The aetiology of Alzheimer's disease (AD) is believed to involve environmental exposure and genetic susceptibility. The aim of our present systematic review and meta-analysis was to roundly evaluate ...the association between AD and its modifiable risk factors.
We systematically searched PubMed and the Cochrane Database of Systematic Reviews from inception to July 2014, and the references of retrieved relevant articles. We included prospective cohort studies and retrospective case-control studies.
16,906 articles were identified of which 323 with 93 factors met the inclusion criteria for meta-analysis. Among factors with relatively strong evidence (pooled population >5000) in our meta-analysis, we found grade I evidence for 4 medical exposures (oestrogen, statin, antihypertensive medications and non-steroidal anti-inflammatory drugs therapy) as well as 4 dietary exposures (folate, vitamin E/C and coffee) as protective factors of AD. We found grade I evidence showing that one biochemical exposure (hyperhomocysteine) and one psychological condition (depression) significantly increase risk of developing AD. We also found grade I evidence indicative of complex roles of pre-existing disease (frailty, carotid atherosclerosis, hypertension, low diastolic blood pressure, type 2 diabetes mellitus (Asian population) increasing risk whereas history of arthritis, heart disease, metabolic syndrome and cancer decreasing risk) and lifestyle (low education, high body mass index (BMI) in mid-life and low BMI increasing the risk whereas cognitive activity, current smoking (Western population), light-to-moderate drinking, stress, high BMI in late-life decreasing the risk) in influencing AD risk. We identified no evidence suggestive of significant association with occupational exposures.
Effective interventions in diet, medications, biochemical exposures, psychological condition, pre-existing disease and lifestyle may decrease new incidence of AD.
Abstract Background Neuropsychiatric symptoms (NPS) are being increasingly recognized as common serious problems in Alzheimer’s disease (AD). However, published data on the prevalence of NPS in ...persons with AD are conflicting. This meta-analysis aimed to estimate the prevalence of NPS in persons with AD. Methods Studies published from 1964 to September 30, 2014, were identified from PubMed and Embase database, reference lists and conference abstracts. We calculated prevalence rates and conducted meta-regression analysis with random-effects model, according to study characteristics, population demographics or condition information. Results We identified 48 eligible articles, which provided data for 12 NPS reported in Neuropsychiatric Inventory (NPI). The most frequent NPS was apathy, with an overall prevalence of 49% (95% CI 41–57%), followed by depression, aggression, anxiety and sleep disorder, the pooled prevalence estimates of which were 42% (95% CI 37–46%), 40% (95% CI 33–46%), 39% (95% CI 32–46%) and 39% (95% CI 30–47%), respectively. The less prevalent NPS were irritability (36%, 31–41%), appetite disorder (34%, 27–41%), aberrant motor behavior (32%, 25–38%), delusion (31%, 27–35%), disinhibition (17%, 12–21%) and hallucination (16%, 13–18%). Least common was euphoria, with an overall prevalence of 7% (95% CI 5–9%). Limitations Several aspects, such as the quality of included studies were not always optimal and there was significant heterogeneity of prevalence estimate across studies. Conclusions NPS were observed to be highly prevalent in AD patients. Disease duration, age, education level, population origin and the severity of cognitive impairment had influence on the prevalence of some NPS.
We sought to identify the risk factors for predicting the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD).
We searched 6 electronic databases for cohort studies published ...from January 1966 to March 2015. Eligible studies were required to be relevant to the subject and provide sufficient data for our needs.
60 cohort studies with 14,821 participants from 16 countries were included in the meta-analysis. The strongest positive associations between risk factors and the progression from MCI to AD were found for abnormal cerebrospinal fluid (CSF), phosphorylated τ (p-τ) (relative risk (RR)=2.43, 95% CI=1.70 to 3.48), abnormal CSF τ/Aβ1-42 (RR=3.77, 95% CI=2.34 to 6.09), hippocampal atrophy (RR=2.59, 95% CI=1.95 to 3.44), medial temporal lobe atrophy (RR=2.11, 95% CI=1.70 to 2.63) and entorhinal atrophy (RR=2.03, 95% CI=1.57 to 2.62). Further positive associations were found for the presence of apolipoprotein E (APOE)ε4ε4 and at least 1 APOEε4 allele, CSF total-τ (t-τ), white matter hyperintensity volume, depression, diabetes, hypertension, older age, female gender, lower mini-mental state examination (MMSE) score and higher AD assessment scale cognitive subscale (ADAS-cog) score. Negative associations were found for high body mass index (RR=0.85, 95% CI=0.76 to 0.96) and higher auditory verbal learning test delay score (RR=0.86, 95% CI=0.77 to 0.96).
