The relationship between atherosclerosis and dementia.

OBJECTIVE: The main objective is to confirm a hypothesis that atherosclerosis, through various mechanisms, considerably influences cognitive impairment and significantly increases the risk for developing dementia. Complete sample should be 920 individuals. The present study aimed to analyse epidemiological data from a questionnaire survey. METHODS: The work was carried out in the form of an epidemiological case control study. Subjects are enrolled in the study based on results of the following examinations carried out in neurology departments and outpatient centres during the project NU20-09-00119 from 2020 to 2023. Respondents were divided into four research groups according to the results of clinical examination for the presence of atherosclerosis and dementia. The survey was mainly concerned with risk factors for both atherosclerosis and dementia. It contained questions on lifestyle factors, cardiovascular risk factors, leisure activities, and hobbies. RESULTS: Analysis of the as yet incomplete sample of 877 subjects has yielded the following selected results: on average, 16% of subjects without dementia had primary education while the proportion was 45.2% in the group with both dementia and atherosclerosis. Subjects with dementia did mainly physical work. Low physical activity was more frequently noted in dementia groups (Group 2 - 54.4% and Group 3 - 47.2%) than in subjects without dementia (Group 1 - 19.6% and Group 4 - 25.8%). Coronary heart disease was more frequently reported by dementia patients (33.95%) than those without dementia (16.05%). CONCLUSION: Cognitively impaired individuals, in particular those with vascular cognitive impairment, have poorer quality of life and shorter survival. Risk factors contributing to such impairment are similar to those for ischaemic or haemorrhagic stroke. It may be concluded that most of the analysed risk factors play a role in the development of both atherosclerosis and dementia.

Association between polymorphism rs2421943 of the insulin-degrading enzyme and schizophrenia: Preliminary report.

BACKGROUND: Insulin-degrading enzyme (IDE) is an important gene in studies of the pathophysiology of type 2 diabetes mellitus (T2DM). Recent studies have suggested a possible link between type 2 diabetes mellitus (T2DM) and the pathophysiology of schizophrenia (SZ). At the same time, significant changes in insulin-degrading enzyme (IDE) gene expression have been found in the brains of people with schizophrenia. These findings highlight the need to further investigate the role of IDE in schizophrenia pathogenesis. METHODS: We enrolled 733 participants from the Czech Republic, including 383 patients with schizophrenia and 350 healthy controls. Our study focused on the single nucleotide polymorphism (SNP) rs2421943 in the IDE gene, which has previously been associated with the pathogenesis of Alzheimer's disease. The SNP was analyzed using the PCR-RFLP method. RESULTS: The G allele of the rs2421943 polymorphism was found to significantly increase the risk of developing SZ (p < 0.01) when a gender-based analysis showed that both AG and GG genotypes were associated with a more than 1.55 times increased risk of SZ in females (p < 0.03) but not in males. Besides, we identified a potential binding site at the G allele locus for has-miR-7110-5p, providing a potential mechanism for the observed association. CONCLUSION: Our results confirm the role of the IDE gene in schizophrenia pathogenesis and suggest that future research should investigate the relationship between miRNA and estrogen influence on IDE expression in schizophrenia pathogenesis.

HPV and RAD51 as Prognostic Factors for Survival in Inoperable Oral and Oropharyngeal Cancer in Patients Unfit for Chemotherapy Treated with Hyperfractionated Radiotherapy.

