Yonggui Yuan

Topologically Convergent and Divergent Structural Connectivity Patterns between Patients with Remitted Geriatric Depression and Amnestic Mild Cognitive Impairment

Alzheimers disease (AD) can be conceptualized as a disconnection syndrome. Both remitted geriatric depression (RGD) and amnestic mild cognitive impairment (aMCI) are associated with a high risk for developing AD. However, little is known about the similarities and differences in the topological patterns of white matter (WM) structural networks between RGD and aMCI. In this study, diffusion tensor imaging and deterministic tractography were used to map the human WM networks of 35 RGD patients, 38 aMCI patients, and 30 healthy subjects. Furthermore, graph theoretical methods were applied to investigate the alterations in the global and regional properties of the WM network in these patients. First, both the RGD and aMCI patients showed abnormal global topology in their WM networks (i.e., reduced network strength, reduced global efficiency, and increased absolute path length) compared with the controls, and there were no significant differences in these global network properties between the patient groups. Second, similar deficits of the regional and connectivity characteristics in the WM networks were primarily found in the frontal brain regions of RGD and aMCI patients compared with the controls, while a different nodal efficiency of the posterior cingulate cortex and several prefrontal brain regions were also observed between the patient groups. Together, our study provides direct evidence for the association of a great majority of convergent and a minority of divergent connectivity of WM structural networks between RGD and aMCI patients, which may lead to increasing attention in defining a population at risk of AD.

Default-mode network activity distinguishes amnestic type mild cognitive impairment from healthy aging: a combined structural and resting-state functional MRI study.

Resting-state functional magnetic resonance imaging (MRI), have revealed coactivation in a distributed network that characterizes the default-mode in the human brain. However, details from resting-state imaging in amnestic type mild cognitive impairment (aMCI) is poorly understand. Regional homogeneity, which characterizes low-frequency blood oxygenation level dependent fluctuation, after statistically controlling for the regional atrophy and age in resting-state, were examined and compared between the two groups. When regional atrophy was controlled, decreased regional homogeneity in posterior cingulate cortex and precuneus still remained significant in aMCI patients. In addition the aMCI subjects displayed several regions of increased homogeneity, typically in right inferior parietal lobule, right fusiform gyrus and bilateral putamen. The impairment of posterior cingulate and precuneus could be an important marker to distinguish aMCI from healthy aging in the resting-state. Moreover, the increased regional homogeneity changes would be consistent with compensation for damage to the medial temporal regions and limbic structures, perhaps by recruitment of alternative regions.

Abnormal resting-state functional connectivity of posterior cingulate cortex in amnestic type mild cognitive impairment.

Amnestic type mild cognitive impairment (aMCI) refers to a transitional stage between normal aging and Alzheimers disease (AD). Whilst posterior cingulate cortex (PCC) is believed to have a key role in a default network and be involved in the pathophysiology of AD, few studies have investigated whole-brain functional connectivity of PCC during resting state, or investigated the relationship between abnormal functional connectivity and disturbance in cognitive function in aMCI patients. Resting-state functional connectivity analysis was used to examine the temporal correlation between PCC and whole-brain regions in 30 aMCI patients and 26 well-matched controls. Further analysis involved evaluation of possible relationships between functional connectivity measures and cognitive function. Regions of decreased functional connectivity were identified in aMCI patients, most notably in temporal cortex, whilst significantly increased functional connectivity was mainly in frontal cortex. In addition, functional connectivity of PCC and temporal cortex was associated with the performance of neuropsychological tests in aMCI patients. This would be consonant with the recruitment of compensatory mechanisms and the process of offset functional impairments appearing as neuropathologic develops, and resting-state connectivity disturbance of PCC-temporal cortex may be a central role in cognitive deficit in aMCI patients.

Abnormal neural activity in the patients with remitted geriatric depression: a resting-state functional magnetic resonance imaging study.

