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Exercise promotes health and wellness, including its operation as a protective factor against a variety of psychological, neurological, and chronic diseases. Selenium and its biomarker, selenoprotein P (SEPP1), have been implicated in health, including cancer prevention, neurological function, and dopamine signaling. SEPP1 blood serum levels were compared with a one-way ANOVA between sedentary (SED), moderately exercised (MOD) [10 m/min starting at 10 min, increasing to 60 min], and high-intensity interval training (HIIT) exercised rats [30 min in intervals of 2-min followed by a 1-min break, speed progressively increased from 10 to 21 m/min]. HIIT rats showed significantly higher serum SEPP1 concentrations compared to MOD and SED. More specifically, HIIT exercise showed an 84% increase in SEPP1 levels compared to sedentary controls. MOD rats had greater serum SEPP1 concentrations compared to SED, a 33% increase. The results indicated that increased exercise intensity increases SEPP1 levels. Exercise-induced increases in SEPP1 may indicate an adaptive response to the heightened oxidative stress. Previous studies found a significant increase in dopamine D2 receptor (D2R) binding in these same rats, suggesting a potential association between SEPP1 and dopamine signaling during exercise. Modulating antioxidants like SEPP1 through personalized therapies, including exercise, has broad implications for health, disease, and addiction.
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Loneliness, an established risk factor for both, mental and physical morbidity, is a mounting public health concern. However, the neurobiological mechanisms underlying loneliness-related morbidity are not yet well defined. Here we examined the role of genes and associated DNA risk polymorphic variants that are implicated in loneliness via genetic and epigenetic mechanisms and may thus point to specific therapeutic targets. Searches were conducted on PubMed, Medline, and EMBASE databases using specific Medical Subject Headings terms such as loneliness and genes, neuro- and epigenetics, addiction, affective disorders, alcohol, anti-reward, anxiety, depression, dopamine, cancer, cardiovascular, cognitive, hypodopaminergia, medical, motivation, (neuro)psychopathology, social isolation, and reward deficiency. The narrative literature review yielded recursive collections of scientific and clinical evidence, which were subsequently condensed and summarized in the following key areas: (1) Genetic Antecedents: Exploration of multiple genes mediating reward, stress, immunity and other important vital functions; (2) Genes and Mental Health: Examination of genes linked to personality traits and mental illnesses providing insights into the intricate network of interaction converging on the experience of loneliness; (3) Epigenetic Effects: Inquiry into instances of loneliness and social isolation that are driven by epigenetic methylations associated with negative childhood experiences; and (4) Neural Correlates: Analysis of loneliness-related affective states and cognitions with a focus on hypodopaminergic reward deficiency arising in the context of early life stress, eg, maternal separation, underscoring the importance of parental support early in life. Identification of the individual contributions by various (epi)genetic factors presents opportunities for the creation of innovative preventive, diagnostic, and therapeutic approaches for individuals who cope with persistent feelings of loneliness. The clinical facets and therapeutic prospects associated with the current understanding of loneliness, are discussed emphasizing the relevance of genes and DNA risk polymorphic variants in the context of loneliness-related morbidity.
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Spinal biomechanical alignment is now able to be altered through the use of unique sound wave technology. This methodological commentary will correlate recent studies demonstrating the ability of sound waves to carry mass, how the EPIC technique spinal procedure uses a sound wave impulse to create measurable changes in spinal alignment, and the clinical safety and efficacy of this approach. The EPIC technique is a direct genealogical descendant of the technique originally developed by the founding family of chiropractic. With sound wave therapies currently being used to break up kidney stones, called lithotripsy, in physical therapy for the treatment of soft tissue injuries, in the treatment of prostate cancer, and in the treatment of Alzheimer's disease, it is possible that the use of sound wave therapies may enter into the realm of altering joint biomechanics. Through a neurovascular examination, the EPIC technique spinal procedure can ascertain the presence of craniocervical subluxation, followed by acquiring multi-dimensional radiographic images for structural analysis. Currently using digital radiographic analysis, the EPIC technique acquires an epigenetic profile of structural asymmetries as well as a multi-directional biomechanical malposition profile of the spine, combining both profiles to ascertain the exact degrees for realignment. EPIC clinics have successfully utilized EPIC on over 20,000 cases. Comparison of pre-treatment biomechanical lateral displacement of the C1 vertebra around the Z-axis measured on digital radiographs, and post-treatment biomechanical lateral displacement of the C1 vertebra measured on digital radiographs immediately following the procedure, demonstrated an average 52% reduction in lateral biomechanical displacement around the Z-axis in a select group of over 2,000 cases. While more research is required, we are encouraged by these preliminary results. WC 265.
