title: Does amyloid deposition produce a specific atrophic signature in cognitively normal subjects?
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.
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Whitwell
authors.forename: Nirubol
authors.initials: N
authors.lastname: Tosakulwong
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Weigand
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Senjem
authors.forename: Val J
authors.initials: VJ
authors.lastname: Lowe
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Gunter
authors.forename: Bradley F
authors.initials: BF
authors.lastname: Boeve
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.forename: Bradford C
authors.initials: BC
authors.lastname: Dickerson
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
keywords: Alzheimer's disease; Amyloid; Cognitively normal; Freesurfer; Preclinical; Voxel-based morphometry