INTRODUCTION: The incidence of advanced oral cavity and oropharyngeal cancers is generally high. Treatment outcomes for patients, especially those unfit for comprehensive cancer treatment, are unsatisfactory. Therefore, the search for factors to predict response to treatment and increase overall survival is underway. OBJECTIVE: This study aimed to analyze the presence of 32 HPV genotypes in tumor samples of 34 patients and the effect of HPV status and RAD51 on overall survival. METHOD: Tumor samples of 34 patients with locally advanced oropharyngeal or oral cavity cancer treated with accelerated radiotherapy in monotherapy were analyzed using reverse hybridization and immunohistochemistry for the presence of HPV and RAD51. Its effect on overall survival was examined. RESULTS: Only two types of HPV were identified-HPV 16 (dominant) and HPV 66 (two samples). The HPV positivity was associated with a borderline insignificant improvement in 2-year (p = 0.083), 5-year (p = 0.159), and overall survival (p = 0.083). Similarly, the RAD51 overexpression was associated with borderline insignificant improvement in 2-year (p = 0.083) and 5-year (p = 0.159) survival. CONCLUSION: We found no statistically significant differences but detected trends toward improvement in the survival of HPV-positive and RAD51 overexpressing patients unfit for surgical treatment or chemotherapy treated with hyperfractionated radiotherapy. The trends, however, indicate that in a larger group of patients, the effects of these two parameters would likely be statistically significant.

Is Alzheimer's disease a type 3 diabetes? A review.

OBJECTIVES: This is a review article that deals with the question of whether type 2 diabetes is a risk factor for the development of Alzheimer's disease. METHODS: We searched the PubMed database and relevant publications were selected for review. The introduction, which describes the possibilities of how type 2 diabetes can affect the development of Alzheimer's disease, is followed by other questions related to this issue: May on the contrary Alzheimer's disease induce type 2 diabetes? What is a relative risk for type 2 diabetes to induce dementia? How type 2 diabetes influence conversion of mild cognitive impairment to Alzheimer's disease? What is the role of antidiabetic medication? Proposition of term "type 3 diabetes" for Alzheimer's disease. RESULTS: Type 2 diabetes mellitus has been shown to increase the risk for cognitive decline and dementia, such as Alzheimer's disease and vascular dementia. Despite extensive research and numerous publications, the mechanisms underlying these associations remain unclear. CONCLUSIONS: Because of similar molecular and cellular features among type 1 and type 2 diabetes and insulin resistance associated with memory deficit and cognitive decline, some researches proposed the term "type 3 diabetes" for Alzheimer's disease.

Neuropsychological tests and prediction of dementia in association with the degree of carotid stenosis.

This study constitutes a cross sectional analysis of the association between cognitive impairment defined by neuropsychological tests and carotid stenosis. The main objective was to compare the results of the Mini-Mental State Examination (MMSE) and Addenbrooke's Cognitive Examination-Revised (ACE-R) with regard to the degree of carotid stenosis. The sample comprised 744 patients who underwent a carotid duplex ultrasound and cognitive function testing (by ACE-R and MMSE). A multivariable analysis of potential confounding factors was completed. The significance of the different number of positive (MMSE ≤ 27, ACE-R ≤ 88) and negative (MMSE ≥ 28, ACE-R ≥ 89) results of the neuropsychological tests was analysed with regard to the degree of carotid stenosis (50-99%). Neuropsychological test results were also compared between carotid stenosis of 50-69%, 70-89%, and 90-99%. For both the MMSE and ACE-R, a difference was observed between positive and negative test results when higher degrees of stenosis were present. However, for the ACE-R only, more severe stenosis (80-89%, 90-99%) was predominantly associated with positive test results (p-value < 0.017). The same dependence for ACE-R (although not statistically significant) was observed in the group of patients without an ischemic stroke (confounding factor). In the case of the MMSE and more severe stenosis, negative results predominated, regardless of the confounding factor. There were no statistically significant differences in test results between carotid stenosis of 50-69%, 70-89%, and 90-99%. The results suggest that for assessing the early risk of cognitive impairment in patients with carotid atherosclerosis, the ACE-R appears more suitable than the MMSE.

Single Nucleotide Polymorphism rs11136000 of CLU Gene (Clusterin, ApoJ) and the Risk of Late-Onset Alzheimer's Disease in a Central European Population.

