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Doumbo, Karamoko Niaré, Sara A. Healy, Issaka Sagara\nand Patrick E. Duffy",authors:[{id:"220804",title:"Prof.",name:"Ogobara",middleName:"Keguerem",surname:"Doumbo",fullName:"Ogobara Doumbo",slug:"ogobara-doumbo"}]},{id:"60183",title:"Newer Approaches for Malaria Vector Control and Challenges of Outdoor Transmission",slug:"newer-approaches-for-malaria-vector-control-and-challenges-of-outdoor-transmission",signatures:"John C. Beier, André B.B. Wilke and Giovanni Benelli",authors:[{id:"212309",title:"Prof.",name:"John C.",middleName:null,surname:"Beier",fullName:"John C. Beier",slug:"john-c.-beier"},{id:"238235",title:"Dr.",name:"Andre",middleName:null,surname:"Wilke",fullName:"Andre Wilke",slug:"andre-wilke"},{id:"238241",title:"Dr.",name:"Giovanni",middleName:null,surname:"Benelli",fullName:"Giovanni Benelli",slug:"giovanni-benelli"}]},{id:"61802",title:"Entomological Surveillance as a Cornerstone of Malaria Elimination: A Critical Appraisal",slug:"entomological-surveillance-as-a-cornerstone-of-malaria-elimination-a-critical-appraisal",signatures:"Gerry F. Killeen, Prosper P. Chaki, Thomas E. Reed, Catherine L.\nMoyes and Nicodem J. 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It currently affects more than 5 million individuals in the United States, and this number is growing daily. It is a whole-body disease, manifested by brain and body function changes during its progression. Clinically, people progressing through dementia demonstrate different manifestations of brain and body functions, including psychiatric manifestations, sensory-motor system disabilities, digestion insufficiency, and multiple bodily system involvement. A diverse combination of symptoms reflects the complexity of vascular, biochemical, physiological, and morphological changes in the brain and body during the development and progression of dementia. The amyloid cascade hypothesis has dominated the field of AD for many years. The intensive research concerning amelioration of the protein abnormalities in AD, based on the amyloid hypothesis, does not have practical value yet despite a very controversial, accelerated FDA approval of Aducanumab, an amyloid monoclonal antibody [1]. Conventional therapies—monotherapy or combinations of multiple medications—are not able to stop the progression of the disease and have very limited modifying effects. Our present understanding of the pathogenesis of AD goes far beyond brain dysfunction and pathology. Clinical and epidemiological studies have helped to identify modifiable factors in the onset and treatment of AD. Among these, hemodynamics, muscle health, and nutritional factors have been researched in animal and clinical studies for many years. The hemodynamic factor is related to vasculature, cerebral blood flow (CBF), and structural changes in the brain. A decrease in CBF is well documented during the progression of dementia. Sensory muscle status, changes in gait, balance, and fine dexterous motor skills are all strongly connected to the initiation and progression of dementia [2].
Nutritional deficiencies begin in the early stages of AD with a loss of taste and smell, which interferes with normal digestive processes. This disruption progresses to digestive disorders, malnutrition, and weight loss in advanced stages of dementia [3].
Rehabilitation is an important part of any treatment and has gained attention from the World Health Organization (WHO). In February 2017, there was a meeting hosted by the WHO, “Rehabilitation 2030: A Call for Action.” At the event, WHO issued a call for action towards “concerted and coordinated global action to scale up rehabilitation.” Rehabilitation is very important for people living on the wide spectrum of our world’s economies and should thus be available for all medical conditions that require it, including dementia [4].
The rehabilitation of patients with dementia is an emerging concept aimed at achieving the optimum level of physical and psychological functioning in the progression of aging, neurodegenerative processes, and chronic medical illnesses. The general hypothesis for this combined therapy is based on the suggestion that every modality has a unique influence on brain functions in AD, and a combination of these modalities could have a synergistic effect, significantly slowing the rate of cognitive decline, improving quality of life, and delaying institutionalization. Nutrition and other non-pharmacological interventions, especially physical and cognitive activities, have shown promising results in delaying the onset of dementia and could potentially improve the outcome of dementia treatment. Research related to simultaneous implementation of medication and multiple non-pharmacological interventions is very limited [5, 6].
Studies relating to cognitive rehabilitation, physical exercises, and nutrition alone have shown a positive effect on cognition in animals and humans in time frames ranging from several months to several years [7, 8, 9, 10].
