Logo Logo
Hilfe
Hilfe
Switch Language to English

Borrego-Ecija, Sergi ORCID logoORCID: https://orcid.org/0000-0003-2557-0010; Juncà-Parella, Jordi; Vandebergh, Marijne ORCID logoORCID: https://orcid.org/0000-0001-9645-2615; Pérez Millan, Agnès; Balasa, Mircea; Llado, Albert; Bouzigues, Arabella ORCID logoORCID: https://orcid.org/0000-0002-0267-8590; Russell, Lucy Louise ORCID logoORCID: https://orcid.org/0000-0001-5023-5893; Foster, Phoebe H. ORCID logoORCID: https://orcid.org/0000-0001-6300-6598; Ferry-Bolder, Eve ORCID logoORCID: https://orcid.org/0009-0006-5083-0901; Swieten, John C. Van ORCID logoORCID: https://orcid.org/0000-0001-6278-6844; Jiskoot, Lize Corrine ORCID logoORCID: https://orcid.org/0000-0002-1120-1858; Seelaar, Harro ORCID logoORCID: https://orcid.org/0000-0003-1989-7527; Laforce, Robert ORCID logoORCID: https://orcid.org/0000-0002-2031-490X; Graff, Caroline ORCID logoORCID: https://orcid.org/0000-0002-9949-2951; Galimberti, Daniela ORCID logoORCID: https://orcid.org/0000-0002-9284-5953; Vandenberghe, Rik ORCID logoORCID: https://orcid.org/0000-0001-6237-2502; Mendonça, Alexandre de ORCID logoORCID: https://orcid.org/0000-0002-0488-1453; Tiraboschi, Pietro ORCID logoORCID: https://orcid.org/0000-0002-2171-1720; Santana, Isabel ORCID logoORCID: https://orcid.org/0000-0002-8114-9434; Gerhard, Alexander ORCID logoORCID: https://orcid.org/0000-0002-8071-6062; Levin, Johannes ORCID logoORCID: https://orcid.org/0000-0001-5092-4306; Sorbi, Sandro ORCID logoORCID: https://orcid.org/0000-0002-0380-6670; Otto, Markus ORCID logoORCID: https://orcid.org/0000-0003-4273-4267; Pasquier, Florence ORCID logoORCID: https://orcid.org/0000-0001-9880-9788; Ducharme, Simon ORCID logoORCID: https://orcid.org/0000-0002-7309-1113; Butler, Christopher ORCID logoORCID: https://orcid.org/0000-0002-7502-9284; Ber, Isabelle Le ORCID logoORCID: https://orcid.org/0000-0002-2508-5181; Finger, Elizabeth ORCID logoORCID: https://orcid.org/0000-0003-4461-7427; Tartaglia, Maria Carmela ORCID logoORCID: https://orcid.org/0000-0002-5944-8497; Masellis, Mario ORCID logoORCID: https://orcid.org/0000-0002-6244-2096; Rowe, James B. ORCID logoORCID: https://orcid.org/0000-0001-7216-8679; Synofzik, Matthis ORCID logoORCID: https://orcid.org/0000-0002-2280-7273; Moreno, Fermin ORCID logoORCID: https://orcid.org/0000-0001-5200-3164; Borroni, Barbara ORCID logoORCID: https://orcid.org/0000-0001-9340-9814; Rademakers, Rosa ORCID logoORCID: https://orcid.org/0000-0002-4049-0863; Rohrer, Jonathan Daniel ORCID logoORCID: https://orcid.org/0000-0002-6155-8417 und Sánchez-Valle, Raquel ORCID logoORCID: https://orcid.org/0000-0001-7750-896X (2024): Association of Initial Side of Brain Atrophy With Clinical Features and Disease Progression in Patients With GRN Frontotemporal Dementia. In: Neurology, Bd. 103, Nr. 11, e209944 [PDF, 828kB]

Abstract

Background and Objectives : Pathogenic variants in the GRN gene cause frontotemporal dementia (FTD-GRN) with marked brain asymmetry. This study aims to assess whether the disease progression of FTD-GRN depends on the initial side of the atrophy. We also investigated the potential use of brain asymmetry as a biomarker of the disease. Methods : Retrospective examination of data from the prospective Genetic Frontotemporal Initiative (GENFI) cohort study that recruits individuals who carry or were at risk of carrying a pathogenic variant causing FTD. GENFI participants underwent a standardized clinical and neuropsychological assessment, MRI, and a blood sample test yearly. We generated an asymmetry index for brain MRI to characterize brain asymmetry in participants with or at risk of FTD-GRN. Depending on the side of the asymmetry, we classified symptomatic GRN patients as right-GRN or left-GRN and compared their clinical features and disease progression. We generated generalized additive models to study how the asymmetry index evolves in carriers and noncarriers and compare its models with others created with volumetric values and plasma neurofilament light chain. Results : A total of 399 participants (mean age 49.7 years, 59% female) were included (63 symptomatic carriers, 177 presymptomatic carriers, and 159 noncarriers). Symptomatic carriers showed higher brain asymmetry (11.6) than noncarriers (1.0, p < 0.001) and presymptomatic carriers (1.0, p < 0.001), making it possible to classify most of them as right-GRN (n = 21) or left-GRN (n = 36). Patients with right-GRN showed more disease severity at baseline (β = 6.9, 95% CI 2.4–11.0, p = 0.003) but a lower deterioration by year (β = −1.5, 95% CI −2.7 to −0.31, p = 0.015) than patients with left-GRN. Brain asymmetry could be found in GRN carriers 10.4 years before the onset of the symptoms (standard difference 0.85, CI 0.01–1.68). Discussion : FTD-GRN affects the brain hemispheres asymmetrically and causes 2 anatomical asymmetry patterns depending on the side of the disease onset. We demonstrated that these 2 anatomical asymmetry patterns present different symptoms, severity at the time of the first visit, and different disease courses. Our results also suggest brain asymmetry as a possible biomarker of conversion in GRN carriers.

Dokument bearbeiten Dokument bearbeiten