Age-related changes in the oral mucosa immunity, including decreased contents of secretory immunoglobulins and antimicrobial peptides in saliva, along with changed balance of pro- and antiinflammatory cytokines, care risks for development of purulent-inflammatory or allergic diseases of the oral cavity. For example, denture stomatitis (DS) caused by Candida albicans occurs in about 30—70% of denture users. The purpose of this study was to assess the secretory immune state of oral mucous membranes in the patients with Candida-associated denture stomatitis. We examined 42 elderly patients (61-72 years old) with one-piece acrylic dentures for at least, 6 months (15 men and 27 women). Based on clinical and microbiological studies, the patients were divided into a group with DS (n = 24) and a group without DS (n = 18). The contents of secretory immunoglobulin A (sIgA) and proinflammatory cytokines was determined, i.e., interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNFα), and anti-inflammatory cytokines, e.g., receptor antagonist of interleukin-1 (RAIL), interleukin-4 (IL-4), interleukin-10 (IL-10), as well as antimicrobial peptides (cathelicidin LL-37, lactoferrin and alphadefensins 1-3 (HNP1-3). The sIgA levels in the salivary fluid of patients with DS (0.92 (0.80-1.26) g/l) were significantly lower (p < 0.05) than in patients without stomatitis (1.71 (1.23-2,13) g/l). In the group with advanced DS, a significant increase of IL-1β levels in saliva was observed, along with simultaneous decrease of IL-8 concentrations, compared to the other group, without differences in TNFα and IL-6 concentrations. Increased contents of IL-10 in saliva was also noted. It was shown that the concentrations of cathelicidin LL-37 in saliva of the DS patients was increased two-fold, whereas the contents of neutrophil-derived alpha-defensins (HNP 1-3) was decreased. Conclusions: The development of inflammation in denture stomatitis caused by usage of removable acrylic dentures associated with Candida albicans infection is characterized by functional insufficiency of the secretory immunity of the oral mucosa associated with decreased amounts of secretory immunoglobulin A and antimicrobial peptides of neutrophilic origin. Low levels of alpha-defensins may suggest a decrease in the functional activity of neutrophils in the elderly, thus leading to higher susceptibility to fungal infection of oral cavity.
The inflammatory process is associated with oxidative stress and the immune system hyperactivity and is aimed at inducing the restoration of damaged biological structures. However, with prolonged persistence of the immune system hyperactivity, various pathologies can form. The essence of the problem is to bring the immune system hyperactivity back to "normal" after starting the process of restoring damaged structures. On an experimental model of Cu-induced liver fibrosis (Wistar rats), we studied the possibility of eliminating the cellular immunity hyperactivity by oral and intraperitoneal injection of chlorogenic acid (CGA) to animals in comparison with the action of retinol. The effect of retinol or CGA on anatomical and histological changes in the liver, the number of immunocompetent cells (leukocytes, lymphocytes, granulocytes and monocytes), erythrocytes and platelets, and their characteristics in the peripheral blood of rats with Cu-induced fibrosis were determined. It was shown that in animals with liver fibrosis there is hyperactivity of the cellular immunity. The administration of retinol to animals with liver fibrosis three times at a dose of 300 IU/100 g of body weight did not affect to immunocompetent cells number. At the same time the number of erythrocytes in these animals decreased, their volume and anisocytosis increased, i.e. the initial stages of anemia development were manifested. Platelet counts, which were elevated in animals with fibrosis, were restored to normal after retinol addition. At the same time, the administration of CGA per os at the initial stages of the liver fibrosis development was accompanied by a decrease in the cellular immunity hyperactivity (the number of leukocytes, granulocytes decreased to the control level, and the number of monocytes remained somewhat elevated), the number of platelets also decreased to control values, i.e. CGA showed an anti-inflammatory effect. If CGA was injected intraperitoneally, it showed effects similar to retinol. CGA can be used as a biologically active substance that can eliminate the immune system hyperactivity in animals with fibrosis, and it depends on the method of administration CGA into the body.