Clusterin (CLU; also known as apolipoprotein J, ApoJ) is a protein of inconstant structure known to be involved in diverse processes inside and outside of brain cells. CLU can act as a protein chaperon or protein solubilizer, lipid transporter as well as redox sensor and be anti- or proapoptotic, depending on context. Primary structure of CLU is encoded by CLU gene which contains single nucleotide polymorphisms (SNP's) associated with the risk of late-onset Alzheimer's disease (LOAD). Studying a sample of Czech population and using the case-control association approach we identified C allele of the SNP rs11136000 as conferring a reduced risk of LOAD, more so in females than in males. Additionally, data from two smaller subsets of the population sample suggested a possible association of rs11136000 with diabetes mellitus. In a parallel study, we found no association between rs11136000 and mild cognitive impairment (MCI). Our findings on rs11136000 and LOAD contradict those of some previous studies done elsewhere. We discuss the multiple roles of CLU in a broad range of molecular mechanisms that may contribute to the variability of genetic studies of CLU in various ethnic groups. The above discordance notwithstanding, our conclusions support the association of rs1113600 with the risk of LOAD.

Assessment of toe brachial index validity in diabetic patients - interim results.

INTRODUCTION: The toe brachial index (TBI) is recommended for the detection of lower extremity arterial disease (LEAD) in case of reduced efficacy of the ankle brachial index (ABI), which most often occurs in diabetics. In this case, TBI is expected to give more accurate results. There are not many studies dealing with the use of TBI specifically in diabetics and the results are different. OBJECTIVE: The purpose of this work is to present the interim results of the study, whose main objective is to assess the validity of TBI in diabetics and to determine whether this method provides improvements over the ABI. METHODS: In the first phase of the study, 42 limbs were examined in 21 patients with type 2 diabetes. ABI was measured using the automatic oscillometric method (ABI OSC) and the manual method using the pencil doppler (ABI DPP). TBI was determined using an automatic plethysmographic method. The reference examination of the arteries of the lower limbs was performed using duplex ultrasonography (DUS). A paired t-test was used to compare the individual TBI and ABI methods. Cut-off points ABI < 0.9; TBI < 0.7; and DUS stenosis > 50 % were used to evaluate validity parameters. RESULTS: The individual ABI and TBI methods gave different results (p < 0.05). In eight limbs of the total number, LEAD was demonstrated using DUS. The best validity parameters were demonstrated by the TBI - sensitivity 0.88; specificity 0.88; positive predictive value 0.64; negative predictive value 0.97, positive likelihood ratio 7.44; negative likelihood ratio 0.14. The ABI method of calculation, that uses lower systolic blood pressure determined from two measurement sites on the ankle as a numerator, had a higher validity parameters. The ABI OSC did not correctly detect a single limb with stenosis > 50 % in this cohort. CONCLUSION: According to the interim results of this work, the TBI was more suitable for the detection of LEAD in diabetics in comparison with ABI.

Epidemiological study on more accurate diagnosis of prostate cancer.

OBJECTIVE: The study aimed at assessing the potential benefit of prostate health index (PHI) for early detection of prostate cancer (PCa) and the use of PHI as a marker predicting the presence of PCa before performing prostate biopsy. METHODS: The study comprised 55 males who underwent prostate biopsy. Before the procedure, blood samples were collected to test prostate specific antigen (PSA) and free/total PSA ratio (%fPSA) and PHI was calculated. Receiver operating characteristic (ROC) analysis was used to assess the benefit of these values for predicting the presence of PCa. RESULTS: Based on histological examination 31 males were diagnosed with PCa, the remaining 24 were negative. Among the PCa patients, 39% had a Gleason score of 6, 26% had a score of 7 and 35% had a score of 8-10. There were statistically significant differences in PHI and PSA between males with and without PCa. The areas under the ROC curve for %fPSA, total PSA and PHI were 0.712, 0.746 and 0.789, respectively. PHI showed the best predictive ability to estimate biopsy results. If the cut-off criterion PHI > 36.4 (77.42% sensitivity, 66.67% specificity) had been used, 41.7% of males would have avoided unnecessary biopsy. CONCLUSION: The use of PHI may considerably improve the accuracy of PCa detection in patients with elevated PSA and thus reduce the number of unnecessary biopsies.

