Application of the National Institute on Aging (NIA)-Reagan Institute Criteria for the Neuropathological Diagnosis of Alzheimer Disease
Abstract
The Khachaturian criteria and the Consortium to Establish a Registry for Alzheimer Disease (CERAD) criteria for the neuropathological assessment of Alzheimer disease (AD) emphasize senile or neuritic plaques, age, and clinical history. A new scheme stressing topographic staging of neurofibrillary changes in addition to neuritic plaques has been proposed by the National Institute on Aging (NIA)-Reagan Institute Consensus Conference. This scheme assigns cases to high, intermediate, or low likelihood categories that the dementia is due to AD. We applied this method to 84 brains from subjects with clinical and neuropathological diagnoses of AD (n = 33), non-AD dementing illnesses (n = 34), including dementia with Lewy bodies (DLB) and progressive supranuclear palsy (PSP), and no neurological disease (n = 17). We also used Khachaturian and CERAD criteria. Neurofibrillary tangle and neuropil thread densities were assessed on 6-micrometer-thick modified Bielschowsky-stained paraffin sections from entorhinal-perirhinal cortex, CA1 of hippocampus, and neocortex including inferior temporal, visual association, and primary visual cortices. Each case was assigned a Braak and Braak stage. Using the NIA-Reagan criteria, we found excellent agreement between clinical history of AD dementia and brains assigned to the high likelihood category that dementia was due to AD. Among brains diagnosed neuropathologically with other degenerative diseases, NIA-Reagan criteria were more conservative than…
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NIA-Reagan provides instructions for classification of only 3 of 25 possible combinations of CERAD neuritic plaque density and Braak stage.
“Because of 25 possible combinations of CERAD neuritic plaque density and Braak neurofibrillary stage, NIA-Reagan provides instructions for classification of only 3 (32, 38).”
From Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer Disease Centers, 2005–2010 (2012) · cites this paper as [38]
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- Authors
- Newell, K. L., Hyman, B. T., Growdon, J. H., & Hedley-Whyte, E. T.
- Affiliations
- Harvard University (US)
- Corresponding author
- Hyman, Bradley T.
- Venue
- Journal of Neuropathology and Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 1999-11
- Volume
- 58
- Issue
- 11
- Pages
- 1147-1155
- ISSN
- 0022-3069 (ISSN-L)
- OpenAlex
- W2038419623
- Cited by
- 289
- References
- 0
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 11 · 2023: 12 · 2022: 13 · 2021: 5 · 2020: 15 · 2019: 8 · 2018: 18 · 2017: 10 · 2016: 7 · 2015: 16 · 2014: 10 · 2013: 10 · 2012: 21
- FWCI
- 5.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (P50AG005134, AG 05134)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, neuropathological diagnosis, neurofibrillary tangles, Braak staging, neuropil threads, dementia with Lewy bodies, progressive supranuclear palsy, differential diagnosis of dementia, hippocampal CA1, neurodegenerative diseases
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cognition Disorders, Diagnosis, Differential, Female, Hippocampus, Humans, Male, Reference Standards, Registries, Supranuclear Palsy, Progressive, Temporal Lobe, Visual Cortex, Lewy Bodies, Neurofibrillary Tangles, Entorhinal Cortex, Neuropil, Plaque, Amyloid
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