Since 2000, we have developed a working rehabilitation model, utilizing all available resources, most of which are accessible to the average individual in the hopes of delaying the progression of dementia and possibly improving function in certain cognitive and physical domains. The objectives of this rehabilitation model are the activation of brain functions through the alteration of neurotransmitter activities and the increase of muscle activity, sensory input to the brain, CBF, and nutrients and oxygen supply.
To the best of our knowledge, there is no rehabilitation model related to the simultaneous implementation of multiple available modalities (medications, physical and cognitive exercises, nutrition, and sensory stimulations) for AD patients living at home. We hypothesize that the simultaneous implementation of all possible rehabilitation modalities could delay the progression of dementia significantly, when compared to the utilization of a single modality. Here, we present the key elements of this working rehabilitation model for patients living at home.
Our understanding of pathophysiology in dementia has shifted in focus from amyloid accumulation to hemodynamic and energetic metabolism changes in the brain. It is a chronic, progressive disorder that affects the entire body [11]. Amyloid accumulation in the brain is a dynamic process in response to different etiological factors: stress, hypoxia, loss of subcortical nuclei (the nucleus basalis of Meynert, the locus coeruleus, and the raphe nucleous) [12, 13, 14].
The hemodynamic factor is related to the development of hypoxia- and hypoxia-related metabolic and structural changes in the brain. Hypoperfusion affects white matter, subcortical nuclei, and the cortex of the brain in people with dementia. Chronic hypoxia decreases energy production in the brain, affecting protein synthesis pathways, which cause the development of reversible and irreversible morphological changes in the brain structure. During dementia progression, there are cerebral cortex and cortical corpus callosum atrophy, white matter damage, and dysfunction of subcortical nuclei. Alzheimer’s dementia often begins as a disease of small blood vessels that are damaged by oxidation-induced inflammation and dysregulated amyloid metabolism, which may be seen as implications for early detection and therapy [15]. Today, there is an overlap between Alzheimer’s disease and cerebral vascular dementia. Vast evidence from epidemiological, neural, physiological, clinical, and pharmacological studies suggests common pathogenic pathways between these two types of dementia and highlights the vital roles of vascular pathways in dementia development and pathology. The deficiency of cerebral blood flow could be a reason for neuronal dysfunction, white matter damage, and death of brain cells in both types of dementia.
The course of dementia is associated with progressive changes in cardiovascular pathology in the brain, increased numbers of micro and lacunar infarcts, cerebral atrophy, white matter changes, and signs of demyelination [16, 17]. CBF changes have been well documented in normal aging, MCI, and dementia by using different imaging techniques, such as single-photon emission computed tomography (SPECT), functional magnetic resonance imaging (fMRI), positron emission tomography (PET), among others. On an rCBF—SPECT test, people with mild AD showed a significant reduction in rCBF in the left parietal cortex during an episodic memory task [18]. The conversion from MCI to AD, as well as the progression of AD, is associated with CBF changes. The lower the patient’s CBF, the faster and more drastic is their decline of Mini-Mental Status Exam (MMSE) scores [19].
The first notable changes in CBF start in the entorhinal and hippocampal areas of the brain, eventually expanding into the temporal and parietal lobes until finally reaching the frontal lobes [20]. In some places of the brain such as the sensory-motor strip areas and the cerebellum, CBF is relatively well-preserved in dementia [21]. This fact helps our understanding and explanation of the preservation of procedural memory in dementia, which is initiated in sensory-motor areas of the brain [22].
Moreover, judging from the same studies, it is quite possible to suggest that regulation of CBF is preserved as well, at least in the sensory-motor strip and cerebellum in moderate stages of the disease. Another example of preserved CBF in dementia is the report concerning increased CBF in frontal-occipital cortex in mild–moderate AD patients (7 affected people), compared to the control group (8 healthy individuals) during a visual face-matching task [23].
Energetic crises include mitochondrial failure and a decrease in the flow of substrate in brain neurons. A decrease in energy production in the central nervous system is one of the key factors in pathogenesis of dementia, which profoundly changes neuron function.
On the peripheral level, there are well-documented changes in sensory-motor system; decrease in feelings of taste, smell, and number of proprioceptive receptors; changes in mobility of joints and spine; increase in muscle spasticity; and decrease in muscles blood flow. Chronic muscles hypoxia is associated with muscle atrophy and sarcopenia. The decreased number of receptors and their functions result in diminished sensory input to the brain, and compromised CBF and neurotransmitters activities.
