scholarly journals Age, sex and APOE-ε4 modify the balance between soluble and fibrillar β-amyloid in cognitively intact individuals: topographical patterns and replication across two independent cohorts

2020 ◽  
Author(s):  
Raffaele Cacciaglia ◽  
Gemma Salvadó ◽  
José Luis Molinuevo ◽  
Mahnaz Shekari ◽  
Carles Falcon ◽  
...  
Keyword(s):  
Risk Factors ◽  
Medial Temporal Lobe ◽  
Posterior Cingulate Cortex ◽  
Position Emission Tomography ◽  
Plaque Deposition ◽  
Preclinical Ad ◽  
Aβ Aggregation ◽  
Candidate Regions ◽  
Aβ Fibrils ◽  
The Impact

ABSTRACTCerebral beta-amyloid (Aβ) accumulation is the earliest detectable pathophysiological event along the Alzheimer’s disease (AD) continuum, therefore an accurate quantification of incipient Aβ abnormality is of great importance to identify preclinical AD. Both cerebrospinal fluid (CSF) Aβ concentrations and Position Emission Tomography (PET) with specific tracers provide established biomarkers of Aβ pathology. Yet, they identify two different biological processes reflecting the clearance rate of soluble Aβ as opposed to the cerebral aggregation of insoluble Aβ fibrils. Studies have demonstrated high agreement between CSF and PET-based Aβ measurements on diagnostic and prognostic levels. However, an open question is whether risk factors known to increase AD prevalence may promote an imbalance between these biomarkers, leading to a higher cumulative Aβ cerebral aggregation for a given level of cleared Aβ in the CSF. Unveiling such interactions in cognitively unimpaired (CU) individuals shall provide novel insights into the biological pathways underlying Aβ aggregation in the brain and ultimately improve our knowledge on disease modelling. With this in mind, we assessed the impact of three major unmodifiable AD risk factors (age, APOE-ε4 and sex) on the association between soluble and deposited Aβ in a sample of 293 middle-aged CU individuals who underwent both lumbar puncture and PET imaging using the [18F]flutemetamol tracer. We looked for interactions between CSF Aβ42/40 concentrations and each of the assessed risk factors, in promoting Aβ PET uptake both in candidate regions of interest and in the whole brain. We found that, for any given level of CSF Aβ42/40, older age and female sex induced higher fibrillary plaque deposition in neocortical areas including the anterior, middle and posterior cingulate cortex. By contrast, the modulatory role of APOE-ε4 was uniquely prominent in areas known for being vulnerable to early tau deposition, such as the entorhinal cortex and the hippocampus bilaterally. Post hoc three-way interactions additionally proved evidence for a synergistic effect among the risk factors on the spatial topology of Aβ deposition as a function of CSF Aβ4/40 levels. Importantly, findings were replicated in an independent sample of CU individuals derived from the ADNI cohort. Our data clarify the mechanisms underlying the higher AD prevalence associated to those risk factors and suggest that APOE-ε4 in particular paves the way for subsequent tau spreading in the medial temporal lobe, thus favoring a spatial co-localization between Aβ and tau and increasing their synergistic interaction along the disease continuum.

scholarly journals Cardiovascular Risk and Hippocampal Thickness in Alzheimer’s Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Markus Donix ◽  
Maria Scharf ◽  
Kira Marschner ◽  
Annett Werner ◽  
Cathrin Sauer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Temporal Lobe ◽  
Cortical Thickness ◽  
Medial Temporal Lobe ◽  
Cortical Thinning ◽  
The Impact

Cardiovascular risk factors influence onset and progression of Alzheimer’s disease. Among cognitively healthy people, changes in brain structure and function associated with high blood pressure, diabetes, or other vascular risks suggest differential regional susceptibility to neuronal damage. In patients with Alzheimer’s disease, hippocampal and medial temporal lobe atrophy indicate early neuronal loss preferentially in key areas for learning and memory. We wanted to investigate whether this regional cortical thinning would be modulated by cardiovascular risk factors. We utilized high-resolution magnetic resonance imaging and a cortical unfolding technique to determine the cortical thickness of medial temporal subregions in 30 patients with Alzheimer’s disease. Cardiovascular risk was assessed using a sex-specific multivariable risk score. Greater cardiovascular risk was associated with cortical thinning in the hippocampus CA2/3/dentate gyrus area but not other hippocampal and medial temporal subregions. APOE genotype, a family history of Alzheimer’s disease, and age did not influence cortical thickness. Alzheimer’s disease-related atrophy could mask the influence of genetic risk factors or age on regional cortical thickness in medial temporal lobe regions, whereas the impact of vascular risk factors remains detectable. This highlights the importance of cardiovascular disease prevention and treatment in patients with Alzheimer’s disease.

