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",isbn:"978-1-80356-966-6",printIsbn:"978-1-80356-965-9",pdfIsbn:"978-1-80356-967-3",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"f86a9f720cc3ac0f1c385d0367ea89b9",bookSignature:"Dr. Fiaz Ahmad and Prof. Muhammad Sultan",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11624.jpg",keywords:"Agricultural Waste, Reuse, Reduction, Soil Health, Recycling, Agriculture and Environment, Modelling and Simulation, Agro-Industrial Waste, Bioresource Processing, Processing and Management, Crop Residue, Forest Waste",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 8th 2022",dateEndSecondStepPublish:"June 16th 2022",dateEndThirdStepPublish:"August 15th 2022",dateEndFourthStepPublish:"November 3rd 2022",dateEndFifthStepPublish:"January 2nd 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"12 days",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Dr. Fiaz Ahmad is a researcher in the field of Agricultural Engineering with fifteen years of field and academic experience, currently in charge of the Agricultural Machinery Design Laboratory at Bahauddin Zakariya University. He applied for two patents at the national level.",coeditorOneBiosketch:"A renowned researcher in the field of Agricultural Engineering with 14 years of academic experience at Bahauddin Zakariya University. Winner of various prestigious fellowships, awards, and research grants. Published 250+ articles along with several books and chapters. Guest editor of seven ISI-SCI journals for publishers like SAGE, MDPI, and Frontiers.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"338219",title:"Dr.",name:"Fiaz",middleName:null,surname:"Ahmad",slug:"fiaz-ahmad",fullName:"Fiaz Ahmad",profilePictureURL:"https://mts.intechopen.com/storage/users/338219/images/system/338219.png",biography:"Dr. Fiaz Ahmad is an assistant professor and lecturer at the Department of Agricultural Engineering, Bahauddin Zakariya University, Multan, Pakistan. He obtained his Ph.D. in Agricultural Bioenvironmental and Energy Engineering from Nanjing Agriculture University, China, in 2015, and completed his postdoctorate in Agricultural Engineering from Jiangsu University, Zhenjiang, China, in 2020. He was awarded a fellowship from the Higher Education Commission of Pakistan for Ph.D. studies and from the Chinese Government for post-doctoral studies. He earned a BSc and MSc (Hons) in Agricultural Engineering from the University of Agriculture, Faisalabad, Pakistan, in 2004 and 2007, respectively. He is the author of more than fifty journal and conference articles. He has supervised six master’s students to date, and is currently supervising six master and two doctoral students. Dr. Ahmad has completed three research projects with his research interest focusing on the design of agricultural machinery, agricultural waste management, artificial intelligence (AI), and agricultural bioenvironment.",institutionString:"Bahauddin Zakariya University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Bahauddin Zakariya University",institutionURL:null,country:{name:"Pakistan"}}}],coeditorOne:{id:"199381",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sultan",slug:"muhammad-sultan",fullName:"Muhammad Sultan",profilePictureURL:"https://mts.intechopen.com/storage/users/199381/images/system/199381.png",biography:"Muhammad Sultan is an Assistant Professor at the Department of Agricultural\r\nEngineering, Bahauddin Zakariya University, Multan (Pakistan). He completed his Ph.D.\r\nand Postdoc from Kyushu University (Japan) in the field of Energy & Environmental\r\nEngineering. He was an awardee of MEXT and JASSO fellowships (from the Japanese\r\nGovernment) during Ph.D. and Postdoc studies, respectively. He also did a Postdoc as\r\na Canadian Queen Elizabeth Advance Scholar at Simon Fraser University (Canada) in\r\nthe field of Mechatronic Systems Engineering. He worked for Kyushu University\r\nInternational Institute for Carbon-Neutral Energy Research (WPI-I2CNER) for two years.\r\nCurrently, he is working on 4 research projects funded by the Higher Education\r\nCommission (HEC) of Pakistan. He has completed six projects in past in the field of\r\nagricultural engineering. He has supervised 10+ M.Eng. and Ph.D. thesis and 10+\r\nstudents are currently working under his supervision. He has published 120+ journal\r\narticles, 100+ conference articles, 13 book chapters, and 6 books. He is serving as guest\r\neditor for the journals like Sustainability (MDPI), Agriculture (MDPI), Energies (MDPI),\r\nAdvances in Mechanical Engineering (SAGE), Frontiers in Mechanical Engineering, and\r\nEvergreen Journal of Kyushu University. His research is focused on developing energy-\r\nefficient temperature and humidity control systems for agricultural storage, greenhouse,\r\nlivestock, and poultry applications. His research keywords include desiccant air-\r\nconditioning, evaporative cooling, adsorption heat pump, Maisotsenko cycle (M-cycle),\r\nenergy recovery ventilators; adsorption desalination; wastewater treatment.",institutionString:"Bahauddin Zakariya University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Bahauddin Zakariya University",institutionURL:null,country:{name:"Pakistan"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"5",title:"Agricultural and Biological Sciences",slug:"agricultural-and-biological-sciences"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"440212",firstName:"Elena",lastName:"Vracaric",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/440212/images/20007_n.jpg",email:"elena@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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It is a highly incapacitating disorder, progressing from gradual deterioration of memory and cognitive functions to a complete incapacity, which consequently leads to death of patients within 3–9 years after diagnosis [2]. Aging is recognized as the major risk factor of all AD cases, and the aging of world population will lead to a steep increase in the prevalence of AD [1]. Despite much effort has been made in AD research in the past few decades, the pathophysiology of AD remains unclear, and to date, there is no effective therapeutic treatment for the disease. Hence, new therapeutic solutions that can effectively combat the disease are of utmost importance.
Recent studies have shown that the gut microbiota is involved in the neurodegenerative disorders and diverse cognitive functions through regulating the gut-brain axis [3, 4]. The concept of microbiota-gut-brain axis is emerging and its dysregulation has now been linked to the progression of AD [5]. In light of this, it is suggested that modulation of the gut microbiota through the use of probiotics might possibly prevent or ameliorate AD symptoms.
In this chapter, we discuss the roles of the gut microbiota in the development of AD, highlighting the specific contribution of probiotics intervention to the amelioration of AD progression. We examine recent scientific literature addressing the beneficial effects of probiotics for the prevention and treatment of AD and point out the possible mechanisms of action of probiotics for preventing cognitive impairments in AD.
