TY - JOUR
T1 - Clinical and volumetric changes with increasing functional impairment in familial frontotemporal lobar degeneration
AU - on behalf of the ARTFL and LEFFTDS consortia
AU - Olney, Nicholas T.
AU - Ong, Elise
AU - Goh, Sheng Yang M.
AU - Bajorek, Lynn
AU - Dever, Reilly
AU - Staffaroni, Adam M.
AU - Cobigo, Yann
AU - Bock, Meredith
AU - Chiang, Kevin
AU - Ljubenkov, Peter
AU - Kornak, John
AU - Heuer, Hilary W.
AU - Wang, Ping
AU - Rascovsky, Katya
AU - Wolf, Amelia
AU - Appleby, Brian
AU - Bove, Jessica
AU - Bordelon, Yvette
AU - Brannelly, Patrick
AU - Brushaber, Danielle
AU - Caso, Christine
AU - Coppola, Giovanni
AU - Dickerson, Bradford C.
AU - Dickinson, Susan
AU - Domoto-Reilly, Kimiko
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
AU - Goldman, Jill
AU - Graff-Radford, Jonathan
AU - Graff-Radford, Neill R.
AU - Grant, Ian
AU - Grossman, Murray
AU - Haley, Dana
AU - Jones, David T.
AU - Kantarci, Kejal
AU - Knopman, David S.
AU - Kremers, Walter
AU - Lapid, Maria I.
AU - Petrucelli, Len
AU - Rademakers, Rosa
AU - Wszolek, Zbigniew
AU - Boeve, Brad F.
N1 - Publisher Copyright:
© 2019 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
KW - C9ORF72
KW - Familial
KW - Frontotemporal lobar degeneration
KW - GRN
KW - Genetic
KW - MAPT
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U2 - 10.1016/j.jalz.2019.08.196
DO - 10.1016/j.jalz.2019.08.196
M3 - Article
C2 - 31784375
AN - SCOPUS:85075806070
SN - 1552-5260
VL - 16
SP - 49
EP - 59
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 1
ER -