scholarly journals Toward personalized cognitive diagnostics of at-genetic-risk Alzheimer’s disease

2019 ◽  
Vol 116 (19) ◽  
pp. 9285-9292 ◽  
Author(s):  
Gillian Coughlan ◽  
Antoine Coutrot ◽  
Mizanur Khondoker ◽  
Anne-Marie Minihane ◽  
Hugo Spiers ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Big Data ◽  
High Risk ◽  
Spatial Navigation ◽  
Apoe Genotype ◽  
Low Risk ◽  
Preclinical Ad ◽  
The Impact

Spatial navigation is emerging as a critical factor in identifying preclinical Alzheimer’s disease (AD). However, the impact of interindividual navigation ability and demographic risk factors (e.g., APOE, age, and sex) on spatial navigation make it difficult to identify persons “at high risk” of AD in the preclinical stages. In the current study, we use spatial navigation big data (n = 27,108) from the Sea Hero Quest (SHQ) game to overcome these challenges by investigating whether big data can be used to benchmark a highly phenotyped healthy aging laboratory cohort into high- vs. low-risk persons based on their genetic (APOE) and demographic (sex, age, and educational attainment) risk factors. Our results replicate previous findings in APOE ε4 carriers, indicative of grid cell coding errors in the entorhinal cortex, the initial brain region affected by AD pathophysiology. We also show that although baseline navigation ability differs between men and women, sex does not interact with the APOE genotype to influence the manifestation of AD-related spatial disturbance. Most importantly, we demonstrate that such high-risk preclinical cases can be reliably distinguished from low-risk participants using big-data spatial navigation benchmarks. By contrast, participants were undistinguishable on neuropsychological episodic memory tests. Taken together, we present evidence to suggest that, in the future, SHQ normative benchmark data can be used to more accurately classify spatial impairments in at-high-risk of AD healthy participants at a more individual level, therefore providing the steppingstone for individualized diagnostics and outcome measures of cognitive symptoms in preclinical AD.

Stress, Cortisol and Suicide Risk

2019 ◽  
Author(s):  
Daryl Brian O'Connor
Keyword(s):  
Risk Factors ◽  
Suicidal Behavior ◽  
Suicide Risk ◽  
Stressful Events ◽  
Additional Risk ◽  
Global Health Issue ◽  
History Of ◽  
Hpa Axis Activity ◽  
The Impact

Suicide is a global health issue accounting for at least 800,000 deaths per annum. Numerous models have been proposed that differ in their emphasis on the role of psychological, social, psychiatric and neurobiological factors in explaining suicide risk. Central to many models is a stress-diathesis component which states that suicidal behavior is the result of an interaction between acutely stressful events and a susceptibility to suicidal behavior (a diathesis). This article presents an overview of studies that demonstrate that stress and dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, as measured by cortisol levels, are important additional risk factors for suicide. Evidence for other putative stress-related suicide risk factors including childhood trauma, impaired executive function, impulsivity and disrupted sleep are considered together with the impact of family history of suicide, perinatal and epigenetic influences on suicide risk.

Stress, anxiety, depression and burnout in frontline health care workers during COVID-19 pandemic: a brief systematic review and new data from Russia

2021 ◽  
Author(s):  
Ekaterina Mosolova ◽  
Dmitry Sosin ◽  
Sergey Mosolov
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Female Gender ◽  
Assessment Tools ◽  
Care Workers ◽  
Younger Age ◽  
Wide Range ◽  
Associated Risk Factors ◽  
Anxiety Depression ◽  
The Impact

During the COVID-19 pandemic, healthcare workers (HCWs) have been subject to increased workload while also exposed to many psychosocial stressors. In a systematic review we analyze the impact that the pandemic has had on HCWs mental state and associated risk factors. Most studies reported high levels of depression and anxiety among HCWs worldwide, however, due to a wide range of assessment tools, cut-off scores, and number of frontline participants in the studies, results were difficult to compare. Our study is based on two online surveys of 2195 HCWs from different regions of Russia during spring and autumn epidemic outbreaks revealed the rates of anxiety, stress, depression, emotional exhaustion and depersonalization and perceived stress as 32.3%, 31.1%, 45.5%, 74.2%, 37.7% ,67.8%, respectively. Moreover, 2.4% of HCWs reported suicidal thoughts. The most common risk factors include: female gender, nurse as an occupation, younger age, working for over 6 months, chronic diseases, smoking, high working demands, lack of personal protective equipment, low salary, lack of social support, isolation from families, the fear of relatives getting infected. These results demonstrate the need for urgent supportive programs for HCWs fighting COVID-19 that fall into higher risk factors groups.

