Modeling grey matter atrophy as a function of time, aging or cognitive decline show different anatomical patterns in Alzheimer's disease.
Aged
Aged, 80 and over
Aging
/ metabolism
Alzheimer Disease
/ diagnostic imaging
Amyloid beta-Peptides
/ metabolism
Atrophy
/ pathology
Cognitive Dysfunction
/ diagnostic imaging
Female
Gray Matter
/ diagnostic imaging
Humans
Longitudinal Studies
Magnetic Resonance Imaging
Male
Mental Status and Dementia Tests
Prodromal Symptoms
Time Factors
Aging
Alzheimer's disease
Amyloid
Atrophy
Cognition
Longitudinal
Journal
NeuroImage. Clinical
ISSN: 2213-1582
Titre abrégé: Neuroimage Clin
Pays: Netherlands
ID NLM: 101597070
Informations de publication
Date de publication:
2019
2019
Historique:
received:
05
12
2018
revised:
12
03
2019
accepted:
16
03
2019
pubmed:
29
3
2019
medline:
22
1
2020
entrez:
29
3
2019
Statut:
ppublish
Résumé
Grey matter (GM) atrophy in Alzheimer's disease (AD) is most commonly modeled as a function of time. However, this approach does not take into account inter-individual differences in initial disease severity or changes due to aging. Here, we modeled GM atrophy within individuals across the AD clinical spectrum as a function of time, aging and MMSE, as a proxy for disease severity, and investigated how these models influence estimates of GM atrophy. We selected 523 individuals from ADNI (100 preclinical AD, 288 prodromal AD, 135 AD dementia) with abnormal baseline amyloid PET/CSF and ≥1 year of MRI follow-up. We calculated total and 90 regional GM volumes for 2281 MRI scans (median [IQR]; 4 [3-5] scans per individual over 2 [1.6-4] years) and used linear mixed models to investigate atrophy as a function of time, aging and decline on MMSE. Analyses included clinical stage as interaction with the predictor and were corrected for baseline age, sex, education, field strength and total intracranial volume. We repeated analyses for a sample of participants with normal amyloid (n = 387) to assess whether associations were specific for amyloid pathology. Using time or aging as predictors, amyloid abnormal participants annually declined -1.29 ± 0.08 points and - 0.28 ± 0.03 points respectively on the MMSE and -12.23 ± 0.47 cm Effects of time, aging and MMSE all explained variance in GM atrophy slopes within individuals. Associations with MMSE were weaker than those for time or age, but specific for amyloid pathology. This suggests that at least some of the atrophy observed in time or age models may not be specific to AD.
Sections du résumé
BACKGROUND
Grey matter (GM) atrophy in Alzheimer's disease (AD) is most commonly modeled as a function of time. However, this approach does not take into account inter-individual differences in initial disease severity or changes due to aging. Here, we modeled GM atrophy within individuals across the AD clinical spectrum as a function of time, aging and MMSE, as a proxy for disease severity, and investigated how these models influence estimates of GM atrophy.
METHODS
We selected 523 individuals from ADNI (100 preclinical AD, 288 prodromal AD, 135 AD dementia) with abnormal baseline amyloid PET/CSF and ≥1 year of MRI follow-up. We calculated total and 90 regional GM volumes for 2281 MRI scans (median [IQR]; 4 [3-5] scans per individual over 2 [1.6-4] years) and used linear mixed models to investigate atrophy as a function of time, aging and decline on MMSE. Analyses included clinical stage as interaction with the predictor and were corrected for baseline age, sex, education, field strength and total intracranial volume. We repeated analyses for a sample of participants with normal amyloid (n = 387) to assess whether associations were specific for amyloid pathology.
RESULTS
Using time or aging as predictors, amyloid abnormal participants annually declined -1.29 ± 0.08 points and - 0.28 ± 0.03 points respectively on the MMSE and -12.23 ± 0.47 cm
CONCLUSION
Effects of time, aging and MMSE all explained variance in GM atrophy slopes within individuals. Associations with MMSE were weaker than those for time or age, but specific for amyloid pathology. This suggests that at least some of the atrophy observed in time or age models may not be specific to AD.
Identifiants
pubmed: 30921610
pii: S2213-1582(19)30136-6
doi: 10.1016/j.nicl.2019.101786
pmc: PMC6439228
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
101786Subventions
Organisme : NIA NIH HHS
ID : U01 AG024904
Pays : United States
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
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