Abnormal characterization of dynamic functional connectivity in Alzheimer's disease.

Numerous studies have shown abnormal brain functional connectivity in individuals with Alzheimer's disease (AD) or amnestic mild cognitive impairment (aMCI). However, most studies examined traditional resting state functional connections, ignoring the instantaneous connection mode of the whole brain. In this case-control study, we used a new method called dynamic functional connectivity (DFC) to look for abnormalities in patients with AD and aMCI. We calculated dynamic functional connectivity strength from functional magnetic resonance imaging data for each participant, and then used a support vector machine to classify AD patients and normal controls. Finally, we highlighted brain regions and brain networks that made the largest contributions to the classification. We found differences in dynamic function connectivity strength in the left precuneus, default mode network, and dorsal attention network among normal controls, aMCI patients, and AD patients. These abnormalities are potential imaging markers for the early diagnosis of AD.

Altered Volume and Structural Connectivity of the Hippocampus in Alzheimer's Disease and Amnestic Mild Cognitive Impairment.

Background: Hippocampal atrophy is a characteristic of Alzheimer's disease (AD). However, alterations in structural connectivity (number of connecting fibers) between the hippocampus and whole brain regions due to hippocampal atrophy remain largely unknown in AD and its prodromal stage, amnestic mild cognitive impairment (aMCI). Methods: We collected high-resolution structural MRI (sMRI) and diffusion tensor imaging (DTI) data from 36 AD patients, 30 aMCI patients, and 41 normal control (NC) subjects. First, the volume and structural connectivity of the bilateral hippocampi were compared among the three groups. Second, correlations between volume and structural connectivity in the ipsilateral hippocampus were further analyzed. Finally, classification ability by hippocampal volume, its structural connectivity, and their combination were evaluated. Results: Although the volume and structural connectivity of the bilateral hippocampi were decreased in patients with AD and aMCI, only hippocampal volume correlated with neuropsychological test scores. However, positive correlations between hippocampal volume and ipsilateral structural connectivity were displayed in patients with AD and aMCI. Furthermore, classification accuracy (ACC) was higher in AD vs. aMCI and aMCI vs. NC by the combination of hippocampal volume and structural connectivity than by a single parameter. The highest values of the area under the receiver operating characteristic (ROC) curve (AUC) in every two groups were all obtained by combining hippocampal volume and structural connectivity. Conclusions: Our results showed that the combination of hippocampal volume and structural connectivity (number of connecting fibers) is a new perspective for the discrimination of AD and aMCI.

Bone marrow stromal cells reverse the microglia type from pro-inflammatory tumour necrosis factor a microglia to anti-inflammatory CD206 microglia of middle cerebral artery occlusion rats through triggering secretion of CX3CL1.

The middle cerebral artery occlusion (MCAO) model has been extensively applied to study ischaemic stroke. This study attempted to clarify effect of bone marrow stromal cells (BMSCs) on infarct injury of MCAO rats. BMSCs were isolated and identified by staining CD29/CD44 and CD31/CD45. CX3CL1 silencing vector (pLVX-shRNA-CX3CL1) was generated and infected to BMSCs. pLVX-shRNA-CX3CL1 infected BMSCs were transplanted into brain tissue of MCAO rats. Real-time PCR was used to determine CX3CL1 expression. Infarct areas were stained with TTC to evaluate infarct size. Double-staining immunofluorescence was conducted to determine anti-inflammatory type CD206 and pro-inflammatory type tumour necrosis factor a (TNF-a) microglia. Isolated BMSCs were positively presented for CD29/CD44, and negatively for CD31/CD45. CX3CL1 was significantly lower in the BMSC + pLVX-shRNA2-CX3-CL1 group compared to the BMSCs + pLVX group (p < 0.05). According to TTC and neurological scores, MCAO rats were successfully generated. BMSCs transplantation significantly increased CD206 microglia and decreased TNF-a microglia. However, shRNA-CX3CL1-infected BMSCs remarkably reduced CD206 microglia and enhanced TNF-a microglia compared to the MCAO + BMSCs group. In conclusion, BMSCs reverse microglia from pro-inflammatory type TNF-a microglia to anti-inflammatory type CD206 microglia in the infarct region of MCAO rats (3rd to 7th days post BMSC transplantation), through triggering of CX3CL1 secretion. Therefore, the potential effects of CX3CL1 secreted by BMSCs would provide an insight for stem cell-dependent therapeutic strategies in treating ischaemic stroke-associated disorders.