Dementia has a progressive course of cognitive decline and physical disability, negatively affecting the quality of life, the capacity to socialize, and the ability to perform everyday activities. From a practical point of view, we developed the 3M’s dementia assessment model™ for dementia evaluation, which includes assessing memory, mood, and movements. It is displayed in Figure 1.
3M’s dementia assessment model™ for dementia.
Dementia can start from any of them, alone or in combination with each other. All factors could be affected at different speeds, and all of them have to be taken into consideration during dementia evaluation [24, 25]. Movements, general slowness, and fine motor skills could start before the development of the cognitive problems in dementia [26].
Each of these modifiable factors could affect disease progression and treatment.
Acute and chronic stresses can affect brain and bodily functions by mobilization of sympathetic nervous system and activation of hypothalamic–pituitary–adrenal (HPA) axis on different stages of stress. Since Hans Selye’s discovery of the general adaptation syndrome, countless publications demonstrate relationships between stressors, stress response, and diseases in animal and clinical studies [27]. Stress affects physiological and biochemical processes in every organ in the body during dementia initiation and progression [28]. Sensitivity to stress events increases with aging and may accelerate cognitive and physical decline in dementia [29]. Acute stress affects attention and memory [30]. Chronic stress could play a role in development and progression of dementia by persistent activation of fundamental surviving pathophysiological, mechanisms [31, 32]. There are links between chronic stress and level of memory loss in MCI and dementia [33]. Stress-related hormones mobilization is manifested in failures of homeostasis, thus leading to various diseases, including dementia [34]. Stress affects physiological and biochemical processes in every organ and system in the body during dementia initiation and progression [28].
They may be bidirectional relationships between stress and dementia. Stress is associated with CBF redistribution, mitochondrial and multiple neural pathways changes, and decreased attention and memory [35]. However, during dementia progression, loss of memory, behavior, and social communications could be stressors and evoke stress response by themselves.
There is related data utilization of different interventions aimed at modulation of stress response; the practical recommendations are in the early stages of research [36]. Effective stress management activities could be helpful for patients with dementia and their caregivers and need to be included in dementia treatment strategy [36, 37].
Depression like dementia is a whole-body disease, affecting brain metabolism, sensory systems, muscle health, and nutrition. Depression could share common pathophysiological mechanisms with dementia, such as hypoperfusion, hypoxia, oxidative stress, and energetic and neurotransmitters failure and stress. Depression is one of the risk factors for developing dementia [24].
Depression could precede dementia and accompany dementia progression. The “vascular depression” hypothesis has been proposed, based on clinical, physiological, and morphological changes in seniors, suffering from persistent depression [38]. Clinical and radiology data and epidemiological studies demonstrate the changes in brain structure in dementia in old-old patients [39]. Treatment of late-life depression with vascular pathology is a challenging task for clinicians.
Apathy and anxiety may be seen in depression and dementia affecting the course of these diseases and associated with detrimental effects on activities of daily living [40, 41, 42, 43].
The fact that cardiovascular pathology occurs in multiple neurodegenerative processes in dementia is well documented. However, it remains necessary to investigate the interconnections and order of occurrence of these two factors [44, 45]. The course of dementia is associated with progressive changes in cardiovascular pathology, increased numbers of microbleeds and lacunar infarcts, cerebral atrophy, white matter changes, and signs of demyelination [17].
Vascular pathology and decrease of CBF contribute to progression of clinical manifestations, improving cognitive and physical functions, and developing morphological changes in dementia. Changes in CBF, cerebral ischemia, and hypoxia negatively affect substrate delivery, necessary for energy production and protein synthesis and essential neuronal activities [46].
In epidemiological studies, nutrition has been under investigation for many years as an important factor contributing to healthy aging and prevention of dementia and multiple chronic diseases.
For the purposes of this discussion, the nutritional aspect in the treatment of dementia can be separated into four components.
The first component is related to the diet. There is currently no consensus regarding a diet geared towards at least partially normalizing brain metabolism in dementia. Along with the well-known Mediterranean diet, calorie-restrictive diets, as well as ketogenic diets, may have a beneficial neuroprotective effect in aging and multiple neurodegenerative diseases [47]. The diet close to that used for cardiovascular pathology and diabetes with some modification geared towards very low carbohydrate products is probably the most suitable diet to be offered for dementia patients.