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Reward Deficiency Syndrome (RDS), particularly linked to addictive disorders, costs billions of dollars globally and has resulted in over one million deaths in the United States (US). Illicit substance use has been steadily rising and in 2021 approximately 21.9% (61.2 million) of individuals living in the US aged 12 or older had used illicit drugs in the past year. However, only 1.5% (4.1 million) of these individuals had received any substance use treatment. This increase in use and failure to adequately treat or provide treatment to these individuals resulted in 106,699 overdose deaths in 2021 and increased in 2022. This article presents an alternative non-pharmaceutical treatment approach tied to gene-guided therapy, the subject of many decades of research. The cornerstone of this paradigm shift is the brain reward circuitry, brain stem physiology, and neurotransmitter deficits due to the effects of genetic and epigenetic insults on the interrelated cascade of neurotransmission and the net release of dopamine at the Ventral Tegmental Area -Nucleus Accumbens (VTA-NAc) reward site. The Genetic Addiction Risk Severity (GARS) test and pro-dopamine regulator nutraceutical KB220 were combined to induce "dopamine homeostasis" across the brain reward circuitry. This article aims to encourage four future actionable items: 1) the neurophysiologically accurate designation of, for example, "Hyperdopameism /Hyperdopameism" to replace the blaming nomenclature like alcoholism; 2) encouraging continued research into the nature of dysfunctional brainstem neurotransmitters across the brain reward circuitry; 3) early identification of people at risk for all RDS behaviors as a brain check (cognitive testing); 4) induction of dopamine homeostasis using "precision behavioral management" along with the coupling of GARS and precision Kb220 variants; 5) utilization of promising potential treatments include neuromodulating modalities such as Transmagnetic stimulation (TMS) and Deep Brain Stimulation(DBS), which target different areas of the neural circuitry involved in addiction and even neuroimmune agents like N-acetyl-cysteine.
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Background: Natural and diet-derived angiogenesis inhibitors/promotors are widely found in diets. These compounds can in several ways impact the results of oncological research of angiogenesis inhibitors. Methods: We very briefly overview some of the most important examples to show how these compounds can create a bias in current research of cancer. Implications of this expert opinion cover similar angiogenesis-related diseases. Results: Significant intra-individual differences in terms of dietary intake and differential effect of food processing techniques result in differential bioactivity and bioavailability of these compounds. There are only a handful of validated dietary questionnaire to quantify natural angiogenesis inhibitors/promotors. A corollary consequence is that participants in non-randomized clinical trials will have different baseline levels of serum/plasma/tissue/organ diet-derived angiogenesis inhibitors/promotors. This will lead to creation of clinical uncertainty and a hidden bias and consequently creation of translational efficiency bias, sampling efficiency, and waste of resources. We call for developing and validating a semi-quantitative food frequency questionnaire (FFQ) to gather data on these agents, specifically designed for oncological research because there is a clear gap in the literature of oncology. Conclusions: This might facilitate the discovery of better prognostic, diagnostic, preventive measures, and therapeutic agents for the management of different cancers. Implications of this paper cover similar settings like ophthalmologic research.
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Since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism in JAMA, there has been an explosion of genetic candidate association studies, including genome-wide association studies (GWAS). To develop an accurate test to help identify those at risk for at least alcohol use disorder (AUD), a subset of reward deficiency syndrome (RDS), Blum's group developed the genetic addiction risk severity (GARS) test, consisting of ten genes and eleven associated risk alleles. In order to statistically validate the selection of these risk alleles measured by GARS, we applied strict analysis to studies that investigated the association of each polymorphism with AUD or AUD-related conditions, including pain and even bariatric surgery, as a predictor of severe vulnerability to unwanted addictive behaviors, published since 1990 until now. This analysis calculated the Hardy-Weinberg Equilibrium of each polymorphism in cases and controls. Pearson's χ2 test or Fisher's exact test was applied to compare the gender, genotype, and allele distribution if available. The statistical analyses found the OR, 95% CI for OR, and the post risk for 8% estimation of the population's alcoholism prevalence revealed a significant detection. Prior to these results, the United States and European patents on a ten gene panel and eleven risk alleles have been issued. In the face of the new construct of the "preaddiction" model, similar to "prediabetes", the genetic addiction risk analysis might provide one solution missing in the treatment and prevention of the neurological disorder known as RDS.
