Application of the National Institute on Aging (NIA)-Reagan Institute criteria for the neuropathological diagnosis of Alzheimer disease

The Khachaturian criteria and the Consortium to Establish a Registry for Al zheimer Disease (CERAD) criteria for the neuropathological assessment of Al zheimer disease (AD) emphasize sl:nile or neuritic plaques, age, and clinic al history. A new scheme stressing topographic staging of neurofibrillary c hanges in addition to neuritic plaques has been proposed by the National In stitute on Aging (NIA)-Reagan Institute Consensus Conference. This scheme a ssigns cases to high, intermediate, or low likelihood categories that the d ementia is due to AD. We applied this method to 84 brains from subjects wit h clinical and neuropathological diagnoses of AD (n = 33), non-AD dementing illnesses (n = 34), including dementia with Lewy bodies (DLB) and progress ive 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 hippoca mpus, and neocortex including inferior temporal, visual association, and pr imary visual cortices. Each case was assigned a Braak and Braak stage. Usin g the NIA-Reagan criteria, we found excellent agreement between clinical hi story of AD dementia and brains assigned to the high likelihood category th at dementia was due to AD. Among brains diagnosed neuropathologically with other degenerative diseases, MA-Reagan criteria were more conservative than previous criteria, and these cases were Likely to be categorized as interm ediate or low likelihood that dementia was due to AD. All brains front nond emented subjects were assigned to the low (81%) or intermediate (19%) categ ories. In summary, we found good correlation between the NIA-Reagan criteri a and clinical dementia, and there was generally good agreement between the se criteria and existing neuropathological methods, Khachaturian and CERAD. in diagnosing AD. In studying several other neurodegenerative diseases, su ch as DLB, which shows neuropathological and clinical overlap with AD, the staging of neurofibrillary changes offered potential diagnostic refinement.