AD is a chronic progressive neurodegenerative disorder characterized by three clinical phases in which the patients exhibit different symptoms over time [6]. The first stage (early stage; mild AD) includes memory loss, language difficulties, and executive dysfunction. The second stage (middle stage; moderate AD) comprises psychiatric symptoms and behavioral disturbances such as depression, hallucinations, delusions, and agitation. The third stage (late stage; severe AD) comprises severe impairment of almost all cognitive functions and difficulties to perform activities of daily living. The symptoms of AD worsen gradually, and the disease may begin to develop decades before the manifestation of the earliest clinical symptoms [7].
Despite the massive worldwide research efforts that have been made in the past few decades, the exact cause and pathogenesis of AD are not fully understood. It is widely believed that the pathogenesis of AD is primarily driven by the abnormal deposition of extracellular β-amyloid peptide (Aβ) plaques in various areas of brain, although such hypothesis may not be the sole explanation [8, 9]. Aβ is a peptide consists of 37–43 amino acids, in which Aβ42 is a more prevalent isoform and is considered to be the most neurotoxic in nature [10]. Aβ is derived from the sequential proteolytic enzymatic cleavage of amyloid precursor protein (APP) by two membrane-bound proteases, β- and γ-secretase [11, 12]. In the amyloid cascade hypothesis of AD, the disease is characterized as a series of abnormalities in the process and secretion of the amyloid precursor protein (APP), where an imbalance between production and clearance of Aβ is the triggering event that leads to the accumulation of Aβ in the brain parenchyma [13]. As a consequence, Aβ spontaneously aggregates into soluble oligomers that are eventually deposited in diffuse senile plaques [14]. The Aβ deposition and diffused senile plaques formation eventually lead to local microglia activation and production of pro-inflammatory cytokines [15, 16]. In turn, these cytokines stimulate reactive astrocytes to produce further amounts of Aβ42 oligomers, thus activating more amyloid plaque formation [17]. In addition, Aβ oligomer aggregations induce oxidative damage, which, in turn, seem to provoke inflammation and facilitate tau hyperphosphorylation, resulting in adverse effects on neuronal synapses and mitochondria [18].
Neurofibrillary tangles (NFTs), which are filamentous inclusions that accumulate in selective neurons of AD brains, are another major pathological hallmark of AD. The major component of NFTs is the microtubule-associated protein tau [19, 20]. The tau protein is a highly soluble protein that promotes microtubule assembly and stabilization for axonal transport and neuronal growth under normal conditions [21]. In AD, the tau protein exhibits altered solubility properties, becomes abnormally hyperphosphorylated, and forms filamentous structures [22]. Hyperphosphorylation of tau is known to induce a lower grade of interaction of tau proteins with microtubules that leads to greater self-aggregation of tau proteins and consequently induces malfunction of axonal transport [23], mis-stabilization of actin [24], synaptic impairment [25], and defects in mitochondrial integrity [26].
Nevertheless, NFTs seem not to be the main toxic entities leading to AD. Recent studies show that the intermediate tau oligomer is likely to be the key attribute of disease onset [27, 28]. Appearing prior to NFTs formation, hyperphosphorylated tau self-assembles into oligomeric forms and insoluble materials as paired-helical filaments (PHFs), triggering neurotoxic actions that affect the normal interaction patterns of the neuronal cytoskeleton and neuronal damage [28, 29]. As a result of neuronal death, tau oligomers are released into the extracellular environment, contributing to microglia activation with overproduction of pro-inflammatory cytokines that trigger deleterious signal cascades leading to progressive neuronal degeneration in AD brains [30]. Although the exact cause on why AD onset takes decades before symptoms occur remains unclear, AD progression is likely related to a reduced ability to eliminate misfolded, oligomerized, and aggregated tau proteins that increase with advancing age. Therefore, tau protein could be another important therapeutic target in AD pathology.
The gut-brain axis has long been recognized as a bidirectional communication between the brain and the gut in which the brain communicates with the gastrointestinal tract by modulating permeability, motility, secretion, and immunity, and concurrently, the gut can affect brain function and behavior [31]. The complex and multifaceted network of gut-brain axis consists of the gastrointestinal tract, central nervous system (CNS), autonomic nervous system (ANS), enteric nervous system (ENS), neuroendocrine system, and immune system which drive various afferent and efferent pathways such as vagus nerve and hypothalamic-pituitary adrenal (HPA) pathway for regulation of immune and metabolic homeostasis [31]. Recently, it is becoming increasingly evident that gut microbiota play a pivotal role in regulating the gut-brain axis, thereafter the term microbiota-gut-brain axis was introduced [32, 33, 34].
Gut microbiota is proposed as a key regulator of centrally mediated events including metabolic homeostasis, immune function, and neurological diseases [33]. Gut microbiota is a complex community composed of trillions of microorganisms, mainly bacteria, but also bacteriophage particles, viruses, fungi, and archaea [35]. A majority of the microbiota belongs to the two bacterial phyla, Bacteroidetes and Firmicutes, while Proteobacteria, Actinobacteria, Fusobacteria, and Verrucomicrobia phyla are present in lower proportions [36]. Notably, it is increasingly evident that alterations in the gut microbiota composition may cause imbalanced gut homeostasis and detrimental effects on CNS [37]. For instance, a variety of gastrointestinal and metabolic diseases including inflammatory bowel disease (IBD), obesity, diabetes, and insulin resistance are common comorbidities in many neurological disorders [38]. More recently, metagenomics studies have revealed that gut dysbiosis is present in a variety of neurological diseases including AD. Consequently, it is inevitably important to maintain a well-balanced and healthy microbiota community in the regulation of gut-brain axis.
