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The following is a summary of “Association of Changes in Cerebral and Hypothalamic Structure With Sleep Dysfunction in Patients With Genetic Frontotemporal Dementia,” published in the November 2024 issue of Neurology by Best et al.
Sleep dysfunction is joined in neurodegenerative disorders, including genetic frontotemporal dementia (FTD), but the neural causes remain poorly understood.
Researchers conducted a prospective study to examine changes in hypothalamic structure and the relationship with sleep dysfunction in genetic FTD.
They analyzed data from the Genetic Frontotemporal Dementia Initiative (GENFI) study, which included adults with pathogenic variants in the microtubule-associated protein tau (MAPT), progranulin (GRN), or chromosome 9 open reading frame 72 (C9orf72) genes. Family members without these variants served as controls, and participants underwent up to seven annual visits, including clinical evaluations, neuropsychological testing, biological sampling, and brain MRI. Only those with at least 1-T1-weighted structural MRI scans were included. Linear mixed-effect models were used to assess differences in sleep dysfunction (measured by the Cambridge Behavioral Inventory-Revised sleep subscale), hypothalamic volume, and the relationships between cortical and hypothalamic atrophy and sleep dysfunction.
The results showed 491 adults with pathogenic variants of FTD (27.9% symptomatic; median age: 49.4 years, 56.4% female) and 321 controls (median age: 44.2 years, 57.3% female). Pathogenic variant carriers showed more significant sleep dysfunction across the adult lifespan (β = [0.25–0.34], q < 0.005), with MAPT carriers alone showing presymptomatic sleep dysfunction (β = 0.34, q = 0.005). Cortical thinning in the frontal and parietal regions was associated with greater sleep disturbances in C9orf72 and GRN carriers (q < 0.05). The MAPT carriers showed significant volume loss over time in all sleep-relevant hypothalamic subunits (β = [−0.56 to −0.39], q < 0.005), and reductions in hypothalamic volumes were linked to increased sleep dysfunction (β = [−0.20 to −0.16], q < 0.05).
They concluded that sleep dysfunction in genetic FTD may be related to atrophy in sleep-relevant hypothalamic subunits, with the most severe deficits observed in MAPT carriers.
Source: neurology.org/doi/10.1212/WNL.0000000000209829
