Multicenter Study

. 2016 Feb;12(2):164-169.

doi: 10.1016/j.jalz.2015.07.492. Epub 2015 Aug 29.

Multisite assessment of NIA-AA guidelines for the neuropathologic evaluation of Alzheimer's disease

Thomas J Montine¹, Sarah E Monsell², Thomas G Beach³, Eileen H Bigio⁴, Yunqi Bu², Nigel J Cairns⁵, Matthew Frosch⁶, Jonathan Henriksen⁷, Julia Kofler⁸, Walter A Kukull², Edward B Lee⁹, Peter T Nelson¹⁰, Aimee M Schantz⁷, Julie A Schneider¹¹, Joshua A Sonnen⁷, John Q Trojanowski⁹, Harry V Vinters¹², Xiao-Hua Zhou², Bradley T Hyman¹³

Affiliations

¹ Department of Pathology, University of Washington, Seattle, WA, USA. Electronic address: tmontine@u.washington.edu.
² National Alzheimer Coordinating Center, University of Washington, Seattle, WA, USA.
³ Banner Sun Health Research Institute, Civin Laboratory for Neuropathology, Sun City, AZ, USA.
⁴ Cognitive Neurology and Alzheimer's Disease Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
⁵ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
⁶ Department of Pathology, C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Charleston, MA, USA.
⁷ Department of Pathology, University of Washington, Seattle, WA, USA.
⁸ Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
⁹ Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
¹⁰ Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Pathology Department, University of Kentucky, Lexington, KY, USA.
¹¹ Department of Pathology Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
¹² Department of Pathology & Laboratory Medicine (Neuropathology) David Geffen School of Medicine at UCLA, and Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA; Department of Neurology, David Geffen School of Medicine at UCLA, and Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA.
¹³ Department of Neurology, Massachusetts General Hospital, Charleston, MA, USA; Massachusetts Alzheimer's Disease Research Center, Massachusetts General Hospital, Charleston, MA, USA.

PMID: 26327235
PMCID: PMC4562409
DOI: 10.1016/j.jalz.2015.07.492

Multicenter Study

Multisite assessment of NIA-AA guidelines for the neuropathologic evaluation of Alzheimer's disease

Thomas J Montine et al. Alzheimers Dement. 2016 Feb.

. 2016 Feb;12(2):164-169.

doi: 10.1016/j.jalz.2015.07.492. Epub 2015 Aug 29.

Authors

Affiliations

¹ Department of Pathology, University of Washington, Seattle, WA, USA. Electronic address: tmontine@u.washington.edu.
² National Alzheimer Coordinating Center, University of Washington, Seattle, WA, USA.
³ Banner Sun Health Research Institute, Civin Laboratory for Neuropathology, Sun City, AZ, USA.
⁴ Cognitive Neurology and Alzheimer's Disease Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
⁵ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
⁶ Department of Pathology, C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Charleston, MA, USA.
⁷ Department of Pathology, University of Washington, Seattle, WA, USA.
⁸ Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
⁹ Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
¹⁰ Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Pathology Department, University of Kentucky, Lexington, KY, USA.
¹¹ Department of Pathology Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
¹² Department of Pathology & Laboratory Medicine (Neuropathology) David Geffen School of Medicine at UCLA, and Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA; Department of Neurology, David Geffen School of Medicine at UCLA, and Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA.
¹³ Department of Neurology, Massachusetts General Hospital, Charleston, MA, USA; Massachusetts Alzheimer's Disease Research Center, Massachusetts General Hospital, Charleston, MA, USA.

PMID: 26327235
PMCID: PMC4562409
DOI: 10.1016/j.jalz.2015.07.492

Abstract

Introduction: Neuropathologic assessment is the current "gold standard" for evaluating the Alzheimer's disease (AD), but there is no consensus on the methods used.

Methods: Fifteen unstained slides (8 brain regions) from each of the 14 cases were prepared and distributed to 10 different National Institute on Aging AD Centers for application of usual staining and evaluation following recently revised guidelines for AD neuropathologic change.

Results: Current practice used in the AD Centers Program achieved robustly excellent agreement for the severity score for AD neuropathologic change (average weighted κ = .88, 95% confidence interval: 0.77-0.95) and good-to-excellent agreement for the three supporting scores. Some improvement was observed with consensus evaluation but not with central staining of slides. Evaluation of glass slides and digitally prepared whole-slide images was comparable.

Discussion: AD neuropathologic evaluation as performed across AD Centers yields data that have high agreement with potential modifications for modest improvements.

Keywords: Alzheimer's disease; Methods; Multisite; Neuropathology; Whole-slide imaging.

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Figures

**Figure 1**
Histogram of paired κ for current practice (independent evaluation of locally-stained slides).

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Multisite assessment of NIA-AA guidelines for the neuropathologic evaluation of Alzheimer's disease

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Multisite assessment of NIA-AA guidelines for the neuropathologic evaluation of Alzheimer's disease

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