Accumulating evidence suggests that gut microbiota alterations can influence the progression of neurological disease and may be a major factor in the development of AD [39, 40]. For instance, a recent preclinical study revealed a remarkable shift in the gut microbiota of APP transgenic mice as compared to healthy, wild-type mice, wherein a significant reduction in bacteria belonging to the phyla Firmicutes, Verrucomicrobia, Proteobacteria, and Actinobacteria with respect to an increase of Bacteroidetes and Tenericutes was observed in the intestine of conventionally raised transgenic APPPS1 AD mice [41]. It was strongly advocated that a distinct microbial constitution in AD mice may contribute to amyloid deposition wherein a remarkable increase in cerebral Aβ pathology was observed in APP transgenic germ-free mice colonized with microbiota from conventional APP transgenic mice, while control mice colonized with microbiota from wild-type mice was less effective in increasing cerebral Aβ levels [41]. In addition, a clinical study characterizing the gut microbiota composition of AD subjects reveals decreased microbial diversity and changes in bacterial abundance compared with controls; these changes include decreased levels of Firmicutes and
It is plausible that microbiota alterations can lead to colonization of intrinsic pathogens and increase gut permeability that could perturb the gut-brain axis. For instance, recent study has demonstrated that enterobacteria infection exacerbated progression of AD by promoting immune hemocyte recruitment to the brain; thereby provoking tumor necrosis factor-c-Jun NH2-terminal kinase (TNF-JNK)-mediated neurodegeneration in a drosophila AD model [43]. Additionally, the intestinal opportunistic bacteria including
Another clinical study involving 83 elderly subjects (40 cognitive-impaired amyloid-positive patients, 33 cognitive-impaired amyloid-negative patients, and 10 cognitively healthy amyloid-negative controls) have demonstrated that an increased abundance of a pro-inflammatory gut microbiota taxon,
The connections between gut microbiota and AD have led to a great interest in modulation of the microbiota-gut-brain axis through probiotics. Probiotics are defined as live microorganisms that, when consumed in sufficient amounts, confer health benefits to the host [50]. The probiotics species that are most commonly studied usually belong to the genera
Studies in rodents indicate that cognition and memory storage, particularly the hippocampal long-term potentiation, begin to decline in aging animals and these brain functions are dramatically disrupted in animal models of AD [51]. Many lines of evidence have shown that probiotics modulation of the gut microbiota could improve age-related cognitive functions in animal models. For instance, treatment with VSL#3, a probiotics mixture containing eight different Gram-positive bacterial species, showed a significant alteration in gut microbiota, with increases in Actinobacteria and Bacteroidetes, both of which were reduced in vehicle-treated animals with a positive impact on long-term potentiation, inflammation, and neural plasticity [52]. Moreover, it was demonstrated that long-term dietary supplementation of multispecies live
A recent study has provided direct evidence for amelioration of cognitive dysfunction by probiotics treatment with the strain of
Probiotics intervention could potentially modulate cognitive decline in Alzheimer’s disease (AD) via the microbiota-gut-brain axis. A prominent strain of probiotic,
The health benefits of probiotics on numerous aspects of host health and homeostasis have been extensively studied in clinical trials. However, a detailed analysis of probiotics modulation in patients with AD is lacking and the effects of probiotics on the onset, symptoms, and pathogenesis of AD remain uncover. To date, there is only one clinical study of probiotics in subjects with AD has been carried out. The randomized, double-blind, and controlled clinical trial involved 60 patients with AD who were randomly assigned into two groups: the probiotics group (n = 30), received 200 ml/day of milk enriched with
Although many lines of evidence have shown the potential effects of probiotics in treating AD, the mechanisms of action are still speculated and unclear. One mechanism is the modulation of immune reactions. Accumulating evidence suggests that neuroinflammation has a causal role in the pathogenesis of AD wherein neuroinflammation is not a passive system activated by senile plaques and NFTs, but instead contributes as much as the plaques and tangles in AD [58]. This is substantiated by the presence of microglia cells in both AD patients and animal models of AD [59], and it is accompanied by increased levels of pro-inflammatory cytokines, such as TNF-α or interleukin (IL)-6 as found in the serum and brain tissue of AD patients [60]. In AD, aggregated Aβ as well as hyperphosphorylated tau proteins interfere with neuronal function and trigger the inflammatory activity of microglia [61]. Microglia activation leads to further accumulation of Aβ, neuronal debris, and, most probably, the sustained production of pro-inflammatory cytokines and reactive oxygen species (ROS), giving rise to a chronic, nonresolving inflammatory process [62]. Inevitably, modulation of neuroinflammation provides compelling targets for interventions in AD.
Probiotics intervention has been reported to improve the age-associated modifications of immunological features. It was demonstrated that probiotic treatments can ameliorate the immune reactions by modulating cytokine production, improving distribution and function of natural killer cells, macrophages, granulocytes, and T cells, and enhancing mucosal and systemic antibody responses [63, 64, 65, 66]. In view of the immunomodulatory properties of probiotics, one might speculate that the probiotic bacteria may ameliorate symptoms of AD by modulating the inflammatory reactions driven by Aβ deposition and other risk factors, including inflammaging, obesity, and traumatic brain injury.
Studies have shown that probiotics could directly mitigate neuroinflammation as observed in the reductions of circulating pro-inflammatory cytokines and microglia activation. For example, chronic inflammation was suppressed after probiotic treatment with
In addition to the established pathology of senile plaques and NFTs, oxidative stress has emerged as an important factor contributing to the development of AD. Oxidative stress represents the mechanism through which Aβ neurotoxic peptides and tau proteins mediate the pathological processes and cause synaptic impairment, neuroinflammation, neuronal apoptosis, and neurotransmitter dyshomeostasis in AD [68] that ultimately correlates with the typical behavioral symptoms of AD [69]. Oxidative stress is characterized as an imbalance between the production of ROS and the activities of antioxidant defense system that resulting in oxidative damage, as observed in AD patients [70]. Mounting evidence suggests that oxidative damage contributed to the onset and progression of AD wherein low antioxidant enzyme levels, high oxygen consumption, the presence of excitotoxic amino acids, and high iron content promote the production of ROS and reactive nitrogen species (RNS) in the brain [71, 72]. In addition, aberrant accumulation of Aβ can also enhance the generation of ROS through an N-methyl-D-aspartate (NMDA) receptor-dependent mechanism [73], and that oxidative stress may augment the production and deposition of Aβ as well as facilitate tau hyperphosphorylation and oligomerization, forming a viscous cycle that promotes the onset and progression of AD [74]. Therefore, it is tempting to postulate that probiotics with strong antioxidant potential may prevent and treat AD by counteracting oxidative stress and the molecular events implicated in the pathogenesis of AD.