OBJECTIVE To investigate regional activity abnormalities of first-episode remitted geriatric depression (RGD) using a resting-state functional magnetic resonance imaging (fMRI) in closely matched patients and healthy controls, and to examine the relationship between performances on neuropsychological tests and regional activity abnormalities. METHOD A newly reported regional homogeneity approach was used to analyze blood oxygen level-dependent fMRI data on resting state in 18 patients with remitted geriatric depression and 14 well-matched healthy controls. All subjects were measured by neuropsychological tests. RESULTS Decreased regional homogeneity (ReHo) in remitted geriatric depression distributed over the frontal, temporal and parietal lobes. In addition, increased ReHo were found mainly in the putamen, frontal and parietal lobes. The RGD patients performed significantly worse in the delayed recall of Rey Auditory Verbal Learning Test (RAVLT) and Trail Making Test A and B (seconds) when compared with the control group. And there are significant negative correlations between ReHo values of right putamen, left superior frontal gyrus and Trail Making Test A (seconds) (r=-0.583, P=0.023; r=-0.598, P=0.018, respectively), Trail Making Test B (seconds) (r=-0.587, P=0.021; r=-0.545, P=0.036, respectively) in the patients with RGD. LIMITATIONS This study is cross-sectional, therefore it cannot determine whether abnormal brain activation is a state marker or trait marker of RGD in resting-state fMRI. CONCLUSION Our study reveals that RGD is associated with abnormal activity of certain brain regions, which are believed to be involved in the psychopathology and pathophysiology of executive function in remitted geriatric depression.

Abnormal functional connectivity of hippocampus during episodic memory retrieval processing network in amnestic mild cognitive impairment.

BACKGROUND Functional connectivity magnetic resonance imaging technique has revealed the importance of distributed network structures in higher cognitive processes in the human brain. The hippocampus has a key role in a distributed network supporting memory encoding and retrieval. Hippocampal dysfunction is a recurrent finding in memory disorders of aging such as amnestic mild cognitive impairment (aMCI) in which learning- and memory-related cognitive abilities are the predominant impairment. The functional connectivity method provides a novel approach in our attempts to better understand the changes occurring in this structure in aMCI patients. METHODS Functional connectivity analysis was used to examine episodic memory retrieval networks in vivo in twenty 28 aMCI patients and 23 well-matched control subjects, specifically between the hippocampal structures and other brain regions. RESULTS Compared with control subjects, aMCI patients showed significantly lower hippocampus functional connectivity in a network involving prefrontal lobe, temporal lobe, parietal lobe, and cerebellum, and higher functional connectivity to more diffuse areas of the brain than normal aging control subjects. In addition, those regions associated with increased functional connectivity with the hippocampus demonstrated a significantly negative correlation to episodic memory performance. CONCLUSIONS aMCI patients displayed altered patterns of functional connectivity during memory retrieval. The degree of this disturbance appears to be related to level of impairment of processes involved in memory function. Because aMCI is a putative prodromal syndrome to Alzheimers disease (AD), these early changes in functional connectivity involving the hippocampus may yield important new data to predict whether a patient will eventually develop AD.

Impairments in cognition and resting-state connectivity of the hippocampus in elderly subjects with type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of Alzheimers disease, which involves hippocampus-mediated cognitive impairment. The present study investigated whether the resting-state functional connectivity of the hippocampus would be changed in patients with T2DM. A region of interest-based resting-state functional magnetic resonance imaging (fMRI) approach was applied to explore functional connectivity differences between 21 elderly patients with T2DM and 19 well-matched healthy controls, with all participants assessed by multi-dimensional neuropsychological tests. We found that T2DM patients performed significantly worse in the Auditory Verbal Learning Test (AVLT) (especially for Delayed Recall and Recognition) and Clock Drawing Test (CDT) when compared with the control group, and cognitive function was negatively related to BMI and HbA(1c). Importantly, the hippocampus showed reduced functional connectivity bilaterally to widespread regions, including fusiform gyrus, frontal gyrus, temporal gyrus, anterior cingulate gyrus, medial frontal gyrus, posterior cingulate gyrus, precuneus and inferior parietal lobule in T2DM patients compared to healthy controls. T2DM is associated with an impaired pattern of default network function, and the specific disconnection pattern identified may be involved in the neuropathophysiology of this disease.

Abnormal insula functional network is associated with episodic memory decline in amnestic mild cognitive impairment

