Does amyloid deposition produce a specific atrophic signature in cognitively normal subjects?

Jennifer L. Whitwell, Nirubol Tosakulwong, Stephen D. Weigand, Matthew L. Senjem, Val J. Lowe, Jeffrey L. Gunter, Bradley F. Boeve, David S. Knopman, Bradford C. Dickerson, Ronald C. Petersen, Clifford R. Jack

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Abstract The objective of our study was to evaluate whether cognitively normal (CN) elderly participants showing elevated cortical beta-amyloid (Aβ) deposition have a consistent neuroanatomical signature of brain atrophy that may characterize preclinical Alzheimer's disease (AD). 115 CN participants who were Aβ-positive (CN +) by amyloid PET imaging; 115 CN participants who were Aβ-negative (CN -); and 88 Aβ-positive mild cognitive impairment or AD participants (MCI/AD +) were identified. Cortical thickness (FreeSurfer) and gray matter volume (SPM5) were measured for 28 regions-of-interest (ROIs) across the brain and compared across groups. ROIs that best discriminated CN - from CN + differed for FreeSurfer cortical thickness and SPM5 gray matter volume. Group-wise discrimination was poor with a high degree of uncertainty in terms of the rank ordering of ROIs. In contrast, both techniques showed strong and consistent findings comparing MCI/AD + to both CN - and CN + groups, with entorhinal cortex, middle and inferior temporal lobe, inferior parietal lobe, and hippocampus providing the best discrimination for both techniques. Concordance across techniques was higher for the CN - and CN + versus MCI/AD + comparisons, compared to the CN - versus CN + comparison. The weak and inconsistent nature of the findings across technique in this study cast doubt on the existence of a reliable neuroanatomical signature of preclinical AD in elderly PiB-positive CN participants.

Original languageEnglish (US)
Pages (from-to)249-257
Number of pages9
JournalNeuroImage: Clinical
Volume2
Issue number1
DOIs
StatePublished - Feb 20 2013

Keywords

  • Alzheimer's disease
  • Amyloid
  • Cognitively normal
  • Freesurfer
  • Keywords
  • Preclinical
  • Voxel-based morphometry

ASJC Scopus subject areas

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

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