophysiological changes in AD.
P2-144
REGIONAL GRAY MATTER LOSS IN LATE-LIFEONSET DEPRESSION IS ASSOCIATED WITH VASCULAR RISKS, BUT NOT WITH CEREBRAL AMYLOIDOSIS
Min Soo Byun1, Young Min Choe1, Bo Kyung Sohn2, Dahyun Yi1, Ji Young Han1, Hyo Jung Choi1, Hyewon Baek1, Hyun Jung Kim1, Yu Kyeong Kim2, Chul-Ho Sohn1, Jong Inn Woo3, Dong Young Lee1, 1 Seoul National University Hospital, Seoul, South Korea; 2SMG-SNU Boramae Medical Center, Seoul, South Korea; 3Medical Research Center Seoul National University, Seoul, South Korea. Contact e-mail: bminsoo@ gmail.com Background: Although some structural brain changes have been reported in late life onset depression (LLOD), only limited information is available for the causes that underlie to such brain changes in LLOD patients. We first tried to identify LLOD-related regional gray matter (GM) changes, and then investigated the influence of vascular risk factors (VRF) and cerebral amyloidosis on the regional brain changes. Methods: Non-demented subjects who first experienced major depressive episode after age of 60 years were recruited as LLOD group (N ¼ 29). As normal control (NC) group, non-demented elderly individuals who had no experience of major depressive episode were also included (N ¼ 27). All participants received comprehensive clinical assessment including vascular risk factor (VRF) evaluation, 11C-labeled Pittsburgh Compound B (PiB) positron emission tomography (PET) and magnetic resonance imaging (MRI). Comparison of regional GM volume between LLOD and NC group was performed by using voxel-based morphometry (VBM) at corrected p < 0.05 after family-wise error correction. The regions where LLOD group showed greater volume loss compared to NC group was set as region-of-interest (ROI) for further analyses on the association of VRF and cerebral amyloid deposition. Results: There were no significant differences in age, gender and educational level between LLOD and NC groups. Compared to NC, LLOD subjects showed significant regional GM volume loss mainly in the bilateral prefrontal regions including the right medial frontal, left anterior cingulate and left orbitofrontal regions. In linear regression analysis that had the mean GM volume of the ROI as a dependent variable, the presence of VRF showed significant association with the ROI volume in LLOD group after controlling PiB positivity status. In contrast, PiB positivity status did not demonstrate significant association with the mean ROI volume in the same regression model. Conclusions: Our findings suggest that vascular risks are major contributors to LLOD and related regional brain changes supporting the ‘vascular depression hypothesis’, while cerebral amyloidosis itself is not likely to be a main player in LLOD.
P2-145
RETINAL IMAGING IN EARLY-ONSET ALZHEIMER’S DISEASE
Sebastian J. Crutch1, Timothy J. Shakespeare2, Lajos Csincsik3, Tunde Peto4, Imre Lengyel3, 1University College London, London, United Kingdom; 2UCL Institute of Neurology, London, United Kingdom; 3UCL Institute of Ophthalmology, London, United Kingdom; 4Moorfields Eye Hospital, London, United Kingdom. Contact e-mail: [email protected]
P542
Poster Presentations: P2
Background: Neuronal cell loss and accumulation of extracellular
deposits in the brain are features of Alzheimer’s disease (AD) that are signatures of its development and progression. Detection of these features is costly and time consuming. In the eye, thinning of the retinal nerve fibre layer (RNFL) as a consequence of ganglion cell loss has also been associated with AD (e.g. Kirbas et al., 2013; Shi et al., 2014). Additionally, increased accumulation of extracellular material under the retinal pigment epithelium, known as drusen, has been shown in AD (especially in the peripheral retina; Ritchie et al., 2011). They contain beta amyloid and a variety of identical macromolecules and micro elements to plaques. Here we describe a study being carried out in collaboration between the Dementia Research Centre and the Institute of Ophthalmology, investigating retinal changes in patients with early onset Alzheimer’s disease. Methods: We are recruiting healthy controls and patients with typical AD (predominant memory impairment) and posterior cortical atrophy (PCA; predominant impairments in visual perception and other posterior cortical functions). Thus far we have tested 62 controls, 15 PCA and 17 tAD patients. Images are being acquired using spectral-domain optical coherence tomography (Optos OCT SLO) and ultra-wide field scanning laser ophthalmoscopy (Optos 200TX). Images are anonymised and sent to Moorfields Eye Hospital Reading Centre for reading. The images are reviewed and any unexpected findings reported in a timely manner. As part of the research programme at the DRC patients also undergo neuroimaging and detailed clinical assessment. Two annual longitudinal follow up visits are planned. Results: Imaging is quick (10-20 minutes), well tolerated, and in the patients tested so far there has been no sight threatening disease. We are investigating differences between patient groups and controls in peripheral drusen deposition, RNFL thickness, and macular volume. We will also study associations between these features and aspects of brain imaging such as cortical thickness and white matter coherence. Conclusions: The findings will have implications for our understanding of how the disease spreads through the brain and whether retinal imaging could be a useful technique for monitoring the progression or even identifying Alzheimer’s disease.
