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BACKGROUND/OBJECTIVES: Memory clinic patients commonly also have declined physical performance. This may be attributable to white matter injury, due to vascular damage or neurodegeneration. Quantifying white matter injury is made possible by new magnetic resonance imaging (MRI) techniques, including diffusion‐weighted imaging (DWI) of network connectivity. We investigated whether physical performance in memory clinic patients is related to white matter network connectivity. DESIGN: Observational cross‐sectional study. SETTING: Memory clinic. PARTICIPANTS: Patients referred to a memory clinic with vascular brain injury on MRI (n = 90; average age = 72 years; 60% male; 34% with diagnosis Alzheimer disease). MEASUREMENTS: We reconstructed structural brain networks from DWI with fiber tractography and used graph theory to calculate global efficiency, fractional anisotropy (FA), and mean diffusivity (MD) of the white matter, and nodal strength (mean FA or MD of all white matter tracts connected to a node). Assessment of physical performance included gait speed, chair stand time, and Short Physical Performance Battery (SPPB) score. RESULTS: Lower global efficiency, lower FA, and higher MD correlated with poorer gait speed, SPPB scores, and chair stand times (R range = 0.23‐0.42). Global efficiency and FA explained 5% to 16% of the variance in gait speed, chair stand times, and SPPB scores, independent of age and sex. Moreover, global efficiency and FA explained an additional 4% to 5% of variance on top of lacunar infarcts and white matter hyperintensities. Regional analyses showed that, in particular, the connectivity strength of prefrontal, occipital, striatal, and thalamic nodes correlated with gait speed. CONCLUSION: Poorer physical performance is related to disrupted white matter network connectivity in memory clinic patients with vascular brain injury. The associations of these network abnormalities are partially independent of visible vascular injury. J Am Geriatr Soc 67:1880–1887, 2019 [ABSTRACT FROM AUTHOR]