The second component is a number of vitamins and nutriceuticals, which have been known to affect critical biochemical pathways involved in the pathophysiology of dementia. Among them are vitamins and nutrients that are a part of the normal metabolic processes and become deficient during stress, lack of exercises, hypoxia, and many other clinical conditions. In a controlled study on institutionalized, moderate-to-severe dementia patients taking a vitamin/nutriceutical combination for 9 months demonstrated a significant delay in decline on the Dementia Rating Scale and clock-drawing test, compared to those receiving placebo. The vitamin-nutriceutical combination in this study was designed to support antioxidant activities, energy production, and protein synthesis. This small study supports the notion that even in severe dementia, there is still room for stabilization of disease progression [48]. The specific research data related to different nutritional substances and vitamins is out of scope of this chapter.
General recommendations include products that are rich in antioxidants and include dietary precursors for mitochondria function, protein metabolism, and membrane phosphatide synthesis [6, 49].
The third component is associated with changes in gastrointestinal functions in every part of the GI system. These begin in the early stages of dementia and worsen with disease progression, frequently manifested as nutritional disorders such as anorexia, poor digestion, malnutrition, and weight loss. The loss of taste and smell develops in the early stages of dementia, results in the loss of appetite, and negatively impacts all stages of digestion. Even in the early stages of AD, community-dwelling patients display poor nutritional consumption [50]. Patients with dementia often forget to eat or drink on time. In the advanced stages of dementia, progressive GI malfunctions occur simultaneously with chewing and swallowing problems, dysphagia, and a decreased feeling of thirst, all of which are connected to poor food digestion and absorption, vitamin deficiencies, decreased immunity, loss of muscle mass, increased frequency of infection, poor balance, and falls [3]. Weight loss is associated with severity and mortality in AD and is an indicator of protein, energy, vitamin, and nutrient deficiency [51]. According to these authors, in the middle stage of AD (MMSE—16.6 ± 4.9), significant weight loss is observed in more than 40% of patients living at home.
The presence of malnutrition in dementia could be a result of GI system dysregulation: changes in appetite, weight, and GI motility, and the probable development of exocrine pancreatic insufficiency.
An indicator of pancreatic exocrine insufficiency is the level of fecal elastase-1 in stool, the concentration of which decreases progressively with age. Pancreatic exocrine insufficiency was seen in 21.7% of people over 65 years without gastrointestinal disorders, surgery, or diabetes [52]. Pancreatic exocrine insufficiency is more prominent in patients with insulin-dependent diabetes [53].
The existence of pancreatic insufficiency during the aging process and in diabetes, as well as changes in glucose metabolism in dementia, makes it quite possible that exocrine pancreatic insufficiency plays an important role in the digestive malfunctions in dementia.
The fourth component is the microbiome. Imbalance in gut flora can negatively affect general health. The first connection between intestinal microbiome and longevity was described over a century ago by Elie Metchnikoff [54]. Research about the gut-brain axis demonstrates the strong bidirectional connections between gut–body health. Gut flora participates in production of serotonin, dopamine, and GABA—neurotransmitters, actively affected in many neurodegenerative illnesses and medical diseases as well. Stress, depression, and dementia negatively influence the health of the gut. A practical recommendation about using probiotics, prebiotics, and postbiotics for depression and dementia is on the horizon [55, 56, 57].
Medical illnesses (cardiac problems, diabetes, etc.) are risk factors for dementia development and progression. In recent years, accumulating evidence of research has suggested that cardiovascular pathology, especially irregular pulse, could be associated with dementia progression. In diabetes mellitus (type 2), there are metabolic changes, which affect vasculature and cell functions in every organ in the body. The cognitive and physical decline in dementia became worse with progression of diabetes.
The treatment and stabilization of these medical illnesses and disorders have a positive effect on people with dementia. The same approach could be applied to diseases related to the transport of oxygen to the organs (anemia, pulmonary pathology, and renal problems).
Mental activities have a positive effect on CBF in healthy individuals and have been shown to delay the onset of dementia [58]. Research related to improving CBF in AD patients through the use of cognitive activities is slowly growing. Recently a program of mental exercises for nursing home residents with mild AD showed an improvement in cognitive function after being implemented for 6 months. This program was based on extensive previous research done by the same research team relating to increased CBF during various mental tasks [59].
