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Patterns of gray matter atrophy in genetic frontotemporal dementia: results from the GENFI study.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Cash, David M 
Bocchetta, Martina 
Thomas, David L 
Dick, Katrina M 
van Swieten, John C 

Abstract

Frontotemporal dementia (FTD) is a highly heritable condition with multiple genetic causes. In this study, similarities and differences of gray matter (GM) atrophy patterns were assessed among 3 common forms of genetic FTD (mutations in C9orf72, GRN, and MAPT). Participants from the Genetic FTD Initiative (GENFI) cohort with a suitable volumetric T1 magnetic resonance imaging scan were included (319): 144 nonmutation carriers, 128 presymptomatic mutation carriers, and 47 clinically affected mutation carriers. Cross-sectional differences in GM volume between noncarriers and carriers were analyzed using voxel-based morphometry. In the affected carriers, each genetic mutation group exhibited unique areas of atrophy but also a shared network involving the insula, orbitofrontal lobe, and anterior cingulate. Presymptomatic GM atrophy was observed particularly in the thalamus and cerebellum in the C9orf72 group, the anterior and medial temporal lobes in MAPT, and the posterior frontal and parietal lobes as well as striatum in GRN. Across all presymptomatic carriers, there were significant decreases in the anterior insula. These results suggest that although there are important differences in atrophy patterns for each group (which can be seen presymptomatically), there are also similarities (a fronto-insula-anterior cingulate network) that help explain the clinical commonalities of the disease.

Description

Keywords

Atrophy, Frontotemporal dementia, Magnetic resonance imaging, Preclinical dementia, Voxel-based morphometry, Adult, Aged, Atrophy, C9orf72 Protein, Cohort Studies, Female, Frontotemporal Dementia, Gray Matter, Heterozygote, Humans, Intercellular Signaling Peptides and Proteins, Magnetic Resonance Imaging, Male, Middle Aged, Mutation, Organ Size, Progranulins, tau Proteins

Journal Title

Neurobiol Aging

Conference Name

Journal ISSN

0197-4580
1558-1497

Volume Title

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (103838/Z/14/Z)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Medical Research Council (MR/J009482/1)
Medical Research Council (MR/M009041/1)
Medical Research Council (MC_U105597119)
Medical Research Council (MR/M024873/1)
Medical Research Council (MC_UU_00005/12)