IDENTIFICATION AND ASSESSMENT OF RISK FACTORS ROLE IN MYOCARDIAL INFARCTION DEVELOPMENT

2019 ◽  
Vol 72 (5) ◽  
pp. 779-783
Author(s):  
Victor A. Ognev ◽  
Anna A. Podpriadova ◽  
Anna V. Lisova
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Cardiovascular System ◽  
Control Group ◽  
Biological Factors ◽  
Prevention And Treatment ◽  
High Level ◽  
Social Importance ◽  
The Impact

Introduction:The high level of morbidity and mortality from cardiovascular disease is largely due toinsufficient influence on the main risk factors that contribute to the development of myocardial infarction.Therefore, a detailed study and assessment of risk factors is among the most important problems of medical and social importance. The aim: To study and evaluate the impact of biological, social and hygienic, social and economic, psychological, natural and climatic risk factors on the development of myocardial infarction. Materials and methods: A sociological survey was conducted in 500 people aged 34 to 85. They were divided into two groups. The main group consisted of 310 patients with myocardial infarction. The control group consisted of 190 practically healthy people, identical by age, gender and other parameters, without diseases of the cardiovascular system. Results: It was defined that 30 factors have a significant impact on the development of myocardial infarction.Data analysis revealed that the leading risk factors for myocardial infarction were biological and socio-hygienic. The main biological factors were: hypertension and hypercholesterolemia. The man socio-hygienic factor was smoking. Conclusions: Identification of risk factors provides new opportunities for the development of more effective approaches for the prevention and treatment of myocardial infarction.

scholarly journals Anti-Parallel β-Hairpin Structure in Soluble Aβ Oligomers of Aβ40-Dutch and Aβ40-Iowa

2021 ◽  
Vol 22 (3) ◽  
pp. 1225
Author(s):  
Ziao Fu ◽  
William E. Van Nostrand ◽  
Steven O. Smith
Keyword(s):  
Amyloid Β ◽  
Amyloid Angiopathy ◽  
Aβ Oligomers ◽  
Dominant Component ◽  
Fibril Structure ◽  
Predominant Component ◽  
Aβ Aggregation ◽  
Aβ Fibrils ◽  
Soluble Aβ Oligomers ◽  
Β Sheet

The amyloid-β (Aβ) peptides are associated with two prominent diseases in the brain, Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA). Aβ42 is the dominant component of cored parenchymal plaques associated with AD, while Aβ40 is the predominant component of vascular amyloid associated with CAA. There are familial CAA mutations at positions Glu22 and Asp23 that lead to aggressive Aβ aggregation, drive vascular amyloid deposition and result in degradation of vascular membranes. In this study, we compared the transition of the monomeric Aβ40-WT peptide into soluble oligomers and fibrils with the corresponding transitions of the Aβ40-Dutch (E22Q), Aβ40-Iowa (D23N) and Aβ40-Dutch, Iowa (E22Q, D23N) mutants. FTIR measurements show that in a fashion similar to Aβ40-WT, the familial CAA mutants form transient intermediates with anti-parallel β-structure. This structure appears before the formation of cross-β-sheet fibrils as determined by thioflavin T fluorescence and circular dichroism spectroscopy and occurs when AFM images reveal the presence of soluble oligomers and protofibrils. Although the anti-parallel β-hairpin is a common intermediate on the pathway to Aβ fibrils for the four peptides studied, the rate of conversion to cross-β-sheet fibril structure differs for each.

scholarly journals Psychological and Behavioral Predictors of Vaccine Efficacy: Considerations for COVID-19

2021 ◽  
pp. 174569162198924
Author(s):  
Annelise A. Madison ◽  
M. Rosie Shrout ◽  
Megan E. Renna ◽  
Janice K. Kiecolt-Glaser
Keyword(s):  
Risk Factors ◽  
Side Effects ◽  
Vaccine Efficacy ◽  
Psychological Factors ◽  
Behavioral Interventions ◽  
Vulnerable Groups ◽  
Behavioral Risk Factors ◽  
Behavioral Risk ◽  
Vaccine Response ◽  
The Impact