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Alzheimer's disease (AD) is a chronic multifactorial and complex neuro-degenerative disorder characterized by memory impairment and the loss of cognitive ability, which is a problem affecting the elderly. The pathological intracellular accumulation of abnormally phosphorylated Tau proteins, forming neurofibrillary tangles, and extracellular amyloid-beta (Aß) deposition, forming senile plaques, as well as neural disconnection, neural death and synaptic dysfunction in the brain, are hallmark pathologies that characterize AD. The prevalence of the disease continues to increase globally due to the increase in longevity, quality of life, and medical treatment for chronic diseases that decreases the mortality and enhance the survival of elderly. Medical awareness and the accurate diagnosis of the disease also contribute to the high prevalence observed globally. Unfortunately, no definitive treatment exists that can be used to modify the course of AD, and no available treatment is capable of mitigating the cognitive decline or reversing the pathology of the disease as of yet. A plethora of hypotheses, ranging from the cholinergic theory and dominant Aß cascade hypothesis to the abnormally excessive phosphorylated Tau protein hypothesis, have been reported. Various explanations for the pathogenesis of AD, such as the abnormal excitation of the glutamate system and mitochondrial dysfunction, have also been suggested. Despite the continuous efforts to deliver significant benefits and an effective treatment for this distressing, globally attested aging illness, multipronged approaches and strategies for ameliorating the disease course based on knowledge of the underpinnings of the pathogenesis of AD are urgently needed. Immunosenescence is an immune deficit process that appears with age (inflammaging process) and encompasses the remodeling of the lymphoid organs, leading to alterations in the immune function and neuroinflammation during advanced aging, which is closely linked to the outgrowth of infections, autoimmune diseases, and malignant cancers. It is well known that long-standing inflammation negatively influences the brain over the course of a lifetime due to the senescence of the immune system. Herein, we aim to trace the role of the immune system in the pathogenesis of AD. Thus, we explore alternative avenues, such as neuroimmune involvement in the pathogenesis of AD. We determine the initial triggers of neuroinflammation, which is an early episode in the pre-symptomatic stages of AD and contributes to the advancement of the disease, and the underlying key mechanisms of brain damage that might aid in the development of therapeutic strategies that can be used to combat this devastating disease. In addition, we aim to outline the ways in which different aspects of the immune system, both in the brain and peripherally, behave and thus to contribute to AD.
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Scientific studies have provided evidence that there is a relationship between violent and aggressive behaviors and addictions. Genes involved with the reward system, specifically the brain reward cascade (BRC), appear to be associated with various addictions and impulsive, aggressive, and violent behaviors. In our previous research, we examined the Taq A1 allele (variant D2 dopamine receptor gene) and the DAT-40 base repeat (a variant of the dopamine transporter gene) in 11 Caucasian boys at the Brown School in San Marcus, Texas, diagnosed with intermittent explosive disorder. Thirty supernormal controls were screened to exclude several reward-deficit behaviors, including pathological violence, and genotyped for the DRD2 gene. Additionally, 91 controls were screened to exclude ADHD, pathological violence, alcoholism, drug dependence, and tobacco abuse, and their results were compared with DAT1 genotype results. In the schoolboys vs. supercontrols, there was a significant association with the D2 variant and a trend with the dopamine transporter variant. Results support our hypothesis and the involvement of at least two gene risk alleles with adolescent violent/aggressive behaviors. This study and the research presented in this paper suggest that violent/aggressive behaviors are associated with a greater risk of addiction, mediated via various genes linked to the BRC. This review provides a contributory analysis of how gene polymorphisms, especially those related to the brain reward circuitry, are associated with violent behaviors.
