- Email: [email protected]
Neuroanatomical correlates of the behavioral and psychiatric symptoms in Alzheimer's disease: A voxel-based morphometry study
P114
Alzheimer’s Imaging Consortium Poster Presentations: IC-P
Hautes Etudes, CHU de Caen, CATI, Caen, France; 2INSERM, Universite de Caen Basse-Normandie, Ecole Pratique des Hautes Etudes, CHU de Caen, Caen, France; 3INSERM, Universite de Caen Basse-Normandie, Ecole Pratique des Hautes Etudes, CHU de Caen, CAEN, France; 4Inserm EPHE-UCBN U1077, Caen, France. Contact e-mail: [email protected] Background: Self-referential processing of personality trait words is generally associated with better remembering compared to words processed in a semantic condition, an effect called self-reference effect (SRE). Previous works suggest that SRE is subserved by neural activity during encoding in several cortical areas including the medial prefrontal cortex (MPFC). Alzheimer’s disease (AD) is characterized by early memory deficits and Ab deposits that predominate in the prefrontal cortex. The goal of the present study was to assess whether SRE was altered in AD and to highlight the neural basis of this effect using fMRI in mild cognitive impairment (MCI) and AD patients with Ab deposits. Methods: We used an fMRI event-related self-referential paradigm in 16 patients (8 MCI and 8 AD) with a florbetapir-positive scan and 27 healthy elderly with a florbetapir-negative scan. The neural activity associated with self-reference processing compared to a semantic control condition during both encoding and retrieval was compared between groups and correlated with behavioral measures of memory and SRE. Results are reported at p<0.005 (uncorrected). Results: Greater memory performance was found after self-related than after semantic processing in controls (p<0.001) but not in patients (p>0.05; condition x group interaction p¼0.01). In both groups, self-related processing was associated with increased activity during encoding in a common brain network involving midline cortical structures. Memory performance correlated with selfrelated activity in the hippocampus during both encoding and retrieval in the patients. SRE score was related to MPFC activity during encoding in controls. In patients, no such relationship was found with SRE, and self-related activity during encoding was decreased in the MPFC and posterior cingulate cortex (PCC) compared to controls. Conclusions: While the PCC and the hippocampus may have a more general role in self and memory processes, the positive effect of self-reference processing on memory appears to be subserved by increased activity in the MPFC. In AD patients, this effect is lost as self-reference processing does not improve memory performance, and this abnormality seems to be due to impaired MPFC activity.
IC-P-204
NEUROANATOMICAL CORRELATES OF THE BEHAVIORAL AND PSYCHIATRIC SYMPTOMS IN ALZHEIMER’S DISEASE: A VOXEL-BASED MORPHOMETRY STUDY
Xiaochen Hu1, Beate Newport2, Dix Meiberth3, Frank Jessen3, 1University of Bonn, Bonn, Germany; 2German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; 3University of Bonn, Bonn, Germany. Contact e-mail: [email protected] Background: Behavioural and psychiatric symptoms (BPS) are frequently observed in the clinical course of Alzheimer’s disease (AD). However, previous studies on neuroanatomical underpinnings of BPS in AD have revealed inconsistent results, which might be biased by the image pre-processing steps and the small samples. The current study aimed to assess the relationship between regional grey matter volume (GMV) atrophy and BPS in a large sample of 424 Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants. Methods: Structural MRI images and the scores of neuropsychiatric inventory questionnaire (NPI-Q) of altogether 85 AD, 208 patients with mild cognitive impairment (MCI), and 131 healthy controls (HC) were collected from the ADNI website. In contrast to the previous studies in this field, we used improved image pre-processing strategies, including the new segmentation and DARTEL normalization tools from SPM8. Voxel-based multiple regression analyses were used to characterize the association between GMVatrophy and each NPI-Q symptoms across the whole sample, with age, gender and total intracranial volume as covariates of non-interest. The results were exclusively masked with regions directly related to general cognitive deterioration, as expressed by the correlation
with the Mini-Mental-State-Examination (MMSE). A statistic threshold of p<0.05 (cluster level family wise error corrected) was applied. Results: Agitation was associated with GMV loss in the bilateral precuneus, the left frontal and insula cortices. Depression was related to GMV decreases in the left frontal cortex. Aberrant motor behaviour was associated with GMV atrophy in bilateral medial orbitofrontal cortices, bilateral putamen and the right inferior frontal gyrus. Conclusions: The current study has shown the neuroanatomical underpinnings of specific BPS by using advanced VBM techniques within a large public available database (ADNI). Our results contribute to the poor understanding of the pathology of BPS in AD.