Background. Ageing is associated with structural changes in brain regions and functional decline in cognitive domains. Noninvasive tools for identifying structural damage in the brains of older adults are relevant for early treatment. Aims. This study aims to evaluate and compare the accuracy of the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA©) in identifying gray and white matter brain damage in older individuals with varying degrees of cognitive impairment. Methods. Ninety older adults (62 women) with an average age of 69 ± 7 years were enrolled and categorized as having no cognitive impairment (NCI), mild cognitive impairment (MCI), or moderate cognitive impairment (MoCI). Magnetic resonance imaging (MRI) was utilized to assess the number, volume, and distribution of brain damage. The Fazekas and Scheltens scales were applied to the brain MRIs, and inferential statistics were employed to compare variables among the groups. Results. Cognitive impairment was observed in 56.7% of the participants (95% confidence interval (CI): 46.4–66.4%), with thirty-six older adults (40%) classified as MCI and 15 (17%) as MoCI. Cognitive impairment and medial temporal lobe (MTL) atrophy were found to be associated ( <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"><a:mi>p</a:mi><a:mo>=</a:mo><a:mn>0.001</a:mn></a:math> ), exhibiting higher mean volume scales of the MTL atrophied area in the MoCI group ( <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"><c:mi>p</c:mi><c:mo><</c:mo><c:mn>0.001</c:mn></c:math> ). The MMSE accurately revealed MTL atrophy based on the Scheltens ( <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"><e:mi>p</e:mi><e:mo><</e:mo><e:mn>0.05</e:mn></e:math> ) and Fazekas ( <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" id="M4"><g:mi>p</g:mi><g:mo><</g:mo><g:mn>0.05</g:mn></g:math> ) scales. At the same time, the MoCA accurately identified periventricular white matter (PWM) abnormalities according to the Fazekas scale ( <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" id="M5"><i:mi>p</i:mi><i:mo><</i:mo><i:mn>0.05</i:mn></i:math> ). Conclusions. The MMSE and MoCA screening tools effectively identified gray and white matter brain damage in older adults with varying degrees of cognitive impairment. Lower MMSE scores are associated with MTL atrophy and lesions, and lower MoCA scores are related to PWM lesions. The concurrent use of MMSE and MoCA is recommended for assessing structural changes in distinct brain regions.
Hearing loss is a major health challenge that can have severe physical, social, cognitive, economic, and emotional consequences on people's quality of life. Currently, the modifiable factors linked to socioeconomic inequalities in hearing health are poorly understood. Therefore, an online database search (PubMed, Scopus, and Psych) was conducted to identify literature that relates hearing loss to health inequalities as a determinant or health outcome. A total of 53 studies were selected to thematically summarize the existing literature, using a critical interpretive synthesis method, where the subjectivity of the researcher is intimately involved in providing new insights with explanatory power. The evidence provided by the literature can be summarized under four key themes: (a) There might be a vicious cycle between hearing loss and socioeconomic inequalities and lifestyle factors, (b) socioeconomic position may interact with less healthy lifestyles, which are harmful to hearing ability, (c) increasing health literacy could improve the diagnosis and prognosis of hearing loss and prevent the adverse consequences of hearing loss on people's health, and (d) people with hearing loss might be vulnerable to receiving low-quality and less safe health care. This study uses elements from theoretical models of health inequalities to formulate a highly interpretive conceptual model for examining hearing health inequalities. This model depicts the specific mechanisms of hearing health and their evolution over time. There are many modifiable determinants of hearing loss, in several stages across an individual's life span; tackling socioeconomic inequalities throughout the life-course could improve the population's health, maximizing the opportunity for healthy aging.
