Pattern and degree of individual brain atrophy predicts dementia onset in dominantly inherited Alzheimer's disease

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 d...

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Autores: Keret, Ophir; Staffaroni, Adam M.; Ringman, John M.; Cobigo, Yann; Goh, Sheng Yang M.; Wolf, Amy; Allen, Isabel Elaine; Salloway, Stephen; Chhatwal, Jasmeer; Brickman, Adam M.; Reyes Dumeyer, Dolly; Bateman, Randal J.; Benzinger, Tammie L.S.; Morris, John C.; Ances, Beau M.; Joseph Mathurin, Nelly; Perrin, Richard J.; Gordon, Brian A.; Levin, Johannes; Vöglein, Jonathan; Jucker, Mathias; la Fougère, Christian; Martins, Ralph N.; Sohrabi, Hamid R.; Taddei, Kevin; Villemagne, Victor L.; Schofield, Peter R.; Brooks, William S.; Fulham, Michael; Masters, Colin L.; Allegri, Ricardo Francisco
Tipo de documento: Artículo
Estado:Published version
Fecha de publicación:2021
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Lenguaje:Inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/211950
Acceso en línea:http://hdl.handle.net/11336/211950
Nivel de acceso:Acceso abierto
Palabra clave:AUTOSOMAL DOMINANT ALZHEIMER'S DISEASE
BRAIN ATROPHY
DOMINANTLY INHERITED ALZHEIMER NETWORK
PRECLINICAL ALZHEIMER'S DISEASE
https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
Sumario: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.

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