- Email: [email protected]
IC-P1-025: Cerebral blood flow, white matter lesions and cognitive performance: The SMART-MR study
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Alzheimer’s Imaging Consortium IC-P1: Poster Presentations at time of MRI, while 9% had minor depression and 5% had major depression. Persons with a history of depression did not have smaller hippocampal volumes than those without a history (p⫽0.95). The adjusted mean total hippocampal volume for those without a history was 3.32 ml (95%CI 3.27-3.38); for those with an early onset of depression it was 3.33 ml (95%CI 3.16-3.50); and for those with a late onset of depression 3.30 ml (95%CI 3.13-3.46). The adjusted mean total hippocampal volume in persons not depressed at time of MRI was 3.32 ml (95%CI 3.27-3.38), and for those with minor depression 3.26 ml (95%CI 3.09-3.43); persons with major depression had nonsignificantly (p⫽0.18) smaller hippocampal volumes (3.15 ml; 95%CI 2.91-3.39) than those without depression. No laterality effects were found. Conclusions: In this population of elderly people no evidence was found for a relation between history of depression or current depression and smaller hippocampal volumes.
Figure 1: Scatter plot of the primary two weights for each participant. The NC cluster to the right and AD to the left.
Figure 2: Mean plus weighted first mode that illustrate a similar pattern of uptake as reported in post-mortem studies.
IC-P1-024
DEPRESSION AND HIPPOCAMPAL VOLUMES IN A LARGE POPULATION-BASED COHORT OF ELDERLY PEOPLE AT RISK OF ALZHEIMER’S DISEASE
Mirjam I. Geerlings1, Nicole Schupf2, Truman R. Brown3, Scott A. Small2, 1University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Clinical Epidemiology, Utrecht, Netherlands; 2Columbia University, Gertrude H Sergievsky Center and Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, New York, NY, USA; 3Columbia University, Department of Radiology, New York, NY, USA. Contact e-mail: [email protected] Background: Many studies have reported smaller hippocampal volumes in patients with major depression compared with controls, although findings are not always consistent. It has been hypothesized that excessive secretion of glucocorticoids with repeated episodes of depression leads to hippocampal atrophy and Alzheimer’s disease. Few studies, however, examined this relation in community-dwelling elders. We estimated hippocampal volumes on MRI in nondemented older people according to history of depression and current depression. Methods: Within the WHICAP-2 cohort, a population-based cohort study in Northern Manhattan, New York, 667 elderly people (mean age 80⫾5.5 years, 67% female) without dementia reported their history of depressive episodes. To assess current depression, the 9 items from the DSMIV regarding feelings during the past week were evaluated, and classified as no depression, minor depression, or major depression. Volumetric assessment of the hippocampus was performed using 3-dimensional MRI and was expressed relative to intracranial volume. ANCOVA was used to estimate mean total hippocampal volumes according to depression status, adjusted for age, gender, ethnicity, education, and objective memory performance. Results: Of the study sample, 18% reported a history of depression (8% with onset ⬍60 years and 10% with onset ⱖ 60 years). Furthermore, 86% were not depressed
IC-P1-025
CEREBRAL BLOOD FLOW, WHITE MATTER LESIONS AND COGNITIVE PERFORMANCE: THE SMART-MR STUDY
Mirjam I. Geerlings1, Auke P. A. Appelman2, Koen L. Vincken3, Willem P. Th M. Mali2, Yolanda van der Graaf1, 1University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Clinical Epidemiology, Utrecht, Netherlands; 2University Medical Center Utrecht, Department of Radiology, Utrecht, Netherlands; 3 University Medical Center Utrecht, Image Sciences Institute, Utrecht, Netherlands. Contact e-mail: [email protected] Background: It has been hypothesized that cerebral hypoperfusion contributes to cognitive deterioration and Alzheimer’s disease. Patients with white matter lesions (WML) are more vulnerable to a decrease in cerebral blood flow (CBF) due to an impaired autoregulation. We investigated the association between total CBF and cognitive performance and assessed whether this relation was modified by WML. Methods: Within the SMART-MR study, a cohort study among patients with manifest arterial disease, cross-sectional analyses were performed in 472 patients (mean age 57⫾10 years, 77% male) without cortical and large subcortical infarcts