IC-P-205
STRUCTURAL MRI MEASURES IN ALZHEIMER’S DISEASE AND EFFECTS OF ETHNICITY
Linda Zhang1, Raymond Tak-Fai Cheung1, Henry Ka Fung Mak1, Leung-wing Chu2, 1University of Hong Kong, Hong Kong, Hong Kong; 2 The University of Hong Kong, Hong Kong, Hong Kong. Contact e-mail: [email protected] Background: Alzheimer’s disease (AD) affects populations worldwide, and there are increasing numbers of AD-focused international neuroimaging studies. For these global cohorts, ethnicity may be a confounding factor. Morphometric differences have been found between European and Japanese brains, though the implications for common AD neuroimaging biomarkers, such as hippocampal volume and cortical thickness, are unknown and should be investigated. Methods: 65 local Chinese participants (33 AD, 32 elderly controls) were recruited, and a matching Caucasian cohort was downloaded from ADNI. All participants underwent T1-weighted MPRAGE scanning with ADNI’s protocol in 3T Philips Achieva scanners, and the raw images were processed using FreeSurfer v5.1. Cortical thickness was compared between groups with FreeSurfer’s GLM analysis tools. Hippocampal volumes were corrected for intracranial volume and analysed using multivariate GLM, with age, gender and years of education as covariates. Results: There were no significant differences between the two ethnicities for age, gender, MMSE and ADAS-cog scores, but local Chinese had significantly fewer years of education than Caucasians (4.863.8 vs. 15.863.3). Several clusters in the bilateral cingulate and precuneus regions showed cortical thinning in Chinese patients whereas Caucasian patients only had thinning in the inferior temporal regions compared to their respective controls. Between ethnicities, clusters in the left parietal area were thicker in Caucasian patients, whereas Chinese controls had thicker paracentral cortices than Caucasian controls. When combined, patients had cortical thinning in the bilateral temporal regions (all results significant at p<0.01). Controls had larger relative hippocampal volumes than patients (0.2760.05 vs. 0.1960.04), and Chinese subjects had larger relative hippocampal volumes than Caucasian subjects, regardless of diagnosis (0.2860.05 vs. 0.2360.03 for controls, 0.2060.04 vs. 0.1760.02 for patients). Conclusions: Chinese subjects have larger relative hippocampal volumes than Caucasian subjects, but Chinese AD patients also display a greater degree of hippocampal atrophy and cortical thinning. As none of these trends are reflected in the cognitive test scores, this may be indicative of a protective effect
Alzheimer’s Imaging Consortium Poster Presentations: IC-P
Hautes Etudes, CHU de Caen, CATI, Caen, France; 2INSERM, Universite de Caen Basse-Normandie, Ecole Pratique des Hautes Etudes, CHU de Caen, Caen, France; 3INSERM, Universite de Caen Basse-Normandie, Ecole Pratique des Hautes Etudes, CHU de Caen, CAEN, France; 4Inserm EPHE-UCBN U1077, Caen, France. Contact e-mail: [email protected] Background: Self-referential processing of personality trait words is generally associated with better remembering compared to words processed in a semantic condition, an effect called self-reference effect (SRE). Previous works suggest that SRE is subserved by neural activity during encoding in several cortical areas including the medial prefrontal cortex (MPFC). Alzheimer’s disease (AD) is characterized by early memory deficits and Ab deposits that predominate in the prefrontal cortex. The goal of the present study was to assess whether SRE was altered in AD and to highlight the neural basis of this effect using fMRI in mild cognitive impairment (MCI) and AD patients with Ab deposits. Methods: We used an fMRI event-related self-referential paradigm in 16 patients (8 MCI and 8 AD) with a florbetapir-positive scan and 27 healthy elderly with a florbetapir-negative scan. The neural activity associated with self-reference processing compared to a semantic control condition during both encoding and retrieval was compared between groups and correlated with behavioral measures of memory and SRE. Results are reported at p<0.005 (uncorrected). Results: Greater memory performance was found after self-related than after semantic processing in controls (p<0.001) but not in patients (p>0.05; condition x group interaction p¼0.01). In both groups, self-related processing was associated with increased activity during encoding in a common brain network involving midline cortical structures. Memory performance correlated with selfrelated activity in the hippocampus during both encoding and retrieval in the patients. SRE score was related to MPFC activity during encoding in controls. In patients, no such relationship was found with SRE, and self-related activity during encoding was decreased in the MPFC and posterior cingulate cortex (PCC) compared to controls. Conclusions: While the PCC and the hippocampus may have a more general role in self and memory processes, the positive effect of self-reference processing on memory appears to be subserved by increased activity in the MPFC. In AD patients, this effect is lost as self-reference processing does not improve memory performance, and this abnormality seems to be due to impaired MPFC activity.