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine candidates are being evaluated, with the goal of conferring immunity on the highest percentage of people who receive the vaccine as possible. It is noteworthy that vaccine efficacy depends not only on the vaccine but also on characteristics of the vaccinated. Over the past 30 years, a series of studies has documented the impact of psychological factors on the immune system’s vaccine response. Robust evidence has demonstrated that stress, depression, loneliness, and poor health behaviors can impair the immune system’s response to vaccines, and this effect may be greatest in vulnerable groups such as the elderly. Psychological factors are also implicated in the prevalence and severity of vaccine-related side effects. These findings have generalized across many vaccine types and therefore may be relevant to the SARS-CoV-2 vaccine. In this review, we discuss these psychological and behavioral risk factors for poor vaccine responses, their relevance to the COVID-19 pandemic, as well as targeted psychological and behavioral interventions to boost vaccine efficacy and reduce side effects. Recent data suggest these psychological and behavioral risk factors are highly prevalent during the COVID-19 pandemic, but intervention research suggests that psychological and behavioral interventions can increase vaccine efficacy.

scholarly journals AB0602 IMPACT OF SOCIOECONOMIC FACTORS ON PAIN AND FUNCTION IN KNEE OSTEOARTHRITIS: A SYSTEMATIC LITERATURE REVIEW

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1337.2-1337
Author(s):  
T. W. Swinnen ◽  
M. Willems ◽  
I. Jonkers ◽  
F. P. Luyten ◽  
J. Vanrenterghem ◽  
...  
Keyword(s):  
Risk Factors ◽  
Literature Review ◽  
Knee Osteoarthritis ◽  
Socioeconomic Factors ◽  
Systematic Literature Review ◽  
Intervention Effects ◽  
Socioeconomic Outcomes ◽  
And Function ◽  
The Impact

Background:The personal and societal burden of knee osteoarthritis (KOA) urges the research community to identify factors that predict its onset and progression. A mechanistic understanding of disease is currently lacking but needed to develop targeted interventions. Traditionally, risk factors for KOA are termed ‘local’ to the joint or ‘systemic’ referring to whole-body systems. There are however clear indications in the scientific literature that contextual factors such as socioeconomic position merit further scientific scrutiny, in order to justify a more biopsychosocial view on risk factors in KOA.Objectives:The aims of this systematic literature review were to assess the inclusion of socioeconomic factors in KOA research and to identify the impact of socioeconomic factors on pain and function in KOA.Methods:Major bibliographic databases, namely Medline, Embase, CINAHL, Web of Science and Cochrane, were independently screened by two reviewers (plus one to resolve conflicts) to identify research articles dealing with socioeconomic factors in the KOA population without arthroplasty. Included studies had to quantify the relationship between socioeconomic factors and pain or function. Main exclusion criteria were: a qualitative design, subject age below 16 years and articles not written in English or Dutch. Methodological quality was assessed via the Cochrane risk of bias tools for randomized (ROB-II) and non-randomized intervention studies (ROBIN-I) and the Newcastle-Ottawa Scale for assessing the quality of non-randomised studies. Due to heterogeneity of studies with respect to outcomes assessed and analyses performed, no meta-analysis was performed.Results:Following de-duplication, 7639 articles were available for screening (120 conflicts resolved without a third reader). In 4112 articles, the KOA population was confirmed. 1906 (25%) were excluded because of knee arthroplasty and 1621 (21%) because of other issues related to the population definition. Socioeconomic factors could not be identified in 4058 (53%) papers and were adjusted for in 211 (3%) articles. In the remaining papers covering pain (n=110) and/or function (n=81), education (62%) and race (37%) were most frequently assessed as socioeconomic factors. A huge variety of mainly dichotomous or ordinal socioeconomic outcomes was found without further methodological justification nor sensitivity analysis to unravel the impact of selected categories. Although the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was the most popular instrument to assess pain and function, data pooling was not possible as socioeconomic factors estimates were part of multilevel models in most studies. Overall results showed that lower education and African American race were consistent predictors of pain and poor function, but those effects diminished or disappeared when psychological aspects (e.g. discrimination) or poverty estimates were taken into account. When function was assessed using self-reported outcomes, the impact of socioeconomic factors was more clear versus performance-based instruments. Quality of research was low to moderate and the moderating or mediating impact of socioeconomic factors on intervention effects in KOA is understudied.Conclusion:Research on contextual socioeconomic factors in KOA is insufficiently addressed and their assessment is highly variable methodologically. Following this systematic literature review, we can highlight the importance of implementing a standardised and feasible set of socioeconomic outcomes in KOA trials1, as well as the importance of public availability of research databases including these factors. Future research should prioritise the underlying mechanisms in the effect of especially education and race on pain and function and assess its impact on intervention effects to fuel novel (non-)pharmacological approaches in KOA.References:[1]Smith TO et al. The OMERACT-OARSI Core Domain Set for Measurement in Clinical Trials of Hip and/or Knee Osteoarthritis J Rheumatol 2019. 46:981–9.Disclosure of Interests:None declared.

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