Mild cognitive impairment with suspected nonamyloid pathology (SNAP)

Abstract

Objectives: The aim of this study was to investigate predictors of progressive cognitive deterioration in patients with suspected non-Alzheimer disease pathology (SNAP) and mild cognitive impairment (MCI). Methods:We measured markers of amyloid pathology (CSF b-amyloid 42) and neurodegeneration (hippocampal volume on MRI and cortical metabolism on [18 F]-fluorodeoxyglucose-PET) in 201 patients with MCI clinically followed for up to 6 years to detect progressive cognitive deterioration. We categorized patients with MCI as A1/A2 and N1/N2 based on presence/absence of amyloid pathology and neurodegeneration. SNAPs were A2N1 cases.Results: The proportion of progressors was 11% (8/41), 34% (14/41), 56% (19/34), and 71%(60/85) in A2N2, A1N2, SNAP, and A1N1, respectively; the proportion of APOE e4 carriers was 29%, 70%, 31%, and 71%, respectively, with the SNAP group featuring a significantly different proportion than both A1N2 and A1N1 groups (p # 0.005). Hypometabolism in SNAP patients was comparable to A1N1 patients (p 5 0.154), while hippocampal atrophy was more severe in SNAP patients (p 5 0.002). Compared with A2N2, SNAP and A1N1 patients had significant risk of progressive cognitive deterioration (hazard ratio 5 2.7 and 3.8, p 5 0.016 and p , 0.001), while A1N2 patients did not (hazard ratio 5 1.13, p 5 0.771). In A1N2 and A1N1 groups, none of the biomarkers predicted time to progression. In the SNAP group, lower time to progression was correlated with greater hypometabolism (r 5 0.42, p 5 0.073). The amyloid cascade hypothesis 1,2 has so far dominated the Alzheimer disease (AD) field. Jack et al. Conclusions:3,4 proposed a dynamic model that relates disease stage to the best established biomarkers of AD pathology. Based on this, a National Institute on Aging-Alzheimer's Association task force developed recommendations for the diagnosis of preclinical AD based on biomarkers of amyloidosis and neuronal injury.5 Soon afterward, these criteria were operationalized and a

Amyloidosis and neurodegeneration result in distinct structural connectivity patterns in mild cognitive impairment

“…These indicators include biomarkers of β-amyloidosis (reductions in CSF Aβ 42 and increased amyloid PET tracer retention) and biomarkers of neuronal injury and neurodegeneration (increased CSF tau, decrease of fluorodeoxyglucose uptake on PET, structural MRI measures of hippocampal atrophy) . Biomarkers have improved the characterization of the heterogeneity of the MCI phenotype by distinguishing patients with and without abnormal biomarkers of amyloidosis and neurodegeneration (Caroli et al, 2015;Petersen et al, 2013;Vos et al, 2015;Wisse et al, 2015). In particular, two subgroups of patients are of high interest.…”

“…The first one is composed of patients with abnormal biomarkers of both amyloidosis and neurodegeneration (MCI A+N+, also called high likelihood MCI due to AD or prodromal AD). This population has been shown to display a high rate of APOE ε4 carriers, a greater cognitive decline over time and a higher rate of progression and conversion to AD (Caroli et al, 2015;Edmonds et al, 2015;Knopman et al, 2012;Prestia et al, 2013;Vos et al, 2013).…”

“…Various studies have analyzed the differences between SNAP and amyloid positive patients, in terms of clinical and cognitive trajectories, APOE genotype and underlying pathology (Caroli et al, 2015;Jack, 2014;Jack et al, 2015Jack et al, , 2014Jack et al, , 2010Knopman et al, 2012;Mormino et al, 2014;Petersen et al, 2013;Prestia et al, 2013;Toledo et al, 2015, Vos et al, 2013Wirth et al, 2013;Wisse et al, 2015). For…”

A Cochrane review on brain [18F]FDG PET in dementia: limitations and future perspectives

“…Thirdly, four of the recent papers did not just study [ [27,28,31,35]. This is indeed a more natural approach, trying to simulate clinical practice and integrating different AD biomarkers, balancing healthcare costs with diagnostic accuracy.…”

Association of postoperative delirium with markers of neurodegeneration and brain amyloidosis: a pilot study

“…cognitive deterioration compared to biomarker negative or amyloid only positive patients (Caroli et al, 2015). Moreover, they displayed less AD-specific hypometabolism and CSF signature compared to typical AD (Landau et al, 2016) and limbic-predominant atrophy compared to controls, characterized by subtle atrophy and hypometabolism mainly restricted to the retrosplenial, orbitofrontal, and dorsomedial prefrontal cortex .…”