A longitudinal study of atrophy in amnestic mild cognitive impairment and normal aging revealed by cortical thickness

Abstract

In recent years, amnestic mild cognitive impairment (aMCI) has attracted significant attention as an indicator of high risk for Alzheimer's disease. An understanding of the pathology of aMCI may benefit the development of effective clinical treatments for dementia. In this work, we measured the cortical thickness of 109 aMCI subjects and 99 normal controls (NC) twice over two years. The longitudinal changes and the cross-sectional differences between the two types of participants were explored using the vertex thickness values. The thickness of the cortex in aMCI was found significantly reduced in both longitudinal and between-group comparisons, mainly in the temporal lobe, superolateral parietal lobe and some regions of the frontal cortices. Compared to NC, the aMCI showed a significantly high atrophy rate in the left lateral temporal lobe and left parahippocampal gyrus over two years. Additionally, a significant positive correlation between brain atrophy and the decline of Mini-Mental State Examination (MMSE) scores was also found in the left superior and left middle temporal gyrus in aMCI. These findings demonstrated specific longitudinal spatial patterns of cortical atrophy in aMCI and NC. The higher atrophy rate in aMCI might be responsible for the accelerated functional decline in the aMCI progression process.

Figure 1. Differences of cortical thickness between the baseline and two years later in aMCI.

The red/yellow showed the significantly different cortical thickness between the MCI_M1 and MCI_M2 groups. Only significantly reduced cortical thickness was found in the MCI_M2 group. The color bar indicated the vertex-wise p-value which ranged from 0 to 0.01 with the correction for multiple comparisons.

Figure 2. Differences of cortical thickness between the baseline and two years later in NC.

The colorized areas indicated the different cortical thickness between the NC_M1 and NC_M2 groups. The range and degree of atrophy in NC_M2 were sight. The p values of the vertices indicated by the color bar were corrected using the FDR correction.

Figure 3. Cortical thinning in aMCI compared to NC at baseline time.

The colorized areas indicated the brain regions with significantly reduced cortical thickness in aMCI compared with NC at baseline time with a correction for multiple comparisons (P<0.05, the cluster-based RFT correction).

Figure 4. Cortical thinning in aMCI compared to NC two years later.

Significant cortical thickness differences were found between aMCI and NC two years after the baseline time. The color bar indicated the cluster-wise p-value with the cluster-based RFT correction.

Figure 5. Differences of atrophy rate between aMCI and normal aging over two years.

Differences of atrophy rate between aMCI subjects and normal controls were obtained using the random field theory (RFT)-based cluster analysis. The colorized areas represented the between-group differences of atrophy rate, which showed the more serious atrophy in aMCI over two years. The color bar indicated the cluster-wise p-value with the correction for multiple comparisons.

Figure 6. Correlation between the decline of MMSE scores and cortical atrophy in aMCI.

The correlations at all significant vertices were positive and the color bar indicated the vertex-wise p-value with the FDR correction at a 0.01 level of significance.