Assessment of executive function declines in presymptomatic and mildly symptomatic familial frontotemporal dementia: NIH-EXAMINER as a potential clinical trial endpoint

ARTFL/LEFFTDS consortium

Research output: Contribution to journalArticle

Abstract

Introduction: Identifying clinical measures that track disease in the earliest stages of frontotemporal lobar degeneration (FTLD)is important for clinical trials. Familial FTLD provides a unique paradigm to study early FTLD. Executive dysfunction is a clinically relevant hallmark of FTLD and may be a marker of disease progression. Methods: Ninety-three mutation carriers with no symptoms or minimal/questionable symptoms (MAPT, n = 31; GRN, n = 28; C9orf72, n = 34; Clinical Dementia Rating scale plus NACC FTLD Module < 1)and 78 noncarriers enrolled through Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects studies completed the Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (NIH-EXAMINER)and the UDS neuropsychological battery. Linear mixed-effects models were used to identify group differences in cognition at baseline and longitudinally. We examined associations between cognition, clinical functioning, and magnetic resonance imaging volumes. Results: NIH-EXAMINER scores detected baseline and differences in slopes between carriers and noncarriers, even in carriers with a baseline Clinical Dementia Rating scale plus NACC FTLD Module = 0. NIH-EXAMINER declines were associated with worsening clinical symptoms and brain volume loss. Discussion: The NIH-EXAMINER is sensitive to cognitive changes in presymptomatic familial FTLD and is a promising surrogate endpoint.

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

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Frontotemporal Lobar Degeneration
Frontotemporal Dementia
Executive Function
Dementia
Clinical Trials
Cognition
Aptitude
Disease Progression
Biomarkers
Magnetic Resonance Imaging
Mutation

Keywords

  • Behavioral variant
  • Cognition
  • Corticobasal syndrome
  • Fluency
  • Genetic
  • Inhibition
  • Neuropsychology
  • Nonfluent variant
  • Primary progressive aphasia
  • Progranulin
  • Progressive supranuclear palsy
  • Semantic variant
  • Set-shifting
  • Tau
  • Working memory

ASJC Scopus subject areas

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

Cite this

@article{283d626b788946d0be80e20503e0f184,
title = "Assessment of executive function declines in presymptomatic and mildly symptomatic familial frontotemporal dementia: NIH-EXAMINER as a potential clinical trial endpoint",
abstract = "Introduction: Identifying clinical measures that track disease in the earliest stages of frontotemporal lobar degeneration (FTLD)is important for clinical trials. Familial FTLD provides a unique paradigm to study early FTLD. Executive dysfunction is a clinically relevant hallmark of FTLD and may be a marker of disease progression. Methods: Ninety-three mutation carriers with no symptoms or minimal/questionable symptoms (MAPT, n = 31; GRN, n = 28; C9orf72, n = 34; Clinical Dementia Rating scale plus NACC FTLD Module < 1)and 78 noncarriers enrolled through Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects studies completed the Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (NIH-EXAMINER)and the UDS neuropsychological battery. Linear mixed-effects models were used to identify group differences in cognition at baseline and longitudinally. We examined associations between cognition, clinical functioning, and magnetic resonance imaging volumes. Results: NIH-EXAMINER scores detected baseline and differences in slopes between carriers and noncarriers, even in carriers with a baseline Clinical Dementia Rating scale plus NACC FTLD Module = 0. NIH-EXAMINER declines were associated with worsening clinical symptoms and brain volume loss. Discussion: The NIH-EXAMINER is sensitive to cognitive changes in presymptomatic familial FTLD and is a promising surrogate endpoint.",
keywords = "Behavioral variant, Cognition, Corticobasal syndrome, Fluency, Genetic, Inhibition, Neuropsychology, Nonfluent variant, Primary progressive aphasia, Progranulin, Progressive supranuclear palsy, Semantic variant, Set-shifting, Tau, Working memory",
author = "{ARTFL/LEFFTDS consortium} and Staffaroni, {Adam M.} and Lynn Bajorek and Casaletto, {Kaitlin B.} and Yann Cobigo and Goh, {Sheng Yang M.} and Amy Wolf and Heuer, {Hilary W.} and Elahi, {Fanny M.} and Ljubenkov, {Peter A.} and Reilly Dever and John Kornak and Brian Appleby and Jessica Bove and Yvette Bordelon and Patrick Brannelly and Danielle Brushaber and Christina Caso and Giovanni Coppola 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 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 Onyike, {Chiadikaobi U} and Alexander Pantelyat",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.jalz.2019.01.012",
language = "English (US)",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Assessment of executive function declines in presymptomatic and mildly symptomatic familial frontotemporal dementia

T2 - NIH-EXAMINER as a potential clinical trial endpoint

AU - ARTFL/LEFFTDS consortium

AU - Staffaroni, Adam M.

