Changes in body composition in genetic C9orf72 carriers: the role of the hypothalamus and thalamus

Rebekah M. Ahmed; Nga Yan Tse; Martina Bocchetta; Carol Dobson‐Stone; John B. Kwok; John R. Hodges; Muireann Irish; Jonathan R. Rohrer; Olivier Piguet; Glenda Halliday

doi:10.1002/alz.71669

Changes in body composition in genetic C9orf72 carriers: the role of the hypothalamus and thalamus

Rebekah M. Ahmed, Nga Yan Tse, Martina Bocchetta, Carol Dobson‐Stone, John B. Kwok, John R. Hodges, Muireann Irish, Jonathan R. Rohrer, Olivier Piguet, Glenda Halliday

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

BACKGROUND: Patients with sporadic frontotemporal dementia (FTD) display changes in metabolism and body composition. No studies have examined body composition changes in pre-symptomatic C9orf72 mutation carriers

METHODS: Asymptomatic C9orf72 expansion carriers between 2017 and 2022 (n = 28 non-carriers, 16 expansion-positive), underwent dual-energy X-ray absorptiometry (measurement of changes in body composition) and brain magnetic resonance imaging (MRI).

RESULTS: Changes in body composition were identified in the C9orf72 expansion carrier group compared to non-carrier group (average 11–12 years prior to onset): lower android-to-gynoid ratio (p = 0.009), and visceral adipose tissue area (p = 0.010). Lower android-to-gynoid ratio and lean mass were associated with lower volumes across the cortex, subcortex, and thalamus.

CONCLUSIONS: The current study highlights that genetically at-risk C9orf72 patients exhibit altered body composition. These findings align with the growing recognition that changes in genetic frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS) extend beyond cognitive/motor symptoms and include early alterations in broader physiological function.

Original language	English
Article number	e71669
Pages (from-to)	1-9
Number of pages	9
Journal	Alzheimer's and Dementia
Volume	22
Issue number	7
DOIs	https://doi.org/10.1002/alz.71669
Publication status	Published - Jul 2026
Externally published	Yes

Bibliographical note

Copyright the Author(s) 2026. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

FTD
genetic
metabolism
neurodegeneration

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Publisher version (open access)Final published version, 784 KBLicence: CC BY

Cite this

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title = "Changes in body composition in genetic C9orf72 carriers: the role of the hypothalamus and thalamus",

abstract = "BACKGROUND: Patients with sporadic frontotemporal dementia (FTD) display changes in metabolism and body composition. No studies have examined body composition changes in pre-symptomatic C9orf72 mutation carriers METHODS: Asymptomatic C9orf72 expansion carriers between 2017 and 2022 (n = 28 non-carriers, 16 expansion-positive), underwent dual-energy X-ray absorptiometry (measurement of changes in body composition) and brain magnetic resonance imaging (MRI). RESULTS: Changes in body composition were identified in the C9orf72 expansion carrier group compared to non-carrier group (average 11–12 years prior to onset): lower android-to-gynoid ratio (p = 0.009), and visceral adipose tissue area (p = 0.010). Lower android-to-gynoid ratio and lean mass were associated with lower volumes across the cortex, subcortex, and thalamus. CONCLUSIONS: The current study highlights that genetically at-risk C9orf72 patients exhibit altered body composition. These findings align with the growing recognition that changes in genetic frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS) extend beyond cognitive/motor symptoms and include early alterations in broader physiological function.",

keywords = "FTD, genetic, metabolism, neurodegeneration",

author = "Ahmed, \{Rebekah M.\} and Tse, \{Nga Yan\} and Martina Bocchetta and Carol Dobson‐Stone and Kwok, \{John B.\} and Hodges, \{John R.\} and Muireann Irish and Rohrer, \{Jonathan R.\} and Olivier Piguet and Glenda Halliday",

note = "Copyright the Author(s) 2026. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

year = "2026",

month = jul,

doi = "10.1002/alz.71669",

language = "English",

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pages = "1--9",

journal = "Alzheimer's and Dementia",

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TY - JOUR

T1 - Changes in body composition in genetic C9orf72 carriers

T2 - the role of the hypothalamus and thalamus

AU - Ahmed, Rebekah M.

AU - Tse, Nga Yan

AU - Bocchetta, Martina

AU - Dobson‐Stone, Carol

AU - Kwok, John B.

AU - Hodges, John R.

AU - Irish, Muireann

AU - Rohrer, Jonathan R.

AU - Piguet, Olivier

AU - Halliday, Glenda

N1 - Copyright the Author(s) 2026. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2026/7

Y1 - 2026/7

N2 - BACKGROUND: Patients with sporadic frontotemporal dementia (FTD) display changes in metabolism and body composition. No studies have examined body composition changes in pre-symptomatic C9orf72 mutation carriers METHODS: Asymptomatic C9orf72 expansion carriers between 2017 and 2022 (n = 28 non-carriers, 16 expansion-positive), underwent dual-energy X-ray absorptiometry (measurement of changes in body composition) and brain magnetic resonance imaging (MRI). RESULTS: Changes in body composition were identified in the C9orf72 expansion carrier group compared to non-carrier group (average 11–12 years prior to onset): lower android-to-gynoid ratio (p = 0.009), and visceral adipose tissue area (p = 0.010). Lower android-to-gynoid ratio and lean mass were associated with lower volumes across the cortex, subcortex, and thalamus. CONCLUSIONS: The current study highlights that genetically at-risk C9orf72 patients exhibit altered body composition. These findings align with the growing recognition that changes in genetic frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS) extend beyond cognitive/motor symptoms and include early alterations in broader physiological function.

AB - BACKGROUND: Patients with sporadic frontotemporal dementia (FTD) display changes in metabolism and body composition. No studies have examined body composition changes in pre-symptomatic C9orf72 mutation carriers METHODS: Asymptomatic C9orf72 expansion carriers between 2017 and 2022 (n = 28 non-carriers, 16 expansion-positive), underwent dual-energy X-ray absorptiometry (measurement of changes in body composition) and brain magnetic resonance imaging (MRI). RESULTS: Changes in body composition were identified in the C9orf72 expansion carrier group compared to non-carrier group (average 11–12 years prior to onset): lower android-to-gynoid ratio (p = 0.009), and visceral adipose tissue area (p = 0.010). Lower android-to-gynoid ratio and lean mass were associated with lower volumes across the cortex, subcortex, and thalamus. CONCLUSIONS: The current study highlights that genetically at-risk C9orf72 patients exhibit altered body composition. These findings align with the growing recognition that changes in genetic frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS) extend beyond cognitive/motor symptoms and include early alterations in broader physiological function.

KW - FTD

KW - genetic

KW - metabolism

KW - neurodegeneration

UR - http://purl.org/au-research/grants/nhmrc/2025228

UR - http://purl.org/au-research/grants/nhmrc/GNT1138223

UR - http://purl.org/au-research/grants/nhmrc/2022387

UR - https://www.scopus.com/pages/publications/105044978010

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SN - 1552-5260

VL - 22

SP - 1

EP - 9

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 7

M1 - e71669

ER -

Changes in body composition in genetic C9orf72 carriers: the role of the hypothalamus and thalamus

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Keywords

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