nping Jia

Abnormal whole-brain functional connection in amnestic mild cognitive impairment patients.

Amnestic mild cognitive impairment (aMCI) patients are thought to be particularly vulnerable to convert to clinical AD where functional disconnection is a major feature of the cortical neuropathology. However, the presence and extent of whole-brain connectivity disturbances is largely unknown in aMCI patients. Twenty-six aMCI patients and eighteen matched healthy subjects were evaluated at baseline and at mean 20 months follow up. Temporal correlations between spatially distinct regions were evaluated by using longitudinal resting-state fMRI. Compared to normal aging controls, patterns of abnormal interregional correlations in widely dispersed brain areas were identified in the patients, which also changed with disease progression. These disturbances were found particularly in subcortical regions and frontal cortex. Importantly, significantly decreased negative functional connection may be specifically associated with the development of aMCI patients. This suggests a compensatory mechanism is underway where local processing deficits are offset by recruitment of more dispersed cortical regions. In addition, the presence of this increased connectivity is seen to eventually weaken with disease progression. The results suggest that patterns of whole-brain functional connection may be a useful risk marker for conversion to AD in aMCI patients.

Abnormal integrity of association fiber tracts in amnestic mild cognitive impairment

The association fiber tracts integrity of the inter-hemispheric and within-hemispheric communication was poor understood in amnestic type mild cognitive impairment (aMCI) patients by diffusion tensor imaging (DTI). A region of interest-based DTI approach was applied to explore fiber tract differences between 22 aMCI patients and 22 well-matched normal aging. Correlations were also sought between fractional anisotropy (FA) values and the cognitive performance scores in the aMCI patients. Extensive impairment of association fiber tracts integrity was observed in aMCI patients, including bilateral inferior fronto-occipital fascicles, the genu of corpus callosum, bilateral cingulate bundles and bilateral superior longitudinal fascicles II (SLE II) subcomponent. In addition, the FA value of right SLE II was significantly negatively correlated to the performance of Trail Making Test A and B, whilst the values of right posterior cingulate bundle was significantly positive correlation with MMSE score. As aMCI is a putative prodromal syndrome to Alzheimers disease (AD), this study suggested that investigation of association fiber tracts between remote cortexes may yield important new data to predict whether a patient will eventually develop AD.

Differential Activation of mTOR Complex 1 Signaling in Human Brain with Mild to Severe Alzheimer's Disease

Mammalian target of rapamycin (mTOR) signaling has been suggested to be effective in modifying cognitive status in animal models of Alzheimers disease (AD), but little is known about its role in AD patients. We hereby tested whether mTOR signaling was activated and whether activated mTOR signaling was related to the degree of cognitive deficits in patients with AD. Autopsy brain hippocampal tissues were obtained from controls and patients with AD and Western blots were performed using antibodies against mTOR signaling molecules and RagC, an upstream component of mTOR complex 1 (mTORC1) signaling. We found that expression of mTOR/p-mTOR and its downstream targets S6/p-S6 and Raptor/p-Raptor were expressed in the control and AD hippocampus. The expression levels of these signaling molecules were significantly increased in the hippocampus at the severe stages of AD, compared to controls and other stages of AD. Interestingly, Rictor expression level was unaltered. In addition, RagC was increased in the hippocampus at the early, moderate, and severe stages of AD. Our data indicate that mTORC1, but not mTORC2, was activated in the AD brains and that the level of mTOR signaling activation was correlated with cognitive severity of AD patients.

Mapping the Altered Patterns of Cerebellar Resting-State Function in Longitudinal Amnestic Mild Cognitive Impairment Patients

The cerebellum is known to be a relatively well preserved structure, but subtle alterations may occur early in the evolution of Alzheimers disease (AD). Amnestic mild cognitive impairment (aMCI) patients appear to be particularly vulnerable to AD. However, little is currently known whether altered patterns of cerebellar function occur in aMCI patients. 26 aMCI patients and 18 well-matched healthy controls underwent a baseline resting-state functional magnetic resonance imaging (fMRI) scan. After a mean follow-up period of 20 months, the subjects who successfully completed baseline fMRI scans underwent a further follow-up scan, while spontaneous activation and functional connectivity of the cerebellum were explored by using resting-state fMRI. Compared to controls, increased amplitude of low frequency fluctuation of the posterior cerebellar lobe may contribute to the underlying mechanisms affected, while greater decreased functional connections to the posterior cerebellar lobe were identified in the longitudinal study of aMCI patients. This suggests that abnormal functional connectivity of the cerebellum may offer a more sensitive and possibly preferred index of functional disturbance than regional activity measures in aMCI patients. The cerebellum may be partly related to the underlying mechanisms of aMCI, and it could help guide subsequent investigations designed to specify the precise functional role of cerebellum in aMCI patients.