CaMKII has molecular memory functions because transient calcium ion stimuli can induce long-lasting increases in its synaptic localization and calcium ion–independent (autonomous) activity, thereby leaving memory traces of calcium ion stimuli beyond their duration. The synaptic effects of two mechanisms that induce CaMKII autonomy are well studied: autophosphorylation at threonine-286 and binding to GluN2B. Here, we examined the neuronal functions of additional autonomy mechanisms: nitrosylation and oxidation of the CaMKII regulatory domain. We generated a knock-in mouse line with mutations that render the CaMKII regulatory domain nitrosylation/oxidation-incompetent, CaMKII ΔSNO , and found that it had deficits in memory and synaptic plasticity that were similar to those in aged wild-type mice. In addition, similar to aged wild-type mice, in which CaMKII was hyponitrosylated, but unlike mice with impairments of other CaMKII autonomy mechanisms, CaMKII ΔSNO mice showed reduced long-term potentiation (LTP) when induced by theta-burst stimulation but not high-frequency stimulation (HFS). As in aged wild-type mice, the HFS-LTP in the young adult CaMKII ΔSNO mice required L-type voltage-gated calcium ion channels. The effects in aged mice were likely caused by the loss of nitrosylation because no decline in CaMKII oxidation was detected. In hippocampal neurons, nitrosylation of CaMKII induced its accumulation at synapses under basal conditions in a manner mediated by GluN2B binding, like after LTP stimuli. However, LTP-induced synaptic CaMKII accumulation did not require nitrosylation. Thus, an aging-associated decrease in CaMKII nitrosylation may cause impairments by chronic synaptic effects, such as the decrease in basal synaptic CaMKII.
Population aging is escalating in numerous countries worldwide; among them is Taiwan, which will soon become an aged society. Thus, aging successfully is an increasing concern. One of the factors for achieving successful aging (SA) is maintaining high physical function. The purpose of this study was to determine the physical fitness factors associated with SA in Taiwanese older adults (OAs), because these factors are intervenable. Community-dwelling OAs aged more than 65 years and residing in Northern Taiwan were recruited in this study. They received a comprehensive geriatric assessment, which includes sociodemographic data, health conditions and behaviors, activities of daily living (ADL) and instrumental ADL (IADL) function, cognitive and depressive status, and quality of life. Physical fitness tests included the grip strength (GS), 30-second sit-to-stand (30s STS), timed up-and-go (TUG), functional reach (FR), one-leg standing, chair sit-and-reach, and reaction time (drop ruler) tests as well as the 6-minute walk test (6MWT). SA status was defined as follows: complete independence in performing ADL and IADL, satisfactory cognitive status (Mini-Mental State Examination ≥ 24), no depression (Geriatric Depression Scale < 5), and favorable social function (SF subscale ≥ 80 in SF-36). Adjusted multiple logistic regression analyses were performed. Among the total recruited OAs (n = 378), 100 (26.5%) met the aforementioned SA criteria. After adjustment for sociodemographic characteristics and health condition and behaviors, some physical fitness tests, namely GS, 30s STS, 6MWT, TUG, and FR tests, were significantly associated with SA individually, but not in the multivariate model. Among the physical fitness variables tested, cardiopulmonary endurance, mobility, muscle strength, and balance were significantly associated with SA in Taiwanese OAs. Early detection of deterioration in the identified functions and corresponding intervention is essential to ensuring SA.
Introduction: Senescent cells are toxic cells. Their number increases every day and after some time it leads to the appearance of signs of aging. Senescent cells cause age-related pathologies. Objective: Simultaneous administration of dasatinib and quercetin in Ercc1-/∆ mice resulted in the partial killing of senolytic cells and improved and prolonged health, age-related symptoms and pathologies. We decided to test the senolytic effect of the combination of dasatinib and quercetin in humans. Study Design: A clinical study was conducted on 64 male volunteers aged 36 years and older. Our volunteers were divided into 4 groups, each with 16 people. The D+Q group received 50 mg dasatinib and 500 mg quercetin together once daily for 5 days. Other groups: D+P - dasatinib + placebo group; Q+P – quercetin + placebo group; P+P – placebo (dasatinib) + placebo (quercetin) group. Methods: The study was completed by screening a blood count and a stair ascending test to register and evaluate the changes. Results: Co-administration of 50 mg dasatinib with 500 mg quercetin showed a clear senolytic effect. This was confirmed by the improved results of the stair ascending test. A general blood test showed that the combination of these two drugs in such a dosage is most likely to be harmless. Conclusion: These results demonstrate the possibility of selective elimination of senescent cells in humans and the effectiveness of senolytic agents in improving health and physical performance.
