A GH42 ß-galactosidase from Bifidobacterium thermophilum: Biochemical characterization and synthesis of galactosyl glycerol by reverse hydrolysis.

In this study, a ß-galactosidase gene (btgal42) was first cloned from Bifidobacterium thermophilum and successfully expressed in Escherichia coli. The molecular weight of the purified BtGal42 was estimated to be 78 kDa by the sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 225 kDa by the size-exclusion chromatography, indicating that the native BtGal42 was a homotrimer. BtGal42 belonged to the glycosidase hydrolase family 42, exhibiting the maximum activity at pH of 7 and at temperature of 50°C. The enzyme displayed a strictly specific activity toward substrates with ß-galactosyl linkages at the nonreducing ends, of which the activity on 4-nitrophenyl-ß-d-galactopyranoside was the highest, followed by 2-nitrophenyl-ß-d-galactopyranoside and lactose. Among the tested metals and reagents, BtGal42 showed tolerance in the presence of various organic solvents. Importantly, BtGal42 exhibited a high reverse hydrolysis activity when using galactose as the donor and the di-alcohol ethylene glycol and the trialcohol glycerol as the acceptors. Under unoptimized reaction conditions, the galactosyl glycerol yield reached 62.2 g/L (galactose conversion rate, 41.2%). This study might provide a feasible method for the biosynthesis of galactosyl glycerol from low-cost glycerol and galactose, which was associated with high conversion efficiency and few byproducts.

Diagnosis and treatment of dementia in neurology outpatient departments of general hospitals in China.

INTRODUCTION: The status of dementia diagnosis and treatment of neurology outpatients in general hospitals in China remains unclear. METHODS: From neurology outpatients at 36 randomly selected hospitals, we first collected baseline data concerning the number of dementia doctors, memory clinics, and patients diagnosed with dementia. In stage 2, we intervened based on drawbacks discovered in stage 1, implementing a dementia initiative program. In stage 3, we reinvestigated the outpatients to determine the effects of intervention. RESULTS: After intervention, all 36 hospitals had established memory clinics (205 dementia doctors) compared with only 6 (47 dementia doctors) before intervention. The percentage of patients diagnosed with dementia significantly increased from 0.10% (536 dementia patients of 553,986 outpatients) in stage 1 to 0.41% (2482 dementia patients of 599,214 outpatients) in stage 3. DISCUSSION: Proper diagnosis and treatment are unavailable to many dementia patients because of a lack of dementia doctors and memory clinics in China.

Elevated plasma angiogenesis factors in Alzheimer's disease.

Evidence has shown that aberrant angiogenesis is an integral part of Alzheimer's disease (AD). Angiogenesis is a complex process requiring successive activation of a rather large series of factors. The aim of this study was to determine which angiogenesis molecule(s) abnormalities were changed in plasma of AD subjects and whether plasma levels of angiogenesis factors were associated with cognitive function and risk of AD. Discovery-phase antibody arrays were used to detect plasma concentrations of 55 angiogenesis-related factors. Enzyme-linked immunosorbent assays (ELISAs) in a large cohort were further performed to identify the association of plasma angiogenesis factors with AD. We found that plasma angiogenin (ANG) and tissue inhibitor of matrix metalloproteinase-4 (TIMP-4) levels were higher in patients with AD than those in normal subjects. Significantly higher ANG and TIMP-4 were observed in the severe AD group relative to the mild AD. There were different levels of plasma ANG and TIMP-4 compared with vascular dementia and other dementias. Age or gender had no major effects on levels of these proteins. Plasma ANG and TIMP-4 levels tended to be higher in ApoE ε4 carriers compared with non-carriers, but not significantly. A multiple regression analysis after adjusting for covariates revealed correlations between plasma ANG and TIMP-4 and the MMSE and CDR. Higher plasma ANG and TIMP-4 levels were associated with significant AD risk. These results demonstrate that plasma ANG and TIMP-4 may reflect the severity of cognitive function impairment, and higher levels were associated with risk of AD.

The prevalence of mild cognitive impairment and its etiological subtypes in elderly Chinese.

BACKGROUND: Epidemiologic studies on mild cognitive impairment (MCI) are limited in China. METHODS: Using a multistage cluster sampling design, a total of 10,276 community residents (6096 urban, 4180 rural) aged 65 years or older were evaluated and diagnosed with normal cognition, MCI, or dementia. MCI was further categorized by imaging into MCI caused by prodromal Alzheimer's disease (MCI-A), MCI resulting from cerebrovascular disease (MCI-CVD), MCI with vascular risk factors (MCI-VRF), and MCI caused by other diseases (MCI-O). RESULTS: The prevalences of overall MCI, MCI-A, MCI-CVD, MCI-VRF, and MCI-O were 20.8% (95% confidence interval [CI] = 20.0-21.6%), 6.1% (95% CI = 5.7-6.6%), 3.8% (95% CI = 3.4-4.2%), 4.9% (95% CI = 4.5-5.4%), and 5.9% (95% CI = 5.5-6.4%) respectively. The rural population had a higher prevalence of overall MCI (23.4% vs 16.8%, P < .001). CONCLUSIONS: The prevalence of MCI in elderly Chinese is higher in rural than in urban areas. Vascular-related MCI (MCI-CVD and MCI-VRF) was most common.

