According to Alzheimer’s Disease International, 55 million people worldwide are living with dementia. Dementia is a disorder that manifests as a set of related symptoms, which usually result from the brain being damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, usually accompanied by emotional problems, difficulties with language, and decreased motivation. The most common variant of dementia is Alzheimer’s disease with symptoms dominated by cognitive disorders, particularly memory loss, impaired personality, and judgmental disorders. So far, all attempts to treat dementias by removing their symptoms rather than their causes have failed. Therefore, in the presented narrative review, I will attempt to explain the etiology of dementia and Alzheimer’s disease from the perspective of energy and cognitive metabolism dysfunction in an aging brain. I hope that this perspective, though perhaps too simplified, will bring us closer to the essence of aging-related neurodegenerative disorders and will soon allow us to develop new preventive/therapeutic strategies in our struggle with dementia, Alzheimer’s disease, and Parkinson’s disease. Consciousness is a physiological state of functioning of the human brain that allows it to receive and interpret signals from the environment. These signals are written into the functional structure of the brain, and their permanent memory traces are used to plan and implement behaviors necessary for survival. Learning and memory, which are the basis of human consciousness, are continuous processes that last throughout life, and their effectiveness depends in turn on the efficiency of many physiological processes carried out at the cellular, tissue, and systemic level. Disruption of each physiological cycle leads, in the long or short term, to the impairment of learning and memory and the disintegration of human consciousness collectively referred to as dementia. Such sequences of pathological phenomena seem to be a natural consequence of the aging processes of the brain and the whole organism. However, their dynamics depend on the weakest link of cognitive processes, which, in the case of their complexity, makes it difficult for scientists to pinpoint the unambiguous cause of dementia and Alzheimer’s disease. In the current attempt to bring closer the problem of diagnosis and possible prevention of dementia, I focused on the analysis of the current knowledge about brain dysfunction in the aging process. The knowledge gathered so far allows us to indicate several pathogenic phenomena leading to the development of dementia. Three of them seem to have a leading role in disturbances of consciousness. The main one is the age-related impairment of energy metabolism at the cellular level. It leads to gradually increasing metabolic disorders and disturbance of homeostasis, which is vital for brain activity. They result in several behavioral dysfunctions accompanying old age, such as limited physical and cognitive activity, and sleep disorders. These dysfunctions further exacerbate the pathophysiological changes in the brain, leading to the massive death of nerve cells. This rapidly growing process of self-destruction of the aging organism leads to dementia, i.e., inhibition of interaction with the environment, which is the meaning of life.The human brain has extraordinary cognitive abilities. This is due in particular to the enlarged neocortex and its unusual susceptibility to plastic changes. This allowed for the development of such human abilities as sentience, consciousness, perception, memory, speech, and abstract thinking . These aThe brain is a highly energy-demanding organ whose functioning depends firstly on a stable and efficient energy supply. In the waking state, the human brain, constituting only 2% of the total body weight, consumes, under physiological conditions, up to 20% of oxygen and 25% circulating glucose . OxidatiCentral nervous system (CNS) complications induced by toxic levels of glucose are multifactorial and are relatively little understood. It is now evident that malfunctioning of the blood–brain barrier may play a significant role in diabetes-dependent CNS disorders. Chronic exposure of cells and tissues to high glucose concentrations results in the non-enzymatic glycation of proteins that elevates the production of reactive oxygen species (ROS) . A combiThe cerebral cortex comprises, by volume, about 80–85% of the adult human brain. It has been estimated that the human cerebral cortex may be composed of 10–20 billion neurons, each of which may be synaptically connected with several thousand other neurons . With eaAll neurochemical processes are energy-dependent, and a growing body of evidence suggests that brain energy-related dysmetabolism can be considered a root cause of brain involution. Dysmetabolism may disrupt all biochemical processes in the brain, both at the cellular and tissue levels. Currently, it seems that energy metabolism, sensory information flows, and adult neurogenesis is essential for the networking of limbic areas and their stability . The eneThe kinetics of neuronal respiration is limited by an uninterrupted cycle of reduction/oxidation of nicotinamide adenine dinucleotide (NAD).NAD is an essential pyridine nucleotide that serves as a cofactor and substrate for critical cellular processes involved in oxidative phosphorylation and ATP production, DNA repair, epigenetically modulated gene expression, intracellular calcium signaling, and immunological functions ,10,18,19Lactate is considered a potential energy substrate capable of supporting neuronal activity in conditions of reduced oxygen supply, e.g., during exercise . Almost During severe energy crises, glucose can be produced in the process of gluconeogenesis , a rescuThe metabolism of the cognitive neuronal networks consists of multiple interconnected metabolic pathways that may happen efficiently and at the required rate only in the state of steady internal, physical, and chemical conditions, including reactants’ concentration, tissue temperature, and energy supply. Energy metabolism is a core set of catabolic pathways that allows the maintenance of the resting cellular homeostasis and its recovery after neuronal activity. Additional energy must be allocated for extracellular metabolic processes including waste and neuronal debris removal, allowing recovery of brain tissue homeostasis. From this perspective, disturbance in any metabolic process may result in the rapid or postponed development of chronic brain dysfunction.The autonomic nervous system (ANS) plays a key role in the control of energy balance and glucose homeostasis ,27,28. IThe hypothalamus is the central controller of homeostasis that regulates basic processes such as food and water intake, energy expenditure, responses to stress, blood pressure, and all processes that are required for survival . The nucWithin a few regions of the brain including the hypothalamus, the blood–brain barrier is not complete, which allows insulin, IGF-1, ghrelin, leptin, other peptides, and even fatty acids to penetrate the barrier and gives a more precise sense of the nutritional value of the food consumed. Unfortunately, the incomplete blood–brain barrier increases the susceptibility of the hypothalamic nuclei to focal damage by free fatty acids and consequent impairment of homeostatic and metabolic control ,33. MetaThe respiratory center is located in the brainstem, in the medulla oblongata, and the pons. The center is responsible for generating and maintaining the rhythm of respiration and also adjusting this in homeostatic response to physiological changes . The resChanges in the blood acid-base balance result from changes in metabolism and breathing. Excess carbon dioxide causes the pH of blood to decrease and its intracellular levels to increase. The increasing level of carbon dioxide increases glycolysis via the phosphorylation of glucose, and glucose 6-phosphate is produced. This leads to a reduction in intracellular phosphate and a consequent shift of phosphate into cells. Serum phosphate falls within 20 min of hyperventilation, and it persists for 90 min after the ventilation returns to normal ,39. The The control of glucose metabolism can be divided into two processes. First is insulin-dependent glucose storage in skeletal muscle, liver, and white adipose tissue . The livBesides oxygen, glucose and phosphate play an essential role in cognitive metabolism ,43. At tThe human body turns over the body weight equivalent in ATP daily . The ATPPhosphate supply to the brain is controlled in a neuronal activity-dