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@ARTICLE{Russell:280115,
author = {Russell, Lucy Louise and Bouzigues, Arabella and Convery,
Rhian S and Foster, Phoebe H and Ferry-Bolder, Eve and Cash,
David M and Van Swieten, John C and Jiskoot, Lize Corrine
and Seelaar, Harro and Moreno, Fermin and Sánchez-Valle,
Raquel and Laforce, Robert and Graff, Caroline and Masellis,
Mario and Tartaglia, Maria Carmela and Rowe, James B and
Borroni, Barbara and Finger, Elizabeth and Synofzik, Matthis
and Galimberti, Daniela and Vandenberghe, Rik and de
Mendonça, Alexandre and Butler, Christopher and Gerhard,
Alexander and Ducharme, Simon and Le Ber, Isabelle and
Santana, Isabel and Pasquier, Florence and Levin, Johannes
and Sorbi, Sandro and Otto, Markus and Rohrer, Jonathan
Daniel},
collaboration = {Initiative, Genetic FTD},
title = {{E}xecutive {F}unction {D}eficits in {G}enetic
{F}rontotemporal {D}ementia: {R}esults {F}rom the {GENFI}
{S}tudy.},
journal = {Neurology / Genetics},
volume = {11},
number = {4},
issn = {2376-7839},
address = {Minneapolis, Minn.},
publisher = {[Verlag nicht ermittelbar]},
reportid = {DZNE-2025-00898},
pages = {e200248},
year = {2025},
abstract = {Executive dysfunction is a core feature of frontotemporal
dementia (FTD). While there has been extensive research into
such impairments in sporadic FTD, there has been little
research in the familial forms.Seven hundred fifty-two
individuals were recruited in total: 214 C9orf72; 205
progranulin (GRN) and 86 microtubule associated protein tau
(MAPT) mutation carriers, stratified into asymptomatic,
prodromal, and fully symptomatic; and 247 mutation-negative
controls. Attention and executive function were measured
using the Weschler Memory Scale-Revised (WMS-R) Digit Span
Backwards (DSB), Wechsler Adult Intelligence Scale-Revised
Digit Symbol task, Trail Making Test Parts A and B, and the
Delis-Kaplan Executive Function System Color Word
Interference Test. Linear regression models with
bootstrapping were used to assess differences between
groups. Correlation of task score with disease severity was
also performed, as well as an analysis of the
neuroanatomical correlates of each task.Fully symptomatic
C9orf72, GRN, and MAPT mutation carriers were significantly
impaired on all tasks compared with controls (all p <
0.001), except on the WMS-R DSB in the MAPT mutation
carriers (p = 0.147). While asymptomatic and prodromal
C9orf72 individuals also demonstrated differences compared
with controls, neither the GRN or MAPT asymptomatic or
prodromal mutation carriers showed significant deficits. All
tasks were significantly correlated with disease severity in
each of the genetic groups (all p < 0.001).Some individuals
with C9orf72 mutations show difficulties with executive
function from very early on in the disease and this
continues to deteriorate with disease severity. By contrast,
similar difficulties occur only in the later stages of the
disease in GRN and MAPT mutation carriers. This differential
performance across the genetic groups will be important in
neuropsychological task selection in upcoming clinical
trials.},
cin = {AG Gasser / Clinical Research (Munich) / AG Levin},
ddc = {610},
cid = {I:(DE-2719)1210000 / I:(DE-2719)1111015 /
I:(DE-2719)1111016},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40703202},
pmc = {pmc:PMC12285671},
doi = {10.1212/NXG.0000000000200248},
url = {https://pub.dzne.de/record/280115},
}