The prevalence of dementia in urban and rural areas of China.

OBJECTIVE: The Chinese population has been aging rapidly and the country's economy has experienced exponential growth during the past three decades. The goal of this study was to estimate the changes in the prevalence of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) among elderly Chinese individuals and to analyze differences between urban and rural areas. METHODS: For the years 2008 to 2009, we performed a population-based cross-sectional survey with a multistage cluster sampling design. Residents aged 65 years and older were drawn from 30 urban (n = 6096) and 45 rural (n = 4180) communities across China. Participants were assessed with a series of clinical examinations and neuropsychological measures. Dementia, AD, and VaD were diagnosed according to established criteria via standard diagnostic procedures. RESULTS: The prevalence of dementia, AD, and VaD among individuals aged 65 years and older were 5.14% (95% CI, 4.71-5.57), 3.21% (95% CI, 2.87-3.55), and 1.50% (95% CI, 1.26-1.74), respectively. The prevalence of dementia was significantly higher in rural areas than in urban ones (6.05% vs. 4.40%, P < .001). The same regional difference was also seen for AD (4.25% vs. 2.44%, P < .001) but not for VaD (1.28% vs. 1.61%, P = .166). The difference in AD was not evident when the sample was stratified by educational level. Moreover, the risk factors for AD and VaD differed for urban and rural populations. CONCLUSIONS: A notably higher prevalence of dementia and AD was found in rural areas than in urban ones, and education might be an important reason for the urban-rural differences.

Associations between sex hormones and cognitive and neuropsychiatric manifestations in vascular dementia (VaD).

Although numerous studies have been carried out to determine the effects of sex hormones on Alzheimer's disease (AD), little is known about the associations between sex hormones and VaD. The aim of this study was to compare serum sex hormone levels between VaD patients and normal controls, and to further determine the link between sex hormones and cognitive and neuropsychiatric manifestations of VaD. Serum levels of total estradiol (TE2), total testosterone (TT), luteinizing hormone (LH), and sex hormone binding globulin (SHBG) were measured in 87 VaD patients and 110 cognitive normal controls. The levels of bioavailable estradiol (BE2) and bioavailable testosterone (BT) were calculated. The VaD patients underwent the tests of global cognitive function, verbal memory, and visuospatial, and executive ability. The Neuropsychiatric Inventory (NPI) was used to assess neuropsychiatric symptoms. Compared to controls, the testosterone and SHBG levels were lower in male VaD patients, and the estradiol levels were higher in female VaD patients. The hormones levels were not correlated with cognitive functions among either male or female VaD patients. There were no associations between hormone levels and neuropsychiatric symptoms among male patients, while the TE2 and TT levels were positively associated with apathy and anxiety, respectively among female patients. Our findings suggested there were sex hormone level changes in VaD patients in comparison with cognitive normal controls. Sex hormones were associated with neuropsychiatric symptoms among female but not male VaD patients.

The Informant Questionnaire on Cognitive Decline in the Elderly individuals in screening mild cognitive impairment with or without functional impairment.

The Informant Questionnaire on Cognitive Decline in the Elderly individuals (IQCODE) is a reliable, validated informant-based instrument. Most of the studies well support the validity of the IQCODE in dementia screening, but the sensitivity of the rating scale at the early stage during the course of dementia is limited. In this study, we investigate the utility of the IQCODE for patients with mild cognitive impairment (MCI) and the discriminative power of the IQCODE in patients having MCI with and without functional impairment. The samples included mild Alzheimer disease (AD, N=280), MCI ([N=657], further divided into 2 subgroups: patients with MCI having functional impairment [MCI-fi, N=357] and patients having MCI without functional impairment [MCI-fn, N=300]), and normal cognition (NC, N=274). The IQCODE, Mini-Mental State Examination (MMSE), and other neuropsychological tests were administered to all participants. Logistic regression and receiver-operating characteristic (ROC) curves were used to evaluate the diagnostic ability of the IQCODE, compared to the MMSE. The optimal cutoff scores of the IQCODE were 3.19 for the MCI (sensitivity/specificity: 0.979/0.714) and MCI-fn (0.900/0.817), 3.25 for the MCI-fi (0.978/0.701), and 3.31 for mild AD (0.893/0.779), while the MMSE was identical, that is 26, for both MCI and its functional normal and functional impaired subgroups (0.892/0.755, 0.867/0.745, and 0.913/0.745, respectively) and 24 for mild AD (0.807/0.836). The discriminating accuracy of the IQCODE was slightly superior to that of the MMSE but did not reach statistical significance. Our study suggests that the IQCODE might be useful in screening for MCI, with hierarchical scores indicating functional normal or impaired.

