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 (Aβ) 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 Aβ 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.
Alcohol and other substance use disorders share comorbidity with other RDS disorders, i.e., a reduction in dopamine signaling within the reward pathway. RDS is a term that connects addictive, ...obsessive, compulsive, and impulsive behavioral disorders. An estimated 2 million individuals in the United States have opioid use disorder related to prescription opioids. It is estimated that the overall cost of the illegal and legally prescribed opioid crisis exceeds one trillion dollars. Opioid Replacement Therapy is the most common treatment for addictions and other RDS disorders. Even after repeated relapses, patients are repeatedly prescribed the same opioid replacement treatments. A recent JAMA report indicates that non-opioid treatments fare better than chronic opioid treatments. Research demonstrates that over 50 percent of all suicides are related to alcohol or other drug use. In addition to effective fellowship programs and spirituality acceptance, nutrigenomic therapies (e.g., KB220Z) optimize gene expression, rebalance neurotransmitters, and restore neurotransmitter functional connectivity. KB220Z was shown to increase functional connectivity across specific brain regions involved in dopaminergic function. KB220/Z significantly reduces RDS behavioral disorders and relapse in human DUI offenders. Taking a Genetic Addiction Risk Severity (GARS) test combined with a the KB220Z semi-customized nutrigenomic supplement effectively restores dopamine homeostasis (WC 199).
In the United States, amid the opioid overdose epidemic, nonaddicting/nonpharmacological proven strategies are available to treat pain and manage chronic pain effectively without opioids. Evidence ...supporting the long-term use of opioids for pain is lacking, as is the will to alter the drug-embracing culture in American chronic pain management. Some pain clinicians seem to prefer classical analgesic agents that promote unwanted tolerance to analgesics and subsequent biological induction of the "addictive brain". Reward genes play a vital part in modulation of nociception and adaptations in the dopaminergic circuitry. They may affect various sensory and affective components of the chronic pain syndromes. The Genetic Addiction Risk Severity (GARS) test coupled with the H-Wave at entry in pain clinics could attenuate pain and help prevent addiction. The GARS test results identify high-risk for both drug and alcohol, and H-Wave can be initiated to treat pain instead of opioids. The utilization of H-Wave to aid in pain reduction and mitigation of hedonic addictive behaviors is recommended, notwithstanding required randomized control studies. This frontline approach would reduce the possibility of long-term neurobiological deficits and fatalities associated with potent opioid analgesics.
This brief commentary aims to provide an overview of the available and relatively new precision management of reward deficiencies manifested as substance and behavioral disorders. Current and future ...advances, concepts, and the substantial evidential basis of this potential therapeutic and prophylactic treatment modality are presented. Precision Behavioral Management (PBM), conceptualized initially as Precision Addiction Management (PAM), certainly deserves consideration as an important modality for the treatment of impaired cognitive control in reward processing as manifested in people with neurobiologically expressed Reward Deficiency Syndrome (RDS).
In 2021, over 100,000 people died prematurely from opioid overdoses. Neuropsychiatric and cognitive impairments are underreported comorbidities of reward dysregulation due to genetic antecedents and ...epigenetic insults. Recent genome-wide association studies involving millions of subjects revealed frequent comorbidity with substance use disorder (SUD) in a sizeable meta-analysis of depression. It found significant associations with the expression of NEGR1 in the hypothalamus and DRD2 in the nucleus accumbens, among others. However, despite the rise in SUD and neuropsychiatric illness, there are currently no standard objective brain assessments being performed on a routine basis. The rationale for encouraging a standard objective Brain Health Check (BHC) is to have extensive data available to treat clinical syndromes in psychiatric patients. The BHC would consist of a group of reliable, accurate, cost-effective, objective assessments involving the following domains: Memory, Attention, Neuropsychiatry, and Neurological Imaging. Utilizing primarily PUBMED, over 36 years of virtually all the computerized and written-based assessments of Memory, Attention, Psychiatric, and Neurological imaging were reviewed, and the following assessments are recommended for use in the BHC: Central Nervous System Vital Signs (Memory), Test of Variables of Attention (Attention), Millon Clinical Multiaxial Inventory III (Neuropsychiatric), and Quantitative Electroencephalogram/P300/Evoked Potential (Neurological Imaging). Finally, we suggest continuing research into incorporating a new standard BHC coupled with qEEG/P300/Evoked Potentials and genetically guided precision induction of "dopamine homeostasis" to diagnose and treat reward dysregulation to prevent the consequences of dopamine dysregulation from being epigenetically passed on to generations of our children.
Background: The United States Centers for Disease Control and Prevention (CDC) estimates a total obesity rate of 30% for 12 states and a 20% obesity rate nationwide. The obesity epidemic continues to ...increase in spite of preventative measures undertaken worldwide. Pharmacological treatments promise to reduce total fat mass. However, medications may have significant side effects and can be potentially fatal. Data Retrieval: This brief review, based on a PUBMED search of the key terms “Obesity” and” Sarcopenia,” will present evidence to corroborate the existence of Reward Deficiency Syndrome (RDS) in obesity and the involvement of catecholaminergic pathways in substance seeking behavior, particularly as it relates to carbohydrates cravings. Expert Opinion: The genetic basis and future genetic testing of children for risk of aberrant generalized craving behavior are considered a prevention method. Here we present evidence supporting the use of precursor amino acid therapy and modulation of enkephalinase, MOA, and COMT inhibition in key brain regions. Such treatments manifest in improved levels of dopamine/norepinephrine, GABA, serotonin, and enkephalins. We also present evidence substantiating insulin sensitivity enhancement via Chromium salts, which affect dopamine neuronal synthesis regulation. We believe our unique combination of natural ingredients will influence many pathways leading to the promotion of well-being and normal healthy metabolic functioning. Sarcopenia has been shown to reduce angiogenesis and possible cerebral blood flow. Exercise seems to provide a significant benefit to overcome this obesity-promoting loss of muscle density. Conclusion: Utilization of proposed nutrigenomic formulae based on coupling genetic obesity risk testing promotes generalized anti-craving of carbohydrates and can inhibit carbohydrate bingeing, inducing significant healthy fat loss and relapse prevention.
Over years, the regular use of cannabis has substantially increased among young adults, as indicated by the rise in cannabis use disorder (CUD), with an estimated prevalence of 8. 3% in the United ...States. Research shows that exposure to cannabis is associated with hypodopaminergic anhedonia (depression), cognitive decline, poor memory, inattention, impaired learning performance, reduced dopamine brain response-associated emotionality, and increased addiction severity in young adults. The addiction medicine community is increasing concern because of the high content of delta-9-tetrahydrocannabinol (THC) currently found in oral and vaping cannabis products, the cognitive effects of cannabis may become more pronounced in young adults who use these cannabis products. Preliminary research suggests that it is possible to induce 'dopamine homeostasis,' that is, restore dopamine function with dopamine upregulation with the proposed compound and normalize behavior in chronic cannabis users with cannabis-induced hypodopaminergic anhedonia (depression) and cognitive decline. This psychological, neurobiological, anatomical, genetic, and epigenetic research also could provide evidence to use for the development of an appropriate policy regarding the decriminalization of cannabis for recreational use.
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