Ultrastructural Hippocampal and White Matter Alterations in Mild Cognitive Impairment: A Diffusion Tensor Imaging Study

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Abstract
Mild cognitive impairment (MCI) is considered to be a transitional stage between normal aging and dementia. In Alzheimer's disease (AD), white matter structural pathology is due to Wallerian degeneration and central angiopathy. However, in MCI patients, the presence and extent of white matter alterations as a possible correlate of impaired memory function and as predictor of subsequent progression to AD is not clarified yet. Diffusion tensor imaging (DTI) reveals the ultrastructural integrity of cerebral white matter tracts. Therefore, it could detect pathological processes that modify tissue integrity in patients with MCI. In our prospective study, conventional and diffusion tensor MR scans were obtained from 14 patients with MCI, 19 patients with AD, and 10 healthy controls. Mean diffusivity (MD) and fractional anisotropy (FA) were measured in temporal, frontal, parietal and occipital white matter regions as well as in the corpus callosum (genu and splenium) and the hippocampus. MCI patients showed higher MD values in the left centrum semiovale (p = 0.013; right: p = 0.026), in the left temporal (p = 0.006), the right temporal (p = 0.014) and the left hippocampal (p = 0.002) region as compared to the control group. FA values of MCI patients and controls did not differ significantly in any region. Compared to controls, AD patients had increased MD values in the left centrum semiovale (p = 0.012), the left parietal (p = 0.001), the right parietal (p = 0.028), the left temporal (p = 0.018), the right temporal (p = 0.011) and the left hippocampal region (p = 0.002). Decreased FA values were measured in the left temporal area (p = 0.017) and in the left hippocampus (p = 0.031) in AD patients compared to controls. FA and MD values did not differ significantly between AD and MCI patients. Elevated MD values indicating brain tissue alterations in MCI patients were found in regions that are typically involved in early changes due to AD, particularly the left hippocampus. The sensitivity of distinguishing MCI patients from controls was 71.4% (with a specificity set at 80%). Therefore, the DTI technique validates the MCI concept, and diffusion tensor MR measurement can be a helpful tool to quantify MCI pathology in vivo.