Stage-specific gender differences in cognitive and neuropsychiatric manifestations of vascular dementia.

Studies on gender differences in the clinical manifestations of vascular dementia (VaD) are still lacking. In the present study, gender comparisons of cognitive and neuropsychiatric profiles were conducted separately for mild and moderate-to-severe VaD in a total of 467 patients with VaD. There were no significant gender differences in cognitive manifestations, except that females performed better on immediate verbal recall than males in mild stage. Women were more likely to exhibit delusions (15.5% vs 7.4%), hallucinations (9.5% vs 3.4%), and depression (43.1% vs 27.3%) in mild stage. The predominance of male patients was observed in apathy at moderate-to-severe stage (50.5% vs 34.8%). To conclude, gender differences existed in neuropsychiatric symptoms of VaD and were especially pronounced in mild stage. Delusions, hallucinations, and depression were more prevalent in females in mild VaD, with the male predominance only in apathy in the later stage.

Combination of plasma biomarkers and clinical data for the detection of sporadic Alzheimer's disease.

Amyloid ß and alpha 1-antichymotrypsin (ACT) play an important role in the pathogenesis of sporadic Alzheimer's disease (AD). The present study was to investigate whether a combination of plasma biomarkers and clinical data would discriminate AD from vascular dementia, other neurodegenerative dementia and non-demented controls. The study included 112 patients with AD, 85 patients with vascular dementia, 30 patients with other neurodegenerative dementia and 116 age-matched, non-demented controls. Although ACT, Aß42 and the ratio of Aß42/Aß40 had significant differences between AD, vascular dementia, other neurodegenerative dementia and non-demented controls (P<0.001), none of them reached the sensitivity and specificity required for AD biomarkers. The combination of biomarkers and clinical data had higher discriminating power than either alone. Our results indicated that plasma biomarkers of ACT and the ratio of Aß42/Aß40 could discriminate AD from non-demented controls, vascular dementia, or other neurodegenerative dementias with higher diagnostic accuracy than clinical data and that if plasma biomarkers were combined with clinical data, the discriminating power was enhanced.

Apolipoprotein E ε4 status modifies the effects of sex hormones on neuropsychiatric symptoms of Alzheimer's disease.

BACKGROUND: Studies on the associations between sex hormones and multiple neuropsychiatric symptoms of Alzheimer's disease (AD) are lacking. Apolipoprotein E (APOE) ε4 status may modify the effects of sex hormones on neuropsychiatric symptoms. METHODS: A total of 86 male and 87 female AD patients participated in the present study. The adjusted associations between symptoms on the Neuropsychiatric Inventory and serum levels of estradiol (total, bioavailable) and testosterone (total, bioavailable) were analyzed. RESULTS: Agitation/aggression was negatively associated with quartiles of bioavailable estradiol among male patients, and positively associated with testosterone levels among female patients. The modifying effects of APOE genotype only existed in female patients. Those females with higher levels of estradiol and the ε4 allele had higher odds of agitation/aggression. Furthermore, the testosterone × APOE ε4 status interaction was positively associated with hallucinations in female patients. CONCLUSION: There were sex-specific effects of sex hormones on agitation/aggression in AD. Sex hormones and APOE ε4 status synergistically influence some neuropsychiatric symptoms among female but not male AD patients.

Montreal cognitive assessment in detecting cognitive impairment in Chinese elderly individuals: a population-based study.

The Montreal Cognitive Assessment (MoCA) has been proved brief and sensitive to screen for mild cognitive impairment (MCI) and early dementia in some developed countries or areas. However, little MoCA data are available from mainland China. In this study, the MoCA was applied to 8411 Chinese community dwellers aged 65 or older (6283 = cognitively normal [CN], 1687 = MCI, and 441 = dementia). The MoCA norms were established considering significant influential factors. The optimal cutoff points were 13/14 for illiterate individuals, 19/20 for individuals with 1 to 6 years of education, and 24/25 for individuals with 7 or more years of education. With the optimal cutoffs, the sensitivity of the MoCA was 83.8% for all cognitive impairments, 80.5% for MCI and 96.9% for dementia, and the specificity for identifying CN was 82.5%. These indicate that with optimal cutoffs, the MoCA is valid to screen for cognitive impairment in elderly Chinese living in communities.