Ethnopharmacological relevance: Dapivirine is one of reverse transcriptase inhibitors (RTIs). It is the prototype of diarylpyrimidines (DAPY), formerly known as TMC120 or DAPY R147681 Aim: The purpose of this study is to investigate the antitumor activity of dapivirine, one of the RTIs, on U87 glioblastoma (GBM) cells in vitro and in vivo. Materials and Methods: U87 GBM cells were cultured and treated with or without dapivirine. Cell viability was evaluated by CCK-8 (Cell Counting Kit 8, CCK-8) assay; apoptosis was analyzed by flow cytometry; cell migration was evaluated by Boyden Chamber assay; Western blotting was performed to detect proteins related to apoptosis, epithelial-to-mesenchymal transition and autophagy. PathScan intracellular signaling array kit was used to detect important and well-characterized signaling molecules. Tumor xenograft model in nude mice was used to evaluate the antitumorigenic effect in vivo. Results: Dapivirine weakened proliferation of glioma cells and induced the apoptosis of U87 glioblastoma cells. Furthermore, dapivirine regulated autophagy and induced Akt, Bad and SAPK/JNK activations. Moreover, the inhibition of glioma cell growth by dapivirine was also observed in nude mice in vivo. Conclusion: In summary, in our study dapivirine exposure induces stress, resulting in JNK and PI3K/Akt pathway activation through diminished inhibition of the apoptosis and autophagy cascade in U87 GBM cells, which inhibits cell growth in vitro and in vivo.
Aging is defined as impaired physiological integrity, decreased function, increased susceptibility to external risk factors and various diseases. Skin, the largest organ in our body, may become more vulnerable to insult as time goes by and behave as aged skin. Here, we systemically reviewed three categories including seven hallmarks of skin aging. These hallmarks including genomic instability and telomere attrition, epigenetic alterations and loss of proteostasis, deregulated nutrient-sensing, mitochondrial damage and dysfunction, cellular senescence, stem cell exhaustion/dysregulation, and altered intercellular communication. These seven hallmarks can generally be divided into three categories including (i) causes of damages as primary hallmarks in skin aging; (ii) responses to damage as antagonistic hallmarks in skin aging; and (iii) culprits of the phenotype as integrative hallmarks in skin aging.
Numerous cities in the Russian Federation have joined the World Health Organization's (WHO) Global Network for Age-Friendly Cities and Communities since 2011. In order to do quantitative evaluations of the age-friendliness of cities, the Age-Friendly Cities and Communities Questionnaire (AFCCQ) was developed in the Netherlands. The purpose of this study was to translate and test the validity and reliability of the AFCCQ for use in the Russian Federation, and to study the views on the age-friendliness of the city of Kazan in the Republic of Tatarstan from an intergenerational perspective. Data were collected in a survey. In total, 208 people from various age cohorts met the inclusion criteria to assess the psychometric validity. Confirmatory factor analysis supported the structure with nine factors. Overall, the people in Kazan experience the age-friendliness of their city as positive. The youngest and oldest generations demonstrated the most positive scores. Only for the domain of respect and social inclusion results were reversed. The Russian language version of the AFCCQ proved a valid and reliable instrument to evaluate age-friendliness of cities and communities in Russia. Data gathered through the instrument can be used as input for planning, implementing and further monitoring of age-friendly initiatives in the country.
