scholarly journals Impact of APOE ε4 genotype on initial cognitive symptoms differs for Alzheimer’s and Lewy body neuropathology

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jagan A. Pillai ◽  
James Bena ◽  
Aaron Bonner-Jackson ◽  
James B. Leverenz
Keyword(s):  
Lewy Body ◽  
Statistical Significance ◽  
Carrier Status ◽  
Initial Symptom ◽  
Cognitive Symptoms ◽  
Clinical Dementia Rating ◽  
Apoe Ε4 ◽  
Initial Symptoms ◽  
Adjusted Model ◽  
The Impact

Abstract Background APOE ε4 carrier status is known to increase odds of amnestic presentations with Alzheimer’s pathology. It is unknown how APOE ε4 carrier status impacts odds of specific initial cognitive symptoms in the presence of Lewy body pathology. Here we evaluate the impact of APOE ε4 genotype on initial cognitive symptoms among those with Alzheimer’s disease pathology (ADP) and Lewy-related pathology (LRP). Methods A retrospective cohort study of 2288 participants with neuropathology confirmed ADP or LRP in the National Alzheimer’s Coordinating Center database, who had initial cognitive symptoms documented and had a Clinical Dementia Rating-Global (CDR-G) score ≤ 1 (cognitively normal, MCI, or early dementia). Unadjusted and adjusted logistic regression models taking into account age at evaluation, sex, and education examined the relationship between APOE ε4 genotype and initial symptoms (memory, executive, language visuospatial) among ADP with LRP and ADP-LRP groups. Results One thousand three hundred three participants met criteria for ADP alone, 90 for LRP alone, and 895 for co-existing ADP and LRP (ADP-LRP). Younger age increased odds of non-amnestic symptoms across all three groups. In the adjusted model among ADP, APOE ε4 carriers had higher odds of amnestic initial symptoms 1.5 [95% CI, 1.7–2.14, p = 0.003] and lower odds of initial language symptoms 0.67 [95% CI, 0.47–0.96, p = 0.03] than non-carriers. The odds for these two symptoms were not different between ADP and mixed ADP-LRP groups. Female sex and higher education increased odds of initial language symptoms in the ADP group in the adjusted model. In the unadjusted model, APOE ε4 carriers with LRP had a higher odds of visuospatial initial symptoms 21.96 [95% CI, 4.02–110.62, p < 0.0001], while no difference was noted for initial executive/attention symptoms. Among LRP, the odds of APOE ε4 on amnestic symptom was not significant; however, the interaction effect evaluating the difference in odds ratios of amnestic symptom between ADP and LRP groups also did not reach statistical significance. Conclusions The odds of specific initial cognitive symptoms differed between ADP and LRP among APOE ε4 carriers compared to non-carriers. The odds of initial amnestic symptom was higher among ADP APOE ε4 carriers and the odds of visuospatial initial symptom was higher with LRP APOE ε4 carriers. This supports the hypothesis that APOE ε4 differentially impacts initial cognitive symptoms together with underlying neuropathology.

scholarly journals CLINICAL APPLICATION OF APOE IN ALZHEIMER’S PREVENTION: A PRECISION MEDICINE APPROACH

2018 ◽  
pp. 1-7
Author(s):  
C.L. Berkowitz ◽  
L. Mosconi ◽  
A. Rahman ◽  
O. Scheyer ◽  
H. Hristov ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Risk Reduction ◽  
Late Onset ◽  
Population Attributable Risk ◽  
Carrier Status ◽  
Risk Factor Modification ◽  
Apoe Ε4 ◽  
Prevention Interventions ◽  
Ad Prevention ◽  
The Impact

Population-attributable risk models estimate that up to one-third of Alzheimer’s disease (AD) cases may be preventable through risk factor modification. The field of AD prevention has largely focused on addressing these factors through universal risk reduction strategies for the general population. However, targeting these strategies in a clinical precision medicine fashion, including the use of genetic risk factors, allows for potentially greater impact on AD risk reduction. Apolipoprotein E (APOE), and specifically the APOE ε4 variant, is one of the most well-established genetic influencers on late-onset AD risk. In this review, we evaluate the impact of APOE ε4 carrier status on AD prevention interventions, including lifestyle, nutrigenomic, pharmacogenomic, AD comorbidities, and other biological and behavioral considerations. Using a clinical precision medicine strategy that incorporates APOE ε4 carrier status may provide a highly targeted and distinct approach to AD prevention with greater potential for success.