Alterations of glycaemia, insulin resistance and body mass index within the C-peptide optimal range in non-diabetic patients.

The study focused on changes or cut-offs of glycaemia, insulin resistance and body mass index within the C-peptide reference range (260-1730 pmol/l). The metabolic profile of individuals in the Czech Republic without diabetes (n = 3186) was classified by whiskers and quartiles of C-peptide into four groups with the following ranges: 290-510 (n = 694), 511-710 (n = 780), 711-950 (n = 720) and 951-1560 pmol/l (n = 673). Fasting levels of glucose, insulin, HOMA IR (Homeostasis Model Assessment for Insulin Resistance) and BMI (body mass index) were compared by a relevant C-peptide range. Participants taking medication to control glycaemia were excluded. The evaluation involved correlations between C-peptides and the above parameters, F-test and t-test. Changes in glucose levels (from 5.3 to 5.6 mmol/l) between the groups were lower in comparison to insulin, which reached relatively greater changes (from 4.0 to 14.2 mIU/l). HOMA IR increased considerably with growing C-peptide concentrations (0.9, 1.5, 2.2 and 3.5) and BMI values showed a similar trend (28.3, 31.0, 33.6 and 37.4). Considerable changes were observed for insulin (5.2 mIU/l, 57.8%) and HOMA IR (1.3, 61.3%) between groups with C-peptide ranges of 711-950 and 951-1560 pmol/l. Although correlations involving C-peptide, insulin, glucose and BMI seemed to be non-significant (up to rxy = 0.25), the mean values of insulin, HOMA IR and BMI showed statistically significant changes between all groups with various C-peptide concentrations (p ≤ 0.001). Generally, most important differences appeared in glucose metabolism and body mass index between C-peptide ranges of 711-950 and 951-1560 pmol/l. Absolute and relative changes of C-peptide concentrations are possible to use for the assessment of glucose regulatory mechanism. The spectrum of investigated parameters could be a useful tool to prevent the risks linked with the alterations of glycaemia.

Optimal Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) Cut-Offs: A Cross-Sectional Study in the Czech Population.

Background and Objectives: The key pathogenetic mechanism of glucose metabolism disorders, insulin resistance (IR), can be assessed using the Homeostasis Model Assessment of IR (HOMA-IR). However, its application in clinical practice is limited due to the absence of cut-offs. In this study, we aimed to define the cut-offs for the Czech population. Methods: After undergoing anthropometric and biochemical studies, the sample of 3539 individuals was divided into either nondiabetics, including both subjects with normal glucose tolerance (NGT, n = 1947) and prediabetics (n = 1459), or diabetics (n = 133). The optimal HOMA-IR cut-offs between subgroups were determined to maximize the sum of the sensitivity and specificity for diagnosing type 2 diabetes mellitus (T2DM) or prediabetes. The predictive accuracy was illustrated using receiver operating characteristic (ROC) curves. Logistic regression was performed to assess the association between a target variable (presence/absence of T2DM) depending on the HOMA-IR score as well as on the age and sex. Results: The HOMA-IR cut-off between nondiabetics and diabetics for both sexes together was 3.63, with a sensitivity of 0.56 and a specificity of 0.86. The area under the ROC curve was 0.73 for T2DM diagnosing in both sexes. The HOMA-IR cut-off between the NGT subjects and prediabetics was 1.82, with a sensitivity of 0.60 and a specificity of 0.66. Logistic regression showed that increased HOMA-IR is a risk factor for the presence of T2DM (odds ratio (OR) 1.2, 95% confidence interval (CI) 1.14-1.28, p < 0.0001). The predictive ability of HOMA-IR in diagnosing T2DM is statistically significantly lower in females (OR 0.66, 95% CI 0.44-0.98). The results are valid for middle-aged European adults. Conclusions: The results suggest the existence of HOMA-IR cut-offs signaling established IR. Introduction of the instrument into common clinical practice, together with the known cut-offs, may contribute to preventing T2DM.

