Eating behavior in frontotemporal dementia: Peripheral hormones vs hypothalamic pathology

Area of Science:

• Neuroscience
• Endocrinology
• Metabolic Disorders

Background:

• Frontotemporal dementia (FTD) encompasses behavioral variant FTD (bvFTD) and semantic variant primary progressive aphasia (svPPA), often presenting with eating abnormalities.
• The interplay between hormonal eating peptides, hypothalamic structure, and metabolic changes in FTD subtypes remains incompletely understood.

Purpose of the Study:

• To investigate the associations between hormonal eating peptides and hypothalamic volumes with eating behaviors and body mass index (BMI) in bvFTD and svPPA.

Main Methods:

• Fasting blood levels of leptin, ghrelin, cholecystokinin, peptide tyrosine tyrosine (PYY), and agouti-related peptide (AgRP) were measured in 75 dementia patients (bvFTD, svPPA, Alzheimer disease dementia) and 23 controls.
• Brain MRI was used to assess anterior, posterior, and total hypothalamic volumes.
• Relationships between endocrine measures, hypothalamic volumes, eating behaviors, and BMI were analyzed.

Main Results:

• Patients with bvFTD and svPPA exhibited significantly higher agouti-related peptide (AgRP) levels compared to controls.
• Elevated eating behavior scores were reported in both bvFTD and svPPA groups.
• Hypothalamic atrophy, particularly in posterior and total regions, was observed exclusively in the bvFTD group.
• Linear regression indicated that both leptin and AgRP levels were significant predictors of BMI.

Conclusions:

• Eating abnormalities in FTD are multifactorial, involving hypothalamic degeneration in bvFTD and altered AgRP levels in both bvFTD and svPPA.
• Elevated AgRP levels, a key predictor of BMI in both FTD subtypes, suggest its potential role in metabolic dysregulation and as a therapeutic target.