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Environmental Research Jun 2024Ozone pollution is increasingly recognized as a serious environmental threat that exacerbates dementia risks, including Alzheimer's Disease (AD) and Mild Cognitive...
Ozone pollution is increasingly recognized as a serious environmental threat that exacerbates dementia risks, including Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI). Amid rapid industrialization, China faces significant air quality challenges. However, there has been a scarcity of detailed studies assessing the health and economic impacts of ozone pollution on these conditions. This study aims to address this gap by utilizing the BenMap-CE tool and incorporating parameters obtained from systematic reviews of epidemiologic studies, official statistics, and weighted averages, to accurately quantify the effects of ozone exposure in China. This research evaluated the health and economic burdens at both national and provincial levels, focusing on the additional impacts attributed to increased ozone levels. The results reveal that in 2023, compared to 2015, ozone pollution contributed to approximately 110,000 new cases (5.6 per 10,000) of AD and 1.6 million new cases (81.7 per 10,000) of MCI, imposing significant economic costs of about 1,200 million USD for AD and 18,000 million USD for MCI, based on 2015 dollar values. Additionally, our projections indicate that reducing the 2023 ozone concentrations to 70 μg/m could significantly curb these conditions, potentially preventing over 210,000 new AD cases (10.7 per 10,000) and 2.9 million (148.1 per 10,000) MCI cases. Such reductions are projected to yield substantial economic benefits, estimated at 2,200 million USD for AD and 34,000 million USD for MCI (2015 dollar values). These findings underscore the profound implications of ozone pollution on public health and the economy in China, highlighting the urgent need for effective ozone management strategies to mitigate these impacts.
PubMed: 38944103
DOI: 10.1016/j.envres.2024.119506 -
International Journal of Biological... Jun 2024BACE1, a crucial enzyme in the amyloid-β deposition theory of Alzheimer's disease (AD), is targeted by Codonopsis pilosula, a traditional tonic believed to impede AD...
BACE1, a crucial enzyme in the amyloid-β deposition theory of Alzheimer's disease (AD), is targeted by Codonopsis pilosula, a traditional tonic believed to impede AD onset. However, the specific active compounds responsible for its effects remain elusive. Our prior network pharmacology research identified C. pilosula polysaccharides (CPPS) and Lobetyolin may serve as potential inhibitors of AD by suppressing amyloidogenesis. Here, we recombinantly expressed BACE1 under varied conditions and assessed its activity using Fluorescence Resonance Energy Transfer technology. Through spectroscopy, molecular docking, and dynamics, we elucidated the interactions of CPPS, Lobetyolin, and BACE1. Optimal BACE1 expression occurred at 22 °C with 0.4 mM IPTG for 6 h, yielding a 72 kDa protein. Enzyme kinetics displayed a maximum rate of 4096 μmol/min and a Michaelis constant of 16 mg/mL for BACE1. Spectroscopic analysis revealed differing binding affinities of the compounds at various temperatures, peaking at 293 K. Lobetyolin exhibited superior binding to BACE1 compared to CPPS, driven by hydrophobic and electrostatic forces. Molecular docking and dynamics highlighted hydrophobic amino acids' role in BACE1 interactions with Lobetyolin and CPPS, with binding energy < -1.2 kcal/mol signifying strong affinities. Notably, Lobetyolin and CPPS showed higher BACE1 affinity than APP, with the Lobetyolin-BACE1 complex being the most stable.