P2-146
TEMPORO-PARIETAL HYPOMETABOLISM IS ASSOCIATED WITH REDUCED FUNCTIONAL CONNECTIVITY OF THE DEFAULT MODE NETWORK IN PRODROMAL ALZHEIMER’S DISEASE Araque Caballero1, Lee Simon-Vermot1, Yifei Zhang1,2, Miguel Angel 1 3 Benno Gesierich , Lana Kambeitz-Ilankovic , Matthias Brendel4, Axel Rominger4, Peter Bartenstein4, Marco Duering1, Michael Ewers1 Alzheimer’s Disease Neuroimaging Initiative (ADNI)1Institute for Stroke and Dementia Research, M€unchen, Germany; 2Shanghai University, Shanghai, China; 3Ludwig Maximillian University, M€unchen, Germany; 4 Nuclear Medicine, Ludwig-Maximilian University, Munich, Germany. Contact e-mail: [email protected] Background: Temporo-parietal FDG-PET measured glucose meta-
bolism is reduced in early stages of AD, including mild cognitive impairment (MCI) with high amyloid-beta (Aß+) biomarker levels. Although previous studies report the spatial correspondence of FDG-PET hypometabolism with areas of the default mode network (DMN), it remains unclear whether changes in resting-state functional connectivity (FC) are associated with FDG-PET hypometabolism within the DMN. Hence, we aimed to investigate whether brain regions of the DMN which show reduced FDG-PET in AD patients
compared to healthy controls (HC), will reveal lower FC between these regions in MCI-Aß+ subjects. Methods: 27 elderly HC, 44 MCI-Aß+ subjects and 25 patients with AD dementia were assessed within the Alzheimer’s Disease Neuroimaging Initiative (ADNI). For FDG-PET, HC and AD patients were compared, using ANCOVA controlling for age and gender (FWE corrected). Peak voxels of hypometabolism within the DMN brain areas were extracted. Seven ROIs were created around cluster peak voxels from the comparison AD
P2-147
THE EFFECT OF EDUCATION ON COGNITION AND CORTICAL THICKNESS IN PURE VASCULAR MILD COGNITIVE IMPAIRMENT AND DEMENTIA OF THE SUBCORTICAL TYPE
Na Yeon Jung1, Hanna Cho2, Juyoun Lee1, Hee Jin Kim1, Yeo Jin Kim1, Young Noh3, Byoung Seok Ye4, Seun Jeon5, Jong Min Lee5, Yearn Seong Cheo1, Kyung Han Lee1, Sung Tae Kim1, Duk L. Na1, Sang Won Seo1, 1Samsung Medical Center, Seoul, South Korea; 2Gangnam Severance Hospital, Seoul, South Korea; 3Gachon University Gil Medical Center, Incheon, South Korea; 4Yonsei University College of Medicine, Seoul, South Korea; 5Hanyang University, Seoul, South Korea. Contact e-mail: [email protected] Background: An impact of education has been studied in Alz-
heimer’s disease, whereas its role in patients with isolated cerebrovascular diseases (CVD) remains unclear. We therefore examined the effect of education on cortical thickness in pure subcortical vascular mild cognitive impairment (svMCI) and pure subcortical vascular dementia (SVaD) patients. Methods: We prospectively recruited 45 patients with svMCI and 47 patients with SVaD who were negative on Pittsburgh compound-B (PiB) PET imaging and underwent structural brain MRI from September 2008 to August 2011. The main outcome was cortical thickness measured using Surface-based morphometric (SBM) analysis. Results: Patients with PiB (-) svMCI showed no significant relationship between education and cortical thickness. However, patients with PiB (-) SVaD showed negative relationship of education and cortical thickness in the bilateral dorsolateral frontal, the left medial frontal and parahippocampal, and the right precuneus and cuneus areas. Conclusions: Our findings suggest that highly educated patients with pure CVD will have a more cortical atrophy than poorly educated patients with pure CVD at the time of clinical dementia, but not MCI.
