TY - JOUR

T1 - Presymptomatic generalized brain atrophy in frontotemporal dementia caused by CHMP2B mutation

AU - Rohrer, Jonathan D

AU - Ahsan, R Laila

AU - Isaacs, Adrian M

AU - Nielsen, Jørgen Erik

AU - Ostergaard, Leif

AU - Scahill, Rachael

AU - Warren, Jason D

AU - Rossor, Martin N

AU - Fox, Nick C

AU - Johannsen, Peter

AU - FReJA Consortium

N1 - Keywords: Aged; Atrophy; Brain; Dementia; Disease Progression; Endosomal Sorting Complexes Required for Transport; Family; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Mutation; Nerve Tissue Proteins; tau Proteins

PY - 2009

Y1 - 2009

N2 - BACKGROUND/AIMS: CHMP2B mutations are a rare cause of familial frontotemporal dementia (FTD). The clinical syndrome is dominated by personality change and behavioural symptoms, but language, memory, calculation and praxis impairments are also seen early in the course of the disease. There are no detailed studies of brain imaging in CHMP2B mutation-associated FTD. This study aimed to investigate whether there were early or presymptomatic changes in this group of patients. METHODS: Subjects comprised 16 members of a Danish family with CHMP2B mutation-associated FTD. Nine subjects were presymptomatic mutation carriers with a control group of 7 mutation-negative family members. Volumetric MRI brain scans were performed on all subjects at two time points, and rates of volume change were compared between the two groups. RESULTS: We demonstrate that generalized atrophy occurs presymptomatically in CHMP2B gene mutation carriers. CONCLUSIONS: This finding suggests that mutations in CHMP2B have widespread effects throughout the brain, leading to a neuro-anatomical signature distinct from other diseases in the frontotemporal lobar degeneration spectrum.

AB - BACKGROUND/AIMS: CHMP2B mutations are a rare cause of familial frontotemporal dementia (FTD). The clinical syndrome is dominated by personality change and behavioural symptoms, but language, memory, calculation and praxis impairments are also seen early in the course of the disease. There are no detailed studies of brain imaging in CHMP2B mutation-associated FTD. This study aimed to investigate whether there were early or presymptomatic changes in this group of patients. METHODS: Subjects comprised 16 members of a Danish family with CHMP2B mutation-associated FTD. Nine subjects were presymptomatic mutation carriers with a control group of 7 mutation-negative family members. Volumetric MRI brain scans were performed on all subjects at two time points, and rates of volume change were compared between the two groups. RESULTS: We demonstrate that generalized atrophy occurs presymptomatically in CHMP2B gene mutation carriers. CONCLUSIONS: This finding suggests that mutations in CHMP2B have widespread effects throughout the brain, leading to a neuro-anatomical signature distinct from other diseases in the frontotemporal lobar degeneration spectrum.

U2 - 10.1159/000200466

DO - 10.1159/000200466

M3 - Journal article

C2 - 19202337

VL - 27

SP - 182

EP - 186

JO - Dementia and Geriatric Cognitive Disorders

JF - Dementia and Geriatric Cognitive Disorders

SN - 1420-8008

IS - 2

ER -