CHAT gene polymorphism rs3810950 is associated with the risk of Alzheimer's disease in the Czech population.

BACKGROUND: Cholinergic hypothesis of Alzheimer's disease (AD) is based on the findings that a reduced and/or perturbed cholinergic activity in the central nervous system correlates with cognitive decline in patients with Alzheimer's disease. The hypothesis resulted in the development of centrally-acting agents potentiating cholinergic neurotransmission; these drugs, however, only slowed down the cognitive decline and could not prevent it. Consequently, the perturbation of the central cholinergic signalling has been accepted as a part of the Alzheimer's aetiology but not necessarily the primary cause of the disease. In the present study we have focused on the rs3810950 polymorphism of ChAT (choline acetyltransferase) gene that has not been studied in Czech population before. METHODS: We carried out an association study to test for a relationship between the rs3810950 polymorphism and Alzheimer's disease in a group of 1186 persons; 759 patients with Alzheimer's disease and 427 control subjects. Furthermore, we performed molecular modelling of the terminal domain (1st-126th amino acid residue) of one of the ChAT isoforms (M) to visualise in silico whether the rs3810950 polymorphism (A120T) can change any features of the tertiary structure of the protein which would have a potential to alter its function. RESULTS: The AA genotype of CHAT was associated with a 1.25 times higher risk of AD (p <  0.002) thus demonstrating that the rs3810950 polymorphism can have a modest but statistically significant effect on the risk of AD in the Czech population. Furthermore, the molecular modelling indicated that the polymorphism is likely to be associated with significant variations in the tertiary structure of the protein molecule which may impact its enzyme activity. CONCLUSIONS: Our findings are consistent with the results of the meta-analytical studies of the relationship between rs3810950 polymorphism and AD and provide further material evidence for a direct (primary) involvement of cholinergic mechanisms in the etiopathogenesis of AD, particularly as a factor in cognitive decline and perturbed conscious awareness commonly observed in patients with AD.

Comprehensive Group Therapy of Obesity and Its Impact on Selected Anthropometric and Postural Parameters.

OBJECTIVE: Obesity is a multifactorial disease. This non-infectious epidemic has reached pandemic proportions in the 21 century. Posture is a dynamic process referring to an active maintenance of body movement segments against the action of external forces. The aim of the study was to investigate the effect of comprehensive group therapy for obese persons on selected anthropometric and postural parameters. METHODS: The study comprised 53 females with a mean age of 44.5 years (range 29­65 years, standard deviation 9.42 years, median 44 years), who completed a controlled weight loss programme. At the beginning and at the end of the programme, anthropometric parameters (Body Mass Index (BMI), weight and waist circumference) were measured and the posturography tests Limits of Stability (LOS) and Motor Control Test (MCT) were performed using the NeuroCom's SMART EquiTest system. The data were statistically analyzed using R software at a level of significance of 0.05. RESULTS: There were positive changes after the controlled weight loss programme in anthropometric parameters (BMI reduction, with p<0.001; waist circumference reduction, with p<0.001; and weight loss, with p<0.001), postural stability with statistically significant (p<0.05) improvements in both postural activity (LOS test parameters) and reactions (MCT parameters). CONCLUSION: The study showed a statistically significant effect of comprehensive group therapy for obesity in terms of reductions in waist circumference, body weight and BMI, and thus the overall reduction of both cardiovascular and metabolic risks, as well as improved postural skills (activity and reactions).

Epidemiology and risk factors of schizophrenia.

Schizophrenia is a severe mental disorder that affects approximately one percent of the general population. The pathogenesis of schizophrenia is influenced by many risk factors, both environmental and genetic. The environmental factors include the date of birth, place of birth and seasonal effects, infectious diseases, complications during pregnancy and delivery, substance abuse and stress. At the present time, in addition to environmental factors, genetic factors are assumed to play a role in the development of the schizophrenia. The heritability of schizo- phrenia is up to 80%. If one parent suffers from the condition, the probability that it will be passed down to the offspring is 13%. If it is present in both parents, the risk is more than 20%. The opinions are varied as to the risk factors affecting the development of schizophrenia. Knowing these factors may greatly contribute to prevention of the condition.

