Interactive association between insomnia symptoms and sleep duration for the risk of dementia-a prospective study in the Swedish National March Cohort.

OBJECTIVE: Given the importance of sleep in maintaining neurocognitive health, both sleep duration and quality might be component causes of dementia. However, the possible role of insomnia symptoms as risk factors for dementia remain uncertain. METHODS: We prospectively studied 22,078 participants in the Swedish National March Cohort who were free from dementia and stroke at baseline. Occurrence of dementia was documented by national registers during a median follow-up period of 19.2 years. Insomnia symptoms and sleep duration were ascertained by Karolinska Sleep Questionnaire. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Compared to participants without insomnia at baseline, those who reported any insomnia symptom experienced a greater incidence of dementia during follow-up (HR 1.08, 95% CI: 1.03, 1.35). Difficulty initiating sleep versus non-insomnia (HR 1.24, 95% CI: 1.02, 1.52), but not difficulty maintaining sleep or early morning awakening was associated with an increased risk of dementia. Short sleep duration was associated with increased risk of dementia (6 h vs. 8 h, HR 1.29, 95% CI: 1.11-1.51; 5 h vs. 8 h, HR 1.26, 95% CI: 1.00-1.57). Stratified analyses suggested that insomnia symptoms increased the risk of dementia only amongst participants with ≥7 h sleep (vs. non-insomnia HR 1.24, 95% CI: 1.00-1.54, P = 0.05), but not amongst short sleepers (<7 h). Short sleep duration also did not further inflate the risk of dementia amongst insomniacs. CONCLUSION: Insomnia and short sleep duration increase the risk of dementia amongst middle-aged to older adults.

Influence of chronic diseases on the occurrence of depression: A 13-year follow-up study from the Survey of Health, Ageing and Retirement in Europe.

The causal association between chronic diseases and depression remains unclear. This study aimed to explore the effects of types and number of chronic diseases on the risk of depression using data from the Survey of Health, Ageing and Retirement in Europe (SHARE). A self-admitted questionnaire was used to obtain data on 14 predefined chronic diseases and the European-Depression Scale (EURO-D) was used to assess depression. Among the 16,080 baseline depression-free participants aged 50+, 31.29% (5032) developed depression over 13 years. Multivariate Cox regression models showed that individuals with any chronic diseases were at higher risk of new onset depression compared to disease-free participants. The risk of new onset depression increased with an increasing number of diseases among both younger (50-64) and older (65+) adults. Individuals with heart attack, stroke, diabetes, chronic lung disease, and arthritis were at increased risk of depression across age groups. However, some age-specific associations were observed, with cancer increasing depression risk among younger- and peptic ulcer, Parkinson's disease and cataracts increasing depression risk among older adults. These findings highlight the importance of managing chronic diseases, especially among those with more than two diseases, to prevent the development of depression among middle-aged and older adults.

Work-Related Stress and Occurrence of Cardiovascular Disease: A 13-Year Prospective Study.

OBJECTIVE: The aim of the study is to investigate the influence of work-related psychological and physical stresses on risk of cardiovascular disease (CVD). METHODS: A total of 5651 CVD-free participants older than 50 years from the Survey of Health, Ageing and Retirement in Europe were followed up for 13 years to detect incident CVD. Work-related stress was assessed using job strain and job reward questionnaire. Cox regression model was used to estimate the association. RESULTS: High physical demands (hazard ratio [HR], 1.30) and low reward (HR, 1.19) compared with their counterparts, as well as active physical jobs (HR, 1.41) and high physical strain (HR, 1.45) in comparison with low physical strain were associated with higher risk of incident CVD after adjusting for confounders. However, combining physically stressful jobs with low reward did not further increase the CVD risk. CONCLUSIONS: Avoiding physically stressful jobs or providing appropriate reward may reduce the occurrence of CVD.

Working life job strain status and cognitive aging in Europe: A 12-year follow-up study.

