A diffusion tensor MRI study of patients with MCI and AD with a 2-year clinical follow-up

Objective The authors assessed whether brain changes detected by diffusion tensor (DT) MRI can improve the understanding of structural damage in Alzheimer's disease (AD) and are associated with different risks of conversion to AD in amnestic mild cognitive impairment (aMCI). Methods Twenty-one aMCI patients, 21 AD patients and 20 healthy subjects underwent conventional and DT MRI at baseline. All subjects were clinically followed up over 2 years; at the end of follow-up, aMCI were grouped into converters to AD (aMCI-C) and non-converters (aMCI-NC). The mean diffusivity (MD) and fractional anisotropy (FA) were obtained from total grey matter (GM) and white matter (WM), and from several GM and WM regions of interest (ROIs). On T1-weighted images, normalised volumes of the whole brain (NBV), GM (NGMV) and WM were measured. Results A significant ‘trend’ of worsening with a trajectory ‘normal/aMCI/AD’ was found for NBV and NGMV, total GM and WM MD, total WM FA, as well as for diffusivity abnormalities in several GM and WM ROIs, mainly located in posterior brain regions. aMCI-C had GM and WM changes similar to those seen in AD, whereas aMCI-NC showed a DT MRI pattern similar to that of healthy subjects. DT MRI metrics that better distinguished aMCI-C from aMCI-NC were MD of total GM and WM, hippocampi, anterior insulae, frontal and parietal WM, occipital GM and WM, and FA of temporal WM. Volumetric variables were not able to distinguish the two aMCI subgroups (aMCI-C and aMCI-NC). Conclusions Subtle brain diffusivity changes occur from the prodromal stages of AD, mainly in posterior brain regions, and spread over the course of the disease to involve the frontal lobe. In aMCI, the severity of microstructural damage within and beyond the medial temporal lobe is associated with an increased short-term risk to develop AD

Neuropsychological testing results from the 10 cases presented.

<p>All tests scores are corrected referring to respective Italian normative data (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0120197#sec008" target="_blank">methods</a>).</p><p>*: These are raw scores, as it was not possible to correct scores for Years of Education and Age.</p><p>**: These scores refer to a modified version of the PPT.</p><p>§: This patient underwent similar naming and comprehension tests from a different battery (BADA); see text for details.</p><p>°: Numeric scores were not available.</p><p><b>Bold scores</b> are pathological.</p><p>Neuropsychological testing results from the 10 cases presented.</p

¹⁸F-FDG-PET analyses of our cohort.

<p><b>A)</b> Single-subject ¹⁸F-FDG-PET, SPM-t maps (FWE p<0.05) overimposed on a standard MNI template. Axial View. Right side showing hemispheric asymmetry. <b>B)</b> Commonalities analyses, inflated view (uncorrected p<0.0001). Dark gray areas represent sulci, light gray areas represent gyri. <b>C)</b> ROIs showing significant negative correlation between hypometabolism and performance in confrontation naming neuropsychological task (uncorrected p<0.05). See text for details. ROIs were visualized with BrainNet Viewer (<a href="http://www.nitrc.org/projects/bnv/" target="_blank">http://www.nitrc.org/projects/bnv/</a>) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0120197#pone.0120197.ref104" target="_blank">104</a>].</p

Demographic summary of the studied cohort.

<p>Statistics are indicated as follows: Mean ±SD (RANGE)</p><p>L>R: Left Hemisphere hypometabolism Asymmetry</p><p>R>L: Right Hemisphere hypometabolism Asymmetry</p><p>Demographic summary of the studied cohort.</p