Air Pollution and Potential Health Risk in Ostrava Region - a Review.

AIM: The aim of this review was to collect all available data about air pollution in Ostrava, which is one of the most polluted area in central Europe and to make a concise assessment of health risks resulting from historical exposures of air pollutants since the beginning of the monitoring, i.e. since 1970 to the present time. METHODS: All available information sources (the Czech Hydrometeorological Institute, the Institute of Public Health in Ostrava or publications) were used. To evaluate the exposures both short-term (hourly and daily) data and long term (yearly) data during 45 years were analysed. For health risk assessment the relationship between exposure and biological effects of pollutants published by the WHO and the US EPA were employed. RESULTS: During the studied period annual average concentrations of PM10 ranged from 25 to 96 µg/m3; PM2.5 from 24 to 45 µg/m3; SO2 from 3.4 to 101.5 µg/m3; NO2 from 17.76 to 51.17 µg/m3; benzene from 0.24 to 9.2 µg/m3; benzo[a]pyrene from 2.1 to 14 ng/m3; arsenic from 1.2 to 9.5 ng/m3. Since the turn of the 80s and 90s of the 20th century trend of air pollutant concentrations has been decreasing until the turn of millennium, when it stopped, and it has been constant until present time. However, presented results demonstrate that the citizens of Ostrava have been exposed to relatively high concentrations of pollutants in comparison to other similar cities. The most significant pollutants contributing to health risks are airborne dust (PM10, PM2.5), benzene and benzo[a]pyrene. The long-term average health risk of PM10 has increased in case of postneonatal infant mortality up to 30%; prevalence of bronchitis in children up to 61%; and incidence of chronic bronchitis in adults up to 89%. The long-term average health risk of PM2.5 increased for all-cause mortality in persons aged 30+ years up to 22%; cardiopulmonary related mortality up to 25%; and lung cancer related mortality up to 39%. The highest carcinogenic risk is observed in benzo[a]pyrene, when the range of individual lifetime carcinogenic risk is up to 1.25*10-3. This assessment is valid according to the strict carcinogenic risk by the WHO, while the maximum carcinogenic risk according the US EPA is 7.2*10-5. CONCLUSIONS: A significant reduction of the pollutants' concentrations in Ostrava in the nineties of the last century does not mean a required improvement of outdoor air quality to the desired level. Persisting episodes with a very strong short-term increase of the concentration of PM10 and PM2.5, as well as long-term load of these substances on the population is very high. Health risks from such burdens are likely to lead to a higher mortality and morbidity especially from specific diseases.

A Summary of Environmental Health Studies in the City of Ostrava and the Surrounding Region in the Czech Republic.

AIM: This study is concerned with environmental health studies conducted in Ostrava (Czech Republic) and the surrounding region since the early nineties. METHODS: Various databases, journals and reports, including internal or unpublished reports, were reviewed to assess the individual publications. A brief description of the studies and main results were collated. RESULTS: The city of Ostrava and the surrounding region is an important industrial centre in the Czech Republic with a long-term heavy environmental and occupational disease burden. In spite of the theoretically assessed decline of health risks related to decreasing concentrations of compounds in the environment in recent years, it still poses a disproportionally high risk for the city residents. There are a number of studies suggesting supportive evidence, but they are highly variable in their approach to this topic resulting in a high uncertainty of observed associations and consistency of results. Most of the studies were focused on specific contexts, without any relation to environmental factors. CONCLUSIONS: A more systematic approach is needed to assess environmental health burden of diseases especially in relation to air pollution, based on the prospective cohort study, that would lead to sufficient new evidence for accurate and updated description of the environmental health burden in Ostrava.

Bioaerosols in the Suburbs of Ostrava during a One Year Period.

