AxisAlzheimer's DiseaseLuteinizing hormoneParaventricular nucleusNeuronsNeuroendocrinePathogenesisCardiovascular diseaseCenters for Diseas2019HypothalamusDementiaGlandStressNucleiMitochondrialEstrogenAnterior2022AutoimmuneHormonesOnsetGeneBrainDistinctMechanismsIrritable bowel syProgressionSimultaneouslyAxonDepressionSymptomsMultipleClinicalPatientsRoleTherapies
Axis29
- The hypothalamic-pituitary-adrenal (HPA) axis, a neuroendocrine network that controls hormonal responses to internal and external challenges in an organism's environment, exhibits strikingly sex-biased activity. (nature.com)
- These gonadal hormones are produced by the hypothalamic-pituitary-gonadal (HPG) axis and have been shown to determine sex differences in adult HPA function after acute stress via their activational and organizational effects. (nature.com)
- The ability of all mammals to cope with any environmental or homeostatic challenge (i.e., stressor), or with perceptual threats to homeostasis, relies upon activation of a neuroendocrine signaling cascade called the hypothalamic-pituitary-adrenal (HPA) axis. (nature.com)
- Strikingly, women are at twice the risk of men for developing many of these diseases, likely due to sex differences in the function and regulation of the HPA axis [ 5 ]. (nature.com)
- Thus, understanding the nature and causes of such sex differences in the HPA axis following stress has important implications for understanding sex-biased risk for disease. (nature.com)
- The hypothalamic-pituitary-gonadal axis (HPG axis, also known as the hypothalamic-pituitary-ovarian/testicular axis) refers to the hypothalamus, pituitary gland, and gonadal glands as if these individual endocrine glands were a single entity. (wikipedia.org)
- In oviparous organisms (e.g. fish, reptiles, amphibians, birds), the HPG axis is commonly referred to as the hypothalamus-pituitary-gonadal-liver axis (HPGL-axis) in females. (wikipedia.org)
- Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, which regulates bodily levels of cortisol in response. (medscape.com)
- 10 , 12 Molecular mechanisms that underlie the pathogenesis of major depression, such as chronic inflammation and hyperactivation of the hypothalamic-pituitary-adrenal axis, might be involved in the pathogenesis of Alzheimer's disease. (psychiatrist.com)
- What the hypothalamic-pituitary-adrenal axis is. (listenaddict.com)
- Neuropeptide Y1 and Y5 Receptors Mediate the Effects of Neuropeptide Y on the Hypothalamic- Pituitary-Thyroid Axis. (deiodinase.org)
- Central administration of NPY not only markedly stimulates food intake, but simultaneously in- hibits the hypothalamic-pituitary-thyroid axis (HPT axis), replicating the central hypothyroid state associated with fast- ing. (deiodinase.org)
- To identify the specific NPY receptor subtypes involved in the action of NPY on the HPT axis, we studied the effects of the highly selective Y1 ([Phe7,Pro34]pNPY) and Y5 ([chicken pancreatic polypeptide1-7, NPY19 -23, Ala31, Aib32 (aminoisobu- tyric acid), Q34]human pancreatic polypeptide) receptor ago- nists on circulating thyroid hormone levels and proTRH mRNA in hypophysiotropic neurons of the hypothalamic paraventricular nucleus. (deiodinase.org)
- The interaction between the hypothalamus, pituitary, and other endocrine glands is known as the hypothalamic-pituitary-endocrine axis. (pharmaceuticalintelligence.com)
- This axis includes the central nervous system, neuroendocrine and neuro-immunological systems including the hypothalamic-pituitary-adrenal axis, sympathetic and parasympathetic arms of the autonomic nervous system, and the gut microbiome. (athenslab.gr)
- Shilajit attenuates behavioral symptoms of chronic fatigue syndrome by modulating the hypothalamic-pituitary-adrenal axis and mitochondrial bioenergetics in rats. (himalayanhealingshilajit.com)
- When the body is under chronic stress it releases a signal to the hypothalamic-pituitary-adrenal (HPA) axis. (naturalnews.com)
- Stress and the hypothalamic-pituitary-adrenal axis: How can the COVID ‐19 pandemic inform our understanding and treatment of acute insomnia? (bordeaux-neurocampus.fr)
- This narrative review outlines why the COVID-19 pandemic is a stressful life event, and why activation of the hypothalamic-pituitary-adrenal axis, as a biological marker of psychological stress, is likely to result in acute insomnia. (bordeaux-neurocampus.fr)
