Aleksandra Lebedeva1, Eric Westman1, Aleksander V Lebedev2, Xiaozhen Li1, Bengt Winblad1, Andrew Simmons3, Lars-Olof Wahlund1, Dag Aarsland4. 1. Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden. 2. Center for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway. 3. Department of Neuroimaging, King's College London, Institute of Psychiatry, London, UK NIHR Biomedical Research Centre for Mental Health, London, UK NIHR Biomedical Research Unit for Dementia, London, UK. 4. Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden Center for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
Abstract
OBJECTIVE: To examine neuroanatomical changes associated with depressive symptoms in Alzheimer's disease (AD) and the relationship between brain structure and cerebrospinal fluid (CSF) AD biomarkers in depressed and non-depressed patients. METHODS: Two independent cohorts were used in this study. The first cohort (KI) was collected from the Memory Clinic at Karolinska University Hospital and consisted of 41 AD patients. The second cohort was selected and downloaded from the Alzheimer's Disease Neuroimaging Initiative database (ADNI) and consisted of 148 patient. Patients underwent medical, neuropsychological assessment, laboratory analyses of CSF, including β amyloid 1-42 (Aβ 42), total τ (t-τ), phosphorylated τ 181 (p-τ) and brain MRI examination. In the KI cohort, depression was assessed using the Cornell Scale for Depression in Dementia, and in the ADNI cohort the Geriatric Depression Scale was applied. 3D T1-weighted MRI images were processed using automated steps for segmentation and surface reconstruction implemented in Freesurfer. General linear model analysis was used as a statistical approach. RESULTS: Cortical thinning in AD patients with depressive symptoms compared with those without was observed in the left parietal and temporal brain regions in both cohorts. Negative correlation between cortical thickness and t-τ was greater in depressed compared with non-depressed AD patients in precuneus and parahippocampal cortex. CONCLUSIONS: Our findings suggest that depressive symptoms in AD patients are associated with cortical thinning in temporal and parietal regions. In addition, our findings suggest that τ protein pathology in these areas may contribute to the development of depressive symptoms in AD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
OBJECTIVE: To examine neuroanatomical changes associated with depressive symptoms in Alzheimer's disease (AD) and the relationship between brain structure and cerebrospinal fluid (CSF) AD biomarkers in depressed and non-depressedpatients. METHODS: Two independent cohorts were used in this study. The first cohort (KI) was collected from the Memory Clinic at Karolinska University Hospital and consisted of 41 ADpatients. The second cohort was selected and downloaded from the Alzheimer's Disease Neuroimaging Initiative database (ADNI) and consisted of 148 patient. Patients underwent medical, neuropsychological assessment, laboratory analyses of CSF, including β amyloid 1-42 (Aβ 42), total τ (t-τ), phosphorylated τ 181 (p-τ) and brain MRI examination. In the KI cohort, depression was assessed using the Cornell Scale for Depression in Dementia, and in the ADNI cohort the Geriatric Depression Scale was applied. 3D T1-weighted MRI images were processed using automated steps for segmentation and surface reconstruction implemented in Freesurfer. General linear model analysis was used as a statistical approach. RESULTS: Cortical thinning in ADpatients with depressive symptoms compared with those without was observed in the left parietal and temporal brain regions in both cohorts. Negative correlation between cortical thickness and t-τ was greater in depressed compared with non-depressedADpatients in precuneus and parahippocampal cortex. CONCLUSIONS: Our findings suggest that depressive symptoms in ADpatients are associated with cortical thinning in temporal and parietal regions. In addition, our findings suggest that τ protein pathology in these areas may contribute to the development of depressive symptoms in AD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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