ORCID: https://orcid.org/0000-0001-5023-5893; Bouzigues, Arabella ORCID: https://orcid.org/0000-0002-0267-8590; Convery, Rhian S. ORCID: https://orcid.org/0000-0002-9477-1812; Foster, Phoebe H. ORCID: https://orcid.org/0000-0001-6300-6598; Ferry-Bolder, Eve ORCID: https://orcid.org/0009-0006-5083-0901; Cash, David M. ORCID: https://orcid.org/0000-0001-7833-616X; Van Swieten, John C. ORCID: https://orcid.org/0000-0001-6278-6844; Jiskoot, Lize Corrine ORCID: https://orcid.org/0000-0002-1120-1858; Seelaar, Harro ORCID: https://orcid.org/0000-0003-1989-7527; Moreno, Fermin ORCID: https://orcid.org/0000-0001-5200-3164; Sánchez-Valle, Raquel ORCID: https://orcid.org/0000-0001-7750-896X; Laforce, Robert ORCID: https://orcid.org/0000-0002-2031-490X; Graff, Caroline ORCID: https://orcid.org/0000-0002-9949-2951; Masellis, Mario ORCID: https://orcid.org/0000-0002-6244-2096; Tartaglia, Maria Carmela ORCID: https://orcid.org/0000-0002-5944-8497; Rowe, James B. ORCID: https://orcid.org/0000-0001-7216-8679; Borroni, Barbara ORCID: https://orcid.org/0000-0001-9340-9814; Finger, Elizabeth ORCID: https://orcid.org/0000-0003-4461-7427; Synofzik, Matthis ORCID: https://orcid.org/0000-0002-2280-7273; Galimberti, Daniela ORCID: https://orcid.org/0000-0002-9284-5953; Vandenberghe, Rik ORCID: https://orcid.org/0000-0001-6237-2502; Mendonça, Alexandre de ORCID: https://orcid.org/0000-0002-0488-1453; Butler, Christopher ORCID: https://orcid.org/0000-0002-7502-9284; Gerhard, Alexander ORCID: https://orcid.org/0000-0002-8071-6062; Ducharme, Simon ORCID: https://orcid.org/0000-0002-7309-1113; Ber, Isabelle Le ORCID: https://orcid.org/0000-0002-2508-5181; Santana, Isabel ORCID: https://orcid.org/0000-0002-8114-9434; Pasquier, Florence ORCID: https://orcid.org/0000-0001-9880-9788; Levin, Johannes ORCID: https://orcid.org/0000-0001-5092-4306; Sorbi, Sandro ORCID: https://orcid.org/0000-0002-0380-6670; Otto, Markus ORCID: https://orcid.org/0000-0003-4273-4267 und Rohrer, Jonathan Daniel ORCID: https://orcid.org/0000-0002-6155-8417
(2025):
Executive Function Deficits in Genetic Frontotemporal Dementia.
In: Neurology Genetics, Bd. 11, Nr. 4, e200248
[PDF, 251kB]
Abstract
Background and Objectives
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.
Methods
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.
Results
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).
Discussion
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.
| Dokumententyp: | Zeitschriftenartikel |
|---|---|
| EU Funded Grant Agreement Number: | 739510 |
| Fakultät: | Medizin > Munich Cluster for Systems Neurology (SyNergy) |
| Themengebiete: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit |
| URN: | urn:nbn:de:bvb:19-epub-129933-4 |
| ISSN: | 2376-7839 |
| Bemerkung: | for the Genetic FTD Initiative (GENFI) |
| Sprache: | Englisch |
| Dokumenten ID: | 129933 |
| Datum der Veröffentlichung auf Open Access LMU: | 01. Dez. 2025 08:07 |
| Letzte Änderungen: | 01. Dez. 2025 08:07 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198 |
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