This paper posits that the most significant long-term existential risk to human civilization is not an acute technological or environmental catastrophe, but a chronic, systemic decay driven by the psychological and demographic consequences of a biologically capped lifespan. The entrenched expectation of mortality before 120 years fosters a condition of "temporal myopia," which cultivates cultural short-termism, consumerist nihilism, and demographic apathy. A critical and compounding aspect of this risk is the observed strong negative correlation between high cognitive ability and reproductive rates, leading to a systematic, dysgenic drain on humanity's problem-solving capacity. This creates a recursive threat far greater than any single hazard, as it erodes the intellectual capital necessary to navigate all other complex challenges. To counter this civilizational trajectory, we propose a novel biomedical paradigm: a strategy of continuous personal rejuvenation. This approach is based on utilizing in-vitro gametogenesis to generate autologous gametes, followed by auto-fertilization to create a new embryonic lineage. This protocol enables a comprehensive reset of cellular age, including the critical de novo formation of young centrioles, addressing the Centriolar Theory of Organismal Aging. The resulting young, perfectly matched adult stem cells are proposed for periodic autologous transplantation to maintain the body's regenerative potential indefinitely. We argue that this intervention transcends its medical purpose. By enabling the indefinite maintenance of cognitive and physical vitality, it allows the most capable individuals to remain active contributors for centuries, provides time for wisdom to accumulate, and transforms detrimental demographic structures. Therefore, rejuvenation biotechnology should be framed not as a mere luxury, but as a necessary civilizational safeguard—a strategic imperative to prevent a slow-motion intellectual and demographic collapse and to secure a flourishing long-term future for humanity.
Whey permeate powder is widely used in technologies of various line groups of food products, but the main limiting factor of its application is its high ash content. This research aimed to establish the efficiency of ash reduction and change of mineral profile at various stages of production for obtaining demineralized whey permeate powder suitable for further usage in technologies of lactose. The experiments were carried out following the referee method and the common methods used in research practice. The objects of research were cheese whey and its concentrate and permeate obtained in the process of ultrafiltration (UF), nanofiltration (NF), electrodialysis (ED), vacuum-evaporating and spray drying. UF made it possible to remove partially Ca2+, total phosphorus, and Mg2+ from cheese whey, NF was effective in removing part of K+, Ca2+, Fe2+, Mg2+, Cu2+, Cl- and total phosphorus from UF-permeate. Using polymer membranes made it possible to obtain the NF-concentrate containing mainly lactose and increase the efficiency of ED due to their high permeability relative to water, as well as their ability to eliminate proteins and partially some ions of mineral salts. The mass fraction of ash in the finished product decreased by 93.0% compared with cheese whey, as well as Na+ and K+ by 89-94%, and Ca2+ and Mg2+ by 60-75%; the total phosphorus – by 78%; chlorides – by 70%. The obtained results allow to justify the technological operation sequence to produce a product suitable for further usage as a raw material for highly purified lactose.
The accepted view is that animal-type organisms originated in the ocean/sea depths and then some of them migrated to land. Consumption of the electrolyte composition of deep sea water (below 200 meters) is expected to moderate the presence of organisms under terrestrial conditions. It is a fact that dehydration caused by prolonged exercise inhibits thermoregulation, reduces endurance and exercise performance. Studies conducted on animals and humans confirm that the water obtained from the depths of the sea and subsequently softened has a positive effect on the physiology of the body and the correction and prevention of pathophysiological changes. Such seawater has been shown to enhance hydration recovery and exercise performance after a dehydration exercise protocol better than bottled (de-chelated) mineral water and/or sports electrolyte drinks. We have found that water taken directly from a mineral water source (rich in chelates) or mineral ice cream made from it (preserved by chelates) is better than water from the deep sea. Chelates are compounds formed by a bond between a trace element ion and an organic ligand. Chelates form stable complexes, protect microelement ions from unwanted reactions in the environment. It is an established fact that the absorption of microelements in the body is improved in the form of chelates. Chelates are diluted in mineral water and remain on the surface of the source for 40-65 minutes. Mineral ice cream is a food product made by pouring fresh water and milk from a spring and then freezing it. Dissolving mineral water in milk preserves more than 76% of the chelates as long as the mineral ice cream is frozen. In this way, it is possible to provide many people with mineral ice cream, so that their bodies can adapt to life on land.