- Further, this review outlines how sleep disturbances might arise as a result of the COVID-19 pandemic, and why simultaneous hypothalamic-pituitary-adrenal axis measurement can inform the pathogenesis of acute insomnia. (bordeaux-neurocampus.fr)
- In particular, we focus on the cortisol awakening response as a marker of hypothalamic-pituitary-adrenal axis function, as cortisol is the end-product of the hypothalamic-pituitary-adrenal axis. (bordeaux-neurocampus.fr)
- Ongoing projects investigate the role of renin-angiotensin system, sympathetic nervous system, and hypothalamic-pituitary adrenal axis in cardiovascular and neurodegenerative diseases. (uiowa.edu)
- The ginsenosides in ginseng are believed to combat fatigue by influencing the hypothalamic-pituitary-adrenal axis and enhancing cellular energy production. (webmedy.com)
- Ginseng has a profound impact on the hypothalamic-pituitary-adrenal axis. (webmedy.com)
- Activation of the hypothalamic‑pituitary‑adrenal axis (HPA) and subsequent release of corticosteroids lead to increased muscle activity. (spandidos-publications.com)
- Overactivation of the sympathetic system and hypothalamic-pituitary-adrenal axis (HPA) axis can make an individual more vulnerable to new stress, as evidenced by animal and human studies ( 15 , 16 ). (spandidos-publications.com)
- One of the major factors associated with fibromyalgia is dysregulation in the Hypothalamic-Pituitary-Adrenal Axis (HPA). (drjockers.com)
- Ashwagandha appears to alter the hypothalamic-pituitary-adrenal axis, which plays a crucial role in response to stress, as indicated by its capacity to lower cortisol levels to relieve stress and anxiety. (starhealth.in)
- The fellow will investigate the basic mechanisms that underlie gonadal aging and/or hypothalamic-pituitary-gonadal axis dysfunction with advancing age. (postdocjobs.com)
Alzheimer's Disease41
- Scientific confirmation of a long-held theory, as well as new research into an association with Alzheimer's disease, helped put stress in the spotlight, resulting in this week's top trending clinical topic. (medscape.com)
- A separate review of human and animal epidemiologic studies found that long-term stress, along with genetic factors, may contribute to the development of Alzheimer's disease. (medscape.com)
- Increased cortisol levels are frequently observed in patients with Alzheimer's disease and "make a major contribution to the disease process," the authors wrote . (medscape.com)
- Moving forward, the researchers plan to further investigate the molecular mechanisms responsible for the role of stress in Alzheimer's disease and how genetic variants affect neurodegeneration. (medscape.com)
- Neurodegenerative diseases like Alzheimer's disease are becoming increasingly more common, but this growing epidemic is not a normal or inevitable part of aging. (listenaddict.com)
- The percentage of Alzheimer's disease diagnoses that are genetically driven. (listenaddict.com)
- The connection between Alzheimer's disease and glucose metabolism in the brain. (listenaddict.com)
- What we know about the metabolic components of Alzheimer's disease. (listenaddict.com)
- The Journal of Alzheimer's Disease is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer's disease. (semcs.net)
- The journal is dedicated to providing an open forum for original research that will expedite our fundamental understanding of Alzheimer's disease. (semcs.net)
- On this basis, failure of axonal transport has been proposed as a key player in the development and/or progression of neurodegenerative disorders such as Alzheimer's disease (AD). (semcs.net)
- Alzheimer's disease (AD) is the most common form of progressive neurodegenerative disease characterized by cognitive impairment and mental disorders. (semcs.net)
- Alzheimer's Disease: Experimental Treatments Page 1 of 22 Aetna Better Health® 2000 Market Street, Suite 850 Philadelphia, PA 19103 AETNA BETTER HE. (kipdf.com)
- Aetna considers the following treatments for Alzheimer's disease (AD) experimental and investigational because their effectiveness for this indication has not been established (not an all inclusive list). (kipdf.com)
- Background Alzheimer's disease (AD) is the most common cause of dementia characterized by progressive neuro-degeneration. (kipdf.com)