PubMed: 38944075
DOI: 10.1016/j.ijbiomac.2024.133440 -
Clinical Neurology and Neurosurgery Jun 2024Parkinson's disease (PD) is the second most prevalent neurodegenerative condition after Alzheimer's disease and it represents one of the fastest emerging neurological... (Review)
Review
Parkinson's disease (PD) is the second most prevalent neurodegenerative condition after Alzheimer's disease and it represents one of the fastest emerging neurological diseases worldwide. PD is usually diagnosed after the third decade of life with symptoms like tremors at rest and muscle stiffness. Rapid Eye Movement sleep behavioral disorder (RBD) is another disorder that is caused by a loss of typical muscle relaxation during sleep with a lot of motor activity. Usually, RBD is strongly associated with PD. Recent studies have demonstrated that PD reduces the life expectancy of patients to 10 and 20 years after being diagnosed. In addition, delayed diagnosis and treatment of these neurological disorders have significant socio-economic impacts on patients, their partners and on the general public. Often, it is not clear about PD associated financial burdens both in low and high-income countries. On the other hand, PD triggers neurological variations that affect differences in the dopamine transporter (DAT) and in glucose metabolism. Therefore, positron emission tomography (PET) using specific DAT radiotracers and fluorine-18 labeled desoxyglucose (FDG) has being considered a key imaging technique that could be applied clinically for the very early diagnosis of RBD and in PD. However, a few myths about PET is that it is very expensive. Here, we looked at the cost of treatment of PD and RBD in relation to early PET imaging. Our finding suggests that PET imaging might also be a cost sparing diagnostic option in the management of patients with PD and RBD, not only for first world countries as it is the case now but also for the third world countries. Therefore, PET is a cost-effective imaging technique for very early diagnostic of RBD and PD.
PubMed: 38944021
DOI: 10.1016/j.clineuro.2024.108404 -
Ecotoxicology and Environmental Safety Jun 2024Millions of adults and children are exposed to high levels of lead, a neurotoxicant, each year. Recent evidence suggests that lead exposure may precipitate...
Millions of adults and children are exposed to high levels of lead, a neurotoxicant, each year. Recent evidence suggests that lead exposure may precipitate neurodegeneration, particularly if the exposure occurs early or late in life, with unique alterations to the structure or function of specific subfields of the hippocampus, a region involved in memory and Alzheimer's disease. It has been proposed that specific hippocampal subfields may thus be useful biomarkers for lead-associated neurological disease. We turned to a population-representative New Zealand birth cohort where the extent of lead exposure was not confounded by social class (the Dunedin Study; born 1972-1973 and followed to age 45) to test the hypothesis that early life lead exposure (blood-lead level at age 11 years) is associated with smaller MRI-assessed gray matter volumes of specific subfields of the hippocampus at age 45 years. Among the 508 Dunedin Study members with childhood lead data and adult MRI data passing quality control (93.9 % of those with lead data who attended the age-45 assessment wave, 240[47.2 %] female), childhood blood-lead levels ranged from 4 to 31 µg/dL (M[SD]=10.9[4.6]). Total hippocampal volumes were lower among adults with higher childhood blood-lead levels (b=-102.6 mm per 5 ug/dL-unit greater blood-lead level, 95 %CI: -175.4 to -29.7, p=.006, β=-.11), as were all volumes of the 24 hemisphere-specific subfields of the hippocampus. Of these 24 subfields, 20 demonstrated negative lead-associations greater than β=-.05 in size, 14 were statistically significant after adjustment for multiple comparisons (p<.05), and 9 remained significant after adjustment for potential confounders and multiple comparisons. Children exposed to lead demonstrate smaller volumes across all subfields of the hippocampus in midlife. The hypothesis that lead selectively impairs specific subfields of the hippocampus, or that specific subfields may be markers for lead-associated neurological disease, requires further evaluation.
PubMed: 38944006
DOI: 10.1016/j.ecoenv.2024.116658 -
The Journal of Nutrition, Health & Aging Jun 2024Ketogenic diets (KD) have shown remarkable effects in many disease areas. It has been demonstrated in numerous animal experiments that KD is effective in the treatment... (Review)
Review
BACKGROUND
Ketogenic diets (KD) have shown remarkable effects in many disease areas. It has been demonstrated in numerous animal experiments that KD is effective in the treatment of Alzheimer's disease (AD). But the clinical effect of treating AD is uncertain.