IC-P-204
NEUROANATOMICAL CORRELATES OF THE BEHAVIORAL AND PSYCHIATRIC SYMPTOMS IN ALZHEIMER’S DISEASE: A VOXEL-BASED MORPHOMETRY STUDY
Xiaochen Hu1, Beate Newport2, Dix Meiberth3, Frank Jessen3, 1University of Bonn, Bonn, Germany; 2German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; 3University of Bonn, Bonn, Germany. Contact e-mail: [email protected] Background: Behavioural and psychiatric symptoms (BPS) are frequently observed in the clinical course of Alzheimer’s disease (AD). However, previous studies on neuroanatomical underpinnings of BPS in AD have revealed inconsistent results, which might be biased by the image pre-processing steps and the small samples. The current study aimed to assess the relationship between regional grey matter volume (GMV) atrophy and BPS in a large sample of 424 Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants. Methods: Structural MRI images and the scores of neuropsychiatric inventory questionnaire (NPI-Q) of altogether 85 AD, 208 patients with mild cognitive impairment (MCI), and 131 healthy controls (HC) were collected from the ADNI website. In contrast to the previous studies in this field, we used improved image pre-processing strategies, including the new segmentation and DARTEL normalization tools from SPM8. Voxel-based multiple regression analyses were used to characterize the association between GMVatrophy and each NPI-Q symptoms across the whole sample, with age, gender and total intracranial volume as covariates of non-interest. The results were exclusively masked with regions directly related to general cognitive deterioration, as expressed by the correlation
with the Mini-Mental-State-Examination (MMSE). A statistic threshold of p<0.05 (cluster level family wise error corrected) was applied. Results: Agitation was associated with GMV loss in the bilateral precuneus, the left frontal and insula cortices. Depression was related to GMV decreases in the left frontal cortex. Aberrant motor behaviour was associated with GMV atrophy in bilateral medial orbitofrontal cortices, bilateral putamen and the right inferior frontal gyrus. Conclusions: The current study has shown the neuroanatomical underpinnings of specific BPS by using advanced VBM techniques within a large public available database (ADNI). Our results contribute to the poor understanding of the pathology of BPS in AD.
IC-P-205
STRUCTURAL MRI MEASURES IN ALZHEIMER’S DISEASE AND EFFECTS OF ETHNICITY
Linda Zhang1, Raymond Tak-Fai Cheung1, Henry Ka Fung Mak1, Leung-wing Chu2, 1University of Hong Kong, Hong Kong, Hong Kong; 2 The University of Hong Kong, Hong Kong, Hong Kong. Contact e-mail: [email protected] Background: Alzheimer’s disease (AD) affects populations worldwide, and there are increasing numbers of AD-focused international neuroimaging studies. For these global cohorts, ethnicity may be a confounding factor. Morphometric differences have been found between European and Japanese brains, though the implications for common AD neuroimaging biomarkers, such as hippocampal volume and cortical thickness, are unknown and should be investigated. Methods: 65 local Chinese participants (33 AD, 32 elderly controls) were recruited, and a matching Caucasian cohort was downloaded from ADNI. All participants underwent T1-weighted MPRAGE scanning with ADNI’s protocol in 3T Philips Achieva scanners, and the raw images were processed using FreeSurfer v5.1. Cortical thickness was compared between groups with FreeSurfer’s GLM analysis tools. Hippocampal volumes were corrected for intracranial volume and analysed using multivariate GLM, with age, gender and years of education as covariates. Results: There were no significant differences between the two ethnicities for age, gender, MMSE and ADAS-cog scores, but local Chinese had significantly fewer years of education than Caucasians (4.863.8 vs. 15.863.3). Several clusters in the bilateral cingulate and precuneus regions showed cortical thinning in Chinese patients whereas Caucasian patients only had thinning in the inferior temporal regions compared to their respective controls. Between ethnicities, clusters in the left parietal area were thicker in Caucasian patients, whereas Chinese controls had thicker paracentral cortices than Caucasian controls. When combined, patients had cortical thinning in the bilateral temporal regions (all results significant at p<0.01). Controls had larger relative hippocampal volumes than patients (0.2760.05 vs. 0.1960.04), and Chinese subjects had larger relative hippocampal volumes than Caucasian subjects, regardless of diagnosis (0.2860.05 vs. 0.2360.03 for controls, 0.2060.04 vs. 0.1760.02 for patients). Conclusions: Chinese subjects have larger relative hippocampal volumes than Caucasian subjects, but Chinese AD patients also display a greater degree of hippocampal atrophy and cortical thinning. As none of these trends are reflected in the cognitive test scores, this may be indicative of a protective effect