- Changes in cognition from baseline to week 76 were assessed with the use of the cognitive subscale of the ADAS-Cog, on which scores range from 0 to 70 and higher scores indicate greater cognitive impairment, and changes in functioning were assessed with the Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL) scale, on which scores range from 0 to 78 and higher scores indicate better functioning. (kipdf.com)
- Objective This study aims to investigate the relationship between diurnal cortisol patterns, cognition and Alzheimer's disease (AD) biomarkers in memory clinic patients. (bmj.com)
- Importantly, studies have shown probiotics (beneficial bacteria) can help decrease pathological hallmarks of Alzheimer's disease (AD), including amyloid plaques and tangles. (onedaymd.com)
- Using Alzheimer's disease model mice, the researchers were able to confirm that daily oral administration of B. breve A1 reduced the cognitive dysfunction normally induced by amyloid beta. (onedaymd.com)
- Microglial activation is a key pathogenic process at the onset of Alzheimer's disease (AD). (shengsci.com)
- EnteroScan ® Neuro investigates and provides answers regarding nervous system diseases such as autism spectrum disorders (ASD), multiple sclerosis, and mood disorders (depression, stress, etc.), while it can provide prevention solutions also in neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. (athenslab.gr)
- The aim of this study was to investigate alterations in cholesterol metabolism during the perimenopausal transition that could increase the long-term risk of neurodegenerative disease in women, particularly Alzheimer's disease. (gremjournal.com)
- Alzheimer's disease (AD) is the leading cause of dementia, presenting a significant unmet medical need worldwide. (biomedcentral.com)
- Genetic and biochemical studies support the apolipoprotein E ( APOE ) ε4 allele as a major risk factor for late-onset Alzheimer's disease (AD), though ~50% of AD patients do not carry the allele. (biomedcentral.com)
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by neuronal and synaptic loss, neurofibrillary tangles in neuronal cytoplasm, and deposition of β-amyloid (Aβ) in extracellular, neuritic plaques. (biomedcentral.com)
- A study published in the Journal of Alzheimer's Disease found that Shilajit reduced cognitive impairment and protected the brain from oxidative stress in rats with Alzheimer's disease. (himalayanhealingshilajit.com)
- Role of mitochondria in Alzheimer's disease: new perspectives on an old theme. (himalayanhealingshilajit.com)
- Journal of Alzheimer's Disease, 30(S2), S277-S289. (himalayanhealingshilajit.com)
- Physical activity has been shown to increase brain-derived neurotrophic factor (BDNF), which reduces beta-amyloid toxicity associated with the progression of Alzheimer's disease. (coeler.pics)
- There also are indications that limonene may help prevent Alzheimer's Disease and help treat Crohn's, irritable bowel syndrome, and fibromyalgia. (cannabistraininguniversity.com)
- Timing of Alzheimer's Disease by Intellectual Disability Level in Down Syndrome. (cam.ac.uk)
- Cognitive outcome measures for tracking Alzheimer's disease in Down Syndrome. (cam.ac.uk)
- Establishing diagnostic thresholds for Alzheimer's disease in adults with Down syndrome: the Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS). (cam.ac.uk)
- Our ultimate goal is to identify novel therapies that can be translated to yield better clinical outcomes in dilated cardiomyopathy, heart failure, hypertension, mood disorders, Alzheimer's disease and ALS. (uiowa.edu)
- According to some research , ginseng may promote cognition and thinking processes and could help in the treatment of neurological conditions, such as Alzheimer's disease . (medicalnewstoday.com)
- I had the great fortune to study with world renowned neuroscientist, Dr. Dale Bredesen, M.D., at the Buck Institute for Research on Aging in Novato, California and at the Advanced Clinical Training in Treating Mild Cognitive Impairment and Early Alzheimer's Disease with the Institute for Functional Medicine. (caringforthebody.org)
- A study by Wake Forest University School of Medicine found that even modest alcohol consumption can expedite brain atrophy and amplify the formation of amyloid plaques, which are linked to Alzheimer's disease. (blogspot.com)
- In the case of Alzheimer's disease, the leading cause of dementia in older adults, we recently described in female wildtype and APP23 mice a survival bias and non-linear chronology of behavioral signatures from middle age to long life. (bvsalud.org)
