title: Chronic Depressive Symptomatology in Mild Cognitive Impairment Is Associated with Frontal Atrophy Rate which Hastens Conversion to Alzheimer Dementia.
abstract: OBJECTIVE
  Investigate the association of chronic depressive symptomatology (chrDS) with cortical atrophy rates and conversion to Alzheimer dementia (AD) over 3 years in mild cognitive impairment (MCI).
  
  
  METHODS
  In a multicenter, clinic-based study, MCI elderly participants were selected from the Alzheimer's Disease Neuroimaging Initiative repository, based on availability of both serial structural magnetic resonance imaging and chrDS endorsed on three depression-related items from the Neuropsychiatric Inventory Questionnaire (chrDS N = 32 or no depressive symptoms N = 62) throughout follow-up. Clinical and laboratory investigations were performed every 6 months during the first 2 years and yearly thereafter (median follow-up: 3 years; interquartile range: 1.5-4.0 years). Cortical atrophy rates in 16 predefined frontotemporoparietal regions affected in major depression and AD and the rate of incident AD at follow-up.
  
  
  RESULTS
  ChrDS in a single domain amnestic MCI sample were associated with accelerated cortical atrophy in the frontal lobe and anterior cingulate but not with atrophy rates in temporomedial or other AD-affected regions. During follow-up, 38 participants (42.7%) developed AD. Participants with chrDS had 60% shorter conversion time to AD than those without depressive symptoms. This association remained significant in survival models adjusted for temporomedial atrophy rates and showed the same trend in models adjusted for frontal cortical atrophy rate, which all increased the risk of AD.
  
  
  CONCLUSIONS
  Our results suggest that chrDS associated with progressive atrophy of frontal regions may represent an additional risk factor for conversion to dementia in MCI as opposite to representing typical prodromal AD symptomatology.
authors.affiliation: Center for Imaging of Neurodegenerative Diseases, Veterans Affairs Medical Center, San Francisco, CA; Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA; Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Simona
authors.initials: S
authors.lastname: Sacuiu
authors.affiliation: Center for Imaging of Neurodegenerative Diseases, Veterans Affairs Medical Center, San Francisco, CA.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Insel
authors.affiliation: Center for Imaging of Neurodegenerative Diseases, Veterans Affairs Medical Center, San Francisco, CA; Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA.
authors.forename: Susanne
authors.initials: S
authors.lastname: Mueller
authors.affiliation: Center for Imaging of Neurodegenerative Diseases, Veterans Affairs Medical Center, San Francisco, CA; Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA.
authors.forename: Duygu
authors.initials: D
authors.lastname: Tosun
authors.affiliation: Center for Imaging of Neurodegenerative Diseases, Veterans Affairs Medical Center, San Francisco, CA; Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA; Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Mattsson
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, CA.
authors.forename: Charles
authors.initials: C
authors.lastname: DeCarli
authors.affiliation: Mayo Alzheimer's Disease Research Center and Mayo Clinic College of Medicine, Rochester, MN.
authors.forename: Ronald
authors.initials: R
authors.lastname: Petersen
authors.affiliation: Department of Neurosciences, University of California, San Diego, CA.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
authors.affiliation: Center for Imaging of Neurodegenerative Diseases, Veterans Affairs Medical Center, San Francisco, CA; Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.affiliation: Center for Imaging of Neurodegenerative Diseases, Veterans Affairs Medical Center, San Francisco, CA; Department of Psychiatry, University of California San Francisco, San Francisco, CA. Electronic address: scottm@lppi.ucsf.edu.
authors.forename: R Scott
authors.initials: RS
authors.lastname: Mackin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000453:epidemiology*; D001284:Atrophy; D002540:Cerebral Cortex / Q000503:physiopathology*; D060825:Cognitive Dysfunction / Q000150:complications*; D003863:Depression / Q000453:epidemiology*; D003865:Major Depressive Disorder / Q000453:epidemiology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales
keywords: Alzheimer dementia; Depressive symptoms; MRI; cohort study; mild cognitive impairment