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BACKGROUND: Erdheim-Chester disease (ECD) is an uncommon aggressive, multisystem form of non-Langerhans' cell histocytosis, which was firstly reported by Jakob Erdheim and William chester in 1930. The disease pathological features encompass an aberrant multiplication, overproduction and accumulation of white blood cells called histiocytes within multiple tissues and organs. Herein, we present a case of ECD owing to the rarity of this disease (roughly 550 cases have been described in the literature to date). METHODS: We discussed the clinical course, diagnostic evaluations, and the possible treatments. Our case was encountered in an Arab male in his 30's who has suffered from an ongoing bones pain for years. RESULTS: At our rheumatologic department we compiled his recent medical history, which consisted of diagnosis of central diabetes insipidus, hyperprolactinemia and secondary hypogonadism along with the previously conducted laboratory evaluations and imaging which brought to our mind the possibility of an infiltrative disease such as ECD. The diagnosis of ECD was done based on the combinations of pathognomonic radiographic osteosclerosis, neuroimaging, bones biopsies along with a careful clinical evaluation. Given the protean clinical manifestations, interferon-α was considered as our first line treatment of ECD, consequently our patient improved noticeably. CONCLUSION: Clinical presentation, imaging studies, distinctive pathological findings, followed by bone biopsy showed a non-Langerhans cell histiocytosis, supported by immunohistochemistry exams are essential for the diagnosis. Radiation therapy and Bisphosphonates in addition to cladribine, anakinra, infliximab and vemurafenib (BRAF Inhibitors) are currently advocated as promising second line treatment for patients whose response to interferon-α is unsatisfactory.
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Medula Óssea/diagnóstico por imagem , Doença de Erdheim-Chester/diagnóstico , Pâncreas/diagnóstico por imagem , Adulto , Biópsia , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Anemia is a common disorder in CKD patients. It is largely attributed to decreased erythropoietin (EPO) production and iron deficiency. Therefore, besides EPO, therapy includes iron replenishment. However, the latter induces oxidative stress. Haptoglobin (Hp) protein is the main line of defense against the oxidative effects of Hemoglobin/Iron. There are 3 genotypes: 1-1, 2-1 and 2-2. Hp 2-2 protein is inferior to Hp 1-1 as antioxidant. So far, there is no evidence whether haptoglobin phenotype affects iron-induced oxidative stress in CKD patients. Therefore, the present study examines the influence of carnitine treatment on the intravenous iron administration (IVIR)-induced oxidative stress in CKD patients, and whether Hp phenotype affects this response. TRIAL REGISTRATION: Current Controlled Trials ISRCTN5700858. This study included 26 anemic (Hb = 10.23 ± 0.28) CKD patients (stages 3-4) that were given a weekly IVIR (Sodium ferric gluconate, [125 mg/100 ml] for 8 weeks, and during weeks 5-8 also received Carnitine (20 mg/kg, IV) prior to IVIR. Weekly blood samples were drawn before and after each IVIR for Hp phenotype, C-reactive protein (CRP), advanced oxidative protein products (AOPP), neutrophil gelatinase-associated lipocalin (NGAL), besides complete blood count and biochemical analyses. RESULTS: Eight percent of CKD patients were Hp1-1, 19 % Hp2-1, and 73 % Hp2-2. IVIR for 4 weeks did not increase hemoglobin levels, yet worsened the oxidative burden as was evident by elevated plasma levels of AOPP. The highest increase in AOPP was observed in Hp2-2 patients. Simultaneous administration of Carnitine with IVIR abolished the IVIR-induced oxidative stress as evident by preventing the elevations in AOPP and NGAL, preferentially in patients with Hp2-2 phenotype. CONCLUSIONS: This study demonstrates that Hp2-2 is a significant risk factor for IVIR-induced oxidative stress in CKD patients. Our finding, that co-administration of Carnitine with IVIR preferentially attenuates the adverse consequences of IVIR, suggests a role for Carnitine therapy in these patients.