Physical fitness is a key element of a healthy life, and being overweight or lacking physical exercise will lead to health problems. Therefore, assessing an individual's physical health status from a non-medical, cost-effective perspective is essential. This paper aimed to evaluate the national physical health status through national physical examination data, selecting 12 indicators to divide the physical health status into four levels: excellent, good, pass, and fail. The existing challenge lies in the fact that most literature on physical fitness assessment mainly focuses on the two major groups of sports athletes and school students. Unfortunately, there is no reasonable index system has been constructed. The evaluation method has limitations and cannot be applied to other groups. This paper builds a reasonable health indicator system based on national physical examination data, breaks group restrictions, studies national groups, and hopes to use machine learning models to provide helpful health suggestions for citizens to measure their physical status. We analyzed the significance of the selected indicators through nonparametric tests and exploratory statistical analysis. We used seven machine learning models to obtain the best multi-classification model for the physical fitness test level. Comprehensive research showed that MLP has the best classification effect, with macro-precision reaching 74.4% and micro-precision reaching 72.8%. Furthermore, the recall rates are also above 70%, and the Hamming loss is the smallest, i.e., 0.272. The practical implications of these findings are significant. Individuals can use the classification model to understand their physical fitness level and status, exercise appropriately according to the measurement indicators, and adjust their lifestyle, which is an important aspect of health management.
Abstract Current editors of the journal Advances in Gerontology dedicate this short obituary paper to Prof. Vladimir N. Anisimov, one of the most famous and outstanding world gerontologists, the founder of this journal, who passed away on November 16, 2024. Vladimir Anisimov’s research interests and his contributions to both experimental and theoretical gerontology and oncology are briefly described. The authors also share their personal impressions from many years of communication with V.N. Anisimov. It is emphasized that, being an extremely versatile person, Prof. Anisimov was engaged not only in science, but also in literary work, wrote excellent books and verses, was interested in music and fine art. And, perhaps his most important characteristic, he possessed an incredible sense of humor, which the authors consider to be a necessary trait of any outstanding scientist.
To improve the health of the population, it is necessary to develop products that contain natural ingredients with antioxidant properties. The development of the technology of meat and fish molded semi-finished products of the Ayurvedic direction is relevant today. The main raw material was poultry meat. After conducting a literary review of scientific publications and comparing the chemical composition of different types of fish, we selected sea fish ‒ hake, pollock and oceanic ‒ saithe, haddock with amount of protein. The technology of molded meat and fish products allows to introduce into the composition of semi-finished products multifunctional ingredients that enrich the chemical composition of the product, increase the nutritional value, improve its taste, and expand the range of processing of raw materials without production waste. This technology makes it possible to create meat and fish semi-finished products, with a targeted change in the chemical composition, corresponding to the physiological needs of the human body, especially for children, the elderly. To identify the most optimal ratios between meat and fish raw materials, have been developed 21 samples of minced meat and fish systems. A study of the organoleptic evaluation of meat and fish semi-finished products was carried out, with the introduction of fish raw materials into the recipe from 10 to 50%. The detailed profilograms were built on the basis of the research results. The general comparative analysis allows us to state that among all the presented research samples, the best marks were obtained for sample No. 5 and No. 4 using ocean fish (haddock in the amount of 50%; saithe fish in the amount of 40%) in terms of taste, smell and consistency. As a result of studies of the physicochemical indicators of the developed minced meat and fish systems, it was found that almost all prototypes were characterized by an increased moisture content with an increase in the amount of fish raw materials. For further research, samples were selected whose recipes were the most optimal in terms of the ratio of meat and fish raw materials, namely chicken fillet and haddock fish in a ratio of 50: 50%, and chicken fillet and saithe fish ‒ 60: 40%.
