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

2021-07-05

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

Ghetti, Bernardino

Saykin, Andrew J

Jack, Clifford R

Graff-Radford, Neill R

Weiner, Michael

Cash, David M

Allegri, Ricardo F

Chrem, Patricio

Yi, Su

Miller, Bruce L

Rabinovici, Gil D

Rosen, Howard J

Dominantly Inherited Alzheimer Network

autosomal dominant Alzheimer's disease

brain atrophy

preclinical Alzheimer's disease

Journal Article

10.1002/dad2.12197

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. 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. 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. Individualized risk scores based on brain atrophy could be useful for establishing enrollment criteria and stratifying DIAD-MC participants for prevention trials.

link

Alzheimer's & Dementia 2021; 13(1): e12197

Alzheimer's & Dementia

2352-8729