Brain and Behavior · Mar 2026

Early Microstructural Changes in the Left Inferior Fronto-Occipital Fasciculus: A Key Factor in Probable Alzheimer's Disease Patients With Slow Gait Speed

By Liu SW, Yao LL, Li FB et al.

OBJECTIVE: To examine the association between alterations in specific fiber tracts and 6-m gait speed and cognitive function in patients with clinically diagnosed Alzheimer's disease (AD) using fixel-based analysis (FBA). METHODS: Participants included 26 probable AD patients with slow gait speed (AD-SGS), 28 without slow gait speed (AD-nSGS), and 28 normal controls (NC). All subjects underwent neuropsychological assessment, 6-m gait speed testing, and cranial magnetic resonance imaging (MRI) scans. FBA was employed to derive white matter (WM) fiber metrics, including fiber density (FD), fiber cross-sectional area (FC), and fiber density and cross-sectional area (FDC). After adjustment for age and sex, the mean index values of the fiber tracts showing significant between-group differences were extracted for the correlation between fiber properties, neuropsychological test scores, and parameters related to physical function. RESULTS: AD-SGS group exhibited significantly reduced FD and FDC in the left inferior fronto-occipital fasciculus (IFOF_L) compared to AD-nSGS group. In probable AD patients, FDC values of IFOF_L were positively correlated with global cognitive function, attention and calculation abilities, executive and visuospatial functions, and information processing speed. Furthermore, FD value of IFOF_L was positively correlated with 6-m gait speed. CONCLUSIONS: In this clinically diagnosed AD patient with slow gait speed, the microstructural integrity of IFOF_L is closely linked to both cognitive decline and motor deficits. The structural deterioration of this tract is associated with the interplay between gait disturbance and impairments in executive and visuospatial functions, and information processing speed in this clinical context.

doi.org/10.1002/brb3.71298 Open access PubMed 41821196 Mechanisms