Although the role of cerebral small vessel disease (SVD), including white matter lesions (WMLs) and lacunar infarcts, in mild parkinsonian signs (MPS) is increasingly being recognized, not all individuals with SVD have MPS. Using diffusion tensor imaging (DTI), we investigated whether the presence of MPS was dependent on the microstructural integrity underlying WMLs, the early loss of integrity of the normal-appearing white matter (NAWM) and location of this damage. We examined 483 elderly subjects with SVD and without parkinsonism. Subjects with severe loss of integrity within their WMLs had a higher risk of MPS, regardless of WML volume (fractional anisotropy odds ratios = 1.9; 95% confidence interval, 1.1-3.4). The same was found in the normal-appearing white matter, but this association disappeared after adjustment for WMLs and lacunar infarcts. The integrity of the periventricular frontal regions-of-interest was significantly lower in subjects with MPS than without, independent of WMLs and lacunar infarcts. This study indicates that integrity of WMLs, especially in the frontal lobe, is associated with MPS. Diffusion tensor imaging may be of added value in investigating the underlying mechanisms of parkinsonian signs in subjects with SVD.

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