Background: Excessive daytime sleepiness (EDS) and caudate nucleus volume alterations have been linked to Alzheimer’s disease (AD), but their relationship remains unclear under the context of subjective cognitive decline (SCD). Objective: This study aimed to investigate the relationship between EDS and caudate nucleus volume in patients with SCD. Methods: The volume of entire brain was measured in 170 patients with SCD, including 37 patients with EDS and 133 non-EDS, from the Sino Longitudinal Study on Cognitive Decline (SILCODE). Participants underwent a comprehensive assessment battery, including neuropsychological and clinical evaluations, blood tests, genetic analysis for APOE ɛ4, and structural MRI scans analyzed using the fully automated segmentation tool, volBrain. Results: Patients with EDS had significantly increased volume in the total and left caudate nucleus compared to non-EDS. The most significant cognitive behavioral factor associated with caudate nucleus volume in the EDS was the Auditory Verbal Learning Test-recognition. Conclusions: These findings suggest that EDS may be associated with alterations in caudate nucleus volume, particularly in the left hemisphere, in the context of SCD. Further research is necessary to understand the underlying mechanisms of this relationship and its implications for clinical management.

Alzheimer’s disease (AD), one of the leading diseases of the nervous system, is accompanied by symptoms such as loss of memory, thinking and language skills. Both mild cognitive impairment (MCI) and very mild cognitive impairment (VMCI) are the transitional pathological stages between normal aging and AD. While the changes in whole-brain structural and functional information have been extensively investigated in AD, The impaired structure–function coupling remains unknown. The current study employed the OASIS-3 dataset, which includes 53 MCI, 90 VMCI, and 100 Age-, gender-, and education-matched normal controls (NC). Several structural and functional parameters, such as the amplitude of low-frequency fluctuations (ALFF), voxel-based morphometry (VBM), and The ALFF/VBM ratio, were used To estimate The whole-brain neuroimaging changes In MCI, VMCI, and NC. As disease symptoms became more severe, these regions, distributed in the frontal-inf-orb, putamen, and paracentral lobule in the white matter (WM), exhibited progressively increasing ALFF (ALFFNC < ALFFVMCI < ALFFMCI), which was similar to the tendency for The cerebellum and putamen in the gray matter (GM). Additionally, as symptoms worsened in AD, the cuneus/frontal lobe in the WM and the parahippocampal gyrus/hippocampus in the GM showed progressively decreasing structure–function coupling. As the typical focal areas in AD, The parahippocampal gyrus and hippocampus showed significant positive correlations with the severity of cognitive impairment, suggesting the important applications of the ALFF/VBM ratio in brain disorders. On the other hand, these findings from WM functional signals provided a novel perspective for understanding the pathophysiological mechanisms involved In cognitive decline in AD.

BACKGROUND The hippocampus with varying degrees of atrophy was a crucial neuroimaging feature resulting in the declining memory and cognitive function in Alzheimer's disease (AD). However, the abnormal dynamic functional connectivity (DFC) in both white matter (WM) and gray matter (GM) from the left and right hippocampus remains unclear. OBJECTIVE To explore the abnormal DFC within WM and GM from the left and right hippocampus across the different stages of AD. METHODS Current study employed the OASIS-3 dataset including 43 mild cognitive impairment (MCI), 71 pre-mild cognitive impairment (pre-MCI), and matched 87 normal cognitive (NC). Adopting the FMRIB's Integrated Registration and Segmentation Tool, we obtained the left and right hippocampus mask. Based on above hippocampus mask as seed point, we calculated the DFC between left/right hippocampus and all voxel time series within whole brain. One-way ANOVA analysis was performed to estimate the abnormal DFC among MCI, pre-MCI, and NC groups. RESULTS We found that MCI and pre-MCI groups showed the common abnormalities of DFC in the Temporal_Mid_L, Cingulum_Mid_L, and Thalamus_L. Specific abnormalities were found in the Cerebelum_9_L and Precuneus of MCI group and Vermis_8 and Caudate_L of pre-MCI group. In addition, we found that DFC within WM regions also showed the common low DFC for the Cerebellum anterior lobe-WM, Corpus callosum, and Frontal lobe-WM in MCI and pre-MCI group. CONCLUSION Our findings provided a novel information for discover the pathophysiological mechanisms of AD and indicate WM lesions were also an important cause of cognitive decline in AD.