and with available data on CBF. Total CBF was measured with MR angiography in the internal carotid arteries and basilar artery, and was expressed per 100 mL brain volume. Brain segmentation was used to obtain volumetric measurements of total brain volume and WML volume. Infarcts were rated visually. Neuropsychological tests assessing executive functioning and verbal memory were performed and scores were transformed into composite z-scores for both domains. We used linear regression analyses, adjusted for age, sex, education and intelligence (DART score), to investigate the association between CBF and cognitive performance and the interaction between CBF and WML on cognitive performance. Results: Mean CBF was 51⫾10 mL/min/100 mL. We found that WML modified the association between CBF and executive functioning (p for interaction ⬍ 0.001). Therefore, we repeated the analysis for patients with WML volumes above increasing cut-off points. The association between lower CBF and worse performance on executive functioning became stronger and significant with increasing volumes of WML (Figure). Additional adjustment for vascular risk factors, intima-media thickness and lacunar infarcts did not materially change the association between CBF and executive functioning. Lower CBF was not associated with poorer memory performance, and WML did not modify this association. Conclusions: In this population, lower cerebral blood flow is associated with worse executive performance, but only in the presence of WML. These findings suggest that patients with WML are more vulnerable to hypoperfusion-related cognitive impairment. Longitudinal studies are needed to determine whether a decrease in cerebral blood flow increases risk for cognitive decline and Alzheimer’s disease.
Alzheimer’s Imaging Consortium IC-P1: Poster Presentations
IC-P1-026
PRECISE NATURE OF THE WHITE MATTER HYPERINTENSITIES: A BIOTECHNOLOGICAL PLATFORM COMBINING POST MORTEM MRI IN SITU WITH COMPREHENSIVE NEUROPATHOLOGY
Lea T. Grinberg1,2, Edson Amaro1, Stefan Teipel3, Alexandre V. Silva4, Silmara P. Pacheco1, Ariadne S. Gonc¸alves4, Denis D. Santos1, Carlos A. G. Pasqualucci1, Helmut Heinsen5, Brazilian Aging Brain Study Group, 1University of Sao Paulo, Sao Paulo, Brazil; 2Instituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, Brazil; 3University of Munich, Sao Paulo, Germany; 4 Federal University of Sao Paulo, Sao Paulo, Brazil; 5University of Wuerzburg, Wuerzburg, Germany. Contact e-mail: [email protected] Background: White matter T2 hyperintensities (WMHs) are commonly detected in Magnetic Resonance Imaging (MRI) scansperformed in routine basis, especially in older subjects. There is growing evidence that these lesions should not be considered as benign age-dependent changes, but may contribute to cognitive decline either alone or associated to neurodegenerative changes as Alzheimer⬘s disease. The histopathological counterpart of WMHs is a matter of debate. Methodological and ethical limitations have prevented this question to be elucidated. We have introduced a new study platform based on state-of-the-art techniques in order to tackle fundamental questions regarding the neuroimaging-neuropathological correlations. Our first approach is to solve uncertainties in location and histological substrates of WMHs seen in MRI. To this purpose we were correlating signal features in in situ post mortem MRI-derived methods, including DTI and MTR supplemented by quantitative and qualitative histopathology. Methods: In order to guarantee the exact co-registration of small lesions in a tridimensional coordinate systems we have based our protocol onto four principles: post mortem MRI in situ performed in a short post mortem interval, minimal brain deformation during processing, thick serial histological sections and computer-assisted 3D reconstruction of the histological sections (Fig. 1). Results: The first 10 cases submitted to this protocol have brought considerable progress supporting this platform as reliable, reproducible and feasible tool. Even minimal neuropathological changes can be unequivocally located and can be subjected to a detailed neuropathological diagnosis, allowing the better recognition of the socalled unspecific white matter changes in MRI radiological reports (Fig. 2). Conclusions: The precise distinction of the different WMHs will greatly facilitate systematic studies of the location, pathogenesis, clinical impact, prognosis and prevention of these changes and their role in cognitive impairment.
