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BMC Neuroscience Jun 2024Diabetes raises the risk of dementia, mortality, and cognitive decline in the elderly, potentially because of hereditary variables such as APOE. In this study, we aim to... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIM
Diabetes raises the risk of dementia, mortality, and cognitive decline in the elderly, potentially because of hereditary variables such as APOE. In this study, we aim to evaluate Diabetes mellitus and the risk of incident dementia in APOE ɛ4 carriers.
METHOD
We thoroughly searched PubMed (Medline), Scopus, and Google Scholar databases for related articles up to September 2023. The titles, abstracts, and full texts of articles were reviewed; data were extracted and analyzed.
RESULT
This meta-analysis included nine cohorts and seven cross-sectional articles with a total of 42,390 population. The study found that APOE ɛ4 carriers with type 2 diabetes (T2D) had a 48% higher risk of developing dementia compared to non-diabetic carriers (Hazard Ratio;1.48, 95%CI1.36-1.60). The frequency of dementia was 3 in 10 people (frequency: 0.3; 95%CI (0.15-0.48). No significant heterogeneity was observed. Egger's test, which we performed, revealed no indication of publication bias among the included articles (p = 0.2).
CONCLUSION
Overall, diabetes increases the risk of dementia, but further large-scale studies are still required to support the results of current research.
Topics: Humans; Dementia; Apolipoprotein E4; Diabetes Mellitus, Type 2; Heterozygote; Risk Factors; Incidence
PubMed: 38918708
DOI: 10.1186/s12868-024-00878-9 -
BioRxiv : the Preprint Server For... Jun 2024The effects of sex, race, and Apolipoprotein E () - Alzheimer's disease (AD) risk factors - on white matter integrity are not well characterized.
INTRODUCTION
The effects of sex, race, and Apolipoprotein E () - Alzheimer's disease (AD) risk factors - on white matter integrity are not well characterized.
METHODS
Diffusion MRI data from nine well-established longitudinal cohorts of aging were free-water (FW)-corrected and harmonized. This dataset included 4,702 participants (age=73.06 ± 9.75) with 9,671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FA) were used to assess differences in white matter microstructure by sex, race, and -ε4 carrier status.
RESULTS
Sex differences in FA in association and projection tracts, racial differences in FA in projection tracts, and -ε4 differences in FW limbic and occipital transcallosal tracts were most pronounced.
DISCUSSION
There are prominent differences in white matter microstructure by sex, race, and -ε4 carrier status. This work adds to our understanding of disparities in AD. Additional work to understand the etiology of these differences is warranted.
PubMed: 38915636
DOI: 10.1101/2024.06.10.598357 -
Clinical Kidney Journal Jun 2024
PubMed: 38915437
DOI: 10.1093/ckj/sfae161 -
International Journal of STD & AIDS Jun 2024We sought to determine the prevalence of sickle cell trait (SCT) and apolipoprotein-1 ( risk variants in people living with HIV (PLWH) in Nigeria, and to establish if...
BACKGROUND
We sought to determine the prevalence of sickle cell trait (SCT) and apolipoprotein-1 ( risk variants in people living with HIV (PLWH) in Nigeria, and to establish if SCT and high-risk status correlate with estimated glomerular filtration rate (eGFR) and/or prevalent chronic kidney disease (CKD).
METHODS
Baseline demographic and clinical data were obtained during three cross-sectional visits. CKD was defined as having an eGFR<60 mL/min/1.73 m. We collected urine specimens to determine urine albumin-creatine ratio and blood samples for sickle cell genotyping, testing, and for creatinine/cystatin C assessment. The associations between SCT, genotype, and eGFR/CKD stages/CKD were investigated using linear/ordinal logistic/logistic regression models, respectively.
RESULTS
Of 2443 participants, 599 (24.5%) had SCT, and 2291 (93.8%) had a low-risk genotype (0 or 1 risk variant), while 152 (6.2%) had high-risk genotype (2 allele copies). In total, 108 participants (4.4%) were diagnosed with CKD. In adjusted analyses, SCT was associated with lower eGFR (adjusted mean difference [aMD]= -2.33, 95% CI -4.25, -0.42), but not with worse CKD stages, or increased odds of developing CKD. Participants with the high risk genotype were more likely to have lower eGFR (aMD= -5.45, 95% CI -8.87, -2.03), to develop CKD (adjusted odds ratio [aOR] = 1.97, 95% CI: 1.03, 3.75), and to be in worse CKD stages (aOR = 1.60, 95% CI: 1.12, 2.29) than those with the low-risk genotype. There was no evidence of interaction between SCT and genotype on eGFR or risk of CKD.
