Revised NIA-AA criteria for the diagnosis of Alzheimer's disease: a step forward but not yet ready for widespread clinical use

Abstract

In clinical medicine, diagnostic criteria are not only useful everyday tools for the practicing physician, but also represent a conceptual concentrate of the understanding of the etiology and pathophysiology of diseases at a given point in time. Although different sets of diagnostic criteria for Alzheimer's disease (AD) have been developed, the most widely used and best validated by clinico-pathological study to date are the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke – Alzheimer's Disease and Related Disorders Association) criteria which were published in 1984 (McKhann et al., 1984). These criteria are largely based on the exclusion of other conditions that may cause dementia and can be succinctly but fairly summarized as defining AD as an “acquired progressive cognitive, behavioral, and functional impairment with no other obvious cause”. Clearly, the NINCDS-ADRDA criteria were etiology- and pathophysiology-agnostic in that they failed to point at any specific etiology, not even a degenerative one. They were also developed before other important causes of dementia, such as dementia with Lewy bodies, fronto-temporal dementia and subcortical vascular dementia had been fully described and characterized. The recent publication of a substantially revised version of these criteria (Sperling et al. 2011; Albert et al., 2011; McKhann et al., 2011), heralded by a largely European initiative four years ago (Dubois et al., 2007) has been greeted with great interest by the field. The newly proposed criteria reflect the substantial insights on disease pathophysiology gained over the last decades, especially regarding the molecular pathology of AD and the time course of such pathology in relation to clinical symptoms and disease.

Regional Fluid-Attenuated Inversion Recovery (FLAIR) at 7 Tesla correlates with amyloid beta in hippocampus and brainstem of cognitively normal elderly subjects

“…In doing so, significant relationships between PiB-PET and FLAIR intensities could be observed for right and left Hippocampus, Brainstem and also a small region including left Basal Ganglia vessels. As the FLAIR contrast reflects a wide spectrum of pathological brain-tissue alterations associated with regional edema (Young et al, 2008; Neema et al, 2009; Carlson et al, 2011), our finding is consistent with earlier reports on signature-regions of AD primarily affected by age-related neurodegeneration: The Hippocampus has been shown by numerous studies to be particularly sensitive to aging related brain change and AD in particular (de Leon et al, 1989; Frisoni et al, 2011; Serrano-Pozo et al, 2011) and neurodegenerative processes can be observed in gray matter nuclei located in Brainstem and Basal Ganglia (Iseki et al, 1989; Parvizi et al, 2001; Simic et al, 2009; Braak and Del Tredici, 2012; Brothers et al, 2013). Notably, significant relationships with FLAIR intensity were not determined by brain regions with highest PiB retention, which may support considerations on pathological relevance of subtle increases of Aβ in vulnerable brain regions (Mormino et al, 2012; Lowe et al, 2014), potentially mediated by additional factors that may determine resilience of distinct neuronal populations (Steffener and Stern, 2012).…”

The National Institute on Aging-Alzheimer’s Association research criteria for mild cognitive impairment due to Alzheimer’s disease: predicting the outcome

“…Consequently, the diagnostic value of biomarkers may differ according to the disease stage. Therefore, the refinement of biomarker algorithms for the NIA-AA criteria constitutes a further challenge [12].…”

Decreased white matter integrity before the onset of delusions in patients with Alzheimer's disease: diffusion tensor imaging

“…However, we started this study in June 2009. The revised criteria require the examination of multiple biomarkers, including the need for a positron emission tomography (PET) examination, and the widespread clinical adoption of the revised criteria remains controversial 14. Thus, we did not adopt the revised criteria that were updated in 2011.…”