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

• 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
• Año de publicación: 2021
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: AUTOSOMAL DOMINANT ALZHEIMER'S DISEASE; BRAIN ATROPHY; DOMINANTLY INHERITED ALZHEIMER NETWORK; PRECLINICAL ALZHEIMER'S DISEASE
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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.
Fil: Keret, Ophir. University of California; Estados Unidos
Fil: Staffaroni, Adam M.. University of California; Estados Unidos
Fil: Ringman, John M.. University of Southern California; Estados Unidos
Fil: Cobigo, Yann. University of California; Estados Unidos
Fil: Goh, Sheng Yang M.. University of California; Estados Unidos
Fil: Wolf, Amy. University of California; Estados Unidos
Fil: Allen, Isabel Elaine. University of California; Estados Unidos
Fil: Salloway, Stephen. Brown University; Estados Unidos
Fil: Chhatwal, Jasmeer. Harvard Medical School; Estados Unidos
Fil: Brickman, Adam M.. Columbia University; Estados Unidos
Fil: Reyes Dumeyer, Dolly. Columbia University; Estados Unidos
Fil: Bateman, Randal J.. University of Washington; Estados Unidos
Fil: Benzinger, Tammie L.S.. University of Washington; Estados Unidos
Fil: Morris, John C.. University of Washington; Estados Unidos
Fil: Ances, Beau M.. University of Washington; Estados Unidos
Fil: Joseph Mathurin, Nelly. University of Washington; Estados Unidos
Fil: Perrin, Richard J.. University of Washington; Estados Unidos
Fil: Gordon, Brian A.. University of Washington; Estados Unidos
Fil: Levin, Johannes. German Center for Neurodegenerative Diseases; Alemania. Ludwig Maximilians Universitat; Alemania
Fil: Vöglein, Jonathan. Ludwig Maximilians Universitat; Alemania. German Center for Neurodegenerative Diseases; Alemania
Fil: Jucker, Mathias. German Center for Neurodegenerative Diseases; Alemania. Eberhard Karls Universität Tübingen; Alemania
Fil: la Fougère, Christian. Eberhard Karls Universität Tübingen; Alemania. German Center for Neurodegenerative Diseases; Alemania
Fil: Martins, Ralph N.. Cooperative Research Centres Australia; Australia. University of Western Australia; Australia. Edith Cowan University; Australia. Australian Alzheimer's Research Foundation; Australia. Macquarie University; Australia
Fil: Sohrabi, Hamid R.. University of Western Australia; Australia. Macquarie University; Australia. Australian Alzheimer's Research Foundation; Australia. Cooperative Research Centres Australia; Australia. Edith Cowan University; Australia
Fil: Taddei, Kevin. Australian Alzheimer's Research Foundation; Australia. Edith Cowan University; Australia
Fil: Villemagne, Victor L.. Austin Health; Australia
Fil: Schofield, Peter R.. Neuroscience Research Australia; Australia. Unsw Medicine; Australia
Fil: Brooks, William S.. Neuroscience Research Australia; Australia. Unsw Medicine; Australia
Fil: Fulham, Michael. Royal Prince Alfred Hospital; Australia
Fil: Masters, Colin L.. University of Melbourne; Australia
Fil: Allegri, Ricardo Francisco. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Instituto de Neurociencias - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Neurociencias; Argentina