Abnormalities of functional connectivity in the default mode network (DMN) recently have been reported in patients with amnestic mild cognitive impairment (aMCI), Alzheimers disease (AD) or other psychiatric diseases. As such, these abnormalities may be epiphenomena instead of playing a causal role in AD progression. To date, few studies have investigated specific brain networks, which extend beyond the DMN involved in the early AD stages, especially in aMCI. The insula is one site affected by early pathological changes in AD and is a crucial hub of the human brain networks. Currently, we explored the contribution of the insula networks to cognitive performance in aMCI patients. Thirty aMCI and 26 cognitively normal (CN) subjects participated in this study. Intrinsic connectivity of the insula networks was measured, using the resting-state functional connectivity fMRI approach. We examined the differential connectivity of insula networks between groups, and the neural correlation between the altered insula networks connectivity and the cognitive performance in aMCI patients and CN subjects, respectively. Insula subregional volumes were also investigated. AMCI subjects, when compared to CN subjects, showed significantly reduced right posterior insula volumes, cognitive deficits and disrupted intrinsic connectivity of the insula networks. Specifically, decreased intrinsic connectivity was primarily located in the frontal-parietal network and the cingulo-opercular network, including the anterior prefrontal cortex (aPFC), anterior cingulate cortex, operculum, inferior parietal cortex and precuneus. Increased intrinsic connectivity was primarily situated in the visual-auditory pathway, which included the posterior superior temporal gyrus and middle occipital gyrus. Conjunction analysis was performed; and significantly decreased intrinsic connectivity in the overlapping regions of the anterior and posterior insula networks, including the bilateral aPFC, left dorsolateral prefrontal cortex, dorsomedial prefrontal cortex, and anterior temporal pole was found. Furthermore, the disrupted intrinsic connectivity was associated with episodic memory (EM) deficits in the aMCI patients and not in the CN subjects. These findings demonstrated that the functional integration of the insula networks plays an important role in the EM process. They provided new insight into the neural mechanism underlying the memory deficits in aMCI patients.

Regional gray matter changes are associated with cognitive deficits in remitted geriatric depression: An optimized voxel-based morphometry study

BACKGROUND We aimed to investigate structural abnormalities in first-episode remitted geriatric depression (RGD) with optimized voxel-based morphometry (VBM) in closely matched patients and healthy control subjects and examine the relationship of performances on neuropsychological tests with regional gray matter volumes. METHODS Nineteen subjects with first-episode RGD and 16 well-matched healthy control subjects were recruited for this study, and neuropsychological tests and magnetic resonance imaging were conducted on the subjects. The differences in regional gray matter volume were determined between these two groups by optimized VBM. RESULTS The volumes of right superior frontal cortex, left postcentral cortex, and right middle temporal gyrus were significantly smaller in patients with RGD relative to healthy control subjects. However, patients with RGD had larger left cingulate gyrus volume compared with healthy control subjects. There was a significant negative correlation between left cingulate gyrus volume and Rey Auditory Verbal Learning Test delayed recall raw score in patients with RGD. CONCLUSION These results reveal that RGD is associated with gray matter changes of certain brain regions hypothesized to influence cognition and might thus be involved in the psychopathology and pathophysiology of cognitive impairment in RGD.

Specifically Progressive Deficits of Brain Functional Marker in Amnestic Type Mild Cognitive Impairment

Background Deficits of the default mode network (DMN) have been demonstrated in subjects with amnestic type mild cognitive impairment (aMCI) who have a high risk of developing Alzheimer’s disease (AD). However, no longitudinal study of this network has been reported in aMCI. Identifying links between development of DMN and aMCI progression would be of considerable value in understanding brain changes underpinning aMCI and determining risk of conversion to AD. Methodology/Principal Findings Resting-state fMRI was acquired in aMCI subjects (n = 26) and controls (n = 18) at baseline and after approximately 20 months follow up. Independent component analysis was used to isolate the DMN in each participant. Differences in DMN between aMCI and controls were examined at baseline, and subsequent changes between baseline and follow-up were also assessed in the groups. Posterior cingulate cortex/precuneus (PCC/PCu) hyper-functional connectivity was observed at baseline in aMCI subjects, while a substantial decrement of these connections was evident at follow-up in aMCI subjects, compared to matched controls. Specifically, PCC/PCu dysfunction was positively related to the impairments of episodic memory from baseline to follow up in aMCI group. Conclusions/Significance The patterns of longitudinal deficits of DMN may assist investigators to identify and monitor the development of aMCI.

White matter integrity of the whole brain is disrupted in first-episode remitted geriatric depression

Previous studies have demonstrated lower-diffusion anisotropy within white matter in late-onset depression measured by diffusion tensor imaging, which provides information about brain white matter integrity. We have examined whether white matter is abnormal in first-episode remitted geriatric depression by using diffusion tensor imaging. Sixteen remitted geriatric depression patients and 14 well matched healthy controls underwent diffusion tensor-imaging scans of magnetic resonance imaging, which were analyzed by a rigorous voxel-based approach. We found that fractional anisotropy in white matter was lower in patients than in controls at the right superior frontal gyrus, left inferior frontal gyrus, left middle temporal gyrus, right inferior parietal lobule, right middle occipital gyrus, left lingual gyrus, right putamen and right caudate. These results suggested that the white matter integrity of the whole brain was disrupted in first-episode remitted geriatric depression, and that these abnormalities were perhaps involved in the psychopathology and pathophysiology of cognitive impairment in remitted geriatric depression.