Aberrant Hippocampal Functional Connectivity Is Associated with Fornix White Matter Integrity in Alzheimer's Disease and Mild Cognitive Impairment.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia in older individuals, and amnestic mild cognitive impairment (aMCI) is currently considered the prodromal stage of AD. The hippocampus and fornix interact functionally and structurally, with the fornix being the major efferent white matter tract from the hippocampus. OBJECTIVE: The main aim of this study was to examine the impairments present in subjects with AD or aMCI and the relationship of these impairments with the microstructure of the fornix and the functional connectivity (FC) and gray matter volume of the hippocampus. METHODS: Forty-four AD, 34 aMCI, and 41 age- and gender-matched normal controls (NCs) underwent neuropsychological assessments and multimode MRI. We chose the bilateral hippocampi as the region of interest in which gray matter alterations and FC with the whole brain were assessed and the fornix body as the region of interest in which the microstructural integrity of the white matter was observed. We also evaluated the relationship among gray matter alterations, the abnormal FC of the hippocampus and the integrity of the fornix in AD/aMCIResults:Compared to the NC group, the AD and aMCI groups demonstrated decreased gray matter volume, reduced FC between the bilateral hippocampi and several brain regions in the default mode network and control network, and damaged integrity of the fornix body (decreased fractional anisotropy and increased diffusivity). We also found that left hippocampal FC with some regions, the integrity of the fornix body, and cognition ability were significantly correlated. Therefore, our findings suggest that damage to white matter integrity may partially explain the reduced resting-state FC of the hippocampus in AD and aMCI. CONCLUSION: AD and aMCI are diseases of disconnectivity including not only functional but also structural disconnectivity. Damage to white matter integrity may partially explain the reduced resting-state FC in AD and aMCI. These findings have significant implications for diagnostics and modeling and provide insights for understanding the disconnection syndrome in AD.

Cognition-related white matter integrity dysfunction in Alzheimer's disease with diffusion tensor image.

Alzheimer's disease (AD) is a worldwide progressive neurodegenerative disorder in the elderly. Previous research has indicated that Alzheimer's disease impairs white matter (WM) tracts. Anatomical and neuroimaging studies have indicated that WM tracts are associated with cognitive function. Whether the abnormal WM integrity in AD is associated with cognitive impairments and the clinical symptoms is still not clear. To this end, we investigated the relationship between the impairments in WM tracts and the decline of cognitive ability in AD. Diffusion tensor imaging (DTI) data were collected from 38 AD patients and 30 normal, cognitively healthy volunteers. The tract-based spatial statistics (TBSS) approach was used to compare the fractional anisotropy (FA) and mean diffusivity (MD) values between the two groups. WM tracts (cingulum, superior longitudinal fasciculus (SLF), uncinate fasciculus (UF), and inferior longitudinal fasciculus (ILF)) associated with cognition function were extracted for region of interest (ROI)-based analysis. Significantly decreased FA values and increased MD values of the cognition-related WM tracts were observed in the AD group compared with the normal cognition (NC) group. In addition, we further demonstrated that the decreased FA values and increased MD values of the cognition-related WM tracts were significantly correlated with MMSE scores. These results indicated that abnormal changes in WM integrity are observed following AD. Finally, we used support vector machine (SVM) with a repeated, stratified 10-fold cross-validated classifier to evaluate the ability of FA and MD values to discriminate disease. The accuracy of the SVM using cognition-related WM as classified features was higher than that using non-cognition-related tracts. Most importantly, our results showed the relationship between abnormal WM tracts and cognitive ability in AD. These findings further suggested that AD-related impairments in cognition-related WM tracts may influence the cognitive ability of AD patients.

An arbuscular mycorrhizal fungus and Epichloë festucae var. lolii reduce Bipolaris sorokiniana disease incidence and improve perennial ryegrass growth.

Leaf spot of perennial ryegrass (Lolium perenne) caused by Bipolaris sorokiniana is an important disease in temperate regions of the world. We designed this experiment to test for the combined effects of the arbuscular mycorrhizal (AM) fungus Claroideoglomus etunicatum and the grass endophyte fungus Epichloë festucae var. lolii on growth and disease occurrence in perennial ryegrass. The results show that C. etunicatum increased plant P uptake and total dry weight and that this beneficial effect was slightly enhanced when in association with the grass endophyte. The presence in plants of both the endophyte and B. sorokiniana decreased AM fungal colonization. Plants inoculated with B. sorokiniana showed the typical leaf spot symptoms 2 weeks after inoculation and the lowest disease incidence was with plants that were host to both C. etunicatum and E. festucae var. lolii. Plants with these two fungi had much higher activity of peroxidases (POD), superoxide dismutase (SOD) and catalase (CAT) and lower values of malondialdehyde (MDA) and hydrogen peroxide (H2O2). The AM fungus C. etunicatum and the grass endophyte fungus E. festucae var. lolii have the potential to promote perennial ryegrass growth and resistance to B. sorokiniana leaf spot.

Rapid eye movement sleep behavior disorder in patients with probable Alzheimer's disease.

BACKGROUND AND AIMS: Rapid eye movement (REM) sleep behavior disorder (RBD) is commonly associated with neurodegenerative disorders characterized by α-synuclein deposition, including Parkinson's disease, multiple system atrophy, and Lewy body dementia. However, this tendency in tauopathy-mediated diseases is rare and only sporadically reported. We systematically illustrate the occurrence of RBD and sleep features among a cohort of patients with Alzheimer's disease (AD), a non-synucleinopathy. METHODS: We recruited 105 clinically probable AD patients. Fifteen clinically probable AD patients with suspected RBD underwent a video-polysomnography (vPSG) examination. RESULTS: Five patients with probable AD exhibited RBD. One of the patients performed repeated touching of the head and the face with his hands and flailed his arms. Three patients exhibited hand twisting, exploring, prominent limb kicking, and jerking. The fifth patient exhibited all of the characteristics of RBD (he recalled a dream about fighting animals), and his wife was awakened by his screaming. Of these five patients, one patient took the acetylcholinesterase inhibitor drug donepezil. The patients with AD + RBD demonstrated increases in both tonic and phasic electromyography activity during REM sleep, but sleep architecture did not differ between the AD + RBD and AD-alone groups. CONCLUSION: RBD can occur in patients with AD. The occurrence of RBD does not change the sleep architecture of AD patients.