BACKGROUND: To examine the association of job strain with cognitive ability and the influence of life-course job strain on later life cognitive decline. METHODS: Data were derived from six waves of the Survey of Health, Aging, and Retirement in Europe. The study sample consists of 13349 participants aged 50 to 98 years at wave 2 and has been followed up for 12-years. Job strain status across working life was assessed using a short demand-control job strain model containing two core dimensions: job demands and job control collected in wave 3. Cognitive abilities concerning episodic memory was assessed by immediate recall and delayed recall tests, executive function was evaluated by verbal fluency test collected in all waves (waves 2-7) except wave 3. Mixed-effects model was used to estimate working life job strain and its cumulative effect on cognitive decline. RESULTS: Both passive and high strain jobs were associated with lower levels of cognitive ability (episodic memory and verbal fluency) in comparison with active job. Long exposure to active- or low strain-job was associated with higher cognitive ability whereas long exposure to passive job or moderate duration of high strain job was associated with lower cognitive ability. The rate of memory decline was positively related to moderate duration of passive job and negatively related to long-term exposure to low strain job. LIMITATIONS: Information on working conditions was based on self-reported recollections. CONCLUSIONS: Working life variation in job strain status and their duration may explain individual differences in cognitive ability in later life.

Depressive symptoms and cognitive impairment: A 10-year follow-up study from the Survey of Health, Ageing and Retirement in Europe.

BACKGROUND: Depressive symptoms and cognitive impairment often coexisted in the elderly. This study investigates the effect of late-life depressive symptoms on risk of mild cognitive impairment (MCI). METHODS: A total of 14,231 dementia- and MCI free participants aged 60+ from the Survey of Health, Ageing, and Retirement in Europe were followed-up for 10 years to detect incident MCI. MCI was defined as 1.5 standard deviation (SD) below the mean of the standardized global cognition score. Depressive symptoms were assessed by a 12-item Europe-depression scale (EURO-D). Severity of depressive symptoms was grouped as: no/minimal (score 0-3), moderate (score 4-5), and severe (score 6-12). Significant depressive symptoms (SDSs) were defined as EURO-D score ≥ 4. RESULTS: During an average of 8.2 (SD = 2.4)-year follow-up, 1,352 (9.50%) incident MCI cases were identified. SDSs were related to higher MCI risk (hazard ratio [HR] = 1.26, 95% confidence intervals [CI]: 1.10-1.44) in total population, individuals aged 70+ (HR = 1.35, 95% CI: 1.14-1.61) and women (HR = 1.28, 95% CI: 1.08-1.51) in Cox proportional hazard model adjusting for confounders. In addition, there was a dose-response association between the severity of depressive symptoms and MCI incidence in total population, people aged ≥70 years and women (p-trend <0.001). CONCLUSIONS: Significant depressive symptoms were associated with higher incidence of MCI in a dose-response fashion, especially among people aged 70+ years and women. Treating depressive symptoms targeting older population and women may be effective in preventing MCI.

The relationship between chronic diseases and depression in middle-aged and older adults: A 4-year follow-up study from the China Health and Retirement Longitudinal Study.

BACKGROUND: Evidence of the association between common chronic diseases and depression is sparse. METHODS: Totally 7819 participants aged 45+ without depression at baseline were followed-up (2011-2015) to detect incident depression. Chronic diseases and depression were defined by self-reported diagnosis and the Center for Epidemiological Studies Depression Scale (CES-D10), respectively. Cox proportional hazards model was used to explore the association between chronic diseases and depression adjusting for age, gender, education, marital/living conditions, area, smoking, drinking, economic status, BMI and health insurance. RESULTS: During an average of 3.42 years follow-up, 2271 participants developed depression (85 per 1000 person-year). Chronic diseases were related to significantly higher risk of depression (HR = 1.38). A higher risk of depression was also associated with specific diseases: stomach/other digestive diseases (HR = 1.19), diabetes (HR = 1.22), arthritis/rheumatism (HR = 1.30), and kidney diseases (HR = 1.34) (P < 0.05). The risk of depression increased with increasing in the number of chronic diseases (1: HR = 1.27, 2: HR = 1.49, and 3+: HR = 1.51, P-trend < 0.001). No significant difference was observed across age, gender, education, and area. LIMITATIONS: Chronic diseases and depression were based on self-reported diagnosis and measurement scale, respectively, which could lead to information bias. Some unmeasured confounders might have biased the results. CONCLUSIONS: The occurrence of depression in people aged 45+ is associated with number of chronic diseases in a dose-response fashion. These results may provide guidance on preventing depression and improving the quality of life in middle and late adulthood.