scholarly journals Interaction of neuropsychiatric symptoms with APOE ε4 and conversion to dementia in MCI patients in a Memory Clinic

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Valero Sergi ◽  
Marquié Marta ◽  
Rojas De Itziar ◽  
Espinosa Ana ◽  
Moreno-Grau Sonia ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Neuropsychiatric Symptoms ◽  
Cox Proportional Hazards ◽  
Carrier Status ◽  
Memory Clinic ◽  
Genetic Trait ◽  
Apoe Ε4 ◽  
Cox Proportional Hazards Models ◽  
Incident Dementia ◽  
The Impact

AbstractTo date, very few studies have been focused on the impact of the convergence of neuropsychiatric symptoms (NPS) and APOE ε4 on the conversion to dementia in patients with Mild Cognitive Impairment patients (MCI), and none has been based in a clinical setting. The objective of the study is to determine the predictive value of additive and multiplicative interactions of NPS and APOE ε4 status on the prediction of incident dementia among MCI patients monitored in a Memory Clinic. 1512 patients (aged 60 and older) with prevalent MCI were followed for a mean of 2 years. Neuropsychiatric symptoms were assessed at baseline using the Neuropsychiatric Inventory Questionnaire. Cox proportional hazards models were calculated. Additive interactions for depression, apathy, anxiety, agitation, appetite, or irritability and a positive ε4 carrier status were obtained, significantly increasing the hazard ratios of incident dementia (HR range 1.3–2.03). Synergistic interactions between NPS and APOE ε4 are identified among MCI patients when predicting incident dementia. The combination of the behavioral status and the genetic trait could be considered a useful strategy to identify the most vulnerable MCI patients to dementia conversion in a Memory Clinic.

Percutaneous Coronary Intervention in Patients with Diabetes and Multivessel or Left Main Disease – a Review

2012 ◽  
Vol 7 (1) ◽  
pp. 37
Author(s):  
Donald E Cutlip ◽  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Coronary Artery ◽  
Statistical Significance ◽  
Bare Metal Stents ◽  
Coronary Intervention ◽  
Metal Stents ◽  
Increased Risk ◽  
Percutaneous Coronary ◽  
Patients With Diabetes ◽  
The Impact

Coronary artery disease in patients with diabetes is frequently a diffuse process with multivessel involvement and is associated with increased risk for myocardial infarction and death. The role of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in patients with diabetes and multivessel disease who require revascularisation has been debated and remains uncertain. The debate has been continued mainly because of the question to what degree an increased risk for in-stent restenosis among patients with diabetes contributes to other late adverse outcomes. This article reviews outcomes from early trials of balloon angioplasty versus CABG through later trials of bare-metal stents versus CABG and more recent data with drug-eluting stents as the comparator. Although not all studies have been powered to show statistical significance, the results have been generally consistent with a mortality benefit for CABG versus PCI, despite differential risks for restenosis with the various PCI approaches. The review also considers the impact of mammary artery grafting of the left anterior descending artery and individual case selection on these results, and proposes an algorithm for selection of patients in whom PCI remains a reasonable strategy.

Dietary Patterns: A New Therapeutic Approach for Depression?

2019 ◽  
Vol 20 (2) ◽  
pp. 123-129 ◽  
Author(s):  
Mariana Jesus ◽  
Tânia Silva ◽  
César Cagigal ◽  
Vera Martins ◽  
Carla Silva
Keyword(s):  
Depressive Symptoms ◽  
Dietary Patterns ◽  
Large Scale ◽  
Randomized Clinical Trials ◽  
Dietary Intervention ◽  
Common Mental Disorder ◽  
Controlled Trial ◽  
Statistical Significance ◽  
Inverse Association ◽  
The Impact

Introduction: The field of nutritional psychiatry is a fast-growing one. Although initially, it focused on the effects of vitamins and micronutrients in mental health, in the last decade, its focus also extended to the dietary patterns. The possibility of a dietary cost-effective intervention in the most common mental disorder, depression, cannot be overlooked due to its potential large-scale impact. Method: A classic review of the literature was conducted, and studies published between 2010 and 2018 focusing on the impact of dietary patterns in depression and depressive symptoms were included. Results: We found 10 studies that matched our criteria. Most studies showed an inverse association between healthy dietary patterns, rich in fruits, vegetables, lean meats, nuts and whole grains, and with low intake of processed and sugary foods, and depression and depressive symptoms throughout an array of age groups, although some authors reported statistical significance only in women. While most studies were of cross-sectional design, making it difficult to infer causality, a randomized controlled trial presented similar results. Discussion: he association between dietary patterns and depression is now well-established, although the exact etiological pathways are still unknown. Dietary intervention, with the implementation of healthier dietary patterns, closer to the traditional ones, can play an important role in the prevention and adjunctive therapy of depression and depressive symptoms. Conclusion: More large-scale randomized clinical trials need to be conducted, in order to confirm the association between high-quality dietary patterns and lower risk of depression and depressive symptoms.