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Anemia Ferropriva/tratamento farmacológico , Carnitina/farmacologia , Compostos Férricos/administração & dosagem , Haptoglobinas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Insuficiência Renal Crônica/genética , Proteínas de Fase Aguda , Produtos da Oxidação Avançada de Proteínas/sangue , Idoso , Anemia Ferropriva/etiologia , Proteína C-Reativa/metabolismo , Estudos Cross-Over , Feminino , Compostos Férricos/efeitos adversos , Genótipo , Haptoglobinas/genética , Humanos , Lipocalina-2 , Lipocalinas/sangue , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/genética , Fenótipo , Estudos Prospectivos , Proteínas Proto-Oncogênicas/sangue , Insuficiência Renal Crônica/complicaçõesRESUMO
Brown tumors are rare focal giant cell lesions of the bone caused by primary hyperparathyroidism (HPT). Brown tumor was reported in 1891; it presents as the end-stage findings of HPT. Common involvements are skull and pelvic girdle. We describe a case of 46-year-old female hemodialysis patient, with secondary HPT in whom multiple masses lesions of the left maxillary sinus and frontal bone were radiologically suspected to be brown tumor. This unusual manifestation of secondary HPT can be expected to occur with increased longevity of patients with renal failure and illustrates the need to include brown tumor in the differential diagnosis.
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Bilateral striopallidodentate calcinosis, commonly known as Fahr's disease is a rare clinical entity present mainly with extrapyramidal signs and accompanied with metabolic, biochemical, neuroradiological and neuropsychiatric situations. It is characterised by the symmetrical and bilateral intracranial deposition of calcium associated with cell loss in the basal ganglia, cerebral cortex and cerebellum.In this study, we discussed two brothers' cases of Fahr's diseases who presented with different symptomatology. The first presented with walking difficulty, cramps and dysarthria and moderate memory impairment whereas the second with vertigo, ataxia, forgetfulness and headache. CT scans of both patients revealed intracranial diffuse bilateral calcifications in the basal ganglia and the cerebellum. The second patient revealed progressive cerebral atrophy but reduction in the calcification. Fahr's disease, although encountered rarely, should also be taken into account in the differential diagnosis of cases with abnormal intracranial calcifications along with other familial, congenital and metabolic diseases and syndromes.
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Doenças dos Gânglios da Base/diagnóstico , Calcinose/diagnóstico , Doenças Neurodegenerativas/diagnóstico , Irmãos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To determine whether the consumption of tobacco used in Water-Pipe by drivers increases the risk of a motor vehicle collision as a consequence of hypoxia. DESIGN: Analytical case-control study. DATA SOURCES: Seventy exclusive Water-Pipe smokers (Experimental Group--EG)--mean age ± SD: 29.47 ± 10.45 years; mean number of weekly WPS, (6.9 ± 3.7); mean duration of WPS (WPS) is (7.5 ± 2.1 years)--and thirty non-smoker (Control Group--CG; mean age ± SD: 36.33 ± 13.92 years) were recruited during 2011 from two Arab villages located in the Galilee, northern Israel. METHODS: We performed a case-control study exclusively among Water-Pipe smokers with an appropriate non smokers control group. Demographic questionnaire, Pulse Oxymeter for blood oxygenation measure and a driver simulator for measuring various participants driving behaviors were utilized. Statistical analysis for analyzing the different variables, Pearson's x2 analysis for the comparison of categorical variables, continuous variable is compared using Student's t-test and for testing the correlation between the different variables and bivariate correlation analysis were applied. RESULTS: In the (EG) following WPS, we observed increase in the pulse rate--from 80 to 95 (t = 11.84, p < 0.05) and decrease in saturation level from 97.9 to 97.32, the decrease is statistically significant (t = 3.01, p < 0.05) versus no change in (CG). An increased number of accidents among EG (OR is 1.333 with CI of 1.008-1.776), while in CG, an insignificantly decrease (t = 3.08, p < 0.05). In EG an increase in centerline crossings (OR is 1.306 with CI of 1.016-1.679), also the total time not being within the lane was increased and the estimated (OR: 1.329; CI: 1.025-1.722). WPS increases the number of accidents by 33% and Hypoxia can cause driving behavioral turbulences. CONCLUSION: The results show that WPS has a significant impact on driving behavior and on the risk of being involved in road accidents and causing driving to become riskier and less careful and stable. To the best of our knowledge, this is the first time such relationships have been tested. After WPS the total number of traffic accidents and driving violations increase. The results show a significant increase in the pulse rate immediately after WPS with a decrease in the saturation rate (the level of blood oxygenation); these changes continue half an hour after WPS.
