•This review describes an integrated and multidisciplinary approach for the “early” diagnosis of Alzheimer's disease (AD).•An overview of epidemiology, genetic risk factors, and different biomarkers ...of AD is provided.•Latest findings suggest EEG rhythms analysis as a valid screening tool to predict AD conversion.
Alzheimer’s disease (AD) is the most common neurodegenerative disease among the elderly with a progressive decline in cognitive function significantly affecting quality of life. Both the prevalence and emotional and financial burdens of AD on patients, their families, and society are predicted to grow significantly in the near future, due to a prolongation of the lifespan. Several lines of evidence suggest that modifications of risk-enhancing life styles and initiation of pharmacological and non-pharmacological treatments in the early stage of disease, although not able to modify its course, helps to maintain personal autonomy in daily activities and significantly reduces the total costs of disease management. Moreover, many clinical trials with potentially disease-modifying drugs are devoted to prodromal stages of AD. Thus, the identification of markers of conversion from prodromal form to clinically AD may be crucial for developing strategies of early interventions. The current available markers, including volumetric magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebral spinal fluid (CSF) analysis are expensive, poorly available in community health facilities, and relatively invasive. Taking into account its low cost, widespread availability and non-invasiveness, electroencephalography (EEG) would represent a candidate for tracking the prodromal phases of cognitive decline in routine clinical settings eventually in combination with other markers. In this scenario, the present paper provides an overview of epidemiology, genetic risk factors, neuropsychological, fluid and neuroimaging biomarkers in AD and describes the potential role of EEG in AD investigation, trying in particular to point out whether advanced analysis of EEG rhythms exploring brain function has sufficient specificity/sensitivity/accuracy for the early diagnosis of AD.
A New Paradigm is needed for Reliable Seismic Hazard Assessment RSHA, not only from consideration of (a) the huge human losses experienced in the many recently destructive earthquakes worldwide; but ...also from (b) theoretical considerations of seismic wave generation and propagation phenomena through often non-homogeneous media within the earth's crust, particularly when large and more complex fault ruptures occur. The Neo-Deterministic Seismic Hazard Assessment (NDSHA) method, proposed some twenty years ago, is found to reliably and realistically simulate the wide suite of earthquake ground motions that may impact civil populations as well as their heritage buildings. The scenario-based NDSHA modeling technique is developed from comprehensive physical knowledge of: (i) the seismic source process; (ii) the propagation of earthquake waves; and (iii) their combined interactions with site effects. Thus, NDSHA effectively accounts for the tensor nature of earthquake ground motions: (a) formally described as the tensor product of the earthquake source functions and the Green's functions of the transmitting (pathway) medium; and (b) more informally described as mathematical arrays of numbers or functions (indices) “that transform according to certain rules under a change of coordinates.” Importantly, NDSHA therefore uses all available information about the spacial distribution of large magnitude earthquake phenomena, including: (a) Maximum Credible Earthquake (MCE) – which is based on seismic history and seismotectonics; and (b) geological and geophysical data. Thus it does not rely on scalar empirical ground motion attenuation models (GMPEs), as these are often both: (a) weakly constrained by available observations; and (b) fundamentally unable to account for the tensor nature of earthquake ground motions.
•“You never change things by fighting the existing reality. To change something, build a new model that makes the existing model obsolete.” — Buckminster Fuller.•The Neo-Deterministic Seismic Hazard Assessment (NDSHA) method, proposed some twenty years ago, is found to reliably and realistically simulate the wide suite of earthquake ground motions that may impact civil populations as well as their heritage buildings.•The scenario-based NDSHA modeling technique is developed from comprehensive physical knowledge of: (i) the seismic source process; (ii) the propagation of earthquake waves; and (iii) their combined interactions with site conditions.•Thus, NDSHA effectively accounts for the tensor nature of earthquake ground motions.•Observations from recent destructive earthquakes in Italy: (i) Mw 5.9 Emilia 2012; (ii) Central Italy Mw 6.3 L'Aquila 2009; and 2016–2017 Seismic Crisis - Mw 6.1 Amatrice; Mw 5.9 Visso; Mw 6.5 Norcia; Mw 5.7 L'Aquila; and (iii) Mw 7.8 Nepal 2015 - have all confirmed the validity of NDSHA's approach and application.•Although damaging earthquakes cannot yet be predicted with ultimate precision, intermediate-term (several months) and middle-range (few 100 s km scale) predictions of main shocks above a pre-assigned threshold (based on seismicity “alarms” generated by interpretive algorithms like CN and M8) may be properly used for the implementation of low-key preventive safety actions.