A remarkable recent study supports the protective role of probiotics in the brain oxidative status of AD mice model and demonstrates the molecular mechanisms involved [75]. For instance, SLAB51 probiotics formulation significantly reduced oxidative damages in AD mice brain through a mechanism that involves the activation of SIRT1-related pathways [75]. SIRT1 is a deacetylase with a strong neuroprotective and antioxidant potential that regulates the expression of several antioxidant genes [76, 77]. Reduction of SIRT1 functionality and expression levels have been reported to contribute to the accumulation of Aβ and tau in the cerebral cortex of AD patients [78]. It was demonstrated that SLAB51 intervention restored the levels of SIRT1 by deactivating its nuclear receptor RARβ in AD mice [75], which, in turn, may stimulate the nonamyloidogenic pathway of APP processing and diminish Aβ production and accumulation [79]. Moreover, several studies have also reported that probiotic bacteria counteracted oxidative damage and improved cognitive impairment in AD rodent models through its antioxidant properties [56, 80]. Collectively, these findings represent the fundamental concept that probiotic ameliorates the symptomatology of AD through its antioxidative mechanism.
Another possible mechanism of action by which probiotics can ameliorate AD is through the production of metabolites such as short-chain fatty acids (SCFAs). SCFAs, mainly acetate, butyrate, lactate, and propionate, are the main metabolites of the fermentation of dietary fibers by the gut microbiota [81]. A study using germ-free mice has revealed a substantial contribution of the gut microbiota, particularly the microbiota-derived SCFAs, to the regulation of microglia maturation and functions [82]. In addition, SCFAs have also been shown to play a role in regulation of several signaling pathways such as inhibition of NF-κB, inhibition of histone deacetylation (HDAc), and activation of G protein-coupled receptors (GPCRs), and are well known to have potent anti-inflammatory effects [83, 84, 85]. For instance, butyrate has a direct stimulation effect on vagal afferents that have been shown in clinical trials to improve cognitive function of AD patients [86, 87]. Butyrate has also been shown to inhibit HDAc and improve memory function in a late-stage AD mouse model [88]. In addition, a study using PC12 cells demonstrated the potential neuroprotective roles of the enteric bacterial metabolites, butyrate and propionate, against AD whereby the expression of Aβ A4 protein precursor was significantly downregulated by these SCFAs [89]. Meanwhile, acetate supplementation was shown to be capable of attenuating neuroglia activation and pro-inflammatory cytokine expression in rat models of neuroinflammation [90].
Recent scientific studies indicate that probiotics modulation of gut microbiota ameliorated the inflammatory status of AD through the production of SCFAs. For example, in the study of the probiotic
In addition, SCFAs were reported to be able to modulate neurotransmitter synthesis and have effect on the neurotrophic genes including brain-derived neurotrophic factor (BDNF) and nerve growth factor [92, 94]. Interestingly, a reduction in BDNF signaling was observed in both the brain and the serum of patients with AD [92], and such decline was reversed by probiotics intervention as demonstrated in rodent model [52, 95, 96]. These findings suggest that probiotic modulation may enhance the production of small ubiquitous microbiota-derived molecules like SCFAs that could act as important molecular signals between the microbiota and host, thereby improving the molecular events associated with cognitive impairment.
Another mechanism to consider is the alteration of gut microbiota composition by probiotics. Emerging evidence suggests that targeting the gut commensals through probiotics intervention could mitigate age-associated inflammation and cognitive impairment [52, 97]. It has also been reported that perturbations of gut microbiota community induced by antibiotic treatment could ameliorate Aβ deposition and inflammatory responses in an aged APP transgenic mice model of AD [98]. Furthermore, many intervention studies in elderly subjects have also demonstrated that probiotics can augment the growth of the gut commensal,
While little is currently known regarding the role of the microbiota-gut-brain axis in AD, several scientific efforts have pointed out that probiotics can modify the gut microbiota for amelioration of AD-related pathological conditions. For instance, administration of the probiotic mixture SLAB51 induced larger shifts in the microbial communities of the 3xTg-AD mice, along with an increase in the proportions of
Altogether, the results of the research summarized in this chapter suggest the potential of probiotics in preventing cognitive impairment in AD. In particular, probiotics intervention could effectively ameliorate cognitive impairment and symptomatology of AD and can be considered as an important advance in the field of AD. It is evident that the gut microbiota composition is altered in AD and the modulation of gut dysbiosis through probiotics could counteract various benchmarks of AD. Probiotics or its bioactive metabolites can improve gut microbiota homeostasis and influence the pathological factors involved in the progression of AD such as inflammatory reaction, oxidative stress, Aβ deposition, and cognitive functions (Figure 2). Despite still being a speculation, accumulated information from animal and human research provides fundamental proofs for the modulating effect of probiotics in AD and underlies the possible mechanisms of action involved. Further studies are definitely needed to fully elucidate the scope of probiotics for this debilitating disease, as well as to clarify the underlying mechanisms of probiotics for preventing cognitive impairment in AD.
Schematic overview of the possible mechanisms of action of probiotics modulation for preventing cognitive impairment in Alzheimer’s disease (AD). Probiotics or its bioactive metabolites such as SCFAs can improve gut microbiota homeostasis and positively influence the pathological factors involved in the progression of AD such as inflammatory reaction and oxidative stress, thereby ameliorating cognitive decline in AD.
AD | Alzheimer’s disease |
Aβ | β-amyloid peptides |
NFTs | neurofibrillary tangles |
According to the WHO World report on disability 2011, About 15% of the world’s population lives with some form of disability, of whom 2–4% experience significant difficulties in functioning. The global disability prevalence is higher than previous WHO estimates, which date from the 1970s and suggested a figure of around 10%. This global estimate for disability is on the rise due to population aging and the rapid spread of chronic diseases, as well as improvements in the methodologies used to measure disability.
Individuals with disabilities have generally poorer health, lower education, fewer economic opportunities, and higher rates of poverty than people without disabilities. This is mainly due to the obstacles they face in their daily lives and the lack of services available to them. Regarding oral health and access to dental care, the same obstacles are of concern. Oral health is mostly ignored, oral hygiene is neglected, and dental treatments are postponed after other health issues. As a result, individuals with special needs present more dental caries, periodontal problems, orthodontic anomalies, and are more prone to dental diseases compared with the healthy population.
