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Open Access 01-12-2013 | Research

Clinical and multimodal biomarker correlates of ADNI neuropathological findings

Authors: Jon B Toledo, Nigel J Cairns, Xiao Da, Kewei Chen, Deborah Carter, Adam Fleisher, Erin Householder, Napatkamon Ayutyanont, Auttawut Roontiva, Robert J Bauer, Paul Eisen, Leslie M Shaw, Christos Davatzikos, Michael W Weiner, Eric M Reiman, John C Morris, John Q Trojanowski, the Alzheimer’s Disease Neuroimaging Initiative

Published in: Acta Neuropathologica Communications | Issue 1/2013

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.

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Title: Clinical and multimodal biomarker correlates of ADNI neuropathological findings
Authors: Jon B Toledo
Nigel J Cairns
Xiao Da
Kewei Chen
Deborah Carter
Adam Fleisher
Erin Householder
Napatkamon Ayutyanont
Auttawut Roontiva
Robert J Bauer
Paul Eisen
Leslie M Shaw
Christos Davatzikos
Michael W Weiner
Eric M Reiman
John C Morris
John Q Trojanowski
the Alzheimer’s Disease Neuroimaging Initiative
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Acta Neuropathologica Communications / Issue 1/2013
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/2051-5960-1-65

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Clinical and multimodal biomarker correlates of ADNI neuropathological findings

Abstract

Background

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusions

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