- The molecules acting through RAS predominantly ARBs and ACEI are found to be effective in various ongoing and completed clinical trials related to cognition, memory, Alzheimer's disease (AD), and pain. (hindawi.com)
- Testosterone replacement therapy (TRT) has been investigated in older men as a preventative treatment against Alzheimer's disease and dementia. (druglib.com)
- OMRF is dedicated to understanding and developing more effective treatments for human diseases, focusing on critical research areas such as Alzheimer's disease, cancer, lupus, Multiple Sclerosis, and cardiovascular disease. (postdocjobs.com)
Luteinizing hormone2
- The anterior portion of the pituitary gland produces luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and the gonads produce estrogen and testosterone. (wikipedia.org)
- Secondary, i.e., hypogonadotropic hypogonadism (congenital or acquired) idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation. (druglib.com)
Paraventricular nucleus1
- Activation of the neuroendocrine response to stressors occurs at the level of the hypothalamic paraventricular nucleus (PVN), which receives varying inputs depending on the nature of the stressor. (nature.com)
Neurons3
- As an extension of the brain, the posterior pituitary contains axons from neurons in the hypothalamus. (pharmaceuticalintelligence.com)
- The neurons that extend into the posterior pituitary produce either the hormone arginine vasopressin (abbreviated AVP) or the hormone oxytocin. (pharmaceuticalintelligence.com)
- Effects of mutant huntingtin in oxytocin neurons on non-motor features of Huntington's disease. (lu.se)
Neuroendocrine1
- The HPA, HPG, and HPT axes are three pathways in which the hypothalamus and pituitary direct neuroendocrine function. (wikipedia.org)
Pathogenesis2
- Advances in knowledge of the pathogenesis of the disease as well as an increase in disease burden have resulted in research on innovative therapies. (kipdf.com)
- Based on findings in neurological diseases ( 20-23 ) and pharmacological interactions ( 24-27 ), it appears that a malfunction of 5-hydroxytryptamine (HT)2 receptors may have a major role in the pathogenesis of bruxism. (spandidos-publications.com)
Cardiovascular disease2
- The disturbances to regular cortisol function may leave them more vulnerable to diseases, including cardiovascular disease and diabetes, researchers report. (neurosciencenews.com)
- Background: Understanding and addressing cardiovascular disease (CVD) risk has implications for maternal and child health outcomes. (cdc.gov)
Centers for Diseas4
- Read Carefully before Using The Public Health Service Act (Section 308 (d)) provides that the data collected by the National Center for Health Statistics (NCHS), Centers for Disease Control and Prevention (CDC), may be used only for the purpose of health statistical reporting and analysis. (cdc.gov)
- The NAMCS is a national probability sample survey conducted by the Division of Health Care Statistics, National Center for Health Statistics (NCHS), Centers for Disease Control and Prevention (CDC). (cdc.gov)
- The National Center for Chronic Disease Prevention and Health Promotion at the Centers for Disease Control and Prevention funds the agency's largest investment in Indian Country, Good Health and Wellness in Indian Country. (cdc.gov)
- This program identified approaches useful for the Centers for Disease Control and Prevention, other federal agencies, or other organizations working with American Indians and Alaska Natives. (cdc.gov)
20191
- Comorbidities and clinical outcomes in adult- and juvenile-onset Huntington's disease: a study of linked Swedish National Registries (2002-2019). (lu.se)
Hypothalamus10
- When the egg is released, the empty follicle sac begins to produce progesterone to inhibit the hypothalamus and the anterior pituitary thus stopping the estrogen-LH positive feedback loop. (wikipedia.org)
- The hormonal control center of the body can be found at the base of the brain, in a tiny pea-sized structure, called the pituitary gland, and an overlying region, called the hypothalamus. (pharmaceuticalintelligence.com)
- However, the hypothalamus wields even greater power, because it controls the pituitary gland. (pharmaceuticalintelligence.com)
- By synthesizing and secreting neurohormones, the nuclei of the hypothalamus act as a conduit between the nervous and endocrine systems via the pituitary gland (hypophysis), regulating homeostatic functions such as hunger, thirst, body temperature, and circadian rhythms. (medscape.com)
