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Open Access CC BY-NC-ND V4.0
Journal article
Pattern and degree of individual brain atrophy predicts dementia onset in dominantly inherited Alzheimer's disease
Alzheimer's & dementia : diagnosis, assessment & disease monitoring, Vol.13(1), e12197
2021
PMID: 34258377
Abstract
Introduction
Asymptomatic and mildly symptomatic dominantly inherited Alzheimer's disease mutation carriers (DIAD-MC) are ideal candidates for preventative treatment trials aimed at delaying or preventing dementia onset. Brain atrophy is an early feature of DIAD-MC and could help predict risk for dementia during trial enrollment.
Methods
We created a dementia risk score by entering standardized gray-matter volumes from 231 DIAD-MC into a logistic regression to classify participants with and without dementia. The score's predictive utility was assessed using Cox models and receiver operating curves on a separate group of 65 DIAD-MC followed longitudinally.
Results
Our risk score separated asymptomatic versus demented DIAD-MC with 96.4% (standard error = 0.02) and predicted conversion to dementia at next visit (hazard ratio = 1.32, 95% confidence interval [CI: 1.15, 1.49]) and within 2 years (area under the curve = 90.3%, 95% CI [82.3%–98.2%]) and improved prediction beyond established methods based on familial age of onset.
Discussion
Individualized risk scores based on brain atrophy could be useful for establishing enrollment criteria and stratifying DIAD-MC participants for prevention trials.
Details
- Title
- Pattern and degree of individual brain atrophy predicts dementia onset in dominantly inherited Alzheimer's disease
- Authors/Creators
- Ophir Keret - Global Brain Health InstituteAdam M. Staffaroni - University Memory and Aging CenterJohn M. Ringman - University of Southern CaliforniaYann Cobigo - University Memory and Aging CenterSheng-Yang M. Goh - Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USAAmy Wolf - University Memory and Aging CenterIsabel Elaine Allen - Global Brain Health InstituteStephen Salloway - Brown UniversityJasmeer Chhatwal - Massachusetts General HospitalAdam M. Brickman - Columbia UniversityDolly Reyes-Dumeyer - Columbia UniversityRandal J. Bateman - Supreme Council Of HealthTammie L. S. Benzinger - Washington University in St. LouisJohn C. Morris - Supreme Council Of HealthBeau M. Ances - Supreme Council Of HealthNelly Joseph-Mathurin - Supreme Council Of HealthRichard J. Perrin - Supreme Council Of HealthBrian A. Gordon - Supreme Council Of HealthJohannes Levin - Ludwig-Maximilians-Universität MünchenJonathan Voeglein - German Ctr Neurodegenerat Dis DZNE, Munich, GermanyMathias Jucker - Hertie Institute for Clinical Brain ResearchChristian Fougere - German Ctr Neurodegenerat Dis DZNE, Tubingen, GermanyRalph N. Martins - Macquarie UniversityHamid R. Sohrabi - Macquarie UniversityKevin Taddei - Edith Cowan University (Australia, Perth)Victor L. Villemagne - Austin HealthPeter R. Schofield - Neuroscience Research AustraliaWilliam S. Brooks - Neuroscience Research AustraliaMichael Fulham - Royal Prince Alfred HospitalColin L. Masters - Florey Institute of Neuroscience and Mental HealthBernardino Ghetti - Indiana University – Purdue University IndianapolisAndrew J. Saykin - Indiana University – Purdue University IndianapolisClifford R. Jack - Mayo ClinicNeill R. Graff-Radford - Mayo Clin, Dept Neurol, Jacksonville, FL USAMichael Weiner - San Francisco VA Medical CenterDavid M. Cash - University College LondonRicardo F. Allegri - Instituto de Neurología CognitivaPatricio Chrem - Instituto de Neurología CognitivaSu Yi - Banner Alzheimers Inst, Phoenix, AZ USABruce L. Miller - Global Brain Health InstituteGil D. Rabinovici - Global Brain Health InstituteHoward J. Rosen - Global Brain Health InstituteDominantly Inherited Alzheimer Net
- Publication Details
- Alzheimer's & dementia : diagnosis, assessment & disease monitoring, Vol.13(1), e12197
- Publisher
- Wiley Periodicals, LLC on behalf of Alzheimer's Association
- Number of pages
- 11
- Grant note
- UF1AG032438 / Dominantly Inherited Alzheimer Network (DIAN) - National Institute on Aging (NIA) Raul Carrea Institute for Neurological Research (FLENI) P01 AG019724; -P30 AG062422; K24 AG045333; U19 AG063911; U01 AG045390; U54 NS092089; U01AG051218; P50AG016570; P50AG005142; K08AG022228; P30 AG066444; P01 AG03991; P01 AG026276; U19 AG032438 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Japan Agency for Medical Research and Development, AMED; Japan Agency for Medical Research and Development (AMED) German Center for Neurodegenerative Diseases (DZNE); Helmholtz Association Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI); Korea Health Industry Development Institute (KHIDI) P30 AG010133; R01 AG019771; R01 AG057739; U01 AG024904; R01 LM013463; R01 AG068193; U01 AG068057 / The National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA AARFD-20-681815 / Alzheimer's Association research fellowship
- Identifiers
- 991005609866907891
- Copyright
- © 2021 The Authors.
- Murdoch Affiliation
- School of Psychology; Centre for Healthy Ageing; Health Futures Institute
- Language
- English
- Resource Type
- Journal article