Late-life depression and the risk of dementia in 14 countries: a 10-year follow-up study from the Survey of Health, Ageing and Retirement in Europe.

BACKGROUND: Depression is the most common mental health problem and often co-occurs with dementia in old age. This study investigates the influence of late-life depression on risk of dementia. METHODS: A total of 16210 dementia-free participants aged 60+ from the Survey of Health, Aging, and Retirement in Europe were followed up for 10 years to detect incident dementia. Depression was assessed by a 12-item Europe-depression scale, dementia was determined by physician diagnosis reported by the participants and their informants. Fine and Gray model was performed to explore the association between depression and incident dementia taking into account competing risk of death. RESULTS: During an average of 8 years follow-up, 1030 (6.35%) incident dementia were identified. Late-life depression was related to higher subdistribution hazard ratio (sHR) of dementia (sHR=1.52, 95%CI: 1.32-1.75) after adjusting for age, gender, country, education, smoking, drinking, living arrangement, BMI, chronic disease, and physical activity. Further, the risk was only existed in those below age of 80 (sHR=1.75, 95%CI: 1.47-2.07). In addition, a dose-response association was observed between the severity of depression and dementia risk (p for trend<0.001). LIMITATION: The ascertainment of depression and dementia was based on information reported by the participants and/or their informants, which might result in information bias. The causal relationship could not be determined because limited follow-up time. CONCLUSIONS: Late-life depression is associated with higher incidence of dementia in a dose-response fashion. Interventions targeting depression patients aged 60-79 years and those with severe depression may be effective strategies to prevent dementia.

Targetting Exosomes as a New Biomarker and Therapeutic Approach for Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disease that mainly occurs in old age and involves progressive cognitive impairment. AD has become a major global issue for public health, with approximately 24 million people currently affected by the disease. Estimates indicted that this number will quadruple by 2050. Because of the high incidence of AD, there is an urgent need to develop new strategies to diagnose and treat AD. Many recent studies have indicated the multiple, yet somewhat controversial, roles of exosomes in AD. Although the underlying mechanisms by which exosomes play a role in AD are still unknown, current evidence suggests that exosomes can carry and spread toxic amyloid-beta, and hyperphosphorylated tau, between cells, and then induce apoptosis, thus contributing to the loss of neurons. In addition, exosomes appear to possess the ability to reduce brain amyloid-beta, and tau hyperphosphorylation, and transfer neuroprotective substances between neural cells. The accumulating data brings hope that the application of exosomes may be helpful for early diagnostics and the identification of new therapeutic targets for AD. Here, we summarized the various roles of exosomes, and how they might relate to the pathogenesis of AD. We also highlight the potential application of exosomes as a therapeutic option in AD therapy.

Impact of effort reward imbalance at work on suicidal ideation in ten European countries: The role of depressive symptoms.

BACKGROUND: Evidence of the association between effort reward imbalance (ERI) and suicidal ideation is sparse. This study examined the influence of ERI at work on suicidal ideation and the mediating effect of depressive symptoms. METHODS: There were 4963 workers aged 50+ without suicidal ideation at baseline in the Survey of Health, Aging and Retirement in Europe, these workers were followed-up for 8-years to detect incident suicidal ideation. ERI was measured by a short ERI questionnaire. Suicidal ideation was evaluated by one item derived from the 12-item Europe-depression scale, and depressive symptoms were assessed by the remaining 11 items in the scale. Cox models were employed to explore the relationship adjusting for potential confounders. Mediation analysis was used to test the mediating effect of depressive symptoms. RESULTS: A significantly higher incidence of suicidal ideation was related with high effort (HR = 1.51) and low reward (HR = 1.42), respectively. A high effort-low reward imbalance was associated with even higher risk of suicidal ideation (HR = 1.96) as compared to low effort-high reward combination. The association was varied by gender, region, education and household income. Depressive symptoms mediated a modest proportion (natural indirect effect 14.4%) of the total association between ERI and suicidal ideation. LIMITATION: Suicidal ideation definition based on self-administered questionnaires which could lead to false negatives. And some unmeasured confounders might have biased the results. CONCLUSIONS: Efforts in promoting balanced effort-reward at work may reduce suicidal ideation among working population aged 50+. Avoiding depressive symptoms may further enhance such efforts.

