Clinical and volumetric changes with increasing functional impairment in familial frontotemporal lobar degeneration

ARTFL and LEFFTDS consortia

Research output: Contribution to journalArticle

Abstract

Introduction: The Advancing Research and Treatment in Frontotemporal Lobar Degeneration and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects longitudinal studies were designed to describe the natural history of familial-frontotemporal lobar degeneration due to autosomal dominant mutations. Methods: We examined cognitive performance, behavioral ratings, and brain volumes from the first time point in 320 MAPT, GRN, and C9orf72 family members, including 102 non–mutation carriers, 103 asymptomatic carriers, 43 mildly/questionably symptomatic carriers, and 72 carriers with dementia. Results: Asymptomatic carriers showed similar scores on all clinical measures compared with noncarriers but reduced frontal and temporal volumes. Those with mild/questionable impairment showed decreased verbal recall, fluency, and Trail Making Test performance and impaired mood and self-monitoring. Dementia was associated with impairment in all measures. All MAPT carriers with dementia showed temporal atrophy, but otherwise, there was no single cognitive test or brain region that was abnormal in all subjects. Discussion: Imaging changes appear to precede clinical changes in familial-frontotemporal lobar degeneration, but specific early clinical and imaging changes vary across individuals.

Original languageEnglish (US)
JournalAlzheimer's and Dementia
DOIs
StateAccepted/In press - Jan 1 2019
Externally publishedYes

Fingerprint

Frontotemporal Lobar Degeneration
Dementia
Trail Making Test
Frontotemporal Dementia
Brain
Natural History
Atrophy
Longitudinal Studies
Mutation
Research

Keywords

  • C9ORF72
  • Familial
  • Frontotemporal lobar degeneration
  • Genetic
  • GRN
  • MAPT

ASJC Scopus subject areas

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

Cite this

Clinical and volumetric changes with increasing functional impairment in familial frontotemporal lobar degeneration. / ARTFL and LEFFTDS consortia.

In: Alzheimer's and Dementia, 01.01.2019.

Research output: Contribution to journalArticle

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abstract = "Introduction: The Advancing Research and Treatment in Frontotemporal Lobar Degeneration and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects longitudinal studies were designed to describe the natural history of familial-frontotemporal lobar degeneration due to autosomal dominant mutations. Methods: We examined cognitive performance, behavioral ratings, and brain volumes from the first time point in 320 MAPT, GRN, and C9orf72 family members, including 102 non–mutation carriers, 103 asymptomatic carriers, 43 mildly/questionably symptomatic carriers, and 72 carriers with dementia. Results: Asymptomatic carriers showed similar scores on all clinical measures compared with noncarriers but reduced frontal and temporal volumes. Those with mild/questionable impairment showed decreased verbal recall, fluency, and Trail Making Test performance and impaired mood and self-monitoring. Dementia was associated with impairment in all measures. All MAPT carriers with dementia showed temporal atrophy, but otherwise, there was no single cognitive test or brain region that was abnormal in all subjects. Discussion: Imaging changes appear to precede clinical changes in familial-frontotemporal lobar degeneration, but specific early clinical and imaging changes vary across individuals.",
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author = "{ARTFL and LEFFTDS consortia} and Olney, {Nicholas T.} and Elise Ong and Goh, {Sheng Yang M.} and Lynn Bajorek and Reilly Dever and Staffaroni, {Adam M.} and Yann Cobigo and Meredith Bock and Kevin Chiang and Peter Ljubenkov and John Kornak and Heuer, {Hilary W.} and Ping Wang and Katya Rascovsky and Amelia Wolf and Brian Appleby and Jessica Bove and Yvette Bordelon and Patrick Brannelly and Danielle Brushaber and Christine Caso and Giovanni Coppola and Dickerson, {Bradford C.} and Susan Dickinson and Kimiko Domoto-Reilly and Kelly Faber and Jessica Ferrall and Julie Fields and Ann Fishman and Jamie Fong and Tatiana Foroud and Forsberg, {Leah K.} and Gearhart, {Debra J.} and Behnaz Ghazanfari and Nupur Ghoshal and Jill Goldman and Jonathan Graff-Radford and Graff-Radford, {Neill R.} and Ian Grant and Murray Grossman and Dana Haley and Gingyuek Hsiung and Huey, {Edward D.} and Irwin, {David J.} and Jones, {David T.} and Kejal Kantarci and Karydas, {Anna M.} and Daniel Kaufer and Diana Kerwin and Knopman, {David S.}",
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AU - Coppola, Giovanni

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AU - Faber, Kelly

AU - Ferrall, Jessica

AU - Fields, Julie

AU - Fishman, Ann

AU - Fong, Jamie

AU - Foroud, Tatiana

AU - Forsberg, Leah K.

AU - Gearhart, Debra J.

AU - Ghazanfari, Behnaz

AU - Ghoshal, Nupur

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AU - Graff-Radford, Jonathan

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