The Standard Babylonian Epic of Gilgamesh is traditionally interpreted through the archetype of the heroic king and his wild companion. This article challenges that reading by arguing that the epic systematically inverts these roles to conduct a profound philosophical investigation into the nature of strength. Through close textual analysis framed by contemporary psychological and ecological theory, it demonstrates that Gilgamesh, despite his divine lineage and royal power, is characterized by profound existential, cognitive, and emotional weaknesses. His rule begins in tyrannical hybris, he depends entirely on others to interpret his own subconscious (dreams), and his response to mortality is a pathological flight into denial. In contrast, Enkidu, created from primal clay, embodies an integrated strength rooted in ecological harmony, hermeneutic wisdom, and, ultimately, stoic acceptance of his fate. The analysis further explores the tragic irony of their bond: Gilgamesh’s civilizing process actively weakens Enkidu, severing his connection to his natural strength and rendering him vulnerable to divine retribution. The epic’s resolution is found not in the victory of one archetype but in their synthesis. Gilgamesh’s journey evolves from a quest for personal immortality to an embrace of symbolic immortality through his cultural legacy—the walls of Uruk. This represents a hard-won integration of Enkidu’s lesson of acceptance with his own rebellious drive to transcend limits. The article concludes that the epic redefines true strength not as an innate attribute of divinity or nature, but as a dynamic, earned wisdom forged through relationship, loss, and the creative confrontation with human finitude.
Alzheimer's disease (AD), the leading cause of dementia, has reached epidemic proportions, with major social, medical and economical burdens. With no currently available curative treatments, both the World Health Organization and the G8 Dementia Summit recently identified dementia and AD prevention as a major public health priority. Dementia and AD have a wide range of risk factors (genetic, vascular/metabolic and lifestyle-related), which often co-occur and thus interact with each other. Previous intervention efforts aimed at preventing dementia and AD focused on the management of single risk factors, with relatively modest findings. Also, the effect of risk factors depends on age at exposure, indicating that the timing of preventive interventions needs to be carefully considered. In view of the complex multifactorial nature of AD, as well as its long pre-clinical (asymptomatic) phase, interventions simultaneously targeting multiple risk factors and disease mechanisms at an early stage of the disease are most likely to be effective. Three large European multidomain prevention trials have been launched with the goal of preventing cognitive decline, dementia and AD in older adults with different risk profiles. Pharmacological trials are also shifting towards prevention of Alzheimer dementia, by targeting at-risk individuals prior to the onset of cognitive symptoms. The current review will summarize and discuss the evidence on risk and protective factors from observational studies, ongoing lifestyle-related and pharmacological randomized controlled trials (RCTs), as well as future directions for dementia and AD prevention.
Individuals aged 80 years and older constitute the fastest growing segment of the population worldwide, leading to an expected increase in dementia cases. Education level and treatment of vascular risk factors has increased during the last decades. We examined whether this has influenced the prevalence of dementia according to DSM-III-R using population-based samples of 85-year-olds (N = 1065) examined with identical methods 1986-87 and 2008-10. The prevalence of dementia was 29.8% in 1986-87 and 21.7% in 2008-10 (OR 0.66; 95%-CI: 0.50-0.86). The decline was mainly observed for vascular dementia. The proportion with more than basic education (25.2% and 57.7%), and the prevalence of stroke (20% and 30%) increased, but the odds ratio for dementia with stroke decreased from 4.3 to 1.8 (interaction stroke*birth cohort; p = 0.008). In a logistic regression, education (OR 0.70; 95%-CI 0.51-0.96), stroke (OR 3.78; 95%-CI 2.28-6.29), interaction stroke*birth cohort (OR 0.50; 95%-CI 0.26-0.97), but not birth cohort (OR 0.98; 95%-CI 0.68-1.41), were related to prevalence of dementia. Thus, the decline in dementia prevalence was mainly explained by higher education and lower odds for dementia with stroke in later born birth cohorts. The findings may be related to an increased cognitive reserve and better treatment of stroke in later-born cohorts.
