Objectives. The relationship between cognitive symptoms and underlying neuropathology in primary SS (PSS) is poorly understood. We used high-resolution quantitative brain MRI to identify potential structural correlates of cognitive symptoms.Methods. Subjects completed a comprehensive neuropsychometric evaluation. Imaging was performed on a 3 T MRI scanner with T1 and proton density-weighted, fluid-attenuated inversion recovery (FLAIR) and Diffusion Tensor ImagingDiffusion Tensor Imaging (DTI)Used to assess the integrity of the white matter and to visualize major tracts for rough anatomical connectivity. Each voxel is assigned a fractional anisotropy (FA) value. Typically, low fractional anisotropy values indicate damage to the white matter. sequences. We compared MRI group metrics (impaired PSS, not-impaired PSS and controls) and tested for correlations between DTIDiffusion Tensor Imaging (DTI)Used to assess the integrity of the white matter and to visualize major tracts for rough anatomical connectivity. Each voxel is assigned a fractional anisotropy (FA) value. Typically, low fractional anisotropy values indicate damage to the white matter. results and neuropsychological measurements (significance threshold P = 0.05).Results. Nineteen PSS patients (who met American-European Consensus Group 2002 criteria) and 17 healthy controls completed the cognitive evaluation. MRI scans were performed in six impaired PSS, seven not-impaired PSS and seven controls. No differences were found in regional volumetrics, nor was there a difference in T2 lesion load between groups. Fractional anisotropy (FA) in the inferior frontal white matter (WM) was lower (P = 0.021) and mean diffusivity higher (P = 0.003) in the impaired PSS relative to the control group. Inferior frontal FA was correlated with cognitive symptoms (P = 0.0064) and with verbal memory (P = 0.0125).Conclusions. In this exploratory study, frontal region WM microstructure alterations accompanied cognitive symptoms and were associated with mild cognitive impairment in PSS. While additional study is warranted to assess the specificity and stability of these results, DTIDiffusion Tensor Imaging (DTI)Used to assess the integrity of the white matter and to visualize major tracts for rough anatomical connectivity. Each voxel is assigned a fractional anisotropy (FA) value. Typically, low fractional anisotropy values indicate damage to the white matter. could provide novel insight into the pathological processes accompanying the subtle cognitive dysfunction commonly experienced by PSS patients.