Demographics and behavioral results
Demographic characteristics and behavioral results were summarized in Table 1 (at the end of the text). A total of 198 participants were included in analysis, including 51 cognitively normal controls(NC), 65 individuals with SCD, 44 individuals with MCI and 38 individuals with AD. There were significant differences observed among 4 groups in terms of age (P<0.05) and gender (P<0.05). No significant difference was found in education years.
Compared with NC, AD showed significant decline in all cognitive performances. Compared with NC, MCI showed significant decline in all memory domain screening tests, except for BVMT-SDR performance. There was no significant difference in cognitive performances between NC and SCD. Compared with SCD, MCI showed obvious decline in MoCA-B and all sub-scores of AVLT performances. In addition, there were no significant difference in language and executive domains performance (AFT, BNT, STT-A, STT-B) among NC, SCD and MCI groups.
Voxel-based morphometry-gray matter volume
VBM analysis revealed group effects were summarized in Tables 2, and illustrated in Figure 1. Six main clusters of GM were detected, including bilateral hippocampus, bilateral parahippocampal and bilateral fusiform.
Post-hoc analysis of every pair of groups comparison were illustrated in Table 3. Compared with the group of NC, GM atrophy in MCI were reported in bilateral hippocampus (P<0.05, FWE corrected, SVC-based, cluster-wise level). Six clusters of GM atrophy in AD were reported in bilateral fusiform, bilateral parahippocampal and bilateral hippocampus (all with P<0.05, FWE corrected, SVC-based, voxel-wise level) comparing to the NC. The results in comparison between SCD and AD were reported as the same pattern as the results in NC and AD, six clusters of GM atrophy were reported. Compared with SCD, GM loss in left parahippocampal (P<0.05, FWE corrected, SVC-based, cluster-wise level) was reported in MCI. Compared with MCI, AD showed significant GM loss in right hippocampus and parahippocampal (P<0.05, FWE corrected, SVC-based, voxel-wise level).
Surface-based morphometry-cortical thickness
SBM analysis revealed group effects on the cortical thickness in right superior temporal, bilateral parahippocampal. The results were summarized in Table 4, and illustrated in Figure 2.
Post hoc analysis were carried out to detect the difference in every pair of groups, Table 5. Compared with NC, MCI participants showed a decreased cortical thickness in right superior temporal (P<0.001, uncorrected, voxel-wise level). Compared with NC, AD showed decreased cortical thickness in right superior temporal (P<0.05, FWE corrected, cluster-wise level), right parahippocammpal (P<0.05, FWE corrected, cluster-wise level). Three clusters of decreased cortical thickness were detected in AD group when comparing with SCD, localized to right hippocampus, right superior temporal and left parahippocampal all with a cluster-level threshold of FWE corrected P<0.05. Compared with MCI, a decreased cortical thickness in right superior temporal (P<0.05, FWE corrected, cluster-wise level) was reported in AD.
Multiple regression analysis
Multiple regression models were established between GM volumes and AVLT-H, BVMT-R, SDMT, controlling for age, gender, TIV as covariates, see in Table 6 and Figure 3. Significant positive correlations were found between AVLT-SDR with bilateral hippocampus and parahippocampal, respectively, with a voxel-wise level threshold of FWE corrected P<0.05. Positive correlations were observed between AVLT-LDR and bilateral hippocampus, parahippocampal, respectively, all with a voxel-wise level threshold of FWE corrected P<0.05. bilateral hippocampus, bilateral parahippocampal, bilateral fusiform were reported positively associated with AVLT-LCR at a voxel-wise level threshold of FWE corrected P<0.05, respectively. AVLT-REC was observed showing positive correlations with bilateral hippocampus, bilateral parahippocampal and left fusiform with a voxel-wise level threshold of FWE corrected P<0.05, respectively. And furthermore, AVLT-L, AVLT-IR and SDMT were all reported showing positive correlations with bilateral hippocampus, and all with voxel-wise level threshold of FWE corrected P<0.05. BVMT-IR, SDR, LDR were reported positively associated with bilateral hippocampus and bilateral parahippocampal, with a voxel-wise level threshold of FWE corrected P<0.05. And BVMT-REC was positively associated with bilateral hippocampus with a voxel-wise level threshold of FWE corrected P<0.05.
Moreover, there were significant positive correlations between cortical thickness and AVLT-H, BVMT-R, using multiple regression models and controlling for age, gender as covariates, in Table 6(at the end of the text) and Figure 4, 5. AVLT-SDR and LDR were both observed showing positive correlations with right superior temporal and right parahippocampal with voxel-wise level threshold of FWE corrected P<0.05. There were positive correlations between AVLT-LCR and right superior temporal, bilateral parahippocampal, all with thresholds of voxel-wise level FWE corrected of P<0.05. In addition, AVLT-REC were reported positively associated with right superior temporal, bilateral parahippocampal at voxel-wise level thresholds of FWE corrected P<0.05. However, there were no significant relationships between CT and AVLT-IR, SDMT after FWE corrected of P<0.05. BVMT-LDR and REC were reported showing positively associated with right superior temporal, bilateral parahippocampal. And furthermore, BVMT-IR was positively associated with right superior temporal and parahippocampal in voxel-wise level FWE corrected of P<0.05.
Correlation analysis
In SCD group, partial correlation analysis was performed to detect the relationships between reginal grey matter volumes atrophy or cortical thickness and AVLT-H sub-scores, in Figure 5. AVLT-IR was observed showing significant positive correlations with left hippocampus (r=0.284, p=0.026) and right hippocampus (r=0.316, p=0.013), respectively. However, we did not find any of other AVHT sub-scores with significant correlations either in grey matter volumes or in cortical thickness areas. There was no significant correlation reported between any structural alternation and BVMT-R sub-sores. In NC and SCD groups, Pearson correlation analysis was performed between SDMT and gray matter volumes atrophy or cortical thickness. SDMT were reported positively correlated with left hippocampus (r=0.250, p=0.007) and right hippocampus (r=0.226 p=0.015). We did not find SDMT with significant correlations in cortical thickness areas. Furthermore, we found SDMT was significantly positively correlated with AVLT-IR (r=0.466 p=0.000).