(Beta¼-0.296, P¼0.142). WCTh positively correlated with WRD in PiB(+) ADCI (Beta¼0.387, P¼0.002), PiB(-) (Beta¼0.779, P<0.001) and PiB (+) SVCI (Beta¼0.880, P<0.001). However, their correlation is weaker in PiB(+) ADCI than in PiB (-) (P value ¼ 0.009) and PiB(+) SVCI (P value ¼ 0.016). Furthermore, there were interactive effects of WAD & WRD on WCTh in PiB(+) SVCI group. sCCA showed that in PiB (+) ADCI, cortical thinning pattern related to WAD were quite different from that related to WRD while two cortical thinning patterns were quite similar in PiB(+) SVCI. Conclusions: Our findings suggested that in PiB(+) ADCI, axonal degeneration rather than myelin break down contributed to cortical thinning while in SVCI, axonal degeneration and myelin breakdown correlated each other, and independently for PiB(-) SVCI or synergistically for PiB(+) SVCI affected cortical thickness.
P2-143
PREDICTION OF ALZHEIMER’S DISEASE PATHOPHYSIOLOGY BASED ON CORTICAL THICKNESS PATTERNS
Jihye Hwang1, Chan Mi Kim1, Seun Jeon2, Jong Min Lee2, Yun Jeong Hong1, Jee Hoon Roh1, Jae-Hong Lee1 Alzheimer’s Disease Neuroimaging Initiative, 1Asan Medical Center, Seoul, South Korea; 2 Hanyang University, Seoul, South Korea. Contact e-mail: laura110@ naver.com Background: Neuropathologically defined subtypes of Alzheimer’s
Disease (AD) have represented distinctive atrophy patterns and clinical characteristics in patients with AD. Cortical thickness based clustering of AD patients represented comparable results with autopsy findings culminating into 3 atrophy patterns: medial temporal (MT); diffuse (D); and parietal dominant (P) subtypes. It is not assessed, however, whether the new clustering method based on cortical thickness can reflect pathophysiologic changes in AD. Methods: A total of 77 AD subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) 2 dataset who completed 3T MRI, 18F-Fludeoxyglucose (FDG)-PET, 18F-Florbetapir-PET, and cerebrospinal fluid (CSF) study were enrolled for analyses. After obtaining cortical thickness using a CLASP algorithm, a hierarchical agglomerative cluster analysis was performed using a Ward’s clustering linkage to classify AD patients. FDG and Florbetabir PET data were compared among the groups using region of interest based analyses after controlling for age, gender, education, and intracranial volume. Differences in neuropsychological tests and CSF levels of amyloid-beta (Ab) and tau were assessed among the groups. Results: Cortical thickness-based clustering methods demonstarated three patterns of cortical thinning in AD patients: MT subtype (19.5%), D subtype (55.8%), and P (24.7%) subtype. Patients in the P subtype (67.567.4 years) were younger than MT (74.867.9) and D (76.166.6) subtypes (p¼0.0002). Patients in the P subtype represented more glucose hypometabolism in the left inferior parietal, right superior parietal, and left middle occipital cortices, which matches well with regions with cortical atrophy. Patients in the MT subtype revealed more glucose hypometabolism in left hippocampus and bilateral frontal cortices compared to the other 2 subtypes. Patients in the P subtype represented marked Ab accumulation in most of brain regions, including superior, middle, inferior frontal cortices, superior, inferior parietal cortices, and precuneus measured by florbetapir-PET. Neuropsychological test results and levels of CSF revealed no difference among the groups. Conclusions: The findings that the P subtype represented more glucose hypometabolism and more accumulation of Ab than the
P541
other groups and that the MT subtype had more glucose hypometabolism in compatible brain regions including the hippocampus indicates cortical thickness patterns can reflect pathophysiological changes in AD.