Reciprocal associations between job strain and depression: A 2-year follow-up study from the Survey of Health, Ageing and Retirement in Europe.

BACKGROUND: A growing number of people suffered from depression. This study examined the depression prevalence in workers across 10 European countries plus Israel and the reciprocal associations between job strain and depression. METHODS: The study population consisted of 7,879 workers aged 50-63 years at baseline (2004) from the Survey of Health, Ageing, and Retirement in Europe (SHARE). Job demands (physical or psychosocial) and job control variables were derived from the Job Content Questionnaire (JCQ). Two 4-category job strains (physical and psychosocial) were obtained based on the cross-tabulation of these dichotomized demands and control variables. There were 4,284 depression-free, 3,259 high physical strain-free and 3,195 high psychosocial strain-free participants at baseline who were followed up for 2 years to detect incident depression, high physical job strain, or high psychosocial strain, respectively. The reciprocal associations between job strain and depression were analyzed by multivariate logistic regression and multivariate multilevel logistic regression adjusting for potential confounders. RESULTS: The prevalence of depression varied from the lowest 12.5% in Germany to the highest 27.2% in France. Compared to individuals with low strain, a significantly higher risk of depression were found in individuals with high physical strain (OR = 1.39) and high psychosocial strain (OR = 1.55), after adjusting for potential confounders. Depression at baseline was not significantly associated with subsequent high job strain. Similar results were observed from multilevel models that took into consideration of the potential country-level influences. CONCLUSIONS: The prevalence of depression varies across countries in Europe. Avoiding high job strain may be an effective preventive strategy to prevent depression epidemic.

Reciprocal relationship between psychosocial work stress and quality of life: the role of gender and education from the longitudinal study of the Survey of Health, Ageing and Retirement in Europe.

OBJECTIVE: To investigate the reciprocal relationship between psychosocial work stress and quality of life (QoL) and to examine whether the relationship can be moderated by gender or education. DESIGN: Longitudinal, population-based study. SETTING: The Survey of Health, Ageing and Retirement in Europe (SHARE). PARTICIPANTS: The study population was derived from the SHARE, and there were 2006 participants with good QoL at baseline, 1109 with high job control and 1072 with high job reward, respectively, who were followed up for 2 years to detect incidence of poor QoL, low job control and low job reward. MAIN OUTCOME MEASURES: Logistic regression models were employed to explore the reciprocal relationship between psychological work stress and QoL. Stratification analyses by gender and education were performed. RESULTS: Participants with low reward (OR=1.53, 95% CI 1.26 to 1.88) and low control (OR=1.40, 95% CI 1.14 to 1.71) at baseline were at higher risk of poor QoL over the 2-year follow-up. The combination of low reward and low control further increased the risk (OR=1.90, 95% CI 1.46 to 2.48). Stratified analyses revealed that these associations were more pronounced among those who had high levels of education. Further, individuals with poor QoL were at significantly higher risk of having low reward (OR=2.14, 95% CI 1.55 to 2.96) but not low control (OR=1.33, 95% CI0.98 to 1.79) at the 2-year follow-up, especially among those who had medium levels of education. No gender differences were found. CONCLUSIONS: There is a reciprocal relationship between psychological work stress and poor QoL. Education may play an important role in the relationship.

High glucose induces formation of tau hyperphosphorylation via Cav-1-mTOR pathway: A potential molecular mechanism for diabetes-induced cognitive dysfunction.

