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.
Document Type
Journal Article
Funding Information
Funding information available in the Acknowledgements section of the PDF
School
Centre of Excellence for Alzheimer's Disease Research and Care / School of Medical and Health Sciences
RAS ID
39721
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Publisher
Wiley
Comments
Keret, O., Staffaroni, A. M., Ringman, J. M., Cobigo, Y., Goh, S. Y. M., Wolf, A., ... & Dominantly Inherited Alzheimer Network. (2021). Pattern and degree of individual brain atrophy predicts dementia onset in dominantly inherited Alzheimer's disease. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 13(1), e12197. https://doi.org/10.1002/dad2.12197