P2-144
REGIONAL GRAY MATTER LOSS IN LATE-LIFEONSET DEPRESSION IS ASSOCIATED WITH VASCULAR RISKS, BUT NOT WITH CEREBRAL AMYLOIDOSIS
Min Soo Byun1, Young Min Choe1, Bo Kyung Sohn2, Dahyun Yi1, Ji Young Han1, Hyo Jung Choi1, Hyewon Baek1, Hyun Jung Kim1, Yu Kyeong Kim2, Chul-Ho Sohn1, Jong Inn Woo3, Dong Young Lee1, 1 Seoul National University Hospital, Seoul, South Korea; 2SMG-SNU Boramae Medical Center, Seoul, South Korea; 3Medical Research Center Seoul National University, Seoul, South Korea. Contact e-mail: bminsoo@ gmail.com Background: Although some structural brain changes have been reported in late life onset depression (LLOD), only limited information is available for the causes that underlie to such brain changes in LLOD patients. We first tried to identify LLOD-related regional gray matter (GM) changes, and then investigated the influence of vascular risk factors (VRF) and cerebral amyloidosis on the regional brain changes. Methods: Non-demented subjects who first experienced major depressive episode after age of 60 years were recruited as LLOD group (N ¼ 29). As normal control (NC) group, non-demented elderly individuals who had no experience of major depressive episode were also included (N ¼ 27). All participants received comprehensive clinical assessment including vascular risk factor (VRF) evaluation, 11C-labeled Pittsburgh Compound B (PiB) positron emission tomography (PET) and magnetic resonance imaging (MRI). Comparison of regional GM volume between LLOD and NC group was performed by using voxel-based morphometry (VBM) at corrected p < 0.05 after family-wise error correction. The regions where LLOD group showed greater volume loss compared to NC group was set as region-of-interest (ROI) for further analyses on the association of VRF and cerebral amyloid deposition. Results: There were no significant differences in age, gender and educational level between LLOD and NC groups. Compared to NC, LLOD subjects showed significant regional GM volume loss mainly in the bilateral prefrontal regions including the right medial frontal, left anterior cingulate and left orbitofrontal regions. In linear regression analysis that had the mean GM volume of the ROI as a dependent variable, the presence of VRF showed significant association with the ROI volume in LLOD group after controlling PiB positivity status. In contrast, PiB positivity status did not demonstrate significant association with the mean ROI volume in the same regression model. Conclusions: Our findings suggest that vascular risks are major contributors to LLOD and related regional brain changes supporting the ‘vascular depression hypothesis’, while cerebral amyloidosis itself is not likely to be a main player in LLOD.
P2-145
RETINAL IMAGING IN EARLY-ONSET ALZHEIMER’S DISEASE
Sebastian J. Crutch1, Timothy J. Shakespeare2, Lajos Csincsik3, Tunde Peto4, Imre Lengyel3, 1University College London, London, United Kingdom; 2UCL Institute of Neurology, London, United Kingdom; 3UCL Institute of Ophthalmology, London, United Kingdom; 4Moorfields Eye Hospital, London, United Kingdom. Contact e-mail: [email protected]
P542
Poster Presentations: P2
Background: Neuronal cell loss and accumulation of extracellular
deposits in the brain are features of Alzheimer’s disease (AD) that are signatures of its development and progression. Detection of these features is costly and time consuming. In the eye, thinning of the retinal nerve fibre layer (RNFL) as a consequence of ganglion cell loss has also been associated with AD (e.g. Kirbas et al., 2013; Shi et al., 2014). Additionally, increased accumulation of extracellular material under the retinal pigment epithelium, known as drusen, has been shown in AD (especially in the peripheral retina; Ritchie et al., 2011). They contain beta amyloid and a variety of identical macromolecules and micro elements to plaques. Here we describe a study being carried out in collaboration between the Dementia Research Centre and the Institute of Ophthalmology, investigating retinal changes in patients with early onset Alzheimer’s disease. Methods: We are recruiting healthy controls and patients with typical AD (predominant memory impairment) and posterior cortical atrophy (PCA; predominant impairments in visual perception and other posterior cortical functions). Thus far we have tested 62 controls, 15 PCA and 17 tAD patients. Images are being acquired using spectral-domain optical coherence tomography (Optos OCT SLO) and ultra-wide field scanning laser ophthalmoscopy (Optos 200TX). Images are anonymised and sent to Moorfields Eye Hospital Reading Centre for reading. The images are reviewed and any unexpected findings reported in a timely manner. As part of the research programme at the DRC patients also undergo neuroimaging and detailed clinical assessment. Two annual longitudinal follow up visits are planned. Results: Imaging is quick (10-20 minutes), well tolerated, and in the patients tested so far there has been no sight threatening disease. We are investigating differences between patient groups and controls in peripheral drusen deposition, RNFL thickness, and macular volume. We will also study associations between these features and aspects of brain imaging such as cortical thickness and white matter coherence. Conclusions: The findings will have implications for our understanding of how the disease spreads through the brain and whether retinal imaging could be a useful technique for monitoring the progression or even identifying Alzheimer’s disease.