AIM: The aim of this paper is to provide information about the concentrations of airborne bioaerosols (airborne bacteria, fungi and endotoxins) in outdoor suburban environments in Ostrava, Moravian-Silesian region, Czech Republic. METHODS: The methods were based on systematic bioaerosol monitoring during one calendar year, subsequent analysis of the samples and statistical processing. The regression, correlation analysis and analysis of variance for one factor and pairwise comparisons were performed on bioaerosol data to determine their dependence on season, daytime, temperature, humidity and dew point. RESULTS: The results show higher fungi concentrations especially in summer (corrected mean 365 colony forming units - CFU per m3) compared to other seasons (75-209 CFU/m3) and higher concentrations of bacteria in the evening (380 CFU/m3) compared to other parts of the day and seasons (in summer 206-252 CFU/m3 and in winter 81-87 CFU/m3). Concentrations of endotoxins were relatively low throughout the year, on average 0,056 endotoxin units (EU) per m3. CONCLUSIONS: The concentration of bioaerosol (bacteria, fungi and endotoxins) were found in ambient air at substantially lower levels than in an indoor environment. Although the concentrations of this bioaerosol greatly fluctuate with temperature, dew point, season and daytime, they do not represent increased health risks.

Is Mild Cognitive Impairment a Precursor of Alzheimer's Disease? Short Review.

Mild Cognitive Impairment (MCI) may be a precursor of Alzheimer's disease (AD). There is a boundary area between normal aging and dementia. In practice, the term "age related cognitive decline" has been used interchangeably with "normal aging". Alternatively, the term "aging associated cognitive decline" was introduced and defined by a performance on a standardized cognitive scale focused on learning and memory, attention and cognitive speed, language, or visuoconstructional abilities. The term "mild cognitive impairment" was adopted by Petersen in 2004 to describe a period in the course of neurodegenerative disease where cognition is no longer normal relative to age expectations, however, daily functions are not sufficiently disrupted to correlate with the diagnosis of dementia. Most of the literature refers to the amnestic form of MCI, which is likely a precursor of AD. The rate of conversion from amnestic form of MCI to AD is estimated to reach 10-15% per year. That is why MCI generated a great deal of research. When considering MCI a precursor of AD, it seems reasonable to study AD genetic markers in the MCI patients. In AD, association studies focus on genetic polymorphisms assumed to have an effect on the expression and modulation function of genes associated with AD pathogenesis (ApoE, APP, presenilin 1, presenilin 2, tau protein), and on polymorphisms related to metabolism of the aforementioned proteins (splicing, degradation). Neuropsychological assesment plays a substantial role in the diagnosis of MCI, especially in the case of identification of different MCI subtypes or typical profiles of cognitive performance in prodromal phases of neurodegenerative diseases. The optimal composition of diet may increase an average age and prevent impairment of cognitive functions at the same time. Despite the progress in early diagnosis of MCI and dementia, further research is needed on differential diagnosis and treatment. In amnestic subtype of MCI some genetic markers may already be present, predicting possible future development of AD. Pointing to the need of secondary prevention, lifestyle modifications and possible early treatment could be implemented.

Cognitive impairment, neurodegenerative disorders, and olfactory impairment: A literature review.

<br><b>Introduction:</b> The early detection and diagnosis of dementia are of key importance in treatment, slowing disease progression, or suppressing symptoms. The possible role of changes in the sense of smell is considered with regard to potential markers for early detection of Alzheimer's disease (AD).</br> <br><b>Materials and methods:</b> A literature search was conducted using the electronic databases PubMed, Scopus, and Web of Science between May 30, 2022 and August 2, 2022. The term "dementia" was searched with keyword combinations related to olfaction.</br> <br><b>Results:</b> A total of 1,288 records were identified through the database search. Of these articles, 49 were ultimately included in the analysis. The results showed the potential role of changes in the sense of smell as potential biomarkers for early detection of AD. Multiple studies have shown that olfactory impairment may be observed in patients with AD, PD, MCI, or other types of dementia. Even though smell tests are able to detect olfactory loss caused by neurodegenerative diseases, they cannot reliably distinguish between certain diseases.</br> <br><b>Conclusions:</b> In individuals with cognitive impairment or neurodegenerative diseases, olfactory assessment has repeatedly been reported to be used for early diagnosis, but not for differential diagnosis.</br>.

