Biphasic cortical macro- and microstructural changes in autosomal dominant Alzheimer's disease.
Alzheimer's disease
autosomal-dominant Alzheimer's disease
biphasic cortical changes
cortical diffusivity
magnetic resonance imaging
preclinical Alzheimer's disease
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
revised:
20
09
2020
received:
26
05
2020
accepted:
09
10
2020
pubmed:
17
11
2020
medline:
4
11
2021
entrez:
16
11
2020
Statut:
ppublish
Résumé
A biphasic model for brain structural changes in preclinical Alzheimer's disease (AD) could reconcile some conflicting and paradoxical findings in observational studies and anti-amyloid clinical trials. In this study we tested this model fitting linear versus quadratic trajectories and computed the timing of the inflection points vertexwise of cortical thickness and cortical diffusivity-a novel marker of cortical microstructure-changes in 389 participants from the Dominantly Inherited Alzheimer Network. In early preclinical AD, between 20 and 15 years before estimated symptom onset, we found increases in cortical thickness and decreases in cortical diffusivity followed by cortical thinning and cortical diffusivity increases in later preclinical and symptomatic stages. The inflection points 16 to 19 years before estimated symptom onset are in agreement with the start of tau biomarker alterations. These findings confirm a biphasic trajectory for brain structural changes and have direct implications when interpreting magnetic resonance imaging measures in preventive AD clinical trials.
Identifiants
pubmed: 33196147
doi: 10.1002/alz.12224
pmc: PMC8043974
mid: NIHMS1640879
doi:
Substances chimiques
Biomarkers
0
tau Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
618-628Subventions
Organisme : NIA NIH HHS
ID : P50 AG008702
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG056850
Pays : United States
Organisme : NIA NIH HHS
ID : UF1 AG032438
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG052550
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002345
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG032438
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG003991
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG059798
Pays : United States
Organisme : NIBIB NIH HHS
ID : R01 EB009352
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066462
Pays : United States
Informations de copyright
© 2020 the Alzheimer's Association.
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