Do we Need Maintenance Chemotherapy in Advanced NSCLC in the Era of Immune and Targeted Therapy?

2019 ◽  
Vol 15 (1) ◽  
pp. 50-55
Author(s):  
Ahmed Nagy ◽  
Omar Abdel Rahman ◽  
Heba Abdullah ◽  
Ahmed Negida
Keyword(s):  
Lung Cancer ◽  
Maintenance Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Statistical Significance ◽  
Small Cell ◽  
Maintenance Chemotherapy ◽  
Small Cell Lung ◽  
The Impact

Background: Although well established for the effective management of hematologic cancers, maintenance chemotherapy has only been recently incorportated as a treatment paradigm for advanced non–small-cell lung cancer. Maintenance chemotherapy aims to prolong a clinically favorable response state achieved after finishing induction therapy which is usually predefined in number before startng treatment. There are 2 modalities for maintenance therapy; continuation maintenance (involving a non-platinum component which was a part of the induction protocol or a targeted agent) and switch maintenance therapy (utilizing a new agent which was not a part of the induction regimen). Methods: The purpose of this article is to review the role of maintenance therapy in the treatment of advanced Non-Small Cell Lung Cancer (NSCLC) and provide a brief overview about induction chemotherapy in NSCLC to address the basis of maintenance therapy as a treatment option. We will also compare the impact of maintenance chemotherapy with the now evolving role of immunotherapy in NSCLC. Results: There have been 4 maintenance studies to date showing prolonged PFS and OS with statistical significance. However, Three out of the four studies (ECOG4599, JMEN, and PARAMOUNT) did not report tumor molecular analysis. As regard Immunotherapy, current data is in favour of strongly an increasing role for immunotherapy in NSCLC. Conclusion: Maintenance therapy in NSCLC continues to be an important therapeutic line to improve outcome in patients with metastatic and recurrent disease.

scholarly journals Treatment of HIV-associated facial lipoatrophy: impact on infection progression assessed by viral load and CD4 count

2013 ◽  
Vol 88 (4) ◽  
pp. 570-577 ◽  
Author(s):  
Flávia Machado Gonçalves Soares ◽  
Izelda Maria Carvalho Costa
Keyword(s):  
Viral Load ◽  
Disease Progression ◽  
Statistical Significance ◽  
Undetectable Viral Load ◽  
Fat Distribution ◽  
Cd4 Count ◽  
Before And After ◽  
Facial Lipoatrophy ◽  
A Prospective Study ◽  
The Impact

BACKGROUND: HIV/AIDS-Associated Lipodystrophy Syndrome includes changes in body fat distribution, with or without metabolic changes. The loss of fat from the face, called facial lipoatrophy, is one of the most stigmatizing signs of the syndrome.OBJECTIVES:To evaluate the effect of FL treatment using polymethylmethacrylate (PMMA) implants on disease progression, assessed by viral load and CD4 cell count.METHODS: This was a prospective study of 44 patients treated from July 2009 to December 2010. Male and female patients, aged over 18 years, with clinically detectable FL and who had never been treated were included in the study. PMMA implantation was done to fill atrophic areas. Laboratory tests were conducted to measure viral load and CD4 count before and after treatment.RESULTS: Of the 44 patients, 72.72% were male and 27.27% female, mean age of 44.38 years. Before treatment, 82% of patients had undetectable viral load, which increased to 88.6% after treatment, but without statistical significance (p = 0.67). CD4 count before treatment ranged from 209 to 1293, averaging 493.97. After treatment, the average increased to 548.61. The increase in CD4 count after treatment was statistically significant with p = 0.02.CONCLUSION: The treatment of FL with PMMA implants showed a statistically significant increase in CD4 count after treatment, revealing the impact of FL treatment on disease progression. Viral load before and after treatment did not vary significantly.

scholarly journals Does Social Support Affect the Health of the Elderly in Rural China? A Meta-Analysis Approach

