title: Biological heterogeneity in ADNI amnestic mild cognitive impairment.
abstract: BACKGROUND
  Previous work examining normal controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI) identified substantial biological heterogeneity. We hypothesized that ADNI mild cognitive impairment (MCI) subjects would also exhibit heterogeneity with possible clinical implications.
  
  
  METHODS
  ADNI subjects diagnosed with amnestic MCI (n=138) were clustered based on baseline magnetic resonance imaging, cerebrospinal fluid, and serum biomarkers. The clusters were compared with respect to longitudinal atrophy, cognitive trajectory, and time to conversion.
  
  
  RESULTS
  Four clusters emerged with distinct biomarker patterns: The first cluster was biologically similar to normal controls and rarely converted to Alzheimer's disease (AD) during follow-up. The second cluster had characteristics of early Alzheimer's pathology. The third cluster showed the most severe atrophy but barely abnormal tau levels and a substantial proportion converted to clinical AD. The fourth cluster appeared to be pre-AD and nearly all converted to AD.
  
  
  CONCLUSIONS
  Subjects with MCI who were clinically similar showed substantial heterogeneity in biomarkers.
authors.affiliation: Department of Psychiatry, University of California-San Francisco, San Francisco, CA, USA. Electronic address: jasmine.nettiksimmons@ucsf.edu.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Nettiksimmons
authors.affiliation: Department of Neurology and Center for Neuroscience, University of California-Davis, Sacramento, CA, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: DeCarli
authors.affiliation: Helen Wills Neuroscience Institute, University of California-Berkeley, Berkeley, CA, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Landau
authors.affiliation: Division of Biostatistics, Department of Public Health Sciences, University of California-Davis, Davis, CA, USA.
authors.forename: Laurel
authors.initials: L
authors.lastname: Beckett
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid; D001284:Atrophy; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology; D016000:Cluster Analysis; D003071:Cognition; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D016875:tau Proteins / Q000097:blood / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; C054369:MAPT protein, human; D016875:tau Proteins
keywords: ADNI; Alzheimer's disease; Amnestic MCI; Clustering; Heterogeneity