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

Dominantly Inherited Alzheimer Network

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere12197
JournalAlzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Volume13
Issue number1
DOIs
StatePublished - 2021

Keywords

  • autosomal dominant Alzheimer's disease
  • brain atrophy
  • Dominantly Inherited Alzheimer Network
  • preclinical Alzheimer's disease

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health

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