Claudia Metzler-Baddeley, Roland J. Baddeley, Derek K. Jones, John P. Aggleton, Michael J. O’Sullivan

The prevalence of obesity and associated health conditions is increasing in the developed world. Obesity is related to atrophy and dysfunction of the hippocampus and hippocampal lesions may lead to increased appetite and weight gain. The hippocampus is connected via the fornix tract to the hypothalamus, orbitofrontal cortex, and the nucleus accumbens, all key structures for homeostatic and reward related control of food intake. The present study employed diffusion MRI tractography to investigate the relationship between microstructural properties of the fornix and variation in Body Mass Index (BMI), within normal and overweight ranges, in a group of community-dwelling older adults (53-93 years old). Larger BMI was associated with larger axial and mean diffusivity in the fornix (r = 0.64 and r = 0.55 respectively), relationships that were most pronounced in overweight individuals. Moreover, controlling for age, education, cognitive performance, blood pressure and global brain volume increased these correlations. Similar associations were not found in the parahippocampal cingulum, a comparison temporal association pathway. Thus, microstructural changes in fornix white matter were observed in older adults with increasing BMI levels from within normal to overweight ranges, so are not exclusively related to obesity. We propose that hippocampal-hypothalamic-prefrontal interactions, mediated by the fornix, contribute to the healthy functioning of networks involved in food intake control. The fornix, in turn, may display alterations in microstructure that reflect weight gain.