title: Structural brain changes associated with depressive symptoms in the elderly with Alzheimer's disease.
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.
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Lebedeva
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
authors.forename: Eric
authors.initials: E
authors.lastname: Westman
authors.affiliation: Center for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Aleksander V
authors.initials: AV
authors.lastname: Lebedev
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
authors.forename: Xiaozhen
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.affiliation: 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.
authors.forename: Andrew
authors.initials: A
authors.lastname: Simmons
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
authors.forename: Lars-Olof
authors.initials: LO
authors.lastname: Wahlund
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden Center for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Dag
authors.initials: D
authors.lastname: Aarsland
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000473:pathology* / Q000523:psychology*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D015331:Cohort Studies; D003863:Depression / Q000473:pathology* / Q000523:psychology*; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000473:pathology; D011569:Psychiatric Status Rating Scales
chemical_list: D015415:Biomarkers
keywords: Alzheimer disease; CSF; MRI; depression; image analysis