The connections between physical activities and rCBF are well established and done on healthy seniors, patients with MCI, and animal dementia models [60]. Physical exercise is considered a preventative or disease-modifying intervention, as it has shown a neuroprotective effect in brain aging [61]. Physical activities increase level of BDNF, which is responsible for brain health [62].
The effects of resistance training and aerobic exercises are connected to increased activity of the entire cardiovascular system and CBF simultaneously. These physical activities increase level of BDNF, which actively participate in learning, memory, and mood [63].
Hand exercises are more suitable and safer for fragile medically ill patients with all stages of AD because they can be done in a seated or laying position and appear to be a practical model for a home-based exercise regimen [11].
Simple hand movements have been shown to increase CBF in contralateral hemisphere of healthy subjects [64]. An increase in CBF during meditation, with simultaneous chanting and finger movements (dual tasks), has been observed by SPECT in healthy volunteers [65].
Physical activities have positive effect on neuropsychiatric symptoms in dementia [37].
Physical and mental exercises alone, as well as a combination of the both, could modify CBF and improve cerebral metabolism, decrease hypoxia, increase availability of oxygen and nutrients to brain cells and structures, increase brain vitality and prolong an active life for patients with dementia.
Rehabilitation of AD patients is an emerging concept aimed at achieving optimum levels of physical cognitive and psychological functioning in the presence of neurodegenerative processes, aging, and progression of chronic medical illnesses.
Given the complexity regarding the pathogenesis of AD, we hypothesize that the simultaneous implementation of multiple rehabilitation modalities could delay the progression of dementia. To the best of our knowledge, there is no rehabilitation model designed for the treatment at home for many years. This program starts in the doctor’s office and continues in the home indefinitely.
From a practical point of view, we approach dementia rehabilitation with the 4M’s dementia rehabilitation model™, which includes treating memory, mood, movements, and mitochondria to increase the vitality of neurons and their connections by increasing CBF, as shown in Figure 2.
4M’s dementia rehabilitation model™.
The in-office part of the model includes (a) an assessment of cognitive functions and movements, with special attention paid to preserved areas in cognition and motor system; (b) education about AD, modifiable factors, which needs to be used; (c) teaching patients and caregivers stress reduction techniques, as well as appropriate physical and cognitive exercises, based on patient’s level of dementia; (d) physical and cognitive training during office visits; and (e) monitoring of treatment progress during subsequent office visits.
The home part of the model includes (a) physical exercises, cognitive training, and stress management techniques practiced as per the workbook and videos (which are given to each patient); (b) sensory activation (light, sound, relaxation videos with tranquil nature scenery; and (c) nutrition.
The physical and cognitive aspects of the rehabilitation program have been developed based on the physiological, real-life interplay between physical activity, attention, and procedural memory. Physical activities require attention and help with procedural memory. All of them have a direct effect on CBF [64, 65, 66]. During the progression of AD, all three components deteriorate at different rates over time. However, they are relatively preserved, compared to other cognitive functions until the late stages of AD.
Over the years, preservation of cognitive function has been demonstrated up to 72 months of treatment. Remaining at the same level of cognitive function at the initial visit is a significant treatment achievement [67, 68].
Even though the progression of dementia is going along with development of chronic hypoxia, there is still room for developing neuroplastic changes in response to sensory-motor stimulation [69]. In recent review, ischemic damages evoke an initiation of network reorganization in spared areas of the brain [70].
There are different goals for rehabilitation for chronic and acute brain diseases; even all available rehabilitation modalities are implemented simultaneously in both types of rehabilitation. The goal of rehabilitation in dementia is to prevent cognitive and physical decline and to preserve the level of functioning and the quality of life for as long as possible. Rehabilitation activities for people living at home have to continue without time limits, for many years. Home program refers to activities designed for joint patient and caregivers, which increase patient–caregiver connections. The office staff get training, related to interaction with patients and their caregivers. Much attention is placed on education and support of caregivers as well. Elements of physical, occupational, and speech therapy in outpatient clinics could be provided by office staff in the office and by caregivers at home. Cognitive and physical stabilization is expected, as demonstrated in Figure 3.
Rehabilitation in chronic brain disease.
