The Revised National Alzheimer's Coordinating Center's Neuropathology Form-Available Data and New Analyses

Abstract

Neuropathologic evaluation remains the gold standard for determining the presence and severity of aging-related neurodegenerative diseases. Researchers at U.S. Alzheimer's Disease Centers (ADCs) have worked for >30 years studying human brains, with the goals of achieving new research breakthroughs. Harmonization and sharing among the 39 current and past ADCs is promoted by the National Alzheimer's Coordinating Center (NACC), which collects, audits, and disburses ADC-derived data to investigators on request. The past decades have witnessed revised disease definitions paired with dramatic expansion in the granularity and multimodality of the collected data. The NACC database now includes cognitive test scores, comorbidities, drug history, neuroimaging, and links to genomics. Relatively, recent advances in the neuropathologic diagnoses of Alzheimer's disease, frontotemporal lobar degeneration (FTLD), and vascular contributions to cognitive impairment and dementia catalyzed a 2014 update to the NACC Neuropathology Form completed by all ADCs. New focal points include cerebrovascular disease (including arteriolosclerosis, microbleeds, and microinfarcts), hippocampal sclerosis, TDP-43, and FTLD. Here, we provide summary data and analyses to illustrate the potential for both hypothesis-testing and also generating new hypotheses using the NACC Neuropathology data set, which represents one of the largest multi-center databases of carefully curated neuropathologic information that is freely available to researchers worldwide.

FIGURE 1.

(A) Temporal change in cognitive status (from most recent evaluation) of autopsied participants in the National Alzheimer’s Coordinating Center’s data set. Note the trend for increased proportion of nondemented participants. (B) A sample of temporal change in underlying neuropathologies reported. Two pathologies that have tended to become more commonly diagnosed in recent years are microinfarcts and hippocampal sclerosis.

FIGURE 2.

Individuals with primary age-related tauopathy ([PART]; no neuritic plaques), stratified by cognitive status at last visit. Excluded from this analysis were persons who died at <70 years of age or who had hippocampal sclerosis or Lewy body disease pathology. Sample sizes: n = 132 with normal cognition; n = 34 with subjective memory complaint; n = 64 with mild cognitive impairment. Cochran-Armitage test for trend: Braak neurofibrillary tangle (NFT) stage II versus all other Braak NFT stages, p = 0.03; Braak NFT stage IV versus all other Braak NFT stages, p = 0.007.