Individualized atrophy scores predict dementia onset in familial frontotemporal lobar degeneration

ARTFL/LEFFTDS consortium

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
JournalAlzheimer's and Dementia
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

Fingerprint

Frontotemporal Lobar Degeneration
Atrophy
Dementia
Logistic Models
Brain
Neurodegenerative Diseases
Mutation

Keywords

  • Frontotemporal dementia
  • Genetics
  • Magnetic resonance imaging (MRI)
  • Tau
  • TDP-43

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

Cite this

Individualized atrophy scores predict dementia onset in familial frontotemporal lobar degeneration. / ARTFL/LEFFTDS consortium.

In: Alzheimer's and Dementia, 01.01.2019.

Research output: Contribution to journalArticle

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title = "Individualized atrophy scores predict dementia onset in familial frontotemporal lobar degeneration",
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.",
keywords = "Frontotemporal dementia, Genetics, Magnetic resonance imaging (MRI), Tau, TDP-43",
author = "{ARTFL/LEFFTDS consortium} and Staffaroni, {Adam M.} and Yann Cobigo and Goh, {Sheng Yang M.} and John Kornak and Lynn Bajorek and Kevin Chiang and Brian Appleby and Jessica Bove and Yvette Bordelon and Patrick Brannelly and Danielle Brushaber and Christina Caso and Giovanni Coppola and Reilly Dever and Christina Dheel and Dickerson, {Bradford C.} and Susan Dickinson and Sophia Dominguez and Kimiko Domoto-Reilly and Kelly Faber and Jessica Ferrall and Fields, {Julie A.} and Ann Fishman and Jamie Fong and Tatiana Foroud and Forsberg, {Leah K.} and Ralitza Gavrilova and Debra Gearhart and Behnaz Ghazanfari and Nupur Ghoshal and Jill Goldman and Jonathan Graff-Radford and Neill Graff-Radford and Ian Grant and Murray Grossman and Dana Haley and Heuer, {Hilary W.} and Hsiung, {Ging Yuek} and Huey, {Edward D.} and Irwin, {David J.} and Jones, {David T.} and Lynne Jones and Kejal Kantarci and Anna Karydas and Kaufer, {Daniel I.} and Kerwin, {Diana R.} and Knopman, {David S.} and Ruth Kraft and Kramer, {Joel H.} and Kremers, {Walter K.}",
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AU - Staffaroni, Adam M.

AU - Cobigo, Yann

AU - Goh, Sheng Yang M.

AU - Kornak, John

AU - Bajorek, Lynn

AU - Chiang, Kevin

AU - Appleby, Brian

AU - Bove, Jessica

AU - Bordelon, Yvette

AU - Brannelly, Patrick

AU - Brushaber, Danielle

AU - Caso, Christina

AU - Coppola, Giovanni

AU - Dever, Reilly

AU - Dheel, Christina

AU - Dickerson, Bradford C.

AU - Dickinson, Susan

AU - Dominguez, Sophia

AU - Domoto-Reilly, Kimiko

AU - Faber, Kelly

AU - Ferrall, Jessica

AU - Fields, Julie A.

AU - Fishman, Ann

AU - Fong, Jamie

AU - Foroud, Tatiana

AU - Forsberg, Leah K.

AU - Gavrilova, Ralitza

AU - Gearhart, Debra

AU - Ghazanfari, Behnaz

AU - Ghoshal, Nupur

AU - Goldman, Jill

AU - Graff-Radford, Jonathan

AU - Graff-Radford, Neill

AU - Grant, Ian

AU - Grossman, Murray

AU - Haley, Dana

AU - Heuer, Hilary W.

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AU - Huey, Edward D.

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AU - Jones, David T.

AU - Jones, Lynne

AU - Kantarci, Kejal

AU - Karydas, Anna

AU - Kaufer, Daniel I.

AU - Kerwin, Diana R.

AU - Knopman, David S.

AU - Kraft, Ruth

AU - Kramer, Joel H.

AU - Kremers, Walter K.

PY - 2019/1/1

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N2 - 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.

AB - 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.

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KW - Genetics

KW - Magnetic resonance imaging (MRI)

KW - Tau

KW - TDP-43

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