In stroke and head trauma (acute brain catastrophes), the goal of rehabilitation is to return to the premorbid level as close as possible. Rehabilitation in this case is a time-limited process, lasting from several months to several years. Cognitive and physical improvement is expected, as shown in Figure 4.
Rehabilitation in acute brain trauma/stroke.
The six pillars of the program consist of pharmacological interventions, mild physical exercises, multisensory stimulation, cognitive training, nutrition, and emotional support. Each pillar has direct and indirect effects on the elements of the 4M’s Dementia Rehabilitation Model™.
Medications and supplements comprise the first pillar in this model. Cholinesterase inhibitors, NMDA receptor antagonists, antidepressants, neuroleptics, and mood stabilizers, along with medication for sleep and pain, are used when clinically appropriate. Supplements include vitamin D3, B-complex, fish oil, folic acid, alpha-lipolic acid, acetyl-l-carnitine, inositol, Ribose, and other vitamins.
Mild physical exercises are the second pillar in this rehabilitation. Muscle activities couple with increasing brain blood flow and simultaneously attention and procedural memory training. Exercises are designed for people with extremely limited physical capacities and problems with gait and ambulation. The physical exercises are safe and done in sitting positions and can be performed in the doctor’s office or at home.
Physical exercises mainly consist of simple, coordinated hand and leg exercises performed both with and without the use of simple objects, such as a tennis ball. Dual-task exercises consist of hand movements, coupled with counting and breathing. Special exercises have been developed for balance training and include eye movements for decreasing visual fields and working with neck movements.
Multisensory stimulations include pleasurable activities related to auditory, visual, and tactile and other sensory channels. For example, patients work on pegboards to increase finger mobility and right–left coordination, or patients read tongue twisters loudly, sing songs, or watch comedians.
Attention and memory training consist of computerized attention (“go, no-go”) and working memory exercises (“N-back” paradigm), tasks that are performed in the doctor’s office with different objects (words, numbers, shapes, pictures, textures) plus pen and paper cognitive exercises, performed at home.
Nutrition includes diet and digestive support for microbiome and pancreatic enzymes, if clinically indicated (loss of weight).
Emotional support consists of implementation of stress management tools, brief educational sessions, related to family relationships, psychotherapy for patient’s emotional reactions in response to decline of cognitive and physical functions. For caregivers, there are psychotherapy sessions for developing coping strategies to manage behavior problems in dementia and to recognize symptoms of burnout syndrome. The family understanding and support help dementia victims stay at home for a long period of time.
Here, we present two cases with mild dementia stabilized over years with an integrative treatment approach.
Patient was an 87-year-old, retired engineer, who first came to our office at age 68. Her diagnosis was mild dementia with episodes of depression, anxiety, insomnia, HTN, diabetes, neuropathy, arthritis, dizziness, and gait problems. Her current psychiatric medications are memantine, gabapentin, clonazepam, zolpidem, buproprion SR, donepezil, vitamin D, lovaza, magnesium oxide, B-complex, and folic acid.
This patient has been treated for 19 years (2001–2020). Cognitive assessments include the MMSE, clock-drawing task, verbal fluency animals, and verbal fluency letters tests. She was doing full rehabilitation protocol with any new modifications, which had been developed during this time interval in our office.
As you can see in Figures 5–8, this patient has been stable for the whole period of treatment based on the results of these 4 tests.
MMSE stabilization.
Clock-drawing task stabilization.
Verbal fluency animals.
Verbal fluency letters.
This patient was a 92-year-old female, retired clerk, who came for treatment at age 74. Her diagnosis was mild dementia with episodes of depression, anxiety, insomnia, HTN, CAD, diabetes, arthritis, dizziness, and gait problems. She had a mini-stroke in 2015. Current medications are Namenda, Trintellix, B-complex, folic acid, and magnesium oxide.
This patient has been treated for 16 years (2002–2020). Cognitive assessments include Mini-Mental Status Examination (MMSE), clock-drawing task, verbal fluency animals, and verbal fluency letters tests. She was doing full rehabilitation protocol with any new modifications as in the previous case 1.
After mini-stroke (2014–2015), her MMSE dropped to 22 and then returned to 25.
As you see in Figures 9–12, this patient has been stable for the whole period of treatment.
MMSE stabilization.
Clock-drawing task stabilization.
Verbal fluency animals.
Verbal fluency letters.
