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

N.T. Olney; E. Ong; S.-Y.M. Goh; L. Bajorek; R. Dever; A.M. Staffaroni; Y. Cobigo; M. Bock; K. Chiang; P. Ljubenkov; J. Kornak; H.W. Heuer; P. Wang; K. Rascovsky; A. Wolf; B. Appleby; J. Bove; Y. Bordelon; P. Brannelly; D. Brushaber; C. Caso; G. Coppola; B.C. Dickerson; S. Dickinson; K. Domoto-Reilly; K. Faber; J. Ferrall; J. Fields; A. Fishman; J. Fong; T. Foroud; L.K. Forsberg; D.J. Gearhart; B. Ghazanfari; N. Ghoshal; J. Goldman; J. Graff-Radford; N.R. Graff-Radford; I. Grant; M. Grossman; D. Haley; G. Hsiung; E.D. Huey; D.J. Irwin; D.T. Jones; K. Kantarci; A.M. Karydas; D. Kaufer; D. Kerwin; D.S. Knopman; J.H. Kramer; R. Kraft; W. Kremers; W. Kukull; M.I. Lapid; I. Litvan; I.R. Mackenzie; M. Maldonado; M. Manoochehri; S.M. McGinnis; E.C. McKinley; M.F. Mendez; B.L. Miller; C. Onyike; A. Pantelyat; R. Pearlman; L. Petrucelli; M. Potter; R. Rademakers; E.M. Ramos; K.P. Rankin; E.D. Roberson; E. Rogalski; P. Sengdy; L.M. Shaw; J. Syrjanen; M.C. Tartaglia; N. Tatton; J. Taylor; A. Toga; J.Q. Trojanowski; S. Weintraub; B. Wong; Z. Wszolek; A.L. Boxer; B.F. Boeve; H.J. Rosen

doi:10.1016/j.jalz.2019.08.196

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

Journal article

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

N.T. Olney, E. Ong, S.-Y.M. Goh, L. Bajorek, R. Dever, A.M. Staffaroni, Y. Cobigo, M. Bock, K. Chiang, P. Ljubenkov, …

Alzheimer's and Dementia, Vol.16(1), pp.49-59

2020

DOI: https://doi.org/10.1016/j.jalz.2019.08.196

PMID: 31784375

Abstract

Atrophy

C9orf72 Protein

Female

Frontotemporal Lobar Degeneration

Genetic Predisposition to Disease

Humans

Image Processing, Computer-Assisted

Longitudinal Studies

Magnetic Resonance Imaging

Male

Middle Aged

Neuropsychological Tests

Progranulins

tau Proteins

Temporal Lobe

guanine nucleotide exchange C9orf72

progranulin

tau protein

C9orf72 protein, human

GRN protein, human

guanine nucleotide exchange C9orf72

MAPT protein, human

tau protein

adult

Article

brain mapping

brain size

California verbal learning test

Clinical Dementia Rating

clinical feature

cohort analysis

controlled study

familial disease

female

frontotemporal dementia

functional disease

gene mutation

genetic screening

Geriatric Depression Scale

gray matter

human

image processing

insula

longitudinal study

major clinical study

male

middle aged

Montreal cognitive assessment

neuroimaging

nuclear magnetic resonance imaging

priority journal

task performance

temporal lobe

thalamus

trail making test

Unified Parkinson Disease Rating Scale

Wechsler memory scale

atrophy

genetic predisposition

genetics

neuropsychological test

pathology

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. © 2019 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.