Alteration of resting brain function by genetic variation in angiotensin converting enzyme in amnestic-type mild cognitive impairment of Chinese Han

Using a cross-sectional case-control study of amnestic-mild cognitive impairment (aMCI), we characterised the relationships among cognitive function, serum levels of angiotensin converting enzyme (ACE), brain activity, and ACE insertion or deletion (I/D) polymorphism. Forty-eight patients with aMCI and 36 well-matched normal controls were assessed by a comprehensive battery of standardized neuropsychological tests. In addition, regional homogeneity (ReHo) approaches were used to analyze blood oxygen level-dependent functional magnetic resonance imaging data on the resting state in all subjects, and genotyping of the serum ACE was measured in aMCI patients. The D carriers with aMCI patients were found to have markedly higher serum ACE levels than I homozygote carriers. Importantly, compared with the carried I homozygote group of patients with aMCI, the D carriers of aMCI patients were significantly impaired in the AVLT-delayed recall and had decreased ReHo over the bilateral precuneus, left middle occipital gyrus, right inferior parietal lobe, and right angular gyrus, whilst increased ReHo was found mainly in the left medial frontal gyrus, right paracentral lobe, and right anterior cingulate cortex. The findings indicated that ACE genotype was associated with episodic memory, serum levels of ACE, and resting-state brain activity in aMCI patients, and the findings of cognitive function and brain activity further suggests that the ACE D allele may have a specific role in semantic memory dysfunction and brain activity in aMCI.

A clinical and gene analysis of late-onset combined methylmalonic aciduria and homocystinuria, cblC type, in China

BACKGROUNDnCombined methylmalonic aciduria and homocystinuria, cblC type (cblC disease), is the most common inborn disorder of cobalamin metabolism. This disorder is caused by MMACHC gene mutations, and it is usually diagnosed in the early neonatal period. Late-onset cblC is rare and difficult to recognize due to a wide diversity of symptoms.nnnMETHODSnThree cases with late-onset combined methylmalonic aciduria and homocystinuria, cblC type, are reported; patients clinical presentation, imaging and MMACHC gene mutations were analyzed.nnnRESULTSnThe age of onset in the three patients was 22 years, 40 years and 7 years of age. Two of the patients had MMACHC gene mutations heterozygous for c.609G>A and c.482G>A (case 1 and case 3). The other patient (case 2) presented with gene mutations heterozygous for c.609G>A and c.1A>G. The three patients presented with a heterogeneous clinical picture, including cognitive impairment, epilepsy, ataxia, pyramidal and peripheral nerve symptoms. Cerebral atrophy and bilateral hyperintensity in the deep white matter were visible in MRI scans of the patients brains; those were significant findings in the three patients with late-onset cblC disease. In contrast with previous reports, bilateral cerebellar cortex abnormalities were also found in one patient (case 2).nnnCONCLUSIONnAlthough its occurrence is rare, late-onset combined methylmalonic aciduria and homocystinuria, cblC type, should be considered in making a differential diagnosis in patients who present with neurological symptoms that are not consistent with common neurological diseases, especially when cognition, the pyramidal tract and peripheral nerves are involved.

The association of the regulatory region of the presenilin-2 gene with Alzheimer's disease in the Northern Han Chinese population

Presenilin-2 is one of the causative genes for familial Alzheimers disease (FAD). Polymorphism of the promoter region of the presenilin-2 gene (PSEN2) has recently been reported in a Russian population to be associated with sporadic Alzheimers disease (SAD). The purpose of this case-control study was to determine whether SAD is associated with the PSEN2 gene polymorphism in a Chinese population. We examined PSEN2 and APOE genotypes in 200 SAD patients and an equal number of age- and sex-matched controls from the same community, using the PCR-RFLP method. Allelic and genotypic distributions were performed using the Pearson Chi-square test for homogeneity. The interactions between variables were examined by logistic regression. The results revealed no significant differences in the frequency of the +A/-A polymorphism between AD and controls (chi(2)=3.857, p=0.145). However, in the subgroup of APOE epsilon4 non-carriers, there were significant differences in the distributions of both alleles (chi(2)=6.095, p=0.047) and genotypes (chi(2)=4.433, p=0.035) of the PSEN2 promoter in AD compared with controls. In APOE epsilon4 non-carrier group, with +A/+A as a reference, the -A/-A genotype was associated with a 4.657-fold increased risk for AD (chi(2)=5.783, p=0.016, OR=4.657, 95% CI=1.195-18.152). Using logistic analysis, there were no statistical interactions between PSEN2 and APOE genotypes, or between PSEN2 genotypes and age of onset. It is concluded that in the Northern Han Chinese population, the +A/-A polymorphism of the PSEN2 promoter is a moderate genetic risk factor for developing SAD, independent of the APOE epsilon4 allele.