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Alzheimer’s Imaging Consortium IC-P1: Poster Presentations at time of MRI, while 9% had minor depression and 5% had major depression. Persons with a history of depression did not have smaller hippocampal volumes than those without a history (p⫽0.95). The adjusted mean total hippocampal volume for those without a history was 3.32 ml (95%CI 3.27-3.38); for those with an early onset of depression it was 3.33 ml (95%CI 3.16-3.50); and for those with a late onset of depression 3.30 ml (95%CI 3.13-3.46). The adjusted mean total hippocampal volume in persons not depressed at time of MRI was 3.32 ml (95%CI 3.27-3.38), and for those with minor depression 3.26 ml (95%CI 3.09-3.43); persons with major depression had nonsignificantly (p⫽0.18) smaller hippocampal volumes (3.15 ml; 95%CI 2.91-3.39) than those without depression. No laterality effects were found. Conclusions: In this population of elderly people no evidence was found for a relation between history of depression or current depression and smaller hippocampal volumes.
Figure 1: Scatter plot of the primary two weights for each participant. The NC cluster to the right and AD to the left.
Figure 2: Mean plus weighted first mode that illustrate a similar pattern of uptake as reported in post-mortem studies.
IC-P1-024
DEPRESSION AND HIPPOCAMPAL VOLUMES IN A LARGE POPULATION-BASED COHORT OF ELDERLY PEOPLE AT RISK OF ALZHEIMER’S DISEASE
Mirjam I. Geerlings1, Nicole Schupf2, Truman R. Brown3, Scott A. Small2, 1University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Clinical Epidemiology, Utrecht, Netherlands; 2Columbia University, Gertrude H Sergievsky Center and Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, New York, NY, USA; 3Columbia University, Department of Radiology, New York, NY, USA. Contact e-mail: [email protected] Background: Many studies have reported smaller hippocampal volumes in patients with major depression compared with controls, although findings are not always consistent. It has been hypothesized that excessive secretion of glucocorticoids with repeated episodes of depression leads to hippocampal atrophy and Alzheimer’s disease. Few studies, however, examined this relation in community-dwelling elders. We estimated hippocampal volumes on MRI in nondemented older people according to history of depression and current depression. Methods: Within the WHICAP-2 cohort, a population-based cohort study in Northern Manhattan, New York, 667 elderly people (mean age 80⫾5.5 years, 67% female) without dementia reported their history of depressive episodes. To assess current depression, the 9 items from the DSMIV regarding feelings during the past week were evaluated, and classified as no depression, minor depression, or major depression. Volumetric assessment of the hippocampus was performed using 3-dimensional MRI and was expressed relative to intracranial volume. ANCOVA was used to estimate mean total hippocampal volumes according to depression status, adjusted for age, gender, ethnicity, education, and objective memory performance. Results: Of the study sample, 18% reported a history of depression (8% with onset ⬍60 years and 10% with onset ⱖ 60 years). Furthermore, 86% were not depressed
IC-P1-025
CEREBRAL BLOOD FLOW, WHITE MATTER LESIONS AND COGNITIVE PERFORMANCE: THE SMART-MR STUDY
Mirjam I. Geerlings1, Auke P. A. Appelman2, Koen L. Vincken3, Willem P. Th M. Mali2, Yolanda van der Graaf1, 1University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Clinical Epidemiology, Utrecht, Netherlands; 2University Medical Center Utrecht, Department of Radiology, Utrecht, Netherlands; 3 University Medical Center Utrecht, Image Sciences Institute, Utrecht, Netherlands. Contact e-mail: [email protected] Background: It has been hypothesized that cerebral hypoperfusion contributes to cognitive deterioration and Alzheimer’s disease. Patients with white matter lesions (WML) are more vulnerable to a decrease in cerebral blood flow (CBF) due to an impaired autoregulation. We investigated the association between total CBF and cognitive performance and assessed whether this relation was modified by WML. Methods: Within the SMART-MR study, a cohort study among patients with manifest arterial disease, cross-sectional analyses were performed in 472 patients (mean age 57⫾10 years, 77% male) without cortical and large subcortical infarcts and with available data on CBF. Total CBF was measured with MR