The theoretical basis of this rehabilitation model is rooted in emerging research related to neuroplasticity data. Other well-known facts regarding AD pathogenesis—including chronic hypoperfusion and hypoxia, oxidative stress, and mitochondrial and bioenergetics failure—also provide a solid theoretical foundation upon which to effectively design and test different treatment modalities available for rehabilitation in AD [69, 70, 71]. Additionally, modifiable risk factors for AD development and progression continue to be identified [72].
In a broader sense, rehabilitation in AD could include medications that are available today (and those that will become available in the future), in addition to all possible non-pharmacological modalities that are aimed at stabilizing brain and body functions, with special attention to physical and cognitive exercises, sensory stimulations, and dietary modifications.
The rehabilitation of AD has to be seen as an ongoing treatment approach not limited by time constraints. It can be adapted to the different stages of this illness, including even the preclinical stage.
Not all motor and cognitive functions are equally affected in AD. At various levels of dementia and in each cognitive domain, there is a time-related evolution of brain disability. Meanwhile, there is a growing body of data related to the preservation of some of the brain functions in AD, including certain learning and procedural memory capacities, emotional and movement controls, and the ability to use external memory aids [72, 73, 74, 75, 76].
The multifaceted rehabilitation model for home usage presented here demonstrates strategies that go beyond the prescribing of medications to alleviate AD progression alone. It is a dynamic framework that is open to the addition of any newfound medications or innovations in nonpharmacological interventions. This model is based on a proactive, 24/7 approach to battling AD—starting with doctor’s office visits and continuing into the patient’s home for an indefinite period of time.
These rehabilitation strategies become meaningful only with ongoing support from caregivers who help the patients at home with nutrition and everyday physical and cognitive activities. This model is flexible, and the key to it is to use all the five elements of the program simultaneously. This kind of simultaneous approach is already commonly used in the treatment of many other progressive chronic ailments, such as cardiac problems, dyslipidemia, hypertension, and diabetes.
The cost for implementation of this home-based rehabilitation model is minimal (workbook, videos, and tennis ball). In addition, this model may ease the financial burden of this deadly disease on the health care system as a whole by reducing secondary medical problems from progressive dementia and delaying nursing home placement.
A multifaceted rehabilitation model for dementia at home offers a promising strategy for postponing cognitive and physical decline in dementia. Modifiable factors in dementia could be implemented at low cost.
The development of comprehensive therapy models for rehabilitation in dementia is a matter of time. There is an urgent need for the designing of long-term studies, in which all available modalities will be simultaneously implemented and for as long as possible. Further research is needed to assess the efficacy and economic impact of this multifaceted rehabilitation model.
Epidemiological studies have identified a number of modifiable factors in the onset and progression of dementia.
A new understanding of the pathogenesis of dementia has revealed that protein changes in the brain develop simultaneously with cerebrovascular pathology.
Progression of clinical dementia depends on the stress, emotional reactions, CBF, digestive system, medical illnesses profile, cognitive activities, and muscle health.
Physical and mental activities may contribute to the delay of the onset of dementia and slow down the disease progression.
A novel treatment model for dementia patients is the simultaneous use of nonpharmacological modifiable factors and pharmacological interventions for many years.
Thank you to Vian Shekhtman and Nora Zagranichny for their assistance in preparation of this chapter.
The authors declare that they have no competing interests. The authors have no financial interests in this project.
No grant support was received for this project.
I want to thank the patients that have been treated in our center. Their participation and feedbacks were very valuable, and we are grateful for it.
