Individualized Atrophy Scores Predict Dementia Onset in Familial Frontotemporal Lobar Degeneration

Alzheimer's and Dementia
11 Jul, 2019 ,

Adam M. Staffaroni et al ascertained if an atrophy-based risk score could be developed to anticipate the onset of dementia. Dementia risk scores were created in 268 familial frontotemporal lobar degeneration family members by entering covariate-adjusted standardized estimates of brain atrophy into a logistic regression to classify asymptomatic vs demented candidates. Good separation of asymptomatic vs demented patients was accomplished by cross-validated logistic regression. Atrophy scores forecast conversion to dementia from asymptomatic or mildly/questionably symptomatic. With 90% accuracy, quantification of the unique atrophy pattern of each individual can separate those with dementia from those without symptoms. A promising predictor of progression in asymptomatic familial frontotemporal lobar degeneration mutation carriers is the individualized quantification of baseline brain atrophy.

 

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Abstract

Introduction

Some models of therapy for neurodegenerative diseases envision starting treatment before symptoms develop. Demonstrating that such treatments are effective requires accurate knowledge of when symptoms would have started without treatment. Familial frontotemporal lobar degeneration offers a unique opportunity to develop predictors of symptom onset.

Methods

We created dementia risk scores in 268 familial frontotemporal lobar degeneration family members by entering covariate-adjusted standardized estimates of brain atrophy into a logistic regression to classify asymptomatic versus demented participants. The score's predictive value was tested in a separate group who were followed up longitudinally (stable vs. converted to dementia) using Cox proportional regressions with dementia risk score as the predictor.

Results

Cross-validated logistic regression achieved good separation of asymptomatic versus demented (accuracy = 90%, SE = 0.06). Atrophy scores predicted conversion from asymptomatic or mildly/questionably symptomatic to dementia (HR = 1.51, 95% CI: [1.16,1.98]).

Discussion

Individualized quantification of baseline brain atrophy is a promising predictor of progression in asymptomatic familial frontotemporal lobar degeneration mutation carriers.