P2-146
TEMPORO-PARIETAL HYPOMETABOLISM IS ASSOCIATED WITH REDUCED FUNCTIONAL CONNECTIVITY OF THE DEFAULT MODE NETWORK IN PRODROMAL ALZHEIMER’S DISEASE Araque Caballero1, Lee Simon-Vermot1, Yifei Zhang1,2, Miguel Angel 1 3 Benno Gesierich , Lana Kambeitz-Ilankovic , Matthias Brendel4, Axel Rominger4, Peter Bartenstein4, Marco Duering1, Michael Ewers1 Alzheimer’s Disease Neuroimaging Initiative (ADNI)1Institute for Stroke and Dementia Research, M€unchen, Germany; 2Shanghai University, Shanghai, China; 3Ludwig Maximillian University, M€unchen, Germany; 4 Nuclear Medicine, Ludwig-Maximilian University, Munich, Germany. Contact e-mail: [email protected] Background: Temporo-parietal FDG-PET measured glucose meta-
bolism is reduced in early stages of AD, including mild cognitive impairment (MCI) with high amyloid-beta (Aß+) biomarker levels. Although previous studies report the spatial correspondence of FDG-PET hypometabolism with areas of the default mode network (DMN), it remains unclear whether changes in resting-state functional connectivity (FC) are associated with FDG-PET hypometabolism within the DMN. Hence, we aimed to investigate whether brain regions of the DMN which show reduced FDG-PET in AD patients
compared to healthy controls (HC), will reveal lower FC between these regions in MCI-Aß+ subjects. Methods: 27 elderly HC, 44 MCI-Aß+ subjects and 25 patients with AD dementia were assessed within the Alzheimer’s Disease Neuroimaging Initiative (ADNI). For FDG-PET, HC and AD patients were compared, using ANCOVA controlling for age and gender (FWE corrected). Peak voxels of hypometabolism within the DMN brain areas were extracted. Seven ROIs were created around cluster peak voxels from the comparison AD
P2-147
THE EFFECT OF EDUCATION ON COGNITION AND CORTICAL THICKNESS IN PURE VASCULAR MILD COGNITIVE IMPAIRMENT AND DEMENTIA OF THE SUBCORTICAL TYPE
Na Yeon Jung1, Hanna Cho2, Juyoun Lee1, Hee Jin Kim1, Yeo Jin Kim1, Young Noh3, Byoung Seok Ye4, Seun Jeon5, Jong Min Lee5, Yearn Seong Cheo1, Kyung Han Lee1, Sung Tae Kim1, Duk L. Na1, Sang Won Seo1, 1Samsung Medical Center, Seoul, South Korea; 2Gangnam Severance Hospital, Seoul, South Korea; 3Gachon University Gil Medical Center, Incheon, South Korea; 4Yonsei University College of Medicine, Seoul, South Korea; 5Hanyang University, Seoul, South Korea. Contact e-mail: [email protected] Background: An impact of education has been studied in Alz-
heimer’s disease, whereas its role in patients with isolated cerebrovascular diseases (CVD) remains unclear. We therefore examined the effect of education on cortical thickness in pure subcortical vascular mild cognitive impairment (svMCI) and pure subcortical vascular dementia (SVaD) patients. Methods: We prospectively recruited 45 patients with svMCI and 47 patients with SVaD who were negative on Pittsburgh compound-B (PiB) PET imaging and underwent structural brain MRI from September 2008 to August 2011. The main outcome was cortical thickness measured using Surface-based morphometric (SBM) analysis. Results: Patients with PiB (-) svMCI showed no significant relationship between education and cortical thickness. However, patients with PiB (-) SVaD showed negative relationship of education and cortical thickness in the bilateral dorsolateral frontal, the left medial frontal and parahippocampal, and the right precuneus and cuneus areas. Conclusions: Our findings suggest that highly educated patients with pure CVD will have a more cortical atrophy than poorly educated patients with pure CVD at the time of clinical dementia, but not MCI.