Structural and functional cortical disconnection in Alzheimer's disease: A combined study using diffusion tensor imaging and transcranial magnetic stimulation

We investigated the functional consequences of compromised white matter integrity in Alzheimer's disease by combining Diffusion Tensor Imaging (DTI) and Transcranial Magnetic Stimulation (TMS) in 19 patients with AD (Alzheimer's disease) and 19 healthy controls. We used a region of interest approach and correlated the ipsilateral silent period (iSP) and the resting motor threshold (RMT) from TMS with fractional anisotropy (FA) and mean diffusivity (MD) values of the corpus callosum and corticospinal tract. AD patients showed significant reductions of FA in intracortical projecting fibre tracts compared to controls and widespread increases in MD. TMS data showed increased latency of iSP in AD patients and a decreased RMT, indicating decreased motor cortical inhibition. Although both TMS and DTI metrics were prominently altered in AD patients, impaired white matter integrity was not associated with increased iSP latency or reduced RMT, as correlation of TMS parameters with FA and MD values in the a priori defined regions showed no significant effects. Therefore, we argue that beside the direct degeneration of the underlying fibre tracts, other pathophysiological mechanisms may account for the observation of decreased transcallosal inhibition and increased motor excitability in AD.