AU - Bajorek, Lynn

AU - Casaletto, Kaitlin B.

AU - Cobigo, Yann

AU - Goh, Sheng Yang M.

AU - Wolf, Amy

AU - Heuer, Hilary W.

AU - Elahi, Fanny M.

AU - Ljubenkov, Peter A.

AU - Dever, Reilly

AU - Kornak, John

AU - Appleby, Brian

AU - Bove, Jessica

AU - Bordelon, Yvette

AU - Brannelly, Patrick

AU - Brushaber, Danielle

AU - Caso, Christina

AU - Coppola, Giovanni

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 - Hsiung, Ging Yuek

AU - Huey, Edward D.

AU - Irwin, David J.

AU - Jones, David T.

AU - Jones, Lynne

AU - Kantarci, Kejal

AU - Karydas, Anna

AU - Kaufer, Daniel I.

AU - Onyike, Chiadikaobi U

AU - Pantelyat, Alexander

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Introduction: Identifying clinical measures that track disease in the earliest stages of frontotemporal lobar degeneration (FTLD)is important for clinical trials. Familial FTLD provides a unique paradigm to study early FTLD. Executive dysfunction is a clinically relevant hallmark of FTLD and may be a marker of disease progression. Methods: Ninety-three mutation carriers with no symptoms or minimal/questionable symptoms (MAPT, n = 31; GRN, n = 28; C9orf72, n = 34; Clinical Dementia Rating scale plus NACC FTLD Module < 1)and 78 noncarriers enrolled through Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects studies completed the Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (NIH-EXAMINER)and the UDS neuropsychological battery. Linear mixed-effects models were used to identify group differences in cognition at baseline and longitudinally. We examined associations between cognition, clinical functioning, and magnetic resonance imaging volumes. Results: NIH-EXAMINER scores detected baseline and differences in slopes between carriers and noncarriers, even in carriers with a baseline Clinical Dementia Rating scale plus NACC FTLD Module = 0. NIH-EXAMINER declines were associated with worsening clinical symptoms and brain volume loss. Discussion: The NIH-EXAMINER is sensitive to cognitive changes in presymptomatic familial FTLD and is a promising surrogate endpoint.

AB - Introduction: Identifying clinical measures that track disease in the earliest stages of frontotemporal lobar degeneration (FTLD)is important for clinical trials. Familial FTLD provides a unique paradigm to study early FTLD. Executive dysfunction is a clinically relevant hallmark of FTLD and may be a marker of disease progression. Methods: Ninety-three mutation carriers with no symptoms or minimal/questionable symptoms (MAPT, n = 31; GRN, n = 28; C9orf72, n = 34; Clinical Dementia Rating scale plus NACC FTLD Module < 1)and 78 noncarriers enrolled through Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects studies completed the Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (NIH-EXAMINER)and the UDS neuropsychological battery. Linear mixed-effects models were used to identify group differences in cognition at baseline and longitudinally. We examined associations between cognition, clinical functioning, and magnetic resonance imaging volumes. Results: NIH-EXAMINER scores detected baseline and differences in slopes between carriers and noncarriers, even in carriers with a baseline Clinical Dementia Rating scale plus NACC FTLD Module = 0. NIH-EXAMINER declines were associated with worsening clinical symptoms and brain volume loss. Discussion: The NIH-EXAMINER is sensitive to cognitive changes in presymptomatic familial FTLD and is a promising surrogate endpoint.

KW - Behavioral variant

KW - Cognition

KW - Corticobasal syndrome

KW - Fluency

KW - Genetic

KW - Inhibition

KW - Neuropsychology

KW - Nonfluent variant

KW - Primary progressive aphasia

KW - Progranulin

KW - Progressive supranuclear palsy

KW - Semantic variant

KW - Set-shifting

KW - Tau

KW - Working memory

UR - http://www.scopus.com/inward/record.url?scp=85065401051&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065401051&partnerID=8YFLogxK

U2 - 10.1016/j.jalz.2019.01.012

DO - 10.1016/j.jalz.2019.01.012

M3 - Article

C2 - 31088775

AN - SCOPUS:85065401051

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

SN - 1552-5260

ER -