The abnormally hyperphosphorylated tau is thought to be implicated in diabetes-associated cognitive deficits. The role of mammalian target of rapamycin (mTOR) / S6 kinase (S6K) signalling in the formation of tau hyperphosphorylation has been previously studied. Caveolin-1 (Cav-1), the essential structure protein of caveolae, promotes neuronal survival and growth, and inhibits glucose metabolism. In this study, we aimed to investigate the role of Cav-1 in the formation of tau hyperphosphorylation under chronic hyperglycemic condition (HGC). Diabetic rats were induced by streptozotocin (STZ). Primary hippocampal neurons with or without molecular intervention such as the transient over-expression or knock-down were subjected to HGC. The obtained experimental samples were analyzed by real time quantitative RT-PCR, Western blot, immunofluorescence or immunohistochemisty. We found: 1) that a chronic HGC directly decreases Cav-1 expression, increases tau phosphorylation and activates mTOR/S6K signalling in the brain neurons of diabetic rats, 2) that overexpression of Cav-1 attenuates tau hyperphosphorylation induced by chronic HGC in primary hippocampal neurons, whereas down-regulation of Cav-1 using Cav-1 siRNA dramatically worsens tau hyperphosphorylation via mTOR/S6K signalling pathway, and 3) that the down-regulation of Cav-1 induced by HGC is independent of mTOR signalling. Our results suggest that tau hyperphosphorylation and the sustained over-activated mTOR signalling under hyperglycemia may be due to the suppression of Cav-1. Therefore, Cav-1 is a potential therapeutic target for diabetes-induced cognitive dysfunction.

Elevations in the Levels of NF-κB and Inflammatory Chemotactic Factors in the Brains with Alzheimer's Disease - One Mechanism May Involve α3 Nicotinic Acetylcholine Receptor.

The purpose of this study was to investigate the alterations in the levels of nuclear factor κBp65 (NF-κBp65), monocyte chemoattractant protein 1 (MCP-1/CCL-2) and macrophage inflammatory protein 1α (MIP-1α/CCL-3) in relationship to the expression of α3 nicotinic acetylcholine receptor (nAChR) during the pathogenesis of Alzheimer's disease (AD). The post-mortem human brains of AD and age-matched control individuals, SH-SY5Y and U87MG cell lines exposed to ß-amyloid peptide (Aß), as well as the SH-SY5Y cells in which α3 nAChR was down-regulated by siRNA were used to study the possible expression changes of the targets such as NF-κBp65, MCP-1, MIP-1α and α3 nAChR. The immunohistochemistry results showed the increased immunoreactivities of NF-κBp65, MCP-1 and MIP-1α in neurons in hippocampal and temporal and frontal regions of AD brains. Levels of NF-κBp65, MCP-1 and MIP-1α at both protein and mRNA levels were all significantly up-regulated in SH-SY5Y and U87MG cells exposed to Aß1-42, while expression of α3 nAChRs in Aß1-42 exposed SH-SY5Y cells was attenuated. Interestingly, in the SH-SY5Y cells subjected to α3 nAChR mRNA silencing, expression of NF-κBp65, MCP-1 and MIP-1α was elevated. The elevated expressions of NF- κB and chemokines may be involved by decreased expression of α3 nAChRs during the pathogenesis of AD.

Comparison of Various Types of Ligand Decorated Nanoliposomes for their Ability to Inhibit Amyloid Aggregation and to Reverse Amyloid Cytotoxicity.