A prolonged preclinical phase of more than two decades before the onset of dementia suggested that initial brain changes of Alzheimer’s disease (AD) and the symptoms of advanced AD may represent a ...unique continuum. Given the very limited therapeutic value of drugs currently used in the treatment of AD and dementia, preventing or postponing the onset of AD and delaying or slowing its progression are becoming mandatory. Among possible reversible risk factors of dementia and AD, vascular, metabolic, and lifestyle-related factors were associated with the development of dementia and late-life cognitive disorders, opening new avenues for the prevention of these diseases. Among diet-associated factors, coffee is regularly consumed by millions of people around the world and owing to its caffeine content, it is the best known psychoactive stimulant resulting in heightened alertness and arousal and improvement of cognitive performance. Besides its short-term effect, some case-control and cross-sectional and longitudinal population-based studies evaluated the long-term effects on brain function and provided some evidence that coffee, tea, and caffeine consumption or higher plasma caffeine levels may be protective against cognitive impairment/decline and dementia. In particular, several cross-sectional and longitudinal population-based studies suggested a protective effect of coffee, tea, and caffeine use against late-life cognitive impairment/decline, although the association was not found in all cognitive domains investigated and there was a lack of a distinct dose-response association, with a stronger effect among women than men. The findings on the association of coffee, tea, and caffeine consumption or plasma caffeine levels with incident mild cognitive impairment and its progression to dementia were too limited to draw any conclusion. Furthermore, for dementia and AD prevention, some studies with baseline examination in midlife pointed to a lack of association, although other case-control and longitudinal population-based studies with briefer follow-up periods supported favourable effects of coffee, tea, and caffeine consumption against AD. Larger studies with longer follow-up periods should be encouraged, addressing other potential bias and confounding sources, so hopefully opening new ways for diet-related prevention of dementia and AD.
Several observational studies investigated risk factors for suicide attempts/completed suicides in older age with contrasting evidence from ongoing population-based research. The risk factors most ...associated to suicide attempts than other variables were: depressive disorders, methods employed to self-harm (particularly poisoning), and psychotropic drug utilization followed by psychological factors and disability. Moreover, male sex, violent methods to self-harm, any psychiatric disorder (depression, anxiety and bipolar disorders), a poor medical condition, stressors/bereavement, and living alone appeared to be more significant for predicting completed suicides in late life. There is growing evidence of a role of environmental exposures in the pathogenesis and epigenetics of suicidal behavior in older age. Little is known about the possible relationship between suicidal ideation in older age and its biopsychosocial predictors, although psychiatric disorders (among which late-life depression, LLD), play a fundamental role. LLD, distinguished as late-onset depression (LOD) and early-onset depression (EOD). Suicidal ideators accounted for 2.32% of subjects, were female, smokers and obese affected by multimorbidity. After adjusting for age, gender, education and social dysfunction, suicidal ideation was associated to LLD (EOD>LOD:OR:21.71, 95% CI:9.22-51.14). In the full random forest model, asthma was the most important contributor to suicidal ideation. Among biomarkers, interleukin (IL)-6 followed by tumor necrosis factor (TNF)-a, Apolipoprotein E e4 allele-carriers, C-reactive protein contributed most to suicidal ideation. Although EOD is a strong determinant of suicidal ideation, other non-psychiatric factors, i.e., serum inflammation biomarkers, APOE e4 allele, and multimorbidity, should be taken into account when evaluating a suicidal ideation phenotype in older age.
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In the neo-deterministic seismic hazard assessment (NDSHA) evaluation, great-earthquake-prone areas (GEPAs) play an important role in defining the ‘controlling earthquakes’ or ‘scenario earthquakes’. ...When considering great earthquakes, their finite rupture attributes, which contribute to determine the strong ground motions and intensities, have to be taken into account. For continental earthquakes in China, the great earthquakes are located mainly within the boundary zones of the ‘tectonic blocks’. The ‘tectonic block’ model indicates the focal mechanisms and some finite rupture attributes of the great earthquakes within the boundary zones. Accordingly, in the NDSHA for China, it is both necessary and feasible for the GEPAs to consider the finite rupture attributes of great earthquakes. The Sichuan-Yunnan border in southwest China has been taken as an example to naturally develop the originally used circular shape of GEPAs into one with more degrees-of-freedom, better reflecting the possible rupture processes of the considered earthquakes.
► In chronic spontaneous urticaria free IL-18 is increased. ► IL-18 binding protein counteracts the inflammatory effects of IL-18. ► IL-33 does not play a role in chronic spontaneous urticaria.