Bickerstaff’s brainstem encephalitis, Miller Fisher syndrome and Guillain-Barré syndrome overlap in an asthma patient with negative anti-ganglioside antibodies

BackgroundBickerstaff’s brainstem encephalitis (BBE), together with Miller Fisher syndrome (MFS) and Guillain-Barré syndrome (GBS) were considered to form a continuous clinical spectrum. An anti-GQ1b antibody syndrome has been proposed to underlie the common pathophysiology for the three disorders; however, other studies have found a positive anti-GM1 instead of anti-GQ1b antibody.Case presentationHere we report a 20-year-old male patient with overlapping BBE, MFS and GBS. The patient had a positive family history of bronchial asthma and had suffered from the condition for over 15u2009years. He developed BBE symptoms nine days after an asthma exacerbation. During the course of illness, he had significantly elevated IgE levels in both serum and cerebrospinal fluid. Serologic analysis of antibodies against ganglioside complexes (anti-GDIa, anti-GDIb, anti-GM1, anti-GM2, anti-GM3, anti-GQIb and anti-GTIb antibodies) showed negative results.ConclusionsSince asthma has recently been related to autoimmune disease, our case supports an autoimmune mechanism underlying the clinical spectrum composed of BBE, MFS and GBS. However, contrary to a proposed anti-GQ1b antibody syndrome, we would suggest that pathogenesis of this clinical spectrum is not limited to anti-ganglioside antibodies.

ACE I/D polymorphism affects cognitive function and gray-matter volume in amnestic mild cognitive impairment

To characterize the correlates of cognitive function, serum concentrations of angiotensin converting enzyme (ACE) and brain structure with the ACE insertion or deletion (I/D) polymorphism were analyzed in subjects with amnestic-mild cognitive impairment (aMCI). A group of 48 subjects meeting criteria for aMCI and 36 age-matched control subjects were assessed using a comprehensive battery of standardized neuropsychological tests and magnetic resonance imaging (MRI). The ACE genes I/D polymorphism was analyzed by means of PCR, and serum ACE concentrations were measured using ultraviolet spectrophotometry. Genotype effects on neuropsychological domains and MRI gray matter volume (GMV) measurements (optimized voxel-based morphometry) were examined using general linear models. The D carriers among the aMCI subjects performed significantly worse on AVLT-delayed recall compared to the I homozygous group. The D carriers had higher serum ACE concentrations than did the I homozygous carriers, though this difference only reached statistical significance in the aMCI group. Compared with the I homozygous carriers, in the aMCI group, D carriers showed smaller GMV of the bilateral middle frontal gyrus, right cuneus, right precentral gyrus, right medial frontal gyrus, right superior frontal gyrus, and left postcentral gyrus. However, there was no significant difference in GMV between I homozygous and D carriers in the normal control group. The study suggests that ACE genotype has considerable effect on the cognitive performance of aMCI subjects, particularly episodic memory, serum activity of ACE, and the structure of specified brain regions. The ACE D allele may be a genetic risk factor for greater atrophy of gray matter in aMCI.

Acute toxic leukoencephalopathy in migrant workers exposed to organic solvents in construction materials

Organic solvents are widely used in the construction industry. Migrant workers, an important source of construction workers in China, are at risk of solvent intoxication. Here we describe two young male migrant workers who were diagnosed with acute toxic leukoencephalopathy due to intense exposure to organic solvents contained in construction materials.nnPatient 1 had been applying tape to pipes in non-ventilated, underground apartments for 5u2005days before he developed a slow reaction time, headache, nausea and vomiting. He worked 10u2005h per day with a 10-min break in both the morning and the afternoon. The adhesive tape he used produced a strong smell, and he did not wear any personal protective equipment. Patient 2 had been painting internal walls for 6u2005days before he developed headache, nausea, vomiting, diplopia and intermittent drowsiness. He worked in confined spaces for up to 8u2005h at a time without any protective equipment. He complained …