Three different amyloid targeting ligands, previously shown to exhibit amyloid specific properties, have been used to develop amyloid -targeted nanoliposomes (AT-NLs. For this a MAb against Aß-peptides (Aß-MAb (immobilized on NLs at 0.015 and 0.05 mol %, and two different curcumin-lipid derivatives were attached to the surface of preformed NLs or incorporated in NL membranes during their formation. Following physicochemical characterization, these AT-NLs were studied for their ability to inhibit or delay amyloid peptide aggregation -using the thioflavin-T assay, and for their potential to reverse amyloid-induced (and Zn, or, amyloid + Zn cytotoxicity, on wild type (N2aWT and transformed (N2aAPP neuroblastoma cells, applying the MTT assay. Experimental results reveal that all formulations were found to strongly delay amyloid peptide aggregation (with no significant differences between the different AT-NL types. However, although Aß-MAb-NLs significantly reversed amyloid-induced cytotoxicity in all cases, both curcumin-NL types did not reverse Zn-induced, nor Zn+Aß-induced cytotoxicity in N2aWT cells, suggesting lower activity against synthetic-Aß peptides (compared to endogenous Aß peptides; perhaps due to different affinity towards different (aggregation stages of peptide species (monomers, oligomers, fibrils, etc. Taken into account that the aggregation stage of amyloid species is an important determinant of their toxicity, the importance of the affinity of each AT-NL type towards specific species, is highlighted.

mTor mediates tau localization and secretion: Implication for Alzheimer's disease.

Abnormally hyperphosphorylated tau aggregates form paired helical filaments (PHFs) in neurofibrillary tangles, a key hallmark of Alzheimer's disease (AD) and other tauopathies. The cerebrospinal fluid (CSF) levels of soluble total tau and phospho-tau from clinically diagnosed AD patients are significantly higher compared with controls. Data from both in vitro and in vivo AD models have implied that an aberrant increase of mammalian target of rapamycin (mTor) signaling may be a causative factor for the formation of abnormally hyperphosphorylated tau. In the present study, we showed that in post-mortem human AD brain, tau was localized within different organelles (autophagic vacuoles, endoplasmic reticulum, Golgi complexes, and mitochondria). In human SH-SY5Y neuroblastoma cells stably carrying different genetic variants of mTor, we found a common link between the synthesis and distribution of intracellular tau. mTor overexpression or the lack of its expression was responsible for the altered balance of phosphorylated (p-)/-non phosphorylated (Np-) tau in the cytoplasm and different cellular compartments, which might facilitate tau deposition. Up-regulated mTor activity resulted in a significant increase in the amount of cytosolic tau as well as its re-localization to exocytotic vesicles that were not associated with exosomes. These results have implicated that mTor is involved in regulating tau distribution in subcellular organelles and in the initiation of tau secretion from cells to extracellular space.

Repeated intraperitoneal injections of liposomes containing phosphatidic acid and cardiolipin reduce amyloid-ß levels in APP/PS1 transgenic mice.

The accumulation of extracellular amyloid-beta (Aß) peptide and intracellular neurofibrillary tangles in the brain are two major neuropathological hallmarks of Alzheimer's disease (AD). It is thought that an equilibrium exists between Aß in the brain and in the peripheral blood and thus, it was hypothesized that shifting this equilibrium towards the blood by enhancing peripheral clearance might reduce Aß levels in the brain: the 'sink effect'. We tested this hypothesis by intraperitoneally injecting APP/PS1 transgenic mice with small unilamellar vesicles containing either phosphatidic acid or cardiolipin over 3weeks. This treatment reduced significantly the amount of Aß in the plasma and the brain levels of Aß were lighter affected. Nevertheless, this dosing regimen did modulate tau phosphorylation and glycogen synthase kinase 3 activities in the brain, suggesting that the targeting of circulating Aß may be therapeutically relevant in AD. FROM THE CLINICAL EDITOR: Intraperitoneal injection of small unilamellar vesicles containing phosphatidic acid or cardiolipin significantly reduced the amount of amyloid-beta (Aß) peptide in the plasma in a rodent model. Brain levels of Aß were also affected - although to a lesser extent - suggesting that targeting of circulating Aß may be therapeutically relevant of Alzheimer's disease.

Lycopene attenuates insulin signaling deficits, oxidative stress, neuroinflammation, and cognitive impairment in fructose-drinking insulin resistant rats.

