Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging‐Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

Abstract

The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long “preclinical” phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer's Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from “normal” cognition to mild cognitive impairment and AD dementia. We propose a conceptual framework and operational research criteria, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies. These recommendations are solely intended for research purposes and do not have any clinical implications at this time. It is hoped that these recommendations will provide a common rubric to advance the study of preclinical AD, and ultimately, aid the field in moving toward earlier intervention at a stage of AD when some disease-modifying therapies may be most efficacious.

Functional brain network centrality is related to APOE genotype in cognitively normal elderly

“…The plots per subgroup show that EC variability against test score is lower in e4 carriers. This indicates differences in brain network organization between carriers and noncarriers that make the brain more vulnerable to AD‐related pathology (De Meyer et al., 2010; Evans et al., 2014; Mintun et al., 2006; Sperling et al., 2011). In an important way, this does not lead to decreased cognitive decline or visuoperceptual performance.…”

Magnetic resonance spectroscopy reveals abnormalities of glucose metabolism in the Alzheimer's brain

“…Demographic data for the groups are summarized in Table 1. AD diagnosis with high probability was based on clinical diagnosis, low CSF A β , high CSF Tau and/or p‐Tau 16, 21…”

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

“…The revised NIA-AA diagnostic criteria for Alzheimer's disease (Sperling et al, 2011;Albert et al, 2011;McKhann et al, 2011) NIA-AA = National Institute on Aging and Alzheimer's Association; AD = Alzheimer's disease; MCI = mild cognitive impairment; Amy = brain amyloidosis; Ndg = neurodegeneration; Ss = cognitive symptoms; n.a. = biomarker untested; UC = biomarker uninformative or conflicting.…”

“…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.…”