Patients with MCI with APOEε4, abnormal CSF τ level, hippocampal and medial temporal lobe atrophy, entorhinal atrophy, depression, diabetes, hypertension, older age, female gender, lower MMSE score and higher ADAS-cog score, had a high risk for the progression to AD.
Supplying exogenous sulfur-rich compounds increases the content of glutathione(GSH) and phytochelatins(PCs) in plant tissues, enabling plants to enhance their cellular defense capacity and/or ...compartmentalize Cadmium(Cd) into vacuoles. However, the mechanism by which surplus S modulates tolerance to Cd stress in different tissues need further investigation. In the present study, we found that supplementing the tartary buckwheat(Fagopyrum tararicum) exposed to Cd with surplus S reversed Cd induced adverse effects, and increased Cd concentrations in roots, but decreased in leaves. Further analysis revealed that exogenous S significantly mitigated Cd-induced oxidative stress with the aids of antioxidant enzymes and agents both in leaves and roots, including peroxidase(POD), ascorbate peroxidase(APX), glutathione peroxidase(GPX), glutathione S-transferase(GST), ascorbic acid(AsA), and GSH, but not superoxide dismutase(SOD) and catalase(CAT). The increased Cd uptake in root vacuoles and decreased translocation in leaves of exogenous S treated plants could be ascribed to the increasing Cd binding on cell walls, chelation and vacuolar sequestration with helps of non-protein thiols(NPT), PCs and heavy metal ATPase 3(FtHMA3) in roots, and inhibiting expression of FtHMA2, a transporter that helps Cd translocation from roots to shoots. Results provide the fundamental information for the application of exogenous S in reversal of heavy metal stress.
•Sesamin (Ses) prevented CCl4-induced liver injury.•Ses inhibited CCl4-induced liver dysfunction and histopathologic changes.•Ses inhibited oxidative stress and apoptosis in liver of CCl4 treated ...mice by JNK pathway.
Sesamin (Ses), one of the major lignan derived from sesame seeds, has been reported to have many benefits and medicinal properties. However, its protective effects against carbon tetrachloride (CCl4) induced injury in liver have not been clarified. The aim of the present study was to investigate the hepatoprotective effects of sesamin on oxidative stress and apoptosis in mice exposed to CCl4. Our data showed that sesamin significantly prevented CCl4-induced hepatotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of liver damage (serum aminotransferase activities) and histopathological analysis. Moreover, CCl4-induced profound elevation of reactive oxygen species (ROS) production and oxidative stress, as evidenced by increasing of lipid peroxidation level and depleting of the total antioxidant capacity (TAC) in liver, were suppressed by treatment with sesamin. Furthermore, TUNEL assay showed that CCl4-induced apoptosis in mouse liver was significantly inhibited by sesamin. In exploring the underlying mechanisms of sesamin action, we found that activities of caspase-3 were markedly inhibited by the treatment of sesamin in the liver of CCl4 treated mice. Sesamin increased expression levels of phosphorylated Jun N-terminal kinases (JNK) in liver, which in turn inactivated pro-apoptotic signaling events restoring the balance between mitochondrial pro- and anti-apoptotic Bcl-2 proteins and decreasing the release of mitochondrial cytochrome c in liver of CCl4 treated mice. JNK was also involved in the mitochondrial extrinsic apoptotic pathways of sesamin effects against CCl4 induced liver injury by regulating the expression levels of phosphorylated c-Jun proteins, necrosis factor-alpha (TNF-α) and Bak. In conclusion, these results suggested that the inhibition of CCl4-induced apoptosis by sesamin is due at least in part to its anti-oxidant activity and its ability to modulate the JNK signaling pathway.
Poly(vinylidenefluoride-
co
-hexafluoropropylene) (P(VDF-HFP))/Li
1.3
Al
0.3
Ti
1.7
(PO
4
)
3
(LATP)/P(VDF-HFP) sandwiched hybrid solid electrolytes were precisely tailored and successfully ...fabricated to assemble into all-solid-state lithium-ion batteries, which were systematically evaluated on microstructure, morphology, thermal stability and electrochemical performance. The sandwiched hybrid solid electrolytes can achieve intimate contact with cathode and anode electrodes to present an excellent interfacial stability. Furthermore, the sandwiched hybrid solid electrolytes possess flexible surface, wide electrochemical working window of 4.7 V, high ionic conductivity of 0.763 mS·cm
−1
and high thermal stability of 460 °C, which may contribute to realizing the practical application in all-solid-state lithium-ion batteries. The assembled cells with the hybrid solid electrolytes can quickly stabilize at a specific discharge capacity of 145.4 mAh·g
−1
at 0.1C after only 5 cycles and present admirable rate performance. In addition, morphology characterizations of the sandwiched hybrid solid electrolytes after long-term cycles show a relatively integrated structure coating with a compact LATP layer. The investigations afford a promising strategy that the sandwiched hybrid solid electrolytes can overcome the mechanical limitations of the interface between electrodes and inorganic solid electrolytes to provide favorable properties for all-solid-state lithium-ion batteries.
