Cognitive Neuroscience


Alzheimer’s & dementia (Amsterdam, Netherlands)




Formal publication: July 2021

Authors: Keret O, Staffaroni AM, Ringman JM, Cobigo Y, Goh SM, Wolf A, Allen IE, Salloway S, Chhatwal J, Brickman AM, Reyes-Dumeyer D, Bateman RJ, Benzinger TLS, Morris JC, Ances BM, Joseph-Mathurin N, Perrin RJ, Gordon BA, Levin J, Vöglein J, Jucker M, la Fougère C, Martins RN, Sohrabi HR, Taddei K, Villemagne VL, Schofield PR, Brooks WS, Fulham M, Masters CL, Ghetti B, Saykin AJ, Jack CR, Graff-Radford NR, Weiner M, Cash DM, Allegri RF, Chrem P, Yi S, Miller BL, Rabinovici GD, Rosen HJ; Dominantly Inherited Alzheimer Network.

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.