Введение. Согласно данным литературы Аппарат лазерной диагностики «ЛАЗМА СТ» не был ранее использован для доклинических исследований тканевых нарушений на мелких лабораторных животных. Цель исследования – изучение возможности использования аппарата лазерной диагностики «ЛАЗМА СТ» на мелких лабораторных животных – мутантных мышах линии С57BL/KsJYLeprdb/+ (db/db) – в качестве новой тест системы, для оценки тканевых изменений при сахарном диабете 2 типа (СД 2). Методика. Патологические изменения у мышей с СД изучали на генетической модели СД 2 у мутантных мышей С57BL/KsJYLeprdb/+ (db/db) (n=40); для контроля использовали группу фенотипически здоровых гетерозиготных мышей той же линии (db/+m) (n=16). Общее количество животных составляло 56 голов. Исследование проводили на аппарате лазерной диагностики «ЛАЗМА СТ», который адаптирован приспособлением, ограничивающим подвижность мышей во время измерений. Аппарат «ЛАЗМА СТ» позволяет осуществлять одновременный неинвазивный контроль состояния микроциркуляци крови и лимфы, а также определять уровень активности митохондриальных окислительных коферментов в тканях. Дополнительно измеряли уровень глюкозы в крови фотометрическим методом на приборе Accu-Chek (Швейцария). Результаты. Использование аппарата ЛАЗМА СТ позволило в реальном времени неинвазивно изучить в динамике нарушения микроциркуляции (крови и лимфы) и окислительного метаболизма (НАДН и ФАД) при СД 2, сопоставить их с нарушениями глюкозы в крови, а также прогнозировать тяжесть выявленных нарушений в условиях компенсации, субкомпенсации и декомпенсации. Аппарат ЛАЗМА СТ позволил одновременно выявить начавшиеся нарушения липидного и белкового обмена (пигменты-липофусцин и порфирин), которые свидетельствуют о тяжести прогноза заболевания. Выводы. Аппарат ЛАЗМА СТ, адаптированный для применения у мышей с генетической моделью СД 2 типа, представляет собой новую неинвазивную, информативную и безопасную тест-систему, позволяющую в динамике контролировать и прогнозировать тяжесть нарушений микроциркуляции и тканевых окислительно-восстановительных коферментов – НАДН и – ФАД. The aim of this study was to evaluate a possibility of using the LAZMA ST laser diagnostic apparatus in small laboratory animals, C57BL/KsJYLeprdb/+ (db/db) mutant mice, as a new test system for assessing changes in tissues in type 2 diabetes mellitus (DM2). Methods. Pathological changes were studied on a genetic model of DM2 in C57BL/KsJYLeprdb/+ (db/db) mutant mice (n=40). Phenotypically healthy heterozygous mice of the same strain (db/+m) (n=16) were used as a control group. The study was performed with a LAZMA ST laser diagnostic apparatus that was adapted for mice with a device limiting their mobility during measurements. LAZMA ST allows simultaneous noninvasive monitoring of blood and lymph microcirculation along with measurements of tissue activity of mitochondrial oxidative coenzymes. Additionally, blood glucose was measured photometrically with an Accu-Chek (Switzerland) glucometer. Results. The use of LAZMA ST allowed noninvasive, real-time evaluation of disorders in blood and lymph microcirculation and oxidative metabolism (NADH and FAD) in DM2, comparing them with glycemic disorders, and also predicting severity of these disorders in the conditions of DM2 compensation, subcompensation and decompensation. The LAZMA ST device provided simultaneous detection of the onset of lipid and protein metabolic disorders (lipofuscin and porphyrin pigments) to predict severity of the disease. Conclusion. The LAZMA ST device adapted for using in a murine genetic model of DM2 is a new, noninvasive, informative, and safe test system that allows to monitor and predict the dynamics of severity of disorders in microcirculation and tissue redox coenzymes, NADH and FAD.