2019 ◽  
Vol 16 (18) ◽  
pp. 3471 ◽  
Author(s):  
Natuya Zhuori ◽  
Yu Cai ◽  
Yan Yan ◽  
Yu Cui ◽  
Minjuan Zhao
Keyword(s):  
Social Support ◽  
Rural Areas ◽  
Rural China ◽  
Statistical Significance ◽  
Empirical Studies ◽  
Relevant Literature ◽  
The Elderly ◽  
Significant Difference ◽  
Meta Regression ◽  
The Impact

As the trend of aging in rural China has intensified, research on the factors affecting the health of the elderly in rural areas has become a hot issue. However, the conclusions of existing studies are inconsistent and even contradictory, making it difficult to form constructive policies with practical value. To explore the reasons for the inconsistent conclusions drawn by relevant research, in this paper we constructed a meta-regression database based on 65 pieces of relevant literature published in the past 25 years. For more valid samples to reduce publication bias, we also set the statistical significance of social support to the health of the elderly in rural areas as a dependent variable. Finally, combined with multi-dimensional social support and its implications for the health of the elderly, meta-regression analysis was carried out on the results of 171 empirical studies. The results show that (1) subjective support rather than objective support can have a significant impact on the health of the elderly in rural areas, and there is no significant difference between other dimensions of social support and objective support; (2) the health status of the elderly in rural areas in samples involving western regions is more sensitive to social support than that in samples not involving the western regions; (3) among the elderly in rural areas, social support for the older male elderly is more likely to improve their health than that for the younger female elderly; and (4) besides this, both data sources and econometric models greatly affect the heterogeneity of the effect of social support on the health of the elderly in rural areas, but neither the published year nor the journal is significant. Finally, relevant policies and follow-up studies on the impact of social support on the health of the elderly in rural areas are discussed.

33 An Evidence Based Laser Therapy Algorithm for the Treatment of Burn Scars

2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S26-S27
Author(s):  
Rajiv Sood
Keyword(s):  
Laser Treatment ◽  
Laser Therapy ◽  
Co2 Laser ◽  
Statistical Significance ◽  
Evidence Based ◽  
Baseline Measurement ◽  
Burn Scar ◽  
Therapy Algorithm ◽  
Laser Treatments ◽  
The Impact

Abstract Introduction Hypertrophic scarring after burn injury can be extremely painful, cause profound itching, and affect the way patients view themselves and how the outside world perceives them. We have utilized laser therapy as a modality for scar modulation for our patients since 2013. In 2014, we initiated and completed a prospective IRB approved study to evaluate the outcome of scars treated with fractional CO2 laser therapy (FLT) utilizing objective and subjective tools. Recently, we have completed a prospective study evaluating the use of pulse dye laser (PDL) therapy and the impact on post-burn pruritis. In reviewing the outcomes from these two studies, we have developed an evidence-based laser therapy algorithm for burn scar management. Methods The FLT study entailed a series of three CO2 laser treatments minimally 4–6 weeks apart with scar measurements and POSAS form completion performed prior to each laser treatment and four weeks after the last FLT. Scar measurements that included color, pliability, and scar thickness; and completion of the POSAS form were obtained prior to each laser therapy session and four weeks after the third laser treatment. The measurements of color, pliability, and scar thickness were measured with the Colorimeter, Cutometer, and ultrasound. The PDL study utilized the 5-D Itch scale to evaluate post-burn pruritis. A baseline measurement was obtained prior to any laser treatments. Each patient underwent two PDL sessions and a 5-D itch scale was completed four to six weeks after the second PDL session. The baseline measurement was then compared to the final 5-D itch scale measurement. Results Data from the FLT study is in Table 1 and shows that there were statistically significant improvements in the Patient and Observer POSAS scores, patient rated Itch score, scar thickness, and measured skin density. Changes to patient rated scar pain, scar color, and pliability were noted but were not of statistical significance. Data from the PDL study is in Table 2 and shows a statistically significant decrease in the treated patients’ post-burn pruritis. Conclusions In reviewing the outcomes of these two studies, we have developed an algorithm based on our studies. All of our patients undergoing laser therapy receive two PDL sessions that are four to six weeks apart followed by 3 FLT sessions. The use of both PDL and FLT decreases post-burn pruritis, decreases scar thickness, decreases pain, and increases patient satisfaction as shown in our research.

