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

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.