Polymorphism Rs2421943 of the Insulin-Degrading Enzyme Gene and the Risk of Late-Onset Alzheimer's Disease.

BACKGROUND: Insulin-degrading enzyme (IDE) is a widely distributed Zn2+-binding metalloprotease that cleaves multiple short and medium-sized peptides prone to form ß-structures. These include insulin and amyloid-ß peptides. Accumulation and fibrillation of amyloid-ß peptides leading to the formation of amyloid plaques is a characteristic sign of Alzheimer's disease (AD) pathology. OBJECTIVE: The study investigated the rs2421943 single nucleotide polymorphism (SNP) of the IDE gene as a risk factor for MCI (mild cognitive impairment) and AD. METHODS: Two independent groups of 1670 patients and controls were included. The AD group consisted of 595 patients and 400 controls; the MCI group involved 135 patients and 540 matched controls. PCR and restriction fragment length analysis were used to analyze the rs2421943 polymorphism. Using the miRBase and RNA22 prediction tools in silico indicated that the rs2421943 polymorphism is a potential target for a specific miRNA (hsa-miR-7110-5p). RESULTS: AG and GG genotypes of rs2421943 significantly increased the risk of AD, and the AG genotype increased the risk of MCI. It seems the G allele both increases the risk of AD and accelerates the transition through the MCI phase. In silico study revealed that rs2421943 is inside the sequence binding miRNA hsa-miR-7110-5p. The polymorphism could affect the rate of IDE pre-RNA (heterogeneous nuclear RNA, hnRNA) processing, resulting in slower translation, lower levels of IDE, deficient removal of amyloid-ß fragments, and greater risk of and/or accelerated progression of AD. CONCLUSION: GG and AG genotypes of the single nucleotide polymorphism rs2421943 of insulindegrading enzyme gene increase the risk of AD and MCI.

What are the real associations of homeostasis model assessment (HOMA) with body mass index and age?

INTRODUCTION: Insulin resistance (IR), a key pathogenesis mechanism of metabolic disorders, can be tested using homeostatic model assessment (HOMA). HOMA-IR quantifies peripheral tissue IR, whereas HOMA-ß determines insulin secretion. The cross-sectional study aimed to examine non-linear associations of HOMA indices with age when adjusting for body mass index (BMI), and thus to investigate the indices' ability to reflect the real development of glucose metabolism disorders over time. MATERIAL AND METHODS: The sample comprised 3406 individuals without diabetes mellitus (DM) divided into those with normal glucose metabolism (NGT, n = 1947) and prediabetes (n = 1459) after undergoing biochemical analyses. Polynomial multiple multivariate regression was applied to objectify associations of HOMA with both age and BMI. RESULTS: Mean values of HOMA-IR and HOMA-ß in individuals with NGT were 1.5 and 82.8, respectively, while in prediabetics they were 2.2 and 74.3, respectively. The regression proved an inverse non-linear dependence of pancreatic b dysfunction, expressed by HOMA-ß, on age, but did not prove a dependence on age for HOMA-IR. Both indices were positively, statistically significantly related to BMI, with a unit increase in BMI representing an increase in HOMA-IR by 0.1 and in HOMA-ß by 3.2. CONCLUSIONS: The mean values of HOMA indices showed that, compared with NGT, prediabetes is associated with more developed IR but lower insulin secretion. Both HOMA-IR and HOMA-b are predicted by BMI, but only HOMA-ß is predicted by age. HOMA indices can reflect non-linear, closer-to-reality dependencies on age, which in many epidemiological studies are simplified to linear ones. The assessment of glucose metabolism using HOMA indices is beneficial for the primary prevention of IR and thus DM.