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

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.

Relationships between Hippocampal Atrophy, White Matter Disruption, and Gray Matter Hypometabolism in Alzheimer's Disease

“…The involvement of this tract as well as the CC, fornix, perforant path, and temporal WM is consistent with previous findings from DTI studies that reported diffusivity increases or anisotropy decreases in the same set of WM areas (Fellgiebel et al, 2004;Medina et al, 2006;Xie et al, 2006;Huang et al, 2007;Teipel et al, 2007;Zhang et al, 2007). Atrophy of the CC and perforant path have also already been highlighted in previous VBM studies of AD (Chaim et al, 2007) and MCI (Stoub et al, 2006), respectively.…”

Lobar Distribution of Changes in Gray Matter and White Matter in Memory Clinic Patients: Detected Using Magnetization Transfer Imaging

“…5,6 In addition, diffusion tensor imaging showed WM damage not only inside but also outside the temporal lobe in patients with MCI. 28 In this MTI study, we were able to expand on these former studies because we showed widespread WM damage in all lobes of patients with both MCI and AD, applying volumetric analysis. We hypothesize that the observed WM changes are caused by chronic hypoperfusion based on cerebral small vessel disease.…”

“…5,28 However, in all the previous studies investigating the lobar distribution of MTR changes in patients with MCI and AD, GM and WM were taken together. [13][14][15] Therefore, it remained unclear whether the widespread MTR changes found in AD and MCI were attributable to damage in the GM only.…”

Can multi-modal neuroimaging evidence from hippocampus provide biomarkers for the progression of amnestic mild cognitive impairment?

“…Furthermore, DTI has been considered to be sensitive in exploring hippocampal changes [36] . For example, Fellgiebel and colleagues have demonstrated that aMCI patients show increased MD and decreased FA in the left hippocampus, with no significant changes in the right hippocampus [37] . However, Mulle and colleagues evaluated the cross-sectional discriminative accuracy of hippocampal volume and DTI measures with regard to aMCI and demonstrated increased MD and reduced FA in the bilateral hippocampus, particularly on the left side [38] .…”