White matter hyperintensities (WMHs) are often identified on T2-weighted magnetic resonance (MR) images in the elderly. The WMHs are generally associated with small vessel ischemic or pre-ischemic changes. However, the association of WMHs with blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal is understudied. In this study, we evaluate how the BOLD signal change is related to the presence of WMHs in the elderly. Data were acquired as part of a study of late-life depression and included elderly individuals with and without major depression. The subjects were pooled because the presence of depression was not significantly associated with task-related BOLD changes, task performance, and WMH distribution. A whole brain voxel-wise regression analysis revealed a significant negative correlation between WMH burden and BOLD signal change during finger-tapping in the parietal white matter. Our observation that WMHs are associated with a significant diminution of the BOLD signal change underscores the importance of considering cerebrovascular burden when interpreting fMRI studies in the elderly. The mechanism underlying the association of WMH and BOLD signal change remains unclear: the association may be mediated by changes in neural activation, changes in coupling between neuronal activity and hemodynamics, or, perhaps, secondary to the effect of the ischemic changes on the sensitivity of the T2* BOLD MR signal.
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