OBJECTIVE
To systematically review the impact of KD on cognitive function in AD.
METHODS
We conducted a search of three international databases-PubMed, Cochrane Library, and Embase-to retrieve RCTs on the KD intervention for AD from the inception of the databases through October 2023. Two reviewers searched and screened the literature, extracted and checked relevant data independently, and assessed the risk of bias of the included studies. The meta-analysis was carried out utilizing RevMan 5.3 software.
RESULTS
A total of 10 RCTS involving 691 patients with AD were included. There were 357 participants in the intervention group and 334 participants in the control group. The duration of the KD intervention ranged from a minimum of 3 months to a maximum of 15 months. Meta-analysis results showed that KD could effectively improve the mental state of the elderly (NM scale) [MD = 7.56, 95%CI (3.02, 12.10), P = 0.001], MMSE [MD = 1.25, 95%CI (0.46, 2.04), P = 0.002], and ADAS-Cog [MD = -3.43, 95%CI (-5.98, -0.88), P = 0.008]. The elevation of ketone body (β-hydroxybutyric) [MD = 118.84, 95%CI (15.20, 222.48), P = 0.02] may also lead to the elevation of triglyceride [MD = 0.19, 95%CI (0.03, 0.35), P = 0.02] and low density lipoprotein [MD = 0.31, 95%CI (0.04, 0.58), P = 0.02].
CONCLUSION
Research conducted has indicated that the KD can enhance the mental state and cognitive function of those with AD, albeit potentially leading to an elevation in blood lipid levels. In summary, the good intervention effect and safety of KD are worthy of promotion and application in clinical treatment of AD.
PubMed: 38943982
DOI: 10.1016/j.jnha.2024.100306 -
Journal of Inorganic Biochemistry Jun 2024The dyshomeostasis of metal ions in the brain leads to the accumulation of excess metals in extracellular and inter-neuronal locations and the Amyloid β peptide (Aβ)...
The dyshomeostasis of metal ions in the brain leads to the accumulation of excess metals in extracellular and inter-neuronal locations and the Amyloid β peptide (Aβ) binds these transition metals, which ultimately cause the Aβ aggregation and severe oxidative stress in the brain. The aggregation of Aβ and oxidative stress are important factors to trigger Alzheimer's disease (AD). Metal chelation therapy is a promising approach to removing metals from Aβ-M species and relieve the oxidative stress. Therefore, 4 tetrahydrosalens containing benzothiazole moiety were designed and synthesized. Their biological activities for Alzheimer's disease therapy in vitro were determined by Turbidity assay, BCA protein assay, MTT assay and fluorescent probe of DCFH-DA. The results were comparing with that of non-specific chelator (cliquinol, CQ) and non-benzothiazole functionalized tetrahydrosalens, the results demonstrated that benzothiazole functionalized chelators had more efficient bio-activities in preventing Cu-induced Aβ aggregation, attenuating cytotoxicity mediated by Aβ-Cu species and decrease the level of reactive oxygen species (ROS) in Cu-Aβ treated PC12 cells than that of cliquinol and non-benzothiazole functionalized analogues.
PubMed: 38943843
DOI: 10.1016/j.jinorgbio.2024.112636 -
American Journal of Industrial Medicine Jun 2024Posttraumatic stress disorder (PTSD) symptomatology and poorer pulmonary function are highly prevalent psychiatric and medical conditions. In the present study, we...
BACKGROUND
Posttraumatic stress disorder (PTSD) symptomatology and poorer pulmonary function are highly prevalent psychiatric and medical conditions. In the present study, we tested for the individual, additive, and modifying associations of PTSD symptomatology and pulmonary function with cognitive performance.
