title: Clinical and multimodal biomarker correlates of ADNI neuropathological findings.
abstract: BACKGROUND
  Autopsy series commonly report a high percentage of coincident pathologies in demented patients, including patients with a clinical diagnosis of dementia of the Alzheimer type (DAT). However many clinical and biomarker studies report cases with a single neurodegenerative disease. We examined multimodal biomarker correlates of the consecutive series of the first 22 Alzheimer's Disease Neuroimaging Initiative autopsies. Clinical data, neuropsychological measures, cerebrospinal fluid Aβ, total and phosphorylated tau and α-synuclein and MRI and FDG-PET scans.
  
  
  RESULTS
  Clinical diagnosis was either probable DAT or Alzheimer's disease (AD)-type mild cognitive impairment (MCI) at last evaluation prior to death. All patients had a pathological diagnosis of AD, but only four had pure AD. A coincident pathological diagnosis of dementia with Lewy bodies (DLB), medial temporal lobe pathology (TDP-43 proteinopathy, argyrophilic grain disease and hippocampal sclerosis), referred to collectively here as MTL, and vascular pathology were present in 45.5%, 40.0% and 22.7% of these patients, respectively. Hallucinations were a strong predictor of coincident DLB (100% specificity) and a more severe dysexecutive profile was also a useful predictor of coincident DLB (80.0% sensitivity and 83.3% specificity). Occipital FDG-PET hypometabolism accurately classified coincident DLB (80% sensitivity and 100% specificity). Subjects with coincident MTL showed lower hippocampal volume.
  
  
  CONCLUSIONS
  Biomarkers can be used to independently predict coincident AD and DLB pathology, a common finding in amnestic MCI and DAT patients. Cohorts with comprehensive neuropathological assessments and multimodal biomarkers are needed to characterize independent predictors for the different neuropathological substrates of cognitive impairment.
authors.affiliation: Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. morrisj@abraxas.wustl.edu.
authors.forename: Jon B
authors.initials: JB
authors.lastname: Toledo
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Cairns
authors.forename: Xiao
authors.initials: X
authors.lastname: Da
authors.forename: Kewei
authors.initials: K
authors.lastname: Chen
authors.forename: Deborah
authors.initials: D
authors.lastname: Carter
authors.forename: Adam
authors.initials: A
authors.lastname: Fleisher
authors.forename: Erin
authors.initials: E
authors.lastname: Householder
authors.forename: Napatkamon
authors.initials: N
authors.lastname: Ayutyanont
authors.forename: Auttawut
authors.initials: A
authors.lastname: Roontiva
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Bauer
authors.forename: Paul
authors.initials: P
authors.lastname: Eisen
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
authors.forename: Christos
authors.initials: C
authors.lastname: Davatzikos
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.forename: Eric M
authors.initials: EM
authors.lastname: Reiman
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000473:pathology* / Q000523:psychology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000473:pathology* / Q000523:psychology; D015331:Cohort Studies; D016208:Databases, Factual; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000473:pathology / Q000523:psychology; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers