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 previous criteria, and these cases were likely to be categorized as intermediate or low likelihood that dementia was due to AD. All brains from nondemented subjects were assigned to the low (81%) or intermediate (19%) categories. In summary, we found good correlation between the NIA-Reagan criteria and clinical dementia, and there was generally good agreement between these criteria and existing neuropathological methods, Khachaturian and CERAD, in diagnosing AD. In studying several other neurodegenerative diseases, such as DLB, which shows neuropathological and clinical overlap with AD, the staging of neurofibrillary changes offered potential diagnostic refinement.

Consortium to Establish a Registry for Alzheimer's Disease (CERAD): The first twenty years

“…It has been critically compared with the Braak and Braak, 47 Khachaturian,13 NIA-Reagan Institute, 46 and the Tierney A3 criteria. [48][49][50][51] The CERAD neuropathology criteria have been and continue to be used in a substantial number of studies, both in the U.S., and abroad.…”

“…It has been critically compared with the Braak and Braak, 47 Khachaturian, 13 NIA-Reagan Institute, 46 and the Tierney A3 criteria. [48][49][50][51] The CERAD neuropathology criteria have been and continue to be used in a substantial number of studies, both in the U.S., and abroad.Some have expressed concerns that the CERAD protocol fails to take into account significant pathological and biochemical factors such as estimations of soluble amyloid load, aberrant tau accumulation, and synaptic density. 52 Nor has the protocol been modified to encompass changes reflecting our latest understanding of certain other dementias (e.g.…”

DNA fragmentation is increased in non-GABAergic neurons in bipolar disorder but not in schizophrenia

“…The presence of senile plaques and neurofibrillary tangles were evaluated in cases obtained prior to 1999 using the CERAD criteria (Davidson et al, 1996) and in those obtained after 1999 using the Braak criteria (Newell et al, 1999). None of the subjects in this study received a neuropathological diagnosis of senile dementia of the Alzheimer's type according to either set of criteria.…”

Isofurans, but not F2‐isoprostanes, are increased in the substantia nigra of patients with Parkinson's disease and with dementia with Lewy body disease

“…All patients had been diagnosed during life with extrapyramidal movement disorders or dementia. Final diagnoses were established by neuropathological examination according to established criteria (McKeith et al 1996;Lowe et al 1997;Mirra 1997;Newell et al 1999). Autopsy protocols, approved by each individual institution, were very similar and included flashfreezing of tissue followed by storage at ) 80°C until analyzed.…”