Defining SNAP by cross-sectional and longitudinal definitions of neurodegeneration

L. E.M. Wisse, S. R. Das, C. Davatzikos, B. C. Dickerson, S. X. Xie, P. A. Yushkevich, D. A. Wolk, for the, Alzheimer's Disease Neuroimaging Initiative

Research output: Contribution to journalArticle


Introduction: Suspected non-Alzheimer's pathophysiology (SNAP) is a biomarker driven designation that represents a heterogeneous group in terms of etiology and prognosis. SNAP has only been identified by cross-sectional neurodegeneration measures, whereas longitudinal measures might better reflect “active” neurodegeneration and might be more tightly linked to prognosis. We compare neurodegeneration defined by cross-sectional ‘hippocampal volume’ only (SNAP/L−) versus both cross-sectional and longitudinal ‘hippocampal atrophy rate’ (SNAP/L+) and investigate how these definitions impact prevalence and the clinical and biomarker profile of SNAP in Mild Cognitive Impairment (MCI). Methods: 276 MCI patients from ADNI-GO/2 were designated amyloid “positive” (A+) or “negative” (A−) based on their florbetapir scan and neurodegeneration ‘positive’ or ‘negative’ based on cross-sectional hippocampal volume and longitudinal hippocampal atrophy rate. Results: 74.1% of all SNAP participants defined by the cross-sectional definition of neurodegeneration also met the longitudinal definition of neurodegeneration, whereas 25.9% did not. SNAP/L+ displayed larger white matter hyperintensity volume, a higher conversion rate to dementia over 5 years and a steeper decline on cognitive tasks compared to SNAP/L− and the A- CN group. SNAP/L− had more abnormal values on neuroimaging markers and worse performance on cognitive tasks than the A- CN group, but did not show a difference in dementia conversion rate or longitudinal cognition. Discussion: Using a longitudinal definition of neurodegeneration in addition to a cross-sectional one identifies SNAP participants with significant cognitive decline and a worse clinical prognosis for which cerebrovascular disease may be an important driver.

Original languageEnglish (US)
Pages (from-to)407-412
Number of pages6
JournalNeuroImage: Clinical
StatePublished - Jan 1 2018



  • Cross-sectional
  • Longitudinal
  • Mild cognitive impairment
  • Neurodegeneration
  • Suspected non-AD pathology

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology
  • Cognitive Neuroscience

Cite this

Wisse, L. E. M., Das, S. R., Davatzikos, C., Dickerson, B. C., Xie, S. X., Yushkevich, P. A., Wolk, D. A., for the, & Alzheimer's Disease Neuroimaging Initiative (2018). Defining SNAP by cross-sectional and longitudinal definitions of neurodegeneration. NeuroImage: Clinical, 18, 407-412.