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Condução de Veículo , Equipamentos e Provisões , Nicotiana , Fumar , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Israel , Masculino , Pessoa de Meia-IdadeRESUMO
It is well established that in both food- and drug-addicted individuals, there is dopamine resistance due to an association with the DRD2 gene A1 allele. Evidence is emerging whereby the potential of utilizing a natural, nonaddicting, safe, putative D2 agonist may find its place in recovery from reward deficiency syndrome (RDS) in patients addicted to psychoactive chemicals. Utilizing quantitative electroencephalography (qEEG) as an imaging tool, we show the impact of Synaptamine Complex Variant KB220™ as a putative activator of the mesolimbic system. We demonstrate for the first time that its intravenous administration reduces or "normalizes" aberrant electrophysiological parameters of the reward circuitry site. For this pilot study, we report that the qEEGs of an alcoholic and a heroin abuser with existing abnormalities (ie, widespread theta and widespread alpha activity, respectively) during protracted abstinence are significantly normalized by the administration of 1 intravenous dose of Synaptamine Complex Variant KB220™. Both patients were genotyped for a number of neurotransmitter reward genes to determine to what extent they carry putative dopaminergic risk alleles that may predispose them for alcohol or heroin dependence, respectively. The genes tested included the dopamine transporter (DAT1, locus symbol SLC6A3), dopamine D4 receptor exon 3 VNTR (DRD4), DRD2 TaqIA (rs1800497), COMT val158 met SNP (rs4680), monoamine oxidase A upstream VNTR (MAOA-uVNTR), and serotonin transporter-linked polymorphic region (5HTTLPR, locus symbol SLC6A4). We emphasize that these are case studies, and it would be unlikely for all individuals to carry all putative risk alleles. Based on previous research and our qEEG studies (parts 1 and 2 of this study), we cautiously suggest that long-term activation of dopaminergic receptors (ie, DRD2 receptors) will result in their proliferation and lead to enhanced "dopamine sensitivity" and an increased sense of happiness, particularly in carriers of the DRD2 A1 allele. This is supported by a clinical trial on Synaptamine Complex Variant KB220™ using intravenous administration in > 600 alcoholic patients, resulting in significant reductions in RDS behaviors. It is also confirmed by the expanded oral study on Synaptose Complex KB220Z™, published as part 2 of this study. Future studies must await both functional magnetic resonance imaging and positron emission tomography scanning to determine the acute and chronic effects of oral KB220™ on numbers of D2 receptors and direct interaction at the nucleus accumbens. Confirmation of these results in large, population-based, case-controlled experiments is necessary. These studies would provide important information that could ultimately lead to significant improvement in recovery for those with RDS and dopamine deficiency as a result of a multiple neurotransmitter signal transduction breakdown in the brain reward cascade.
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Alcoolismo/genética , Agonistas de Dopamina/uso terapêutico , Dependência de Heroína/genética , Polimorfismo de Nucleotídeo Único , Receptores de Dopamina D2/efeitos dos fármacos , Recompensa , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Síndrome de Abstinência a Substâncias/genética , Alcoolismo/diagnóstico , Alcoolismo/tratamento farmacológico , Alelos , Eletroencefalografia/efeitos dos fármacos , Seguimentos , Dependência de Heroína/diagnóstico , Dependência de Heroína/tratamento farmacológico , Humanos , Injeções Intravenosas , Masculino , Projetos Piloto , Polimorfismo Genético , Receptores de Dopamina D2/genética , Medição de Risco , Síndrome de Abstinência a Substâncias/diagnóstico , Resultado do Tratamento , Adulto JovemRESUMO
We have found an unusually high prevalence of Alzheimer's disease (AD) in Wadi Ara, an inbred Arab community in northern Israel. Allele frequencies of 4.5% and 3.5% were found for the apolipoprotein E e4 allele among AD cases and nondemented controls, respectively, showing that other genetic or environmental influences must be responsible. Family studies revealed that more than one-third of the AD cases are members of one hamula (tribal group) within Wadi Ara. We hypothesize that the high risk of AD in this genetic isolate may be attributable to a founder effect enhanced by consanguinity. It is also possible that smoking or high fat diet are responsible. To map chromosomal loci contributing to AD susceptibility, we conducted a genome scan from specific hamulas and followed candidate regions found to be linked to disease. Markers from 18 chromosomal regions showed significant allelic association with AD. Smoking was very common in men but was not linked to the presence of AD in Wadi Ara, The unique characteristics of this community, together with the large amount of human genome data, should allow for the identification of AD genes in candidate regions.