Mild cognitive impairment (MCI) is clinically characterized by memory loss and cognitive impairment closely associated with the hippocampal atrophy. Accumulating studies have confirmed the presence of neural signal changes within white matter (WM) in resting-state functional magnetic resonance imaging (fMRI). However, it remains unclear how abnormal hippocampus activity affects the WM regions in MCI. The current study employs 43 MCI, 71 very MCI (VMCI) and 87 age-, gender-, and education-matched healthy controls (HCs) from the public OASIS-3 dataset. Using the left and right hippocampus as seed points, we obtained the whole-brain functional connectivity (FC) maps for each subject. We then perform one-way ANOVA analysis to investigate the abnormal FC regions among HCs, VMCI, and MCI. We further performed probabilistic tracking to estimate whether the abnormal FC correspond to structural connectivity disruptions. Compared to HCs, MCI and VMCI groups exhibited reduced FC in the right middle temporal gyrus within gray matter, and right temporal pole, right inferior frontal gyrus within white matter. Specific dysconnectivity is shown in the cerebellum Crus II, left inferior temporal gyrus within gray matter, and right frontal gyrus within white matter. In addition, the fiber bundles connecting the left hippocampus and right temporal pole within white matter show abnormally increased mean diffusivity in MCI. The current study proposes a new functional imaging direction for exploring the mechanism of memory decline and pathophysiological mechanisms in different stages of Alzheimer’s disease.

Abstract Background Alzheimer's disease, one of the most leading nervous system diseases, is accompanied by symptoms including loss of memory, thinking, and language ability. Both mild cognitive impairment (MCI) and very MCI (VMCI) are the transitional pathological stage between normal ageing and AD. While the changes to whole-brain structural and functional information have been extensively investigated in AD, the impaired structure-function coupling within whole brain remains unknown. Methods Current study employed the OASIS-3 dataset including 53 MCI, 90 VMCI and 100 age-, gender- and education-matched normal controls (NC). Several structural and functional parameters including amplitude of low frequency fluctuations (ALFF), voxel-based morphometry and ALFF/VBM ratio analysis were used to estimate the whole-brain abnormalities among MCI, VMCI and NC. Results As the disease symptoms became more severe, these regions distributing in the cerebellum and putamen within gray matter exhibited progressively increasing ALFF (ALFFNC < ALFFVMCI < ALFFMCI). Similar results were also found in the frontal-inf-orb, putamen, and paracentral-lobule within white matter. More importantly, as the symptoms of disease got worse, parahippocampal gyrus and hippocampus within gray matter showed progressively decreasing structure-function coupling, and was also applicable to the cuneus and frontal lobe within WM. In addition, the structure-function coupling values in the parahippocampal gyrus and hippocampus were positive relationship with severity of cognitive impairment, suggesting the important applications of the structure-function coupling index in brain disorders. Conclusion Our findings provided a novel information for discovering the pathophysiological mechanisms and indicated that WM lesions were also an important cause of cognitive decline in AD.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with memory loss and cognitive impairment. The white matter (WM) BOLD signal has recently been shown to provide an important role in understanding the intrinsic cerebral activity. Although the altered homotopic functional connectivity within gray matter (GM-HFC) has been examined in AD, the abnormal HFC to WM remains unknown. The present study sought to identify changes in the WM-HFC and anatomic characteristics by combining functional magnetic resonance imaging with diffusion tensor imaging (DTI). Resting-state and DTI magnetic resonance images were collected from the OASIS-3 dataset and consisted of 53 mild cognitive impairment (MCI) patients, 90 very MCI (VMCI), and 100 normal cognitive (NC) subjects. Voxel-mirrored HFC was adopted to examine whether WM-HFC was disrupted in VMCI and MCI participants. Moreover, the DTI technique was used to investigate whether specific alterations of WM-HFC were associated with anatomic characteristics. Support vector machine analyses were used to identify the MCI and VMCI participants using the abnormal WM-HFC as the features. Compared with NC, MCI, and VMCI participants showed significantly decreased GM-HFC in the middle occipital gyrus and inferior parietal gyrus and decreased WM-HFC in the bilateral middle occipital and parietal lobe-WM. In addition, specific WM-functional network alteration for the bilateral sub-lobar-WM was found in MCI subjects. MCI subjects showed abnormal anatomic characteristics for bilateral sub-lobar and parietal lobe-WM. Results of GM-HFC mainly showed common neuroimaging features for VMCI and MCI subjects, whereas analysis of WM-HFC showed specific clinical neuromarkers and effectively compensated for the lack of GM-HFC to distinguish NC, VMCI, and MCI subjects.