Cerebral palsy is a non-progressive movement, posture, and tone disorder characterized by the impairment of motor activities in the developing fetal or infant brain. Motor disorders are often accompanied by sensory, perception, communication, and behavioral disorders, epilepsy, and musculoskeletal problems [1]. In these patients, muscle weakness or paralysis, unbalanced and irregular gait, uncoordinated movements, sudden seizures, mental retardation, emotional disorders, learning, speech communication disorders, and weakness of swallowing, and coughing reflexes are seen. Because brain development continues during the first 2 years of life, cerebral palsy may develop as a result of brain damage occurring in the prenatal, perinatal, or postnatal periods [2]. However, more than 80% of cases are due to problems in the prenatal period.
Etiologically, in the prenatal period; maternal diseases, trauma, genetics, drug use, bleeding, consanguineous marriage, radiation, in the natal period; premature/late birth, birth trauma due to inappropriate position, low/high birth weight, cord entanglement, lack of oxygen, multiple pregnancies, difficult birth, birth trauma, in the postnatal period; febrile diseases, trauma, hyperbilirubinemia, hypoglycemia, seizure, and cerebral hemorrhage are risk factors for cerebral palsy [3].
It has been reported that the rate of drooling in children with cerebral palsy is 10–58% [4]. Although drooling is normal in infants and young children, it is considered pathological after 4 years of age. Most children with cerebral palsy, who are drooling, are unable to swallow normal saliva due to oral-motor dysfunction, although not much saliva is produced. Perioral eczema, infection, and dehydration occur as a result of drooling out of the mouth [5].
Bruxism, especially in the “Spastic” type, is commonly observed in individuals with cerebral palsy [6]. It has been reported that 36.9–51% of children with cerebral palsy have bruxism. In addition to bruxism, the presence of parafunctional habits such as pacifier-finger sucking, biting objects have also been detected [7].
Periodontal diseases occur more often in children with cerebral palsy due to physical inadequacies, malocclusions, poor oral hygiene, chewing, swallowing difficulties, and consumption of soft food with high carbohydrate content. Besides, the use of phenytoin for seizure control causes gingival hyperplasia [8].
Caries formation is observed at a high rate in children with cerebral palsy. The most important reason for this situation is poor oral hygiene. Other risk factors for caries formation are mouth breathing, the effect of drugs used, and enamel hypoplasia [8]. Differences in food form, increased duration of food consumption, difficult cooperation, and structural defects in the teeth cause an increase in the prevalence of dental caries in children with cerebral palsy, and it has been reported that there are more extracted and untreated teeth compared with healthy children [9].
Malocclusions are observed two times more when compared with healthy individuals, and these patients have unilateral crossbite with excessive overbite and overjet. It has been reported that patients with cerebral palsy have a higher prevalence of malocclusion than healthy individuals, but the severity of malocclusion varies according to the degree of neurological disorder. In these individuals, musculoskeletal anomalies, altered cranial base relationships, premature tooth eruption, mouth breathing, and inadequate lip closure, as well as increased overjet and overbite, can be observed [10, 11].
It has been reported that cerebral palsy is not an etiological factor for erosion, but an increase in erosion since gastro-esophageal reflux is frequently observed in these individuals [12]. It has been reported that in children with cerebral palsy accompanied by gastro-esophageal reflux, especially in the quadriplegia type, the risk of dental erosion is considerably increased and the incidence of oral diseases is quite high [13].
Neuromuscular problems specific to cerebral palsy affect oral health in different ways. Changes in the orofacial region cause nutritional problems as well as the development of parafunctional habits and difficulties in maintaining oral hygiene [14]. In addition, dyskinetic movements cause pathological oral reflexes such as sudden biting or nausea. Gastric reflux associated with a blended diet, often rich in sugar, further puts these patients’ oral health at risk. Neuromuscular problems also prevent the patient from brushing their teeth correctly [15]. Patients with cerebral palsy have difficulty in chewing and swallowing due to changes in tongue, cheek, and lip motility. In these patients, there is an imbalance in the oral microbiota, which favors the proliferation of acidogenic bacterial species, which initiate the caries process [15].
Treatment sessions should be kept brief for patients with cerebral palsy. Patients may need to be moved from a wheelchair to a dental chair. The patient should be placed in the middle of the dental chair with arms and legs as close to the body as possible. After the patient is placed properly in a dental chair, the patient should be checked whether he/she is comfortable and the position of the extremities is correct. To keep the airway open, the patient should be seated at a 45-degree angle, but not in the supine position. The dental chair should be moved slowly, and the light reflector should be turned on slowly to prevent spastic muscle movements and to eliminate the risk of seizure. Myorelaxant agents should be used when necessary.
During dental treatment procedures, it is crucial to balance the patient’s head at all stages. Various mouthguards should be used to control involuntary jaw movements and accidental bites. The airway should be controlled, and frequent breaks should be given to allow the patient to relax and breathe normally. To minimize the startle reflex, the patient should be warned at every stage. The use of stimuli such as sudden movements, sounds, and lights should be avoided. Efficient, fast treatment should be done, and chair time should be minimized to reduce muscle fatigue. In patients with more complex situations, sedation or general anesthesia may be an option [15, 16, 17].
Down syndrome, defined by Down in 1866, is an autosomal anomaly associated with the trisomy of the 21st chromosome pair. Its incidence in the population is 1/800, and it is the most common chromosomal change. There is an extra 21st chromosome (trisomy) in 95% of cases. In some cases, there are 46 normal chromosomes, but the 21st chromosome has been replaced with another chromosome [18, 19]. Mosaic Down syndrome, on the other hand, is caused by the inability of chromosomes to fully divide during cell division in the embryonic period. Some cells of the mosaic type have 47 chromosomes, while others have 46 chromosomes [19]. Individuals with Down syndrome represent learning difficulties, neuropsychiatric disorders, and behavioral problems as well as congenital cardiac anomalies, thyroid problems, seizures, visual and hearing disorders, early-onset dementia, and frequent infections. Also, some individuals with Down syndrome are hepatitis B carriers, and leukemia can be seen in patients with Down syndrome [20].