Longitudinal alteration of amygdalar functional connectivity in mild cognitive impairment subjects revealed by resting-state FMRI.

Mild cognitive impairment (MCI) is considered to be the prodromal stage of Alzheimer's disease. The amygdala, which is considered to be a hub, has been shown to have widespread brain connections with many cortical regions. Longitudinal alterations in the functional connectivity of the amygdala remain unclear in MCI. We hypothesized that the impairment in the amygdala-cortical loop would be more severe in a follow-up MCI group than in a baseline MCI group and that these alterations would be related to the disease processes. To test this hypothesis, we used resting-state functional magnetic resonance imaging to investigate alterations in amygdalar connectivity patterns based on longitudinal data from 13 MCI subjects (8 males and 5 females). Compared to the baseline, decreases in functional connectivity were mainly found located between the amygdala and regions at the conjunction of the temporal-occipital system and the regions included in the default mode network in the follow-up MCI individuals. The alterations in the functional connectivity of the identified regions were validated in an independent dataset. Specifically, reduced amygdalar connectivity was significantly correlated with cognitive abilities. These findings indicate that impairments in the functional connectivity of the amygdala may be potential biomarkers of the progression of MCI.

Altered functional connectivity of the marginal division in Alzheimer's disease.

The marginal division (MrD) is a neostriatum subregion that links the limbic system and basal nucleus of Meynert; it is an important subcortical center that is involved in learning and memory. Alzheimer's disease (AD) is a neurodegenerative disorder and the most common cause of dementia in the elderly. AD clinically manifests as gradually progressive cognitive decline with behavioral disorders. Prior to full dementia, AD patients typically experience a transient state, i.e., mild cognitive impairment (MCI). Amnestic MCI individuals, but not all MCI individuals, frequently convert to AD dementia. To specify whether and how the functional relationships between the MrD and other brain regions change during AD, functional connectivity was assessed using resting-state functional MRI data and associated neuropsychological tests in AD and MCI patients (amnestic-type). Compared with normal controls, a different decreased functional connectivity pattern was observed between the MrD and caudate, the amygdala/parahippocampal region, the inferior frontal gyrus, the superior temporal gyrus, and the cerebellum for AD/MCI patients. Moreover, the functional connectivity between the MrD and the identified regions was significantly correlated with the neuropsychological scores among the MCI and AD subjects. Our results suggest that the MrD functional network is disrupted during AD.

[A cross-sectional study of neurological disease in the veterans of military communities in Beijing].

OBJECTIVE: To investigate the prevalence of cognitive and motor disorders as well as emotional and sleep abnormality in the veterans from military communities in Beijing. METHODS: The participants underwent a comprehensive in-person evaluation including detailed neuropsychological testing, Hospital Anxiety and Depression Scale and special questionnaires for movement and sleep disorders. RESULTS: The overall prevalence of cognitive impairment, extrapyramidal diseases was 32.7%, 8.8%. The prevalence of mild cognitive impairment, dementia, Parkinson disease, essential tremor, anxiety and depression was 26.2%, 6.5%, 2.0%, 6.1%, 1.4% and 4.1% respectively. Prevalence of all kinds of sleep disorders ranged from 10.3% to 53.9%. The prevalence of cognitive impairment had no significant difference of sex, but were correlated to age and education, the correlation coefficient was 0.326 and -0.221 (P<0.01). CONCLUSION: Veterans from military communities had higher prevalence of cognitive impairment, extrapyramidal diseases and sleep disorders and lower that of anxiety and depression relatively.

[A retrospective study of clinical features of migraine].

OBJECTIVE: To observe the clinical features of migraine based on out-patient clinic data and provide help for the diagnosis and treatment of migraine. METHODS: In a retrospective study of 309 patients with migraine, we investigated the clinical characteristics of migraine of both genders and different types, and the risk factors for MOH transformed from migraine. RESULTS: The female to male ratio was about 3:1, 76.1% of the patients had triggering factors. The most common characteristics of headache were moderate to severe intensity of the pain (97.7%), aggravation by routine physical activity (75.1%), and association with nausea (90.9%) and/or vomiting (70.6%). There were significant differences in some clinical characteristics of migraine in females as compared with those in males and in patients with migraine without aura (MWOA) as compared with those with aura (MWA). The risk factors for MOH transformed from migraine were elder age of onset, high attack frequency and the analgesics frequently used (P < 0.05). CONCLUSION: It is suggested that carefully collecting the characteristics of headache, triggering factors and therapeutic history is the foundation of correct diagnosis and effective treatment for migraine.