- 2] Superiorly, the hypothalamus is divided from the thalamus by a groove in the lateral wall of the third ventricle, the hypothalamic sulcus. (medscape.com)
- 2] Through the MFB, signals from the brainstem, amygdala, hippocampus, retina, and olfactory system are conveyed to hypothalamic nuclei, underlying the crucial role of the hypothalamus in systemic homeostasis. (medscape.com)
- D) coronal sections of the hypothalamus, reflecting relative positions of hypothalamic nuclei. (medscape.com)
- Nuclei within the anterior subdivision of the hypothalamus include the medial/lateral preoptic, periventricular, supraoptic, suprachiasmatic, and anterior/lateral hypothalamic nuclei. (medscape.com)
- IKKβ signaling mediates metabolic changes in the hypothalamus of a Huntington's disease mouse model. (lu.se)
- Effects of excitotoxicity in the hypothalamus in transgenic mouse models of Huntington disease. (lu.se)
Dementia2
- Understanding the risk factors of dementia is essential for preventing this disease. (psychiatrist.com)
- Alzheimer's and Dementia: Diagnosis, Assessment & Disease Monitoring , 14 (1). (cam.ac.uk)
Gland5
- It links the two by sending and receiving signals from other regions of the nervous system while also controlling the body's "master gland"-the pituitary gland. (pharmaceuticalintelligence.com)
- In one animation, we examine the hypothalamic control of the pituitary gland, and we show the endocrine glands that the pituitary controls. (pharmaceuticalintelligence.com)
- Because the pituitary controls many other endocrine glands, it is known as the "master gland" of the body. (pharmaceuticalintelligence.com)
- The pituitary gland consists of two distinct parts. (pharmaceuticalintelligence.com)
- This projection continues as the infundibulum, terminating inferiorly on the pituitary gland. (medscape.com)
Stress4
- It is known to be an antidepressant because it inhibits the secretion of hypothalamic-pituitary-adrenal (HPA) stress hormones. (cannabistraininguniversity.com)
- NaturalNews) Many experts have hypothesized that increased stress cycles in the body produce the environment for disease development within the body. (naturalnews.com)
- People exposed to chronic social conflict experience high levels of stress and consequent dysregulation of the immune system , thereby increasing vulnerability to infectious and autoimmune disease," said lead author Mary Meagher. (naturalnews.com)
- By contrast, stress and negativity can trigger and perpetuate a lot of diseases because the brain holds an enormous influence over the rest of the body. (theholisticprotocols.com)
Nuclei2
- the important ones for the posterior pituitary are the paraventricular and supraoptic nuclei. (pharmaceuticalintelligence.com)
- Although the lateral region is the most voluminous, the medial and periventricular regions contain the majority of hypothalamic nuclei. (medscape.com)
Mitochondrial1
- Many studies shown that neurological diseases are associated with neural mitochondrial dysfunctions and microbiome composition alterations. (frontiersin.org)
Estrogen1
- Chronic pituitary and adrenal fatigue reduces sex hormone (estrogen, progesterone and testosterone) production and human growth hormone (HGH) production. (drjockers.com)
Anterior3
- GnRH travels down the anterior portion of the pituitary via the hypophyseal portal system and binds to receptors on the secretory cells of the adenohypophysis. (wikipedia.org)
- One part, the anterior pituitary, originates from glandular tissue. (pharmaceuticalintelligence.com)
- Unlike the posterior pituitary, the anterior pituitary consists of glandular tissue. (pharmaceuticalintelligence.com)
20221
- The World Alzheimer Report 2022 revealed that more than 55 million people have AD or related conditions worldwide, and this number is projected to reach 82 million by 2030 and 138 million by 2050 [ 1 ]. (biomedcentral.com)
Autoimmune1
- EnteroScan ® is a group of specialized laboratory tests that analyze the intestinal microbiome and its functions and, along with other innovative and conventional laboratory tests, shed light on the causal relationships and underlying causes of gastrointestinal diseases, nervous system diseases, allergies, and autoimmune diseases, obesity, metabolic syndrome, type 2 diabetes, and many other chronic diseases and conditions. (athenslab.gr)