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Title: Clinical and volumetric changes with increasing functional impairment in familial frontotemporal lobar degeneration
Creators: N.T. Olney - University of California, San Francisco
E. Ong - University Memory and Aging Center
S.-Y.M. Goh
L. Bajorek - University Memory and Aging Center
R. Dever - University of California, San Francisco
A.M. Staffaroni - University of California, San Francisco
Y. Cobigo - University Memory and Aging Center
M. Bock - University Memory and Aging Center
K. Chiang - University of California, San Francisco
P. Ljubenkov - University of California, San Francisco
J. Kornak - University of California, San Francisco
H.W. Heuer - University of California, San Francisco
P. Wang - University of California, San Francisco
K. Rascovsky - University of Pennsylvania
A. Wolf - University Memory and Aging Center
B. Appleby - Case Western Reserve University
J. Bove - University of Pennsylvania
Y. Bordelon - University of California, Los Angeles
P. Brannelly - Rainwater Charitable Foundation
D. Brushaber - Mayo Clinic in Florida
C. Caso - University of Washington
G. Coppola - University of California, Los Angeles
B.C. Dickerson - Massachusetts General Hospital
S. Dickinson - Association for Frontotemporal Degeneration
K. Domoto-Reilly - University of Washington
K. Faber - Alzheimer’s Disease Neuroimaging Initiative
J. Ferrall - University of North Carolina at Chapel Hill
J. Fields - Mayo Clinic in Arizona
A. Fishman - Johns Hopkins University
J. Fong - University of California, San Francisco
T. Foroud - Alzheimer’s Disease Neuroimaging Initiative
L.K. Forsberg - Mayo Clinic in Arizona
D.J. Gearhart - Mayo Clinic in Arizona
B. Ghazanfari - University of Toronto
N. Ghoshal - Washington University in St. Louis
J. Goldman - Columbia University
J. Graff-Radford - Mayo Clinic in Arizona
N.R. Graff-Radford - Mayo Clinic in Florida
I. Grant - Northwestern University
M. Grossman - University of Pennsylvania
D. Haley - Jacksonville College
G. Hsiung - University of British Columbia
E.D. Huey - Columbia University
D.J. Irwin - University of Pennsylvania
D.T. Jones - Mayo Clinic in Arizona
K. Kantarci - Mayo Clinic in Arizona
A.M. Karydas - University of California, San Francisco
D. Kaufer - University of North Carolina at Chapel Hill
D. Kerwin - The University of Texas Southwestern Medical Center
D.S. Knopman - Mayo Clinic in Arizona
J.H. Kramer - University of California, San Francisco
R. Kraft - Mayo Clinic in Arizona
W. Kremers - Mayo Clinic in Florida
W. Kukull - University of Washington
M.I. Lapid - Mayo Clinic in Arizona
I. Litvan - University of California San Diego
I.R. Mackenzie - University of British Columbia
M. Maldonado - University of California, Los Angeles
M. Manoochehri - Columbia University
S.M. McGinnis - Harvard University
E.C. McKinley - University of Alabama at Birmingham
M.F. Mendez - University of California, Los Angeles
B.L. Miller - University of California, San Francisco
C. Onyike - Johns Hopkins University
A. Pantelyat - Johns Hopkins University
R. Pearlman - Bluefield State College
L. Petrucelli - Mayo Clinic in Florida
M. Potter - Indiana University – Purdue University Indianapolis
R. Rademakers - WinnMed
E.M. Ramos - University of California, Los Angeles
K.P. Rankin - University of California, San Francisco
E.D. Roberson - University of Alabama at Birmingham
E. Rogalski
P. Sengdy - University of British Columbia
L.M. Shaw - University of Pennsylvania
J. Syrjanen - Mayo Clinic in Florida
M.C. Tartaglia - Occupational Cancer Research Centre
N. Tatton - Association for Frontotemporal Degeneration
J. Taylor - University of California, San Francisco
A. Toga - Cognitive Neuroimaging Lab
J.Q. Trojanowski - University of Pennsylvania
S. Weintraub
B. Wong - Harvard University
Z. Wszolek
A.L. Boxer - University of California, San Francisco
B.F. Boeve - Mayo Clinic in Arizona
H.J. Rosen - University Memory and Aging Center
Publication Details: Alzheimer's and Dementia, Vol.16(1), pp.49-59
Publisher: John Wiley and Sons Inc; HOBOKEN
Number of pages: 11
Grant note: National Institutes of Health: AG045390, NS092089, AG032306, AG021886, AG016976, AG019724, AG038791, AG056749, AG045333 Larry L. Hillblom Foundation: 2018-A-025-FEL National Institute on Aging (NIA): AG21886 National Institute on Aging: K24AG045333, P30AG066509, P01AG019724, P30AG062421, U24AG021886, P01AG066597, T32AG023481, K23AG061253 National Institute on Aging; National Institute of Neurological Disorders and Stroke: U19AG063911
The authors extend their appreciation to Drs. John Hsiao and Dallas Anderson from the National Institute on Aging, Drs. Marg Sutherland and Codrin Lungu from the National Institute of Neurological Disorders and Stroke, the staff of all centers, and particularly to our patients and their families for their participation in this protocol. This work is supported by the National Institutes of Health (grants AG045390 [LEFFTDS], NS092089 [ARTFL], AG032306, AG021886, AG016976, AG019724, AG038791, AG056749 and AG045333) and the Larry L. Hillblom Foundation (2018-A-025-FEL). Samples from the National Centralized Repository for Alzheimer Disease and Related Dementias (NCRAD), which receives government support under a cooperative agreement grant (AG21886) awarded by the National Institute on Aging (NIA), were used in this study.
Comment: Export Date: 27 February 2026; Cited By: 43
Academic Unit: Level 02 - Executives; Executives; UMMG Department of Neurology
Resource Type: Journal article
PMID: 31784375
Record Identifier: 991032996192102976