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Sex differences in clinical phenotypes of behavioral variant frontotemporal dementia

Title: Sex differences in clinical phenotypes of behavioral variant frontotemporal dementia
Authors: Liu, X; de Boer, SCM; Cortez, K; Poos, JM; Illán-Gala, I; Heuer, H; Forsberg, LK; Casaletto, K; Memel, M; Appleby, BS; Barmada, S; Bozoki, A; Clark, D; Cobigo, Y; Darby, R; Dickerson, BC; Domoto-Reilly, K; Galasko, DR; Geschwind, DH; Ghoshal, N; Graff-Radford, NR; Grant, IM; Hsiung, GYR; Honig, LS; Huey, ED; Irwin, D; Kantarci, K; Léger, GC; Litvan, I; Mackenzie, IR; Masdeu, JC; Mendez, MF; Onyike, CU; Pascual, B; Pressman, P; Bayram, E; Ramos, EM; Roberson, ED; Rogalski, E; Bouzigues, A; Russell, LL; Foster, PH; Ferry-Bolder, E; Masellis, M; van Swieten, J; Jiskoot, L; Seelaar, H; Sanchez-Valle, R; Laforce, R; Graff, C; Galimberti, D; Vandenberghe, R; de Mendonça, A; Tiraboschi, P; Santana, I; Gerhard, A; Levin, J; Sorbi, S; Otto, M; Pasquier, F; Ducharme, S; Butler, CR; Ber, IL; Finger, E; Rowe, JB; Synofzik, M; Moreno, F; Borroni, B; Boeve, BF; Boxer, AL; Rosen, HJ; Pijnenburg, YAL; Rohrer, JD; Tartaglia, MC
Publisher Information: Wiley https://doi.org/10.1002/alz.14608 Alzheimer S and Dementia 2025-04-25T11:47:34Z 2025 2024-08-23 2025-04-25T11:47:33Z
Document Type: Electronic Resource
Abstract: Publication status: Published; Funder: Lewy Body Dementia Association; doi: http://dx.doi.org/10.13039/100017312; Funder: EU Joint Programme‐Neurodegenerative Disease Research‐Prefrontals; Funder: Swedish FTD Inititative‐Schörling Foundation; Funder: Alzheimer Foundation; Funder: Brain Foundation; doi: http://dx.doi.org/10.13039/501100000942; Funder: Dementia Foundation; Funder: Region Stockholm ALF‐project; Funder: Germany's Federal Ministry of Education and Research; Funder: Weston Brain Institute; doi: http://dx.doi.org/10.13039/100012479; Funder: Ontario Brain Institute; doi: http://dx.doi.org/10.13039/100008914; Funder: Bluefield Project; Funder: National Institute for Health; Funder: Care Research University College London Hospitals Biomedical Research Centre; Funder: Miriam Marks Brain Research UK Senior Fellowship; Funder: European Reference Network for Rare Neurological Diseases; Funder: Cambridge University Centre for Frontotemporal Dementia; Funder: National Institute for Health Research Cambridge Biomedical Research Centre; Grant(s): NIHR203312: BRC‐1215‐20014;

Introduction

Higher male prevalence in sporadic behavioral variant frontotemporal dementia (bvFTD) has been reported. We hypothesized differences in phenotypes between genetic and sporadic bvFTD females resulting in underdiagnosis of sporadic bvFTD females.

Methods

We included genetic and sporadic bvFTD patients from two multicenter cohorts. We compared behavioral and cognitive symptoms, and gray matter volumes, between genetic and sporadic cases in each sex.

Results

Females with sporadic bvFTD showed worse compulsive behavior (p = 0.026) and language impairments (p = 0.024) compared to females with genetic bvFTD (n = 152). Genetic bvFTD females had smaller gray matter volumes than sporadic bvFTD females, particularly in the parietal lobe.

Discussion

Females with sporadic bvFTD exhibit a distinct clinical phenotype compared to females with genetic bvFTD. This difference may explain the discrepancy in prevalence between genetic and sporadic cases, as some females without genetic mutations may be misdiagnosed due to atypical bvFTD symptom presentation.

Highlights

Sex ratio is equal in genetic behavioral variant of frontotemporal dementia (bvFTD), whereas more males are present in sporadic bvFTD. Distinct neuropsychiatric phenotypes exist between sporadic and genetic bvFTD in females. Phenotype might explain the sex ratio difference between sporadic and genetic cases.
Index Terms: behavioral variant frontotemporal dementia; clinical diagnosis; diversity; sex difference; Article
URL: https://www.repository.cam.ac.uk/handle/1810/383365
Availability: Open access content. Open access content
Note: text/xml; application/pdf; English; English
Other Numbers: HS1 oai:www.repository.cam.ac.uk:1810/383365; 1528763572
Contributing Source: UNIV OF CAMBRIDGE; From OAIster®, provided by the OCLC Cooperative.
Accession Number: edsoai.on1528763572
Database: OAIster