title: Regional cortical thinning predicts worsening apathy and hallucinations across the Alzheimer disease spectrum.
abstract: OBJECTIVE
  To examine regions of cortical thinning and cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers associated with apathy and hallucinations in a continuum of individuals including clinically normal elderly, mild cognitive impairment, and mild AD dementia.
  
  
  METHODS
  Cross-sectional and longitudinal studies.
  
  
  METHODS
  Fifty-seven research sites across North America.
  
  
  METHODS
  Eight-hundred twelve community-dwelling volunteers; 413 participants in the CSF sub-study.
  
  
  METHODS
  Structural magnetic resonance imaging data and CSF concentrations of amyloid-β 1-42, total tau, and phosphorylated tau derived from the Alzheimer Disease Neuroimaging Initiative database were analyzed. Apathy and hallucinations were measured at baseline and over 3 years using the Neuropsychiatric Inventory-Questionnaire. General linear models and mixed effects models were used to evaluate the relationships among baseline cortical thickness in seven regions, and baseline CSF biomarkers, apathy, and hallucinations at baseline and longitudinally. Covariates included diagnosis, sex, age, apolipoprotein E genotype, premorbid intelligence, memory performance, processing speed, antidepressant use, and AD duration.
  
  
  RESULTS
  Reduced baseline inferior temporal cortical thickness was predictive of increasing apathy over time, and reduced supramarginal cortical thickness was predictive of increasing hallucinations over time. There was no association with cortical thickness at baseline. CSF biomarkers were not related to severity of apathy or hallucinations in cross-sectional or longitudinal analyses.
  
  
  CONCLUSIONS
  These results suggest that greater baseline temporal and parietal atrophy is associated with worsening apathy and hallucinations in a large AD spectrum cohort, while adjusting for multiple disease-related variables. Localized cortical neurodegeneration may contribute to the pathophysiology of apathy and hallucinations and their adverse consequences in AD.
authors.affiliation: Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Electronic address: njdonovan@partners.org.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Donovan
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Lauren P
authors.initials: LP
authors.lastname: Wadsworth
authors.affiliation: Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Natacha
authors.initials: N
authors.lastname: Lorius
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Locascio
authors.affiliation: Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Dorene M
authors.initials: DM
authors.lastname: Rentz
authors.affiliation: Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Johnson
authors.affiliation: Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
authors.affiliation: Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Gad A
authors.initials: GA
authors.lastname: Marshall
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000150:complications / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D057565:Apathy; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002540:Cerebral Cortex / Q000473:pathology*; D003430:Cross-Sectional Studies; D005260:Female; D006212:Hallucinations / Q000209:etiology* / Q000473:pathology; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Alzheimer disease; Apathy; CSF biomarkers; MRI; cortical thinning; hallucinations
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