Assessing the Influence of Tractography Methods on White Matter Microstructure and Tractometry Analysis in Alzheimer's Disease

Tractometry enables detailed mapping of white matter microstructure along individual tracts and is widely used to study disease effects such as those seen in Alzheimer's disease (AD). However, how different tractography algorithms influence tractometry outcomes remains unclear. Here, we compared whole-brain deterministic and probabilistic tractography using the BUndle ANalytics (BUAN) framework in the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, including 118 AD and 728 cognitively normal (CN) participants. Both approaches revealed the expected pattern of lower fractional anisotropy (FA) and higher mean, radial, and axial diffusivity (MD, RD, AxD) in AD, consistent with white matter degeneration. Despite broadly similar global trends, substantial bundle-level differences emerged between the two tractography methods. Probabilistic tracking produced stronger and more spatially extended effects in the fornix, a small and highly curved limbic pathway vulnerable to AD-related degeneration, whereas deterministic tracking showed greater sensitivity in the posterior segments of the right superior longitudinal fasciculus (SLF\_R). These discrepancies highlight that the choice oftractography algorithm can alter detecting disease effects, emphasizing the need for cross-method validation to ensure the robustness and interpretability of along-tract measures.