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

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

Research output: Contribution to journalArticle

27 Citations (Scopus)

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 - 2013

Fingerprint

Amyloid
Alzheimer Disease
Entorhinal Cortex
Parietal Lobe
Brain
Temporal Lobe
Uncertainty
Atrophy
Hippocampus

Keywords

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

ASJC Scopus subject areas

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

Cite this

Does amyloid deposition produce a specific atrophic signature in cognitively normal subjects? / Whitwell, Jennifer Lynn; Tosakulwong, Nirubol; Weigand, Stephen D.; Senjem, Matthew L.; Lowe, Val; Gunter, Jeffrey L.; Boeve, Bradley F; Knopman, David S; Dickerson, Bradford C.; Petersen, Ronald Carl; Jack, Clifford R Jr.

In: NeuroImage: Clinical, Vol. 2, No. 1, 2013, p. 249-257.

Research output: Contribution to journalArticle

Whitwell, Jennifer Lynn ; Tosakulwong, Nirubol ; Weigand, Stephen D. ; Senjem, Matthew L. ; Lowe, Val ; Gunter, Jeffrey L. ; Boeve, Bradley F ; Knopman, David S ; Dickerson, Bradford C. ; Petersen, Ronald Carl ; Jack, Clifford R Jr. / Does amyloid deposition produce a specific atrophic signature in cognitively normal subjects?. In: NeuroImage: Clinical. 2013 ; Vol. 2, No. 1. pp. 249-257.
@article{604b77f66e524dceb785bed54577f712,
title = "Does amyloid deposition produce a specific atrophic signature in cognitively normal subjects?",
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.",
keywords = "Alzheimer's disease, Amyloid, Cognitively normal, Freesurfer, Keywords, Preclinical, Voxel-based morphometry",
author = "Whitwell, {Jennifer Lynn} and Nirubol Tosakulwong and Weigand, {Stephen D.} and Senjem, {Matthew L.} and Val Lowe and Gunter, {Jeffrey L.} and Boeve, {Bradley F} and Knopman, {David S} and Dickerson, {Bradford C.} and Petersen, {Ronald Carl} and Jack, {Clifford R Jr.}",
year = "2013",
doi = "10.1016/j.nicl.2013.01.006",
language = "English (US)",
volume = "2",
pages = "249--257",
journal = "NeuroImage: Clinical",
issn = "2213-1582",
publisher = "Elsevier BV",
number = "1",

}

TY - JOUR

T1 - Does amyloid deposition produce a specific atrophic signature in cognitively normal subjects?

AU - Whitwell, Jennifer Lynn

AU - Tosakulwong, Nirubol

AU - Weigand, Stephen D.

AU - Senjem, Matthew L.

AU - Lowe, Val

AU - Gunter, Jeffrey L.

AU - Boeve, Bradley F

AU - Knopman, David S

AU - Dickerson, Bradford C.

AU - Petersen, Ronald Carl

AU - Jack, Clifford R Jr.

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Amyloid

KW - Cognitively normal

KW - Freesurfer

KW - Keywords

KW - Preclinical

KW - Voxel-based morphometry

UR - http://www.scopus.com/inward/record.url?scp=84873927638&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84873927638&partnerID=8YFLogxK

U2 - 10.1016/j.nicl.2013.01.006

DO - 10.1016/j.nicl.2013.01.006

M3 - Article

VL - 2

SP - 249

EP - 257

JO - NeuroImage: Clinical

JF - NeuroImage: Clinical

SN - 2213-1582

IS - 1

ER -