METHODS
In this cross-sectional study, a total of 1,401 World Trade Center (WTC) responders (mean age = 53, SD = 8 years, 92% males) participated in the study. Cogstate assessment measured cognitive performance. PTSD symptomatology was measured using the trauma-specific version of the posttraumatic stress disorder checklist (PCL-17) adapted for the WTC attacks. The 1-second forced expiratory volume and forced vital capacity (FEV1/FVC) ratio was used to measure pulmonary function. Linear regressions with cognitive performance as the outcome were conducted to assess individual, additive, and moderating associations of PTSD symptomatology and pulmonary function.
RESULTS
Higher PTSD symptomatology and poorer pulmonary function were negatively associated with cognitive performance. A 10% increase on the FEV1/FVC ratio moderated the association between PTSD symptomatology and cognition, whereby its association with cognition was stronger when PTSD symptomatology was higher (est. = 0.01, 95%CI = 0.004, 0.01, p < 0.001). When stratified by responder type, these associations persisted in trained (est. = 0.01, 95%CI = 0.01, 0.02, p < 0.001), but not in non-trained (est. = 0.004, 95% C.I. = -0.01, 0.02, p = 0.39) responders.
CONCLUSIONS
In the presence of higher PTSD, better pulmonary functioning is associated with better cognitive performance. Early intervention efforts to mitigate preventable cognitive decline in high-risk populations should be studied, especially since intervention in one modality may have an impact on others.
PubMed: 38943489
DOI: 10.1002/ajim.23631 -
Sleep Jun 2024The association between snoring, a very common condition that increases with age, and dementia risk is controversial. We aimed to investigate the observational and...
STUDY OBJECTIVES
The association between snoring, a very common condition that increases with age, and dementia risk is controversial. We aimed to investigate the observational and causal relationship between snoring and dementia, and to elucidate the role of body mass index (BMI).
METHODS
Using data from 451,250 participants who were dementia-free at baseline, we examined the association between self-reported snoring and incident dementia using Cox proportional-hazards models. Causal relationship between snoring and Alzheimer's disease (AD) was examined using bidirectional two-sample Mendelian randomization (MR) analysis.
RESULTS
During a median follow-up of 13.6 years, 8,325 individuals developed dementia. Snoring was associated with a lower risk of all-cause dementia (hazard ratio [HR] 0.93; 95% confidence interval [CI] 0.89 to 0.98) and AD (HR 0.91; 95% CI 0.84 to 0.97). The association was slightly attenuated after adjusting for BMI, and was stronger in older individuals, APOE ε4 allele carriers, and during shorter follow-up periods. MR analyses suggested no causal effect of snoring on AD, however, genetic liability to AD was associated with a lower risk of snoring. Multivariable MR indicated that the effect of AD on snoring was primarily driven by BMI.
CONCLUSIONS
The phenotypic association between snoring and lower dementia risk likely stems from reverse causation, with genetic predisposition to AD associated with reduced snoring. This may be driven by weight loss in prodromal AD. Increased attention should be paid to reduced snoring and weight loss in older adults as potential early indicators of dementia risk.
PubMed: 38943476
DOI: 10.1093/sleep/zsae149 -
Journal of Alzheimer's Disease : JAD Jun 2024
PubMed: 38943404
DOI: 10.3233/JAD-249011 -
Journal of Alzheimer's Disease : JAD Jun 2024This commentary critically examines the long-standing emphasis on amyloid-β (Aβ)-based therapies in Alzheimer's disease (AD), despite numerous clinical trial failures....
This commentary critically examines the long-standing emphasis on amyloid-β (Aβ)-based therapies in Alzheimer's disease (AD), despite numerous clinical trial failures. It highlights the urgency to reassess research methodologies and challenges the initiation of anti-Aβ trials in preclinical stages of the disease without conclusive proofs of their safety and efficacy. Instead, a comprehensive approach that considers Aβ's physiological roles and addresses AD complex nature is suggested, encouraging the idea that clinical trial failures may result from targeting the wrong mechanism. Evidence-based scientific research is needed to advance with AD treatment, moving beyond the current conception of Aβ hypothesis.
PubMed: 38943395
DOI: 10.3233/JAD-240406