Brain atrophy pattern in patients with mild cognitive impairment: MRI study

Abstract

We evaluated the accuracy of the quantitative and semiquantitative analysis in detecting regional atrophy patterns and differentiating mild cognitive impairment patients who remain stable (aMCI-S) from patients who develop Alzheimer's disease (aMCI-AD) at clinical follow-up. Baseline magnetic resonance imaging was used for quantitative and semiquantitative analysis using visual rating scales. Visual rating scores were related to gray matter thicknesses or volume measures of some structures belonging to the same brain regions. Receiver operating characteristic (ROC) analysis was performed to assess measures' accuracy in differentiating aMCI-S from aMCI-AD. Comparing aMCI-S and aMCI-AD patients, significant differences were found for specific rating scales, for cortical thickness belonging to the middle temporal lobe (MTL), anterior temporal (AT), and fronto-insular (FI) regions, for gray matter volumes belonging to MTL and AT regions. ROC curve analysis showed that middle temporal atrophy, AT, and FI visual scales showed better diagnostic accuracy than quantitative measures also when thickness measures were combined with hippocampal volumes. Semiquantitative evaluation, performed by trained observers, is a fast and reliable tool in differentiating, at the early stage of disease, aMCI patients that remain stable from those patients that may progress to AD since visual rating scales may be informative both about early hippocampal volume loss and cortical thickness reduction.

Keywords: brain MRI; regional atrophy patterns; regional thickness and volume measures; visual rating scales.

Figure 1

A representative image segmentation flowchart using Freesurfer image analysis software and selection of the structures used to differentiate aMCI-AD from aMCI-S. WM, white matter; GM, gray matter.

Figure 2

Workflow diagram showing the steps of MRI analysis. High resolution T1 MRI images of aMCI-S and aMCI-AD patients were used for quantitative and semiquantitative analysis. Correlations between semiquantitative visual ratings score and thickness measures/volumes of corresponding regions were used to assess the relationship between each visual rating scales and corresponding quantitative regional measures. Only the significant qualitative and quantitative measures (thicknesses and volumes) were used to differentiate aMCI-AD from aMCI-S. Only significant visual rating scores, cortical thickness, and volume measures between aMCI-S and aMCI-AD were used to calculate the diagnostic accuracy. Moreover, the multivariate analysis was conducted by logistic regression models for combined scores or thickness/volume measurements in order to evaluate if the capability in differentiating aMCI-AD from aMCI-S improved. AUC, area under the curve; MTA-s, medial temporal atrophy score; AT-s, anterior-temporal score; PA-s, posterior atrophy score; FI-s, fronto-insula score; OF-s, orbito-frontal score; AC-s, anterior cingulate score; MTL, medial temporal lobe; AT-r, anterior-temporal region; PA-r, posterior atrophy region; FI-r, fronto-insula region; OF-r, orbito-frontal region; AC-r, anterior cingulate region; and aMCI, amnesic mild cognitive impairment.

Figure 3

GM thickness and volume maps corresponding to brain regions evaluated by MTA, AT, and FI visual rating scales. MTA, AT, and FI visual rating scores are delimited by a white square while in the contralateral side white dotted line delimits some cortical gyri whose thickness or volume was assessed. MTA, medial temporal atrophy; AT, anterior temporal; and FI, fronto-insula.

Figure 4

Whisker plots show MTA, AT, and FI visual rating scores (a–c), a set of matched cortical thickness measures (d–f), and normalized volumes (g, h) useful to differentiate aMCI-AD from aMCI-S. Plots show higher visual rating scores and lower GM thickness and volume measures in aMCI-AD than aMCI-S. The width of the plot shows the distribution of score values and thickness or volume measures for each corresponding rating scale. Whisker plots display the median values and IQR. Y-as: respectively, visual rating scores (a–c), GM average thickness (d–f), and GM normalized volumes (g, h) for aMCI-S and aMCI-AD groups. *Indicates significant difference between groups. MTA, medial temporal atrophy; AT, anterior temporal; FI, fronto-insula; MTL, medial temporal lobe; AT-r, anterior temporal region; FI-r, fronto-insula region; and aMCI, amnesic mild cognitive impairment.

Figure 5

ROC curves of visual rating scales useful in differentiating aMCI-S from aMCI-AD (a). AUC = 0.83 for MTA score, 0.80 for AT score, 0.80 for FI score. ROC curves of a set of GM thickness measures belonging to brain regions assessed by visual rating scale, able to discriminate between aMCI-AD and aMCI-S (b). AUC = 0.59 for thickness measures of MTL, 0.61 for thickness measures of AT region, and 0.58 for thickness measures of FI region. ROC curves of a set of GM normalized volumes belonging to brain regions assessed by visual rating scale, able to discriminate between aMCI-AD and aMCI-S (c). AUC = 0.73 for normalized volumes of MTL, 0.69 for normalized volumes of AT region. AUC, area under the curve; MTA, medial temporal atrophy; AT, anterior-temporal; FI, fronto-insula; MTL, medial temporal lobe; AT-r, anterior-temporal region; FI-r, fronto-insula region; and aMCI, amnesic mild cognitive impairment.