CD34 immunostain increases sensitivity of the diagnosis of fetal vascular malperfusion in placentas from ex-utero intrapartum treatment

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Jerzy Stanek
Keyword(s):  
Statistical Significance ◽  
Treatment Procedure ◽  
Fetal Survival ◽  
Ex Utero Intrapartum Treatment ◽  
Life Threatening ◽  
Group 2 ◽  
Cd34 Immunostain ◽  
The Impact ◽  
Diaphragmatic Hernias ◽  
Group 1

AbstractShort CommunicationsEXIT (ex-utero intrapartum treatment) procedure is a fetal survival-increasing modification of cesarean section. Previously we found an increase incidence of fetal vascular malperfusion (FVM) in placentas from EXIT procedures which indicates the underlying stasis of fetal blood flow in such cases. This retrospective analysis analyzes the impact of the recently introduced CD34 immunostain for the FVM diagnosis in placentas from EXIT procedures.Objectives and MethodsA total of 105 placentas from EXIT procedures (48 to airway, 43 to ECMO and 14 to resection) were studied. In 73 older cases, the placental histological diagnosis of segmental FVM was made on H&E stained placental sections only (segmental villous avascularity) (Group 1), while in 32 most recent cases, the CD34 component of a double E-cadherin/CD34 immunostain slides was also routinely used to detect the early FVM (endothelial fragmentation, villous hypovascularity) (Group 2). 23 clinical and 47 independent placental phenotypes were compared by χ2 or ANOVA, where appropriate.ResultsThere was no statistical significance between the groups in rates of segmental villous avascularity (29 vs. 34%), but performing CD34 immunostain resulted in adding and/or upgrading 12 more cases of segmental FVM in Group 2, thus increasing the sensitivity of placental examination for FVM by 37%. There were no other statistically significantly differences in clinical (except for congenital diaphragmatic hernias statistically significantly more common in Group 2, 34 vs 56%, p=0.03) and placental phenotypes, proving the otherwise comparability of the groups.ConclusionsThe use of CD34 immunostain increases the sensitivity of placental examination for FVM by 1/3, which may improve the neonatal management by revealing the increased likelihood of the potentially life-threatening neonatal complications.

scholarly journals Clinicopathological features of Egyptian colorectal cancer patients regarding somatic genetic mutations especially in KRAS gene and microsatellite instability status: a pilot study

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Neemat M. Kassem ◽  
Gamal Emera ◽  
Hebatallah A. Kassem ◽  
Nashwa Medhat ◽  
Basant Nagdy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Cpg Island ◽  
Human Cancer ◽  
Statistical Significance ◽  
Public Health Problem ◽  
World Health ◽  
Cpg Island Methylator Phenotype ◽  
Number Of Patients ◽  
The Impact

Abstract Background Colorectal cancer (CRC) is the third most common cause of cancer-related deaths which contributes to a significant public health problem worldwide with 1.8 million new cases and almost 861,000 deaths in 2018 according to the World Health Organization. It exhibits 7.4% of all diagnosed cancer cases in the region of the Middle East and North Africa. Molecular changes that happen in CRCs are chromosomal instability, microsatellite instability (MSI), and CpG island methylator phenotype. The human RAS family (KRAS, NRAS, and HRAS) is the most frequently mutated oncogenes in human cancer appearing in 45% of colon cancers. Determining MSI status across CRCs offers the opportunity to identify patients who are likely to respond to targeted therapies such as anti-PD-1. Therefore, a method to efficiently determine MSI status for every cancer patient is needed. Results KRAS mutations were detected in 31.6% of CRC patients, namely in older patients (p = 0.003). Codons 12 and 13 constituted 5/6 (83.3%) and 1/6 (16.7%) of all KRAS mutations, respectively. We found three mutations G12D, G12C, and G13D which occur as a result of substitution at c.35G>A, c.34G>T, and c.38G>A and have been detected in 4/6 (66.6%), 1/6 (16.7%), and 1/6 (16.7%) patients, respectively. Eleven (57.9%) patients had microsatellite instability-high (MSI-H) CRC. A higher percentage of MSI-H CRC was detected in female patients (p = 0.048). Eight patients had both MSI-H CRC and wild KRAS mutation with no statistical significance was found between MSI status and KRAS mutation in these studied patients. Conclusion In conclusion, considering that KRAS mutations confer resistance to EGFR inhibitors, patients who have CRC with KRAS mutation could receive more tailored management by defining MSI status. MSI-high patients have enhanced responsiveness to anti-PD-1 therapies. Thus, the question arises as to whether it is worth investigating this association in the routine clinical setting or not. Further studies with a larger number of patients are needed to assess the impact of MSI status on Egyptian CRC care.

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