The only factor known to cause Down syndrome is the age of the mother during pregnancy, the risk increases in pregnancies over the age of 35. However, because young women, in general, have more babies, 75–80% of children with Down syndrome are babies of young mothers. There is no difference between country, nationality, or socioeconomic status [21].
Craniofacial features of individuals with Down syndrome include brachycephaly, broad and short neck, maxillary hypoplasia, sloping palpebral fissures, short ears, midface hypoplasia, curved eyes, narrow, flat nose [22].
Although individuals with Down syndrome have usually a cooperative personality, providing sufficient oral hygiene depends on the family’s knowledge and education level. Down syndrome children might also experience anxiety or fear of dental visits and parents are usually not aware of the dental problems of their children. Also, Down syndrome children using medical agents suffering from seizures experience dry mouth due to a decrease in the salivary flow rate, which may lead to xerostomia preparing a suitable environment for caries and periodontal problems [29, 30]. In addition, high levels of tooth wear are observed in these patients. This is mainly due to bruxism and the acidic oral environment (reflux and vomiting) [22].
The behavior management skills of the dental professional are the key factor in a child’s acceptance of dental treatment [19]. Before determining the right approach to the Down syndrome child, the dentist should consider the level of the mental, emotional, and social development of the child [31]. Most Down syndrome children are affectionate and cooperative for their dental treatment and can be treated easily with the tell-show-do technique [32].
When treating Down Syndrome children, the need for prophylaxis of subacute bacterial endocarditis and the patient’s compliance level should be considered [22]. During treatment, the gag reflex can be reduced by behavioral management techniques, as comforting and distracting patients. It can also be reduced by intraoral massage and pharmacological or non-pharmacological interventions [33]. The recalls should be planned frequently, and preventive dental treatments should be included in the treatment plan. The education of caregivers is crucial for sufficient oral hygiene provision and follow-ups. Mild sedation may be used in children with moderate anxiety. Extremely resistant patients may require general anesthesia [17].
Autism was first described in 1943 by an American child psychiatrist, Leo Kanner. Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by difficulties in communication, social relationships, and limited and repetitive behaviors [34, 35].
Individuals with ASD have characteristics such as stereotypical or repetitive motor behavior (flapping, rocking back and forth), repetitive use of objects (turning coins, putting objects in order), or making repetitive speeches. Many patients adhere to rigid routines in their lives and may have a more rigid thinking pattern. They react negatively to even minor changes or transitions [36].
No specific etiology has been identified for ASD. However, studies indicate a combination of genetical and environmental factors before and after birth, such as parental age, fetal environment (e.g., sex steroids, maternal infections/immune activation, obesity, diabetes, hypertension, or ultrasound examinations), perinatal and obstetric events (e.g., hypoxia), medication (valproate, selective serotonin reuptake inhibitors), smoking and alcohol use, nutrition (e.g., short inter-pregnancy intervals, e.g., vitamin D, iron, zinc, and copper), vaccination, and toxic exposures (air pollution, heavy metals, pesticides, organic pollutants) and low birth weight [37, 38].
In addition, problems such as tongue thrusting, erosion, hyperactive gag reflex, and some malocclusions such as anterior open bite and maxillary retrognathia were also reported in these individuals [42, 43].
Clinical conditions that ASD children present, such as sensorimotor and attention deficits, anxiety and related emotion regulation, comprehensive difficulties, and general speech disorders, create various difficulties for families, educators, and dentists in the provision of oral health care of these children [44]. Besides, parents face difficulties in brushing the teeth of the ASD children due to the sensory sensitivities of their children and the unpredictable or aggressive behavior that may require physical restraints.
In the literature, the caries experience of ASD individuals is controversial. Research reports state that ASD children are more prone to dental caries due to the consumption of sugar-containing food [45, 46, 47]. Besides, insufficient chewing and prolonged time of food staying in the mouth also increase caries formation [48]. The fact that autistic individuals are more difficult to accept oral and dental health care than healthy individuals and that their hand skills are not sufficiently developed and that they cannot perform adequate and effective tooth brushing is also effective in the formation of caries [49].
The impaired behavioral activities and complicated medical conditions make the dental management of patients with ASD challenges. Children with ASD have remarkable difficulties in establishing relationships with other people, understanding and the following information, and dentists may be insufficient in providing cooperation during the dental treatment process [40]. Furthermore, the invasive nature of dental treatment procedures along with the hypersensitivity of children with ASD to sensory stimulation (sound, touch, and light) may trigger undesired responses during dental treatment.
In the dental treatment of autistic individuals, many basic behavior management techniques such as tell-show-do, desensitization, and voice control behavior management can be successfully applied [50].
The dental treatment sessions of autistic individuals should be kept short and the sensory stimulation should be minimized. However, it has been reported that in many cases it may be necessary to use advanced behavior management techniques including sedation and general anesthesia [51, 52]. Also, a dental office filled with unpleasant smells, sounds, and colors can be an overstimulating environment for patients with autism [53].
To minimize anxiety and uncooperative behavior pattern, soothing light, rhythmic music with or without headphones, and having minimal visual stimuli on the walls should be considered. It may also be beneficial to improve cooperation by having the same dental professional in the same operating room at all sessions [54].
If traumatic ulcers or lesions are observed on oral mucosa or gingiva, a mouth guard may be prescribed for patients who have problems with self-injurious behavior or bruxism.
The term intellectual disability (ID) is generally used to describe mental retardation. The most widely used current definition of disability is the World Health Organization’s (WHO) International Classification of Functioning, Disability and Health (ICF), which incorporates the complex interactions between health conditions, environmental factors, and personal factors. Regarding a person with an ID, this definition would consider how their factors, health condition, and environment affect their lives (WHO 2001). Three elements are common for people with ID:
Significant impairment of intelligence,
A resultant significant reduction in adaptive behavior/social functioning and
The development of the condition (which persists throughout life) before the age of 18 years.
Mental retardation is a developmental disorder that occurs before the age of 18. In addition to having significant retardation in normal functions, there is an inadequacy in the adaptive skills necessary to maintain daily life. Adaptive skills cover skill areas such as self-care skills such as feeding, dressing, bathing, home life skills such as housekeeping, speaking and understanding language, as well as communication skills, social skills, social usefulness, and professional skills [55].
