148 Ventral Mammillo-tegmental Tract Atrophies With Normal Aging

Abstract

INTRODUCTION: We recently characterized the Ventral Mammillo-tegmental tract (VMTT) throug Klingler’s microdissections and fiber tractography using an averaged template generated from diffusion MRI (dMRI) data of 1065 human healthy subjects acquired from the Human Connectome Project (HCP) and the 50/200 μm cadaveric brainstem dMRI Duke database. The VMTT interconnects the ventral tegmental area with mammillary bodies, regions that are profoundly affected in dementia. We hypothesize that his tract is involved in memory which is inherently affected by normal brain aging and thus atrophy over time. METHODS: We performed fiber tractography of the VMTT and the corticospinal tract (CST), using individual subject data from multiple HCP databases spanning neonatal, developmental, healthy adult, and aging populations. These data were generated using an averaged template from diffusion MRI (dMRI) data of 1065 healthy human subjects acquired from the Human Connectome Project (HCP) and the Duke database of cadaveric brainstem dMRI. The CST served as a control in this study. Tract diameter, volume, and fractional anisotropy were measured using DSI Studio developed by FCY. Trends analysis was performed evaluating diameter changes by age. RESULTS: The tract was reconstructed in total of 20 subjects for ages ranging from 9 to 100 years old. Our analysis revealed a significant age-related atrophy of the VMTT (p < 0.0001) while no age-related atrophy was observed in the CST (p = 0.161). CONCLUSIONS: Our findings indicate that the VMTT experiences disproportionate atrophy with normal aging as compared to CST which served as a control tract. This highlights the distinct age-related changes in the VMTT. Future dMRI studies on this tract across diverse patient populations will shed light on its potential role as a biomarker for early diagnosis of dementia disorders and its utility as a deep brain stimulation (DBS) target.