Fructose intake is linked with the increasing prevalence of insulin resistance, and insulin resistance links Alzheimer's disease with impaired insulin signaling, oxidative damage, neuroinflammation, and cognitive impairment. As a member of the carotenoid family of phytochemicals, lycopene is used as a potent free scavenger, and has been demonstrated to be effective in anti-oxidative stress and anti-inflammatory reaction in the models of AD and other neurodegenerative diseases. Here, we investigated the effect of lycopene on learning and memory impairment and the possible underlying molecular events in fructose-drinking insulin resistant rats. We found that long-term fructose-drinking causes insulin resistance, impaired insulin signaling, oxidative stress, neuroinflammation, down-regulated activity of cholinergic system, and cognitive impairment, which could be significantly ameliorated by oral lycopene administration. The results from this study provide experimental evidence for using lycopene in the treatment of brain damage caused by fructose-drinking insulin resistance.

mTor is a signaling hub in cell survival: a mass-spectrometry-based proteomics investigation.

mTor plays a central role in controlling protein homeostasis and cell survival. Recently, we have demonstrated that perturbations of mTor signaling are implicated in Alzheimer's disease (AD) and that mTor complex 1 (mTorC1) is involved in the formation of toxic phospho-tau. Therefore, we employed mass-spectrometry-based proteomics to identify specific protein expression changes in relation with cell survival in human neuroblastoma SH-SY5Y cells expressing genetically modified mTor. Cell death in SH-SY5Y cells was induced by moderate serum deprivation. Using flow cytometry we observed that up-regulated mTor complex 2 (mTorC2) increases the number of viable cells. By using a combination approach of proteomic and enrichment analysis we have identified several proteins (Thioredoxin-dependent peroxide reductase, Peroxiredoxin-5, Cofilin 1 (non-muscle), Annexin A5, Mortalin, and 14-3-3 protein zeta/delta) involved in mitochondrial integrity, apoptotosis, and pro-survival functions (caspase inhibitor activity and anti-apoptosis) that were significantly altered by mTor activity modulation. The major findings of this study are the implication of mTorC2 but not mTorC1 in cell viability modulation by activating the pro-survival machinery. Taken together, these results suggest that up-regulated mTorC2 might be playing an important role in promoting cell survival by suppressing the mitochondria-caspase-apoptotic pathway in vitro.

Dementia studies in Chinese populations.

Variations in the prevalence of dementia in different ethnic groups have been reported worldwide, and a number of reviews have provided a picture of epidemiological studies in dementia research. However, little is known about epidemiological studies in Chinese populations. In this review, we searched PubMed and the Web of Science for original research articles published in English up to July 2013 on the prevalence, incidence, risk factors, and prognosis of dementia in Chinese populations worldwide. Except for the prevalence, we included only population-based follow-up studies. We identified 25 studies in elderly Chinese residents in Mainland China, Hong Kong, Taiwan, and Singapore, and found a higher prevalence of dementia in Mainland China than in the other locations, which may be due to that the studies from Mainland China are more recent than those from other locations. A notable increase in incidence was observed when dementia cases were diagnosed using 10/66 diagnostic criteria compared to other criteria. Studies on risk factors for dementia were limited and mostly from Mainland China. Age, gender, education, smoking, and alcohol consumption were related to the risk of dementia in Chinese populations. Only two prognostic studies were identified, and age, gender, and residential area were related to the prognosis of dementia. In conclusion, the prevalence, incidence, and risk factors for dementia found in Chinese populations were comparable to other ethnic groups, but no conclusive results on prognosis were found. The differences in prevalence and incidence were influenced by the diagnostic criteria and the time of study. Longitudinal population-based studies on the incidence, risk factors, and prognosis of dementia in Chinese populations are required.

Dysregulated mTOR-dependent signaling in neurodegeneration or carcinogenesis: implication for Alzheimer's disease and brain tumors.

Recent evidence implicated aberrant mammalian target of rapamycin (mTOR)-dependent signaling in both Alzheimer's disease (AD) and brain tumors. This review focuses on the potential mechanisms shared by both neurodegeneration and carcinogenesis. In particular, attention was paid to the possible roles of mTOR-dependent signaling in these two fundamental pathophysiological processes. We hypothesize that common stresses could lead either to progressive degeneration or uncontrolled carcinogenesis via cell type specific upregulation of mTOR-dependent signaling in the central nervous system while mTOR-mediated carcinogenesis might permit glial cells to escape from degeneration.