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Firstly, it is a very effective way of communication between the technical idea and the final solution of the problem in engineering. The process engineering design (design) begins with visualization, i.e., reviewing the problem and possible solutions. Then, sketching leads to the preparation of the initial idea. Next step is preparation of geometric models, which are used for a variety of engineering analysis and, finally, creating detailed drawings and/or 3D models, which are used for the production process. Visualization, sketching, modelling and preparation of technical documentation are ways in which engineers and technologists communicate in creating new products and structures in the modern technical world. Essentially, graphic communication, which is done via engineering drawings and models, is the clean, practical language with defined rules that need to be overcome if one wants to be successful in engineering design (any kind of design). When that language can overcome any approach to solving engineering problems. Ninety‐two percent of the engineering design process is based on the graphic display. The remaining 8% is divided between the mathematical calculations and written and oral communication. Fifty percent of the projecting time a designer spends on are purely visual and graphic activities. We like precision in communication. Engineers use graphical tools, some of which are centuries old and are used day‐to‐day, while others are very new and conditioned by the rapid development of computer technology, such as Computer Aided Design (CAD) systems. 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She is now a lecturer at the University of Witwatersrand, South Africa, and a principal researcher at the Health Economics and Epidemiology Research Office (HE2RO), South Africa. Dr. Moolla holds a Ph.D. in Psychology with her research being focused on mental health and resilience. In her professional work capacity, her research has further expanded into the fields of early childhood development, mental health, the HIV and TB care cascades, as well as COVID. She is also a UNESCO-trained International Bioethics Facilitator.",institutionString:"University of the Witwatersrand",institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419588",title:"Ph.D.",name:"Sergio",middleName:"Alexandre",surname:"Gehrke",slug:"sergio-gehrke",fullName:"Sergio Gehrke",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038WgMKQA0/Profile_Picture_2022-06-02T11:44:20.jpg",biography:"Dr. Sergio Alexandre Gehrke is a doctorate holder in two fields. The first is a Ph.D. in Cellular and Molecular Biology from the Pontificia Catholic University, Porto Alegre, Brazil, in 2010 and the other is an International Ph.D. in Bioengineering from the Universidad Miguel Hernandez, Elche/Alicante, Spain, obtained in 2020. In 2018, he completed a postdoctoral fellowship in Materials Engineering in the NUCLEMAT of the Pontificia Catholic University, Porto Alegre, Brazil. He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. In addition, he is also a Collaborating Professor in several Postgraduate programs at different universities all over the world.",institutionString:null,institution:{name:"Universidad Católica San Antonio de Murcia",country:{name:"Spain"}}},{id:"342152",title:"Dr.",name:"Santo",middleName:null,surname:"Grace Umesh",slug:"santo-grace-umesh",fullName:"Santo Grace Umesh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/342152/images/16311_n.jpg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"333647",title:"Dr.",name:"Shreya",middleName:null,surname:"Kishore",slug:"shreya-kishore",fullName:"Shreya Kishore",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333647/images/14701_n.jpg",biography:"Dr. Shreya Kishore completed her Bachelor in Dental Surgery in Chettinad Dental College and Research Institute, Chennai, and her Master of Dental Surgery (Orthodontics) in Saveetha Dental College, Chennai. She is also Invisalign certified. She’s working as a Senior Lecturer in the Department of Orthodontics, SRM Dental College since November 2019. She is actively involved in teaching orthodontics to the undergraduates and the postgraduates. Her clinical research topics include new orthodontic brackets, fixed appliances and TADs. She’s published 4 articles in well renowned indexed journals and has a published patency of her own. Her private practice is currently limited to orthodontics and works as a consultant in various clinics.",institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"323731",title:"Prof.",name:"Deepak M.",middleName:"Macchindra",surname:"Vikhe",slug:"deepak-m.-vikhe",fullName:"Deepak M. Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. 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. His research interests include root canal morphology, functionally graded concept, dental biomaterials, epidemiology and dental education, biomimetic restoration, finite element analysis and endodontic regeneration. Dr. Madfa has numerous international publications, full articles, two patents, a book and a book chapter. Furthermore, he won 14 international scientific awards. Furthermore, he is involved in many academic activities ranging from editorial board member, reviewer for many international journals and postgraduate students' supervisor. Besides, I deliver many courses and training workshops at various scientific events. Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. 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"}}}]}},subseries:{item:{id:"9",type:"subseries",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. 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Dr. Villarreal is the editor in chief and founder of the Revista de Ciencias Tecnológicas (RECIT) (https://recit.uabc.mx/) and is a member of several editorial and reviewer boards for numerous international journals. He has published more than thirty international papers and reviewed more than ninety-two manuscripts. His research interests include biomaterials, nanomaterials, bioengineering, biosensors, drug delivery systems, and tissue engineering.",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,series:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343"},editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",slug:"cecilia-cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",slug:"gil-goncalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",slug:"johann-f.-osma",fullName:"Johann F. 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Thus all studies on metabolism will be considered for publication.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation"},{id:"18",title:"Proteomics",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:{title:"Biochemistry",id:"11"},selectedSubseries:null},seriesLanding:{item:null},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"chapter.detail",path:"/chapters/40320",hash:"",query:{},params:{id:"40320"},fullPath:"/chapters/40320",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()