Hormones1
- However, these hormones are only released (or, in some cases, inhibited from being released) in response to hypothalamic hormones. (pharmaceuticalintelligence.com)
Onset2
Gene2
- The reversal of risk embodied in this interaction powerfully supports the importance of considering the role gene-gene interactions play in the etiology of complex biological diseases and demonstrates the importance of using multiple analytic methods to detect well-supported gene-gene interactions. (biomedcentral.com)
- Microarray profiling of hypothalamic gene expression changes in Huntington's disease mouse models. (lu.se)
Brain3
- The message here is that inflammation is directly determined by the health and diversity of our gut bacteria, and this has major implications in terms of brain health, function, and disease resistance. (onedaymd.com)
- The other part, the posterior pituitary, consists of neural tissue and is essentially an extension of the brain. (pharmaceuticalintelligence.com)
- As the disease progresses, the gradual spread of tau pathology throughout brain regions has been suggested to be caused by the transfer of abnormal types of tau protein from one neuron to another [ 18 ]. (biomedcentral.com)
Distinct1
- Hypothalamic expression of huntingtin causes distinct metabolic changes in Huntington's disease mice. (lu.se)
Mechanisms2
- The BiancoLab at University of Chicago investigates the physiological roles played by these enzymes and their involvement in disease mechanisms. (deiodinase.org)
- The ideal treatment for AD should be able to modulate the disease through multiple mechanisms rather than targeting a single dysregulated pathway. (semcs.net)
Irritable bowel sy1
- On the flip side, flares of gastrointestinal issues like irritable bowel syndrome (IBS), Crohn's disease, or chronic constipation may trigger anxiety or depression. (onedaymd.com)
Progression1
- The cause of MSA remains unknown, and no current therapy can reverse or halt progression of the disease. (medscape.com)
Simultaneously1
- This 5-year program, launched in 2014, supports American Indian and Alaska Native communities and tribal organizations to address chronic diseases and risk factors simultaneously and in coordination. (cdc.gov)
Axon1
- The axon terminals abut tiny capillaries in the posterior pituitary. (pharmaceuticalintelligence.com)
Depression1
- Notably, depression is recognized by the World Health Organization (WHO) as a major contributor to the overall global burden of disease. (psychiatrist.com)
Symptoms2
- In addition to improving the quality of life for people with non-psychiatric conditions, such as peripheral artery disease and fibromyalgia, regular physical activity can help reduce symptoms of these specific conditions. (coeler.pics)
- This project aimed at increasing and assessing awareness of risk, symptoms, and recommended screenings and prevention activities in underserved women, through unique collaboration between the Centers for Disease Control and Prevention's (CDC) Inside Knowledge (IK) campaign, which was designed to educate women about gynecologic cancer, and the CDC's national network of organizations to reduce cancer-related disparities. (cdc.gov)
Multiple2
- Appropriate adrenal cortical and thyroid hormone replacement therapy may be necessary in patients with multiple pituitary or hypothalamic abnormalities. (druglib.com)
- Dialogue with tribal members and leaders helped shape the program, and unlike previous programs that funded a small number of tribes to work on specific diseases, this program funds multiple tribal entities to reach widely into Indian Country. (cdc.gov)
Clinical1
- 2. Premio para la comunicación ¿Record of preanalytical errors in the laboratory information system¿ en el XXII National Congress of the Spanish Society of Clinical Biochemistry and Molecular Pathology, celebrado en Barcelona del 1 al 5 de Junio de 2003. (unav.edu)
Patients1
- Decreased CSF oxytocin relates to measures of social cognitive impairment in Huntington's disease patients. (lu.se)
Role1
- 2] . The role of physical activity in the prevention of a variety of chronic diseases and premature mortality has been widely studied and studied. (coeler.pics)
Therapies1
- The main trends in these trials involve pathophysiology-based, disease-modifying therapies and the recruitment of participants in earlier stages of the disease. (biomedcentral.com)