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

Alzheimer's & dementia (Amsterdam, Netherlands)

Alzheimers Dement (Amst). 2021 Jul 5;13(1):e12197. doi: 10.1002/dad2.12197. eCollection 2021.


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.

PMID:34258377 | PMC:PMC8256623 | DOI:10.1002/dad2.12197


Ophir Keret
Adam M Staffaroni
John M Ringman
Yann Cobigo
Sheng-Yang M Goh
Amy Wolf
Isabel Elaine Allen
Stephen Salloway
Jasmeer Chhatwal
Adam M Brickman
Dolly Reyes-Dumeyer
Randal J Bateman
Tammie L S Benzinger
John C Morris
Beau M Ances
Nelly Joseph-Mathurin
Richard J Perrin
Brian A Gordon
Johannes Levin
Jonathan Vöglein
Mathias Jucker
Christian la Fougère
Ralph N Martins
Hamid R Sohrabi
Kevin Taddei
Victor L Villemagne
Peter R Schofield
William S Brooks
Michael Fulham
Colin L Masters
Bernardino Ghetti
Andrew J Saykin
Clifford R Jack
Neill R Graff-Radford
Michael Weiner
David M Cash
Ricardo F Allegri
Patricio Chrem
Su Yi
Bruce L Miller
Gil D Rabinovici
Howard J Rosen
Dominantly Inherited Alzheimer Network