Most studies in which the SNAP concept was used have not been focused on SNAP as a primary aim, but were designed to evaluate diagnostic criteria of AD that incorporate biomarkers. Controversies followed the publication of the SNAP concept. This observation supported the view that SNAP was not simply the result of measurement or classification errors, but rather had a biological basis. 1 The proportion of APOE4 carriers in the SNAP group was 13%, much lower than that in individuals with preclinical AD (~40%), and half that in individuals at stage 0 (24%). The term SNAP was used to convey the notion that the latter group did not represent preclinical AD, but rather had biomarker evidence of non-AD neurodegenerative processes ( Figure 2). 1 23% of participants had neurodegeneration without amyloidosis (A−N+). 1 Of this sample, 31% of participants were at NIA–AA preclinical AD stages 1–3 43% had neither amyloidosis nor neurodegeneration (A−N−) and were classified as being at stage 0. a | 18F-FDG–PET maps (FWE threshold set at P 70 years were classified using amyloid plaque density assessed by PET, brain metabolism assessed by 18F-FDG–PET and hippocampal volume assessed by MRI (see Supplementary Table online). Individuals with AD dementia ( n = 50) were age-matched and sex-matched with cognitively normal elderly individuals ( n = 50).
Which abbreviation stands for pathological condition plus#
2 The NIA–AA staging framework for preclinical AD 2 is based on biomarker combinations and cognition: stage 1 refers to amyloidosis without neurodegeneration (A+N−), stage 2 refers to amyloidosis plus neurodegeneration (A+N+) and stage 3 refers to amyloidosis plus neurodegeneration (A+N+) plus subtle cognitive deficit(s) ( Box 1). 2 The NIA–AA preclinical AD workgroup who proposed this concept operated under the assumption that the term ‘AD’ referred to the pathological condition and that clinical symptoms resulting from the pathological condition are not required in the definition of AD. Preclinical AD was a new concept, in which clinically normal individuals with biomarker evidence of AD pathology were hypothesized to be on the trajectory towards symptomatic AD. 5 Signature topographic patterns characteristic of AD 6 revealed by 18F-FDG–PET and MRI are used as evidence of AD-related neurodegeneration ( Figure 1). The biomarkers of AD-related neurodegeneration are high levels of tau in CSF, brain hypometabolism as assessed by 18F-FDG–PET and atrophy as assessed by anatomic MRI. Biomarkers of fibrillary β-amyloid deposition are high ligand retention on amyloid PET and low levels of amyloid-β 42 in the cerebrospinal fluid (CSF). 2– 5 Five biomarkers are used in the NIA–AA classification.
The NIA–AA criteria rely on biomarkers to classify individuals as either amyloid-β-positive or amyloid-β-negative, and as neurodegeneration-positive or neurodegeneration-negative. SNAP was first described in a study 1 in which the National Institute on Aging–Alzheimer’s Association (NIA–AA) criteria of preclinical AD 2 were examined. Suspected non-Alzheimer disease (AD) pathophysiology (SNAP) is a biomarker-based concept denoting AD-like neurodegeneration in individuals without β-amyloidosis. In this Perspectives article we describe the available data on SNAP and address topical controversies in the field. Clinically normal and mildly impaired individuals with SNAP have worse clinical and/or cognitive outcomes than individuals with normal levels of neurodegeneration and amyloid-β biomarkers. APOE4 is underrepresented in individuals with SNAP compared with amyloid-positive individuals. SNAP is present in ~23% of clinically normal individuals aged >65 years and in ~25% of mildly cognitively impaired individuals. The term SNAP has been applied to individuals who are clinically normal for their age and to individuals with mild cognitive impairment, but is applicable to any amyloid-negative, neurodegeneration-positive individual regardless of clinical status, except when the pathology underlying neurodegeneration can be confidently inferred from the clinical presentation. Suspected non-Alzheimer disease pathophysiology (SNAP) is a biomarker-based concept that applies to individuals with normal levels of amyloid-β biomarkers in the brain, but in whom biomarkers of neurodegeneration are abnormal.
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