SUSPECTED NON-ALZHEIMER DISEASE PATHOPHYSIOLOGY (SNAP) CATEGORIZATION IN THE INSIGHT COHORT

Abstract

Background Suspected non-Alzheimer disease pathophysiology (SNAP) individuals are participants to studies on Alzheimer’s disease (AD) biomarkers that are considered positive for markers of neurodegeneration and negative for markers of brain amyloidosis in the absence of a major neurocognitive disorder. This concept probably encompasses numerous neurological diseases in which the mildness of symptoms is responsible for a generic term to be proposed instead of a diagnosis. Methods We categorized SNAP subjects in the INSIGHT cohort, a mono-centric French cohort at the University Salpetriere Hospital in Paris including 317 individuals with subjective cognitive decline (SCD) between 70-85 year. Standardized demographic, cognitive, MRI, 18FDG and AV45 PET imaging were performed in each subject. The SNAP population was determined based on cut-offs scores adapted from the literature. Each SNAP participant’s complete medical file was analyzed by an expert committee comprised of 3 neurologists, 1 geriatrician, 1 neuropsychologist, 1 neuroradiologist and 1 nuclear medicine MD. Diagnostic algorithms were adapted from international consensus criteria for various neurological conditions (eg Rascovsky’s criteria for Fronto-temporal dementia). Results Among the INSIGHT participants, 88 are considered amyloid (+) with a significantly increased cortical uptake of the tracer above threshold on PET imaging, and 229 are amyloid (-). The 229 amyloid negative individuals were categorized in 4 groups determined by their clinico-radiological status: Healthy control, SNAP-AD when neurodegeneration was suggestive of AD, SNAP-NONAD when the neurodegeneration was incompatible with typical AD and SNAP-MIXED in all other participants. We have then applied our diagnostic procedure in the SNAP participants to determine if this group can be divided into known neurological diseases. Conclusions This is one of the first attempts to refine the diagnostic procedure in SNAP, a frequent condition in the elderly population. Similarly to AD, a presymptomatic/early symptomatic phase of different brain affections can be diagnosed instead of using the SNAP acronym.