CONCLUSION
Our findings highlight the multifaceted interplay of genetic factors in the pathogenesis of CKD in PLWH.
PubMed: 38915133
DOI: 10.1177/09564624241262397 -
BMC Cardiovascular Disorders Jun 2024This study investigated the possible relationship between the Apo lipoprotein A1 /high-density lipoprotein cholesterol (ApoA1/HDL-C) ratio and coronary artery disease...
INTRODUCTION
This study investigated the possible relationship between the Apo lipoprotein A1 /high-density lipoprotein cholesterol (ApoA1/HDL-C) ratio and coronary artery disease (CAD) in patients with type 2 diabetes (T2D).
METHODS
This was a matched case-control study of 482 patients with T2D in two groups of CAD and (n = 241) non-CAD (n = 241). The patients were classified into four quartiles according to the ApoA1/HDL-C ratio, and multivariate logistic regression analysis was performed to assess the relationship between ApoA1/HDL-C and CAD. ROC analysis was also conducted.
RESULTS
This study showed that the ApoA1/HDL-C ratio has an independent association with CAD in individuals with T2D. The CAD group exhibited a significantly higher ApoA1/HDL-C ratio than those without CAD (p-value = 0.004). Moreover, the risk of CAD increased significantly across the ApoA1/HDL-C ratio quartiles, with the highest odds in the fourth quartile. The second quartile showed an odds ratio (OR) of 2.03 (p-value = 0.048) compared to the first. Moving to the third quartile, the OR increased to 2.23 (p-value = 0.023). The highest OR was noted in the fourth, reaching 3.41 (p-value = 0.001). Employing a cut-off value of 2.66 and an area under the curve (AUC) of 0.885, the ApoA1/HDL-C ratio predicts CAD among patients with T2D with a sensitivity of 75% and a specificity of 91% (p-value < 0.001).
CONCLUSION
The current study revealed an independent association between ApoA1/HDL-C ratio and CAD in patients with T2D. This ratio can be a promising tool for predicting CAD during the follow-up of patients with T2D, aiding in identifying those at higher risk for CAD.
Topics: Humans; Diabetes Mellitus, Type 2; Apolipoprotein A-I; Coronary Artery Disease; Male; Female; Middle Aged; Cholesterol, HDL; Case-Control Studies; Aged; Biomarkers; Predictive Value of Tests; Risk Assessment; Risk Factors; Prognosis
PubMed: 38914982
DOI: 10.1186/s12872-024-03986-w -
Sexually Transmitted Infections Jun 2024The 2022 global outbreak of monkeypox virus (MPXV), previously confined to Central and West Africa, necessitates an enhanced understanding of its spread. Comprehensive...
OBJECTIVES
The 2022 global outbreak of monkeypox virus (MPXV), previously confined to Central and West Africa, necessitates an enhanced understanding of its spread. Comprehensive genomic surveillance to understand the virus's evolution and spread is needed, particularly in Asia.
METHODS
Genomic data from 169 MPXV genome sequences in Asia were analysed. Through advanced genomic sequencing of clinical samples, we analysed the distribution and mutations of MPXV lineages in Asia.
RESULTS
Phylogenetic analysis revealed a distinct clustering of C.1 strains rise in Northeast Asia in 2023, while genomic examination identified specific consensus mutations like R84K, R665C and L16F in C.1 strains. The mutations, coupled with an increased rate of apolipoprotein B mRNA-editing catalytic polypeptide-like 3 motif G-to-A mutations in C.1 (OR 24.87±8.81), indicate a potential adaptation mechanism.
CONCLUSIONS
Our findings underscore the need for ongoing surveillance and provide vital insights into MPXV's evolving dynamics, aiding in public health strategy formulation against this emerging infectious threat.
PubMed: 38914476
DOI: 10.1136/sextrans-2024-056119 -
Ageing Research Reviews Jun 2024Being age-related disorders, both Alzheimer's disease (AD) and stroke share multiple risk factors, such as hypertension, smoking, diabetes, and apolipoprotein E (APOE)... (Review)
Review
Being age-related disorders, both Alzheimer's disease (AD) and stroke share multiple risk factors, such as hypertension, smoking, diabetes, and apolipoprotein E (APOE) Ɛ4 genotype, and coexist in patients. Accumulation of amyloid-β plaques and neurofibrillary tangled impair cognitive potential, leading to AD. Blocked blood flow in the neuronal tissues, causes neurodegeneration and cell death in stroke. AD is commonly characterized by cerebral amyloid angiopathy, which significantly elevates the risk of hemorrhagic stroke. Patients with AD and stroke have been both reported to exhibit greater cognitive impairment, followed by multiple pathophysiological mechanisms shared between the two. The manuscript aims to elucidate the relationship between AD and stroke, as well as the common pathways and risk factors while understanding the preventive therapies that might limit the negative impacts of this correlation, with diagnostic modalities and current AD treatments. The authors provide a comprehensive review of the link and aid the healthcare professionals to identify suitable targets and risk factors, that may retard cognitive decline and neurodegeneration in patients. However, more intricate research is required in this regard and an interdisciplinary approach that would target both the vascular and neurodegenerative factors would improve the quality of life in AD patients.