angiography in the internal carotid arteries and basilar artery, and was expressed per 100 mL brain volume. Brain segmentation was used to obtain volumetric measurements of total brain volume and WML volume. Infarcts were rated visually. Neuropsychological tests assessing executive functioning and verbal memory were performed and scores were transformed into composite z-scores for both domains. We used linear regression analyses, adjusted for age, sex, education and intelligence (DART score), to investigate the association between CBF and cognitive performance and the interaction between CBF and WML on cognitive performance. Results: Mean CBF was 51⫾10 mL/min/100 mL. We found that WML modified the association between CBF and executive functioning (p for interaction ⬍ 0.001). Therefore, we repeated the analysis for patients with WML volumes above increasing cut-off points. The association between lower CBF and worse performance on executive functioning became stronger and significant with increasing volumes of WML (Figure). Additional adjustment for vascular risk factors, intima-media thickness and lacunar infarcts did not materially change the association between CBF and executive functioning. Lower CBF was not associated with poorer memory performance, and WML did not modify this association. Conclusions: In this population, lower cerebral blood flow is associated with worse executive performance, but only in the presence of WML. These findings suggest that patients with WML are more vulnerable to hypoperfusion-related cognitive impairment. Longitudinal studies are needed to determine whether a decrease in cerebral blood flow increases risk for cognitive decline and Alzheimer’s disease.
Alzheimer’s Imaging Consortium IC-P1: Poster Presentations
IC-P1-026
PRECISE NATURE OF THE WHITE MATTER HYPERINTENSITIES: A BIOTECHNOLOGICAL PLATFORM COMBINING POST MORTEM MRI IN SITU WITH COMPREHENSIVE NEUROPATHOLOGY
Lea T. Grinberg1,2, Edson Amaro1, Stefan Teipel3, Alexandre V. Silva4, Silmara P. Pacheco1, Ariadne S. Gonc¸alves4, Denis D. Santos1, Carlos A. G. Pasqualucci1, Helmut Heinsen5, Brazilian Aging Brain Study Group, 1University of Sao Paulo, Sao Paulo, Brazil; 2Instituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, Brazil; 3University of Munich, Sao Paulo, Germany; 4 Federal University of Sao Paulo, Sao Paulo, Brazil; 5University of Wuerzburg, Wuerzburg, Germany. Contact e-mail: [email protected] Background: White matter T2 hyperintensities (WMHs) are commonly detected in Magnetic Resonance Imaging (MRI) scansperformed in routine basis, especially in older subjects. There is growing evidence that these lesions should not be considered as benign age-dependent changes, but may contribute to cognitive decline either alone or associated to neurodegenerative changes as Alzheimer⬘s disease. The histopathological counterpart of WMHs is a matter of debate. Methodological and ethical limitations have prevented this question to be elucidated. We have introduced a new study platform based on state-of-the-art techniques in order to tackle fundamental questions regarding the neuroimaging-neuropathological correlations. Our first approach is to solve uncertainties in location and histological substrates of WMHs seen in MRI. To this purpose we were correlating signal features in in situ post mortem MRI-derived methods, including DTI and MTR supplemented by quantitative and qualitative histopathology. Methods: In order to guarantee the exact co-registration of small lesions in a tridimensional coordinate systems we have based our protocol onto four principles: post mortem MRI in situ performed in a short post mortem interval, minimal brain deformation during processing, thick serial histological sections and computer-assisted 3D reconstruction of the histological sections (Fig. 1). Results: The first 10 cases submitted to this protocol have brought considerable progress supporting this platform as reliable, reproducible and feasible tool. Even minimal neuropathological changes can be unequivocally located and can be subjected to a detailed neuropathological diagnosis, allowing the better recognition of the socalled unspecific white matter changes in MRI radiological reports (Fig. 2). Conclusions: The precise distinction of the different WMHs will greatly facilitate systematic studies of the location, pathogenesis, clinical impact, prognosis and prevention of these changes and their role in cognitive impairment.
T19