...Overproduction of IL-18 has been described in chronic urticaria. To evaluate free IL-18 and IL-33 in chronic spontaneous urticaria (CSU). IL-18, its inhibitor IL-18BP, IL-33 and its soluble receptor ST2 (sST2) were measured (ELISA) in the sera of 73 CSU patients. Free IL-18 was calculated (law of mass action). Autologous serum skin test (ASST) was performed in all patients. Total IL-18, IL-18BP and free IL-18 serum levels were significantly higher in CSU than in controls. IL-18 and IL-18BP increased significantly in both ASST-positive and negative subgroups. Free IL-18 resulted significantly higher in the ASST-negative, but not in the ASST-positive subgroup. No differences in IL-33/sST2 levels were detected between CSU and controls. Increased levels of free IL-18 and IL-18BP, but not IL-33, was detected in CSU. Whether IL-18 up-regulation is a consequence of inflammation or one of the causes of the pathology needs to be addressed.
There is a critical need to potentially individualize new strategies able to prevent and to slow down the progression of predementia and dementia syndromes. Only recently higher adherence to a ...Mediterranean-type diet was associated with decreased cognitive decline although the Mediterranean diet (MeDi) combines several foods, micro- and macronutrients already separately proposed as potential protective factors against dementia and predementia syndromes. In fact, elevated saturated fatty acids could have negative effects on age-related cognitive decline and mild cognitive impairment (MCI). Furthermore, at present, epidemiological evidence suggested a possible association among fish consumption, monounsaturated fatty acids and polyunsaturated fatty acids (PUFA) (particularly, n-3 PUFA) and reduced risk of cognitive decline and dementia. Light to moderate alcohol use may be associated with a reduced risk of incident dementia and Alzheimer's disease (AD), while for vascular dementia, cognitive decline, and predementia syndromes the current evidence is only suggestive of a protective effect. Finally, the limited epidemiological evidence available on fruit and vegetable consumption and cognition generally supported a protective role of these macronutrients against cognitive decline, dementia, and AD. Moreover, recent prospective studies provided evidence that higher adherence to a Mediterranean-type diet could be associated with slower cognitive decline, reduced risk of progression from MCI to AD, reduced risk of AD, and decreased all-causes mortality in AD patients. These findings suggested that adherence to the MeDi may affect not only the risk for AD, but also for predementia syndromes and their progression to overt dementia. Nonetheless, at present, no definitive dietary recommendations are possible. However, high levels of consumption of fats from fish, vegetable oils, non-starchy vegetables, low glycemic fruits, and diet low in foods with added sugars and with moderate wine intake should be encouraged. In fact, this dietary advice is in accordance with recommendations for lowering the risk of cardiovascular disease, obesity, diabetes, and hypertension and might open new ways for the prevention and management of cognitive decline and dementia.
This paper introduces a novel architecture for optimizing radiation shielding using a genetic algorithm with dynamic penalties and a custom parallel computing architecture. A practical example ...focuses on minimizing the Total Ionizing Dose for a silicon slab, considering only the layer number and the total thickness (additional constraints, e.g., cost and density, can be easily added). Genetic algorithm coupled with Geant4 simulations in a custom parallel computing architecture demonstrates convergence for the Total Ionizing Dose values. To address genetic algorithm issues (premature convergence, not perfectly fitted search parameters), a Total Ionizing Dose Database Vault object was introduced to enhance search speed (data persistence) and to preserve all solutions’ details independently. The Total Ionizing Dose Database Vault analysis highlights boron carbide as the best material for the first layer for neutron shielding and high-Z material (e.g., Tungsten) for the last layers to stop secondary gammas. A validation point between Geant4 and MCNP was conducted for specific simulation conditions. The advantages of the custom parallel computing architecture introduced here, are discussed in terms of resilience, scalability, autonomy, flexibility, and efficiency, with the benefit of saving computational time. The proposed genetic algorithm-based approach optimizes radiation shielding materials and configurations efficiently benefiting space exploration, medical devices, nuclear facilities, radioactive sources, and radiogenic devices.
At present, the search for preventive strategies for cognitive decline and dementia appears to be of crucial importance, given that the therapeutic options currently available have demonstrated ...limited efficacy. Cumulative epidemiological evidence suggested that vascular and vascular-related factors may be important for the development of age-related cognitive decline (ARCD), mild cognitive impairment (MCI), and cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia, VaD). Among vascular-related factors, metabolic syndrome (MetS) has been associated with the reduced risk of predementia syndromes (ARCD and MCI), overall dementia, and VaD, but contrasting findings also exist on the possible role of MetS in AD. In the next future, trials could then be undertaken to determine if modifications of these risks including inflammation, another factor probably related to MetS, could lower risk of developing cognitive decline. If MetS is associated with increased risk of developing cognitive impairment, then early identification and treatment of these individuals at risk might offer new avenues for disease course modification. Future research aimed at identifying mechanisms that underlie comorbid associations will not only provide important insights into the causes and interdependencies of predementia and dementia syndromes, but will also inspire novel strategies for treating and preventing these disorders. At present, vascular risk factor management could be decisive in delaying the onset of dementia syndromes or in preventing the progression of predementia syndromes.
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