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Doença de Alzheimer/etnologia , Doença de Alzheimer/genética , Árabes/etnologia , Árabes/genética , Predisposição Genética para Doença/etnologia , Idoso , Apolipoproteína E4 , Apolipoproteínas E/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 18/genética , Consanguinidade , Análise Mutacional de DNA , Meio Ambiente , Feminino , Frequência do Gene , Marcadores Genéticos/genética , Testes Genéticos , Humanos , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fumar/efeitos adversosRESUMO
Dementia of the Alzheimer type (DAT) and vascular dementia (VaD) are the two major subtypes of dementia. In our epidemiological study of DAT in an Arab community in Wadi Ara, Israel, we found a high prevalence of late onset DAT. Illiteracy, smoking, diabetes mellitus (DM) and hypertension are very frequent in Wadi Ara. These factors led us to study the prevalence of VaD and various risk factors in this population. All people aged 60 years or older (n=823) in a defined region were examined for identification of DAT and VaD (DSM-IV criteria), using clinical examinations and a semi-structured questionnaire for detecting cognitive dysfunction. We identified 49 demented patients (29 males) fulfilling criteria of VaD with a prevalence rate of 49/823 (5.9%), compared to 168/823 (20.5%) for DAT. All had suffered from strokes. Male gender and hypertension were more common among VaD cases. Illiteracy was significantly more common among VaD patients than among healthy subjects (79.6% vs. 40.2%, P=0.001) but less common than among DAT patients (94.6%, P=0.001). Thus, our results show that VaD constitutes about 22% of the total dementia population in Wadi Ara. We confirm the association between VaD, illiteracy and hypertension. Smoking and gender do not represent risk factors for VaD in this population. While suggestive, DM is not a statistically significant risk factor for VaD.
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Demência Vascular/epidemiologia , Idoso , Árabes , Estudos Transversais , Demência Vascular/complicações , Demência Vascular/psicologia , Complicações do Diabetes , Diabetes Mellitus/epidemiologia , Educação , Feminino , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fatores de Risco , Fumar/epidemiologia , Fumar/psicologiaRESUMO
OBJECTIVE: We studied the genetic and environmental risk factors and prevalence, and incidence of dementia of the Alzheimer type (DAT) among the elderly in an Arab community in Israel. BACKGROUND: Epidemiological and genetic studies of dementia have rarely been reported in an Arab population. METHODS: All persons aged 60 years or older who were residents of the rural area of Wadi Ara were examined for identification of DAT, vascular dementia (VaD) and conversion from age related cognitive decline (ARCD) to DAT using DSM-IV criteria and a semi-structured questionnaire for collection of demographic and medical data. ApoE genotype was also determined. Total plasma homocysteine (tHcy) was determined using HPLC with fluorescence detection. Vitamins B12 and plasma folate were determined using a commercial radioisotope dilution kit assay (ICN). RESULTS: DAT was diagnosed in 20.5% of this population. Its prevalence increased steeply with age. Illiteracy was very common, and strongly associated with higher prevalence of DAT. The annual incidence of DAT among ARCD cases was 4.4%. Subjects with ARCD who developed DAT were older than ARCD subjects who did not develop dementia. Hypertension was significantly more common among converted patients than among non-converted. Illiteracy was insignificantly more common among those who developed DAT than among those who remained ARCD. Vascular dementia (VaD) constitutes about 22% of the total dementia population. We also confirm the association between VaD, illiteracy and hypertension. Smoking did not represent a risk factor for VaD. The survival rates among the three groups (healthy subjects, ARCD and DAT) was 80.5%, 58.8% and 55.5% respectively. Homocysteine levels were significantly higher than found in studies in Cleveland. Plasma B12 and plasma folate levels did not differ significantly between DAT patients and controls after adjusting for year of birth. CONCLUSIONS: Our findings suggest that the Wadi Ara population is unique because of high prevalence rates of dementia. We found old age, female gender and lack of education to be risk factors for the development of DAT. The ApoE epsilon4 allele is relatively uncommon in this population and it cannot explain the high DAT prevalence. We also confirm the association between VaD, illiteracy and hypertension and older age and hypertension are risk factors for the transformation of ARCD to DAT.