Intellectual disability may be caused by a problem that starts any time before a child turns 18 years old—even before birth. It can be caused by injury, disease, or a problem in the brain. For many children, the cause of their intellectual disability is not known. Some of the most common known causes of intellectual disability—such as Down syndrome, fetal alcohol syndrome, fragile X syndrome, genetic conditions, birth defects, and infections—occur before birth. Others occur during or soon after birth. Besides, other reasons for intellectual disability do not occur until a child is older; these include serious head injury, stroke, or certain infections [56].
Patients with intellectual disability associated with a syndrome may present typical facial appearance; e.g., in these individuals, the tongue is placed in a protruding position due to macroglossia with micrognathia. Malocclusion, enamel defects, short conical roots, delayed eruption of teeth, congenital tooth agenesis, and tooth malformation are other common intraoral findings [57]. Due to certain genetic conditions or a history of high fever, children with disabilities may have their enamel defects or malformation and thus be more prone to dental caries.
These individuals also have inadequate lip closure, impaired tongue movement, and destabilization of the chewing muscles [55]. Salivary flow rate alterations due to the use of multiple medications along with poor oral hygiene may increase dental plaque and calculus formation, which may lead to dental and periodontal disease and halitosis.
Due to early loss of teeth, speech disorders may also be observed in these individuals [58]. Individuals with intellectual disabilities often consume a cariogenic and soft diet. Besides, individuals consuming daily medicine in the form of syrup constantly have a high risk of caries due to the high sugar content.
It has been shown that individuals with MR (mental retardation) aged 4–18 present significantly higher mean DMFT and dental erosion scores than healthy individuals [59].
Individuals with severe intellectual disability present impaired oral motor functions and weakened muscles, which cause chewing and swallowing problems. These patients often consume a soft diet including puree or semi-solid foods. In addition, individuals with an intellectual disability usually need the help of their caregivers to consume liquids and do not benefit enough from the washing and cleansing effect of liquids because they consume less liquid than healthy individuals. Oral hygiene procedures such as tooth brushing, which require manual dexterity, may not be performed adequately due to varying degrees of motor dysfunction as well as cognitive deficiencies in mentally retarded individuals [55].
Medical history is quite essential to assess the degree and type of ID and associated medical problems [60]. Complete information should be obtained from the parents/caregivers about the medical background, the medicine consumption, the level of communication of the child, the daily functions she/he can perform individually, and if there are behavior problems at home/institution [61].
It may be helpful to familiarize patients and/or caregivers with the clinical environment without any treatment at the first appointment. Dental office and instruments should be introduced patiently, and the tell-show-do method may be also introduced.
In the next session, the dental instruments that may cause anxiety are introduced, and then treatment may start. It is essential to keep the sessions short. The treatment session should begin with the easy-to-tolerate procedures and no pain stimulus should be created during the first procedure.
Behavior management with positive direction and distraction with movies or music may be applied. Perception difficulties are observed in patients with MR. In these patients, directions and explanations should be short and simple and the instructions should be repeated. General anesthesia or sedation should be considered in patients who do not comply and cannot cooperate [55].
Visual impairment was defined as visual acuity less than 20/40 in the better eye. Hearing impairment was defined as the pure-tone average air-conduction hearing threshold worse than 25-dB hearing level (dB HL) in the better ear, averaged over four frequencies: 500, 1000, 2000, and 4000 Hz. [62] Hearing loss can be mild, moderate, moderate, severe, or profound and can affect one or both ears.
Major causes of hearing loss include congenital or early-onset childhood hearing loss due to various chronic middle ear infections, noise-induced hearing loss, age-related hearing loss, and ototoxic drugs that damage the inner ear [62]. Hereditary hearing loss can be conductive, sensorineural, or mixed and is sometimes the result of a genetic trait passed down from a parent.
Children with hearing loss experience social isolation, loneliness, and frustration, and delayed language development due to the loss of ability to communicate with others [62].
Visual impairment is usually defined as a best-corrected visual acuity worse than 20/40 or 20/60 [63]. Visual impairment, or vision loss, is a degree of reduced vision that causes problems that cannot be corrected by general methods, such as with glasses [64]. The term blindness is used for complete or near-complete loss of vision. Physical injury risks such as falling, hitting, and traumatic injuries are reported higher in visually impaired children. Besides, their conceptual development and cognitive skills may be delayed, and they have challenges especially in skills that require abstract thinking [65].
The most common causes of visual impairment are globally uncorrected refractive error (43%), cataracts (33%), and glaucoma (2%). Refractive errors include myopia, hypermetropia, presbyopia, and astigmatism. Cataracts are the most common cause of blindness [66]. Other disorders that may cause visual problems include age-related macular degeneration, diabetic retinopathy, corneal clouding, childhood blindness, and several infections [67]. Visual impairment can also be caused by problems in the brain due to stroke, premature birth, or trauma, among others [68].
Visual impairment may have a negative impact on an individual’s oral hygiene. As a result of the inability to remove the microbial dental plaque appropriately, visually impaired individuals experience more dental caries, calculus, and gingivitis compared with healthy individuals [69]. Reluctance to consume solid foods due to prolonged infantile swallowing patterns and poor oral hygiene may be the main reason for the oral health problems. Besides, enamel hypomineralization has been identified as a possible oral manifestation in visually impaired children.
Visually impaired children are more prone to traumatic dental injuries, especially in the anterior teeth is also a predisposing factor. Visually impaired people generally require a high level of orthodontic treatment due to the increasing prevalence and severity of malocclusions [70].
Hard tissue anomalies such as enamel hypoplasia and higher rates of demineralization in the teeth are seen in patients with hearing impairment. Also, a high incidence of bruxism is one of the problems that occur especially when the individual has both hearing loss and visual impairment [71].
Due to the difficulties of providing oral hygiene, diet type, and problems of accessibility to the routine dental check-ups, dental caries are quite often seen in patients with hearing impairment [72]. The prevalence of gingivitis is also higher in these individuals due to poor oral hygiene and mouth breathing, and they are more prone to develop periodontitis early in life [73, 74].
