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.
To investigate the association of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) with post-thrombolysis early neurological outcomes ...including early neurological improvement (ENI) and early neurological deterioration (END) in patients with acute ischemic stroke (AIS).
AIS patients undergoing intravenous thrombolysis were enrolled from April 2016 to September 2019. Blood cell counts were sampled before thrombolysis. Post-thrombolysis END was defined as the National Institutes of Health Stroke Scale (NIHSS) score increase of ≥ 4 within 24 h after thrombolysis. Post-thrombolysis ENI was defined as NIHSS score decrease of ≥ 4 or complete recovery within 24 h. Multinomial logistic regression analysis was performed to explore the relationship of NLR, PLR, and LMR to post-thrombolysis END and ENI. We also used receiver operating characteristic curve analysis to assess the discriminative ability of three ratios in predicting END and ENI.
Among 1060 recruited patients, a total of 193 (18.2%) were diagnosed with END and 398 (37.5%) were diagnosed with ENI. Multinomial logistic model indicated that NLR (odds ratio OR, 1.385; 95% confidence interval CI 1.238-1.551, P = 0.001), PLR (OR, 1.013; 95% CI 1.009-1.016, P = 0.001), and LMR (OR, 0.680; 95% CI 0.560-0.825, P = 0.001) were independent factors for post-thrombolysis END. Moreover, NLR (OR, 0.713; 95% CI 0.643-0.791, P = 0.001) served as an independent factor for post-thrombolysis ENI. Area under curve (AUC) of NLR, PLR, and LMR to discriminate END were 0.763, 0.703, and 0.551, respectively. AUC of NLR, PLR, and LMR to discriminate ENI were 0.695, 0.530, and 0.547, respectively.
NLR, PLR, and LMR were associated with post-thrombolysis END. NLR and PLR may predict post-thrombolysis END. NLR was related to post-thrombolysis ENI.
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.
Abstract
Carbapenemase-producing E. coli is a grave public health concern as the potential emergence of resistant strains and their transmission. Isoorientin belongs to a potential antimicrobial ...flavonoid compound existing in several plants, while the research on the antimicrobial activity of isoorientin is limited thus far. We evaluated the antimicrobial and antibiofilm effects of isoorientin against biofilm-forming carbapenem non-sensitive Escherichia coli (E. coli) from raw milk of goats, and explored its molecular mechanisms. Isoorientin showed obvious antimicrobial ability with the minimum inhibitory concentration (MIC), and it exhibited synergistic activity with traditional antimicrobials against the carbapenem non-sensitive E. coli. Isoorientin could also significantly inhibit the carbapenem non-sensitive E. coli biofilm formation and destroy the established biofilms, with the percentage of inhibition ranging from 27.8% to 75% at MIC, and the corresponding percentage of eradication ranging from 15.3% to 61.6%, respectively. Confocal laser scanning microscopy (CLSM) observation and scanning electron microscopy (SEM) images indicated that the E. coli biofilm reduced in thickness with increasing concentrations of isoorientin. Dose-dependent decrease in eDNA revealed that isoorientin interacted with the extracellular polymeric substances (EPS) of the biofilm. qRT-PCR assay for the biofilm-forming associated genes further confirmed the above results. Overall, these results concluded that the isoorientin has significant antimicrobial and antibiofilm activity against carbapenem non-sensitive E. coli, and has potential application in prevention of food contamination and spoilage.
This result concluded that isoorientin is a promising biofilm inhibitor for curtailing drug resistant foodborne pathogens, and this study could provide a scientific basis for its practical application of isoorientin.
Lay Summary
Escherichia coli (E. coli) has been the major foodborne bacteria that can cause diarrhea, gastroenteritis, and some complications, and also used as fecal bacteria pollution indicator in food. Carbapenems are considered as the last resort to life-threatening E. coli infections. We evaluated the antimicrobial and antibiofilm effects of isoorientin against biofilm-forming carbapenem non-sensitive E. coli from raw milk of goats, and explored its molecular mechanisms. This study firstly demonstrated the potential antimicrobial and antibiofilm properties of isoorientin against the carbapenem non-sensitive E. coli for the first time, and it has the properties of inhibiting the biofilm formation and destroying the preformed biofilms. Therefore, isoorientin is a promising biofilm inhibitor for curtailing drug resistant foodborne pathogens, and this study could provide a scientific basis for its practical application of isoorientin.
Numbers on branches indicate bootstrap percentages for 1000 replicates. (b) Subcellular localization of MtDMP8-RFP and MtDMP9-RFP proteins in Arabidopsis leaf protoplasts; pm-GFP was used as a plasma ...membrane marker. Consistent with this prediction, both proteins colocalized with the PIP2A (At3g53420)-based plasma membrane marker pm-GFP (Zhu et al., 2020) when MtDMP8 and MtDMP9 were transiently expressed as red fluorescent protein (RFP) fusions in Arabidopsis leaf protoplasts (Figure 1b). The haploid plants were morphologically similar to the female parent A17 (Figure 1k). ...the simultaneous inactivation of MtDMP8 and MtDMP9 can trigger in vivo maternal haploid induction in M. truncatula.