PubMed: 38914265
DOI: 10.1016/j.arr.2024.102388 -
JAMA Neurology Jun 2024Sleep disturbances are common among older adults and have been associated with the development of Alzheimer disease (AD), such as amyloid-β (Aβ) pathology. For...
IMPORTANCE
Sleep disturbances are common among older adults and have been associated with the development of Alzheimer disease (AD), such as amyloid-β (Aβ) pathology. For effective AD prevention, it is essential to pinpoint the specific disturbances in sleep and the underlying 24-hour activity rhythms that confer the highest risk of Aβ deposition.
OBJECTIVE
To determine the associations of 24-hour activity rhythms and sleep with Aβ deposition in adults without dementia, to evaluate whether disrupted 24-hour activity and sleep may precede Aβ deposition, and to assess the role of the apolipoprotein E ε4 (APOE4) genotype.
DESIGN, SETTING, AND PARTICIPANTS
This was an observational cohort study using data from the Rotterdam Study. Of 639 participants without dementia who underwent Aβ positron emission tomography (PET) from September 2018 to November 2021, 319 were included in the current study. Exclusion criteria were no APOE genotyping and no valid actigraphy data at the baseline visits from 2004 to 2006 or from 2012 to 2014. The mean (SD) follow-up was 7.8 (2.4) years. Data were analyzed from March 2023 to April 2024.
EXPOSURES
Actigraphy (7 days and nights, objective sleep, and 24-hour activity rhythms), sleep diaries (self-reported sleep), Aβ42/40, phosphorylated tau (p-tau)181 and p-tau217 plasma assays, 18F-florbetaben PET (mean standard uptake value ratio [SUVR] in a large cortical region of interest), and APOE4 genotype.
MAIN OUTCOMES AND MEASURES
Association of objective and self-reported sleep and 24-hour activity rhythms at baseline with brain Aβ PET burden at follow-up.
RESULTS
The mean (range) age in the study population was 61.5 (48-80) years at baseline and 69.2 (60-88) years at follow-up; 150 (47%) were women. Higher intradaily variability at baseline, an indicator of fragmented 24-hour activity rhythms, was associated with higher Aβ PET burden at follow-up (β, 0.15; bootstrapped 95% CI, 0.04 to 0.26; bootstrapped P = .02, false discovery rate [FDR] P = .048). APOE genotype modified this association, which was stronger in APOE4 carriers (β, 0.38; bootstrapped 95% CI, 0.05 to 0.64; bootstrapped P = .03) compared to noncarriers (β, 0.07; bootstrapped 95% CI, -0.04 to 0.18; bootstrapped P = .19). The findings remained largely similar after excluding participants with AD pathology at baseline, suggesting that a fragmented 24-hour activity rhythm may have preceded Aβ deposition. No other objective or self-reported measure of sleep was associated with Aβ.
CONCLUSIONS AND RELEVANCE
Among community-dwelling adults included in this study, higher fragmentation of the 24-hour activity rhythms was associated with greater subsequent Aβ burden, especially in APOE4 carriers. These results suggest that rest-activity fragmentation could represent a modifiable risk factor for AD.
PubMed: 38913396
DOI: 10.1001/jamaneurol.2024.1755 -
American Journal of Cardiovascular... Jun 2024Cardiovascular disease was the leading cause of death worldwide in 2021, with atherosclerotic cardiovascular disease, encompassing hypercholesterolemia, being a major...
BACKGROUND
Cardiovascular disease was the leading cause of death worldwide in 2021, with atherosclerotic cardiovascular disease, encompassing hypercholesterolemia, being a major contributing factor. A range of lipid-lowering medications is used for the management of hyperlipidemia, but the use of statins is considered as standard therapy. Unfortunately, some patients do not respond to this therapy, necessitating novel therapeutic approaches. Tafolecimab is a novel proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody that inhibits the binding of PCSK9 with low-density lipoprotein receptors (LDLRs) and increases LDLR recycling, and thus it indirectly lowers circulating low-density lipoprotein cholesterol (LDL-C) levels by increasing LDL-C uptake. The primary objective of this study is to assess the efficacy of tafolecimab in reducing LDL-C levels.