Visually impaired individuals experience difficulties maintaining oral hygiene since they cannot visualize plaque on the tooth surface and adequately assess whether dental plaque is removed effectively. This leads to the progression of dental caries and also to oral inflammatory diseases [74].
Compared with healthy children, individuals with hearing impairment may have a higher risk of experiencing oral diseases, including dental caries or periodontal disease, as they have difficulties maintaining good oral hygiene [75].
Individuals with hearing impairment should be informed about the procedures to be performed at the first appointment, and an individual method should be developed for the communication during treatment sessions.
The degree of hearing loss should be noted in the patient’s medical history. In the first appointment, it is necessary to avoid exaggerated facial movements and mimics when communicating with the patient, not to cause difficulty to read lips. Comforting the child patient and increasing the sense of trust by smiling will help to establish confidence and healthy communication with the dental professional.
Before starting the dental treatment session, the instruments should be introduced using the show-tell-do method. If the hearing-impaired patient feels that she/he is unable to understand directions, she/he may show fear or aggression. For this reason, communication should be facilitated by reducing external sounds such as high-speed air turbines, dental aspirator, and radio or TV as much as possible. Mirrors, models, pictures, and written information should be used to establish communication [71].
In visually impaired individuals, treatment should be explained using the senses of touch, taste, and smell instead of the tell-show-do technique. The environment should be introduced, and necessary definitions should be made before each treatment. The dental professional should speak to the patient in a clear, warm tone of voice and should use a descriptive manner to explain the procedures. Also, patients should be informed about how the equipment may feel and sound and how the procedures will be performed before the instruments are inserted into the mouth.
The dental restorative materials should be placed in small pieces as the sharp taste may irritate the patient. Since such patients cannot see and remove dental plaque, tooth brushing should be explained by the dentist by holding the brush together with the patient. Oral hygiene education and motivation should be given by the doctor to whom he is accustomed to the treatment of the patient [70, 75].
Special healthcare need patients are literally special patients who need special attention by means of healthcare provision including dental care. The major challenges they have with their overall health may create barriers to access to proper oral healthcare. Oral healthcare for this special group is often neglected or down the list, and as a result, they often attend to dental clinics with emergency.
Individuals with special needs are the most underserved regarding healthcare needs in almost all populations. Due to the challenges of nutrition and insufficient oral hygiene provision, this population is usually more prone to dental caries, periodontal disease, and orthodontic problems. Besides, they face more difficulties accessing professional dental care than other segments of the population.
The field of special care dentistry is attracting more interest of pediatric dentists and general dental practitioners. The inclusion of the specialty programs in the dentistry faculty curriculum may initiate the ideal treatment procedures and regular recalls of these special patients, which may facilitate the access to sufficient dental care provision and regular check-ups for this special group.
Though many countries developed community-based systems to improve oral health for people with special needs, providing good oral health mainly depends on the effort of the families. Therefore the education of the caregiver about oral hygiene provision is also critical for the special needs patient to enjoy a lifetime of oral health the same as other members of the society.
The author declares no conflict of interest.
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He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. 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Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. 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She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Univeristy of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:null},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:null},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. After graduating from TED Ankara College in 1986, she attended the Hacettepe University, Faculty of Dentistry in Ankara. \nIn 1993 she attended the Gazi University, Faculty of Dentistry, Department of Orthodontics for her PhD education. After finishing the PhD education, she worked as orthodontist in Ankara Dental Hospital under the Turkish Government, Ministry of Health and in a special Orthodontic Clinic till 2011. Between 2011 and 2016, Dr. Deniz Uzuner worked as a specialist in the Department of Orthodontics, Faculty of Dentistry, Gazi University in Ankara/Turkey. In 2016, she was appointed associate professor. Dr. Deniz Uzuner has authored 23 Journal Papers, 3 Book Chapters and has had 39 oral/poster presentations. She is a member of the Turkish Orthodontic Society. Her knowledge of English is at an advanced level.",institutionString:null,institution:null},{id:"332914",title:"Dr.",name:"Muhammad Saad",middleName:null,surname:"Shaikh",slug:"muhammad-saad-shaikh",fullName:"Muhammad Saad Shaikh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jinnah Sindh Medical University",country:{name:"Pakistan"}}},{id:"315775",title:"Dr.",name:"Feng",middleName:null,surname:"Luo",slug:"feng-luo",fullName:"Feng Luo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sichuan University",country:{name:"China"}}},{id:"423519",title:"Dr.",name:"Sizakele",middleName:null,surname:"Ngwenya",slug:"sizakele-ngwenya",fullName:"Sizakele Ngwenya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419270",title:"Dr.",name:"Ann",middleName:null,surname:"Chianchitlert",slug:"ann-chianchitlert",fullName:"Ann Chianchitlert",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419271",title:"Dr.",name:"Diane",middleName:null,surname:"Selvido",slug:"diane-selvido",fullName:"Diane Selvido",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419272",title:"Dr.",name:"Irin",middleName:null,surname:"Sirisoontorn",slug:"irin-sirisoontorn",fullName:"Irin Sirisoontorn",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"355660",title:"Dr.",name:"Anitha",middleName:null,surname:"Mani",slug:"anitha-mani",fullName:"Anitha Mani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"355612",title:"Dr.",name:"Janani",middleName:null,surname:"Karthikeyan",slug:"janani-karthikeyan",fullName:"Janani Karthikeyan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"334400",title:"Dr.",name:"Suvetha",middleName:null,surname:"Siva",slug:"suvetha-siva",fullName:"Suvetha Siva",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"334239",title:"Prof.",name:"Leung",middleName:null,surname:"Wai Keung",slug:"leung-wai-keung",fullName:"Leung Wai Keung",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Hong Kong",country:{name:"China"}}}]}},subseries:{item:{id:"22",type:"subseries",title:"Applied Intelligence",keywords:"Machine Learning, Intelligence Algorithms, Data Science, Artificial Intelligence, Applications on Applied Intelligence",scope:"This field is the key in the current industrial revolution (Industry 4.0), where the new models and developments are based on the knowledge generation on applied intelligence. The motor of the society is the industry and the research of this topic has to be empowered in order to increase and improve the quality of our lives.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11418,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. 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