Graphic abstract
Educational level has been regarded as one of the most widely accepted risk factors in the epidemiological studies for dementia, despite with discordant qualitative results. However, the ...dose-response relation between education and incident dementia was still unknown. To quantitatively evaluate the association between exposure level to high and low education and risk of dementia, we searched PubMed, EMBASE, and the Cochrane Library up to November 2014 and references of retrieved literatures. Specific prospective cohort studies, in which educational attainment was categorized into at least three levels, were included. Newcastle-Ottawa scale was used to assess the quality of included studies. Fifteen prospective cohort studies with 55655 for low education and eight prospective cohort studies with 20172 for high education were included. In the qualitative analysis, both low and high education showed a dose-response trend with risk of dementia and Alzheimer’s disease (AD). In the quantitative analysis, the dementia risk was reduced by 7 % for per year increase in education (RR, 0.93; 95 % CI, 0.92–0.94;
p
for overall trend = 0.000;
p
for nonlinearity = 0.0643). Nonetheless, we did not find statistically significant association between per year decrease in education and dementia (RR, 1.03; 95 % CI, 0.96–1.10;
p
for overall trend = 0.283;
p
for nonlinearity = 0.0041) or AD (RR, 1.03; 95 % CI, 0.97–1.10;
p
for overall trend = 0.357;
p
for nonlinearity = 0.0022). Both low and high education showed a trend of dose-response relation with risk of dementia and AD. The dementia risk was reduced by 7 % for per year increase in education.
Parkinson's disease (PD), like many common age-related conditions, has been recognized to have a substantial genetic component. Multiple lines of evidence suggest that Leucine-rich repeat kinase 2 ...(LRRK2) is a crucial factor to understanding the etiology of PD. LRRK2 is a large, widely expressed, multi-domain and multifunctional protein. LRRK2 mutations are the major cause to inherited and sporadic PD. In this review, we discuss the pathology and clinical features which show diversity and variability of LRRK2-associated PD. In addition, we do a thorough literature review and provide theoretical data for gene counseling. Further, we present the evidence linking LRRK2 to various possible pathogenic mechanism of PD such as α-synuclein, tau, inflammatory response, oxidative stress, mitochondrial dysfunction, synaptic dysfunction as well as autophagy-lysosomal system. Based on the above work, we investigate activities both within GTPase and outside enzymatic regions in order to obtain a potential therapeutic approach to solve the LRRK2 problem.
Autophagy, a conserved cellular degradation and recycling process, can be enhanced by nutrient depletion, oxidative stress or other harmful conditions to maintain cell survival. ...6-Hydroxydopamine/ascorbic acid (6-OHDA/AA) is commonly used to induce experimental Parkinson's disease (PD) lesions by causing oxidative damage to dopaminergic neurons. Activation of autophagy has been observed in the 6-OHDA-induced PD models. However, the mechanism and exact role of autophagy activation in 6-OHDA PD model remain inconclusive. In this study, we report that autophagy was triggered via mucolipin 1/calcium/calcineurin/TFEB (transcription factor EB) pathway upon oxidative stress induced by 6-OHDA/AA. Interestingly, overexpression of TFEB alleviated 6-OHDA/AA toxicity. Moreover, autophagy enhancers, Torin1 (an mTOR-dependent TFEB/autophagy enhancer) and curcumin analog C1 (a TFEB-dependent and mTOR-independent autophagy enhancer), significantly rescued 6-OHDA/AA-induced cell death in SH-SY5Y cells, iPSC-derived DA neurons and mice nigral DA neurons. The behavioral abnormality of 6-OHDA/AA-treated mice can also be rescued by Torin 1 or C1 administration. The protective effects of Torin 1 and C1 can be blocked by autophagy inhibitors like chloroquine (CQ) or by knocking down autophagy-related genes TFEB and ATG5. Taken together, this study supports that TFEB-mediated autophagy is a survival mechanism during oxidative stress and pharmacological enhancement of this process is a neuroprotective strategy against oxidative stress-associated PD lesions.
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