METHODS
A thorough search was conducted on Medline (PubMed), Cochrane CENTRAL, Scopus, and Google Scholar from inception until December 2023. Review Manager was used for statistical analysis. The random effects model was used to calculate risk ratios (RRs), mean differences (MDs), and 95% confidence intervals (CIs). Heterogeneity was assessed using the Higgins I index. The risk of bias was assessed using Cochrane's RoB 2 tool. This review has been registered with PROSPERO (CRD42023471020).
RESULTS
A total of four Chinese studies matched the inclusion criteria and were included in this review. A total of 726 patients were included in this review, out of which 476 patients were males. Out of four, three studies that studied the efficacy of 450 mg tafolecimab every 4 weeks in patients (n = 462) as compared to placebo (n = 224) were included in the meta-analysis. According to the pooled results, tafolecimab caused a significant decrease in LDL-C levels from baseline to week 12 as compared to placebo (MD = - 63.78, 95% CI - 65.88 to - 61.68, p value < 0.00001, I = 97%). The pooled results showed that more patients achieved ≥ 50% reductions in LDL-C levels (RR = 52.33, 95% CI 18.51-147.95, p value < 0.00001, I = 0%) and LDL-C < 1.8 mmol/L (RR = 17.27, 95% CI 9.59-31.11, p value < 0.00001, I = 0%) at week 12 in the tafolecimab group than the placebo group. Additionally, tafolecimab also caused a robust decrease in non-HDL-C, apolipoprotein B, and lipoprotein(a) levels from baseline to week 12 compared to placebo. The overall risk of bias was low, as determined by the RoB 2 tool.
CONCLUSIONS
Tafolecimab showed promising lipid-lowering efficacy and a well-tolerated safety profile. Our findings suggest its potential as an innovative therapeutic option for individuals with hypercholesterolemia; however, significant heterogeneity was observed in some results, making it difficult to come to a firm conclusion. Therefore, large-scale randomized trials are required to confirm our findings, particularly exploring the most effective dosage regimens across varied populations.
REGISTRATION
PROSPERO identifier number CRD42023471020.
PubMed: 38913274
DOI: 10.1007/s40256-024-00654-4 -
Journal of Immunology (Baltimore, Md. :... Jun 2024Neutrophils play important roles in inflammatory airway diseases. In this study, we assessed whether apolipoprotein A-I modifies neutrophil heterogeneity as part of the...
Neutrophils play important roles in inflammatory airway diseases. In this study, we assessed whether apolipoprotein A-I modifies neutrophil heterogeneity as part of the mechanism by which it attenuates acute airway inflammation. Neutrophilic airway inflammation was induced by daily intranasal administration of LPS plus house dust mite (LPS+HDM) to Apoa1-/- and Apoa1+/+ mice for 3 d. Single-cell RNA sequencing was performed on cells recovered from bronchoalveolar lavage fluid on day 4. Unsupervised profiling identified 10 clusters of neutrophils in bronchoalveolar lavage fluid from Apoa1-/- and Apoa1+/+ mice. LPS+HDM-challenged Apoa1-/- mice had an increased proportion of the Neu4 neutrophil cluster that expressed S100a8, S100a9, and Mmp8 and had high maturation, aggregation, and TLR4 binding scores. There was also an increase in the Neu6 cluster of immature neutrophils, whereas neutrophil clusters expressing IFN-stimulated genes were decreased. An unsupervised trajectory analysis showed that Neu4 represented a distinct lineage in Apoa1-/- mice. LPS+HDM-challenged Apoa1-/- mice also had an increased proportion of recruited airspace macrophages, which was associated with a reciprocal reduction in resident airspace macrophages. Increased expression of a common set of proinflammatory genes, S100a8, S100a9, and Lcn2, was present in all neutrophils and airspace macrophages from LPS+HDM-challenged Apoa1-/- mice. These findings show that Apoa1-/- mice have increases in specific neutrophil and macrophage clusters in the lung during acute inflammation mediated by LPS+HDM, as well as enhanced expression of a common set of proinflammatory genes. This suggests that modifications in neutrophil and macrophage heterogeneity contribute to the mechanism by which apolipoprotein A-I attenuates acute airway inflammation.
PubMed: 38912868
DOI: 10.4049/jimmunol.2300459