The role of currently available drugs for Alzheimer's disease (AD) has been controversial, with some national formularies restricting their use, and health economists questioning whether the small ...clinical effects are economically worthwhile.
To estimate the efficacy and safety of donepezil, galantamine, rivastigmine, and memantine for the treatment of AD.
Double-blind, placebo-controlled, with random assignment to a cholinesterase inhibitor or memantine trials were included into the pooled studies.
Cognitive effects were significant for all drugs, ranging from a -1.29 points mean difference (95% CI -2.30 to -0.28) in the 20 mg daily memantine trials to -3.20 points (95% CI -3.28 to -3.12) in the 32 mg daily galantamine group. Only memantine had no effect on the Clinicians' Global Impression of Change scale. No behavioral benefits were observed, except for -2.72 (95% CI -4.92 to -0.52) in the 10 mg daily donepezil group and -1.72 (95% CI -3.12 to -0.33) for 24 mg daily galantamine trial. Only 5 mg daily donepezil had no effect on the function outcome. Compared with placebo, more dropouts and adverse events occurred with the cholinesterase inhibitors, but not with memantine.
Cholinesterase inhibitors and memantine are able to stabilize or slow decline in cognition, function, behavior, and global change.
Innate immunity and inflammatory response plays an important role in the pathogenesis of Alzheimer’s disease (AD). As the major resident immune cells in the brain, microglial cells constantly survey ...the microenvironment and are activated by and recruited to senile plaques. Subsequently, they can phagocytose amyloid-β (Aβ) and secrete pro-inflammatory cytokines that influence the surrounding brain tissue. Recently, a wealth of information linking the microglia-specific activation of NLRP3 inflammasome to AD pathogenesis has emerged. We review here the activation mechanisms of NLRP3 inflammasome in microglia and several downstream effects in the brain, demonstrating that toxic Aβ peptide can light a fire in NLRP3 inflammasome and eventually induce AD pathology and tissue damage. More importantly, it has been demonstrated that inhibition of NLRP3 could largely protect from memory loss and decrease Aβ deposition in AD transgenic mouse model. So, we further discuss the recent advances and challenges in targeting NLRP3 inflammasome for AD therapy.
At present, the etiology of Alzheimer's disease (AD) is still unclear, but both genetic and non-genetic factors are thought to take part in the etiopathogenesis of AD. Epidemiologic researches ...revealed that genetic factors played a decisive role in the development of both early-onset AD (EOAD) and late-onset AD (LOAD). The mutations in APP, PSEN1 and PSEN2 are inherited in a Mendelian fashion and directly lead to the EOAD, while recent genome-wide association studies have identified numbers of risky genes, which influences the susceptibility to LOAD. Although genetic factors are inherited and fixed, non-genetic factors, such as occupational exposures (exposure to pesticides, electromagnetic fields, organic solvents and volatile anesthetics), pre-existing medical conditions (cerebrovascular disease, hypertension, diabetes, dyslipidemia, traumatic brain injury, depression and cancer) and lifestyle factors (smoking, consumptions of alcohol and coffee, body mass index, physical activity and cognitive activity), are partly environmentally-determined. Timely interventions targeted at these non-genetic risk factors may offer opportunities for prevention and treatment of AD. In the future, more high-quality and large-sample epidemiologic studies are needed to identify risk factors for AD, and the interaction models between genetic and non-genetic risk factors required further investigation. In addition, public health campaigns targeted at modification of non-genetic risk factors should be developed among population at high risk of AD.
Dietary patterns and some dietary components have been linked with dementia. We therefore performed a meta-analysis of available studies to determine whether there is an association between diet and ...risk of dementia. We included eligible articles and estimated risk ratio (RR) with 95 % confidence intervals (95 % CIs). Finally, there were 43 trials that met the inclusion standard. Some food intake was related with decrease of dementia, such as unsaturated fatty acids (RR: 0.84, 95 % CI: 0.74–0.95,
P
= 0.006), antioxidants (RR: 0.87, 95 % CI: 0.77–0.98,
P
= 0.026), vitamin B (RR: 0.72, 95 % CI: 0.54–0.96,
P
= 0.026), and the Mediterranean diet (MeDi) (RR: 0.69, 95 % CI: 0.57–0.84,
P
< 0.001). Some material intakes were related with increase of dementia, such as aluminum (RR: 2.24, 95 % CI: 1.49–3.37,
P
< 0.001), smoking (RR: 1.43, 95 % CI: 1.15–1.77,
P
= 0.001), and low levels of vitamin D (RR: 1.52, 95 % CI: 1.17–1.98,
P
= 0.002). The effect of some materials needs further investigation, such as fish (RR: 0.79, 95 % CI: 0.59–1.06,
P
= 0.113), vegetables and fruits (RR: 0.46, 95 % CI: 0.16–1.32,
P
= 0.149), and alcohol (RR: 0.74, 95 % CI: 0.55- 1.01,
P
= 0.056). Thus, the MeDi and higher consumption of unsaturated fatty acids, antioxidants, and B vitamins decrease the risk of dementia while smoking and higher consumption of aluminum increase the risk of dementia. Low levels of vitamin D were associated with cognitive decline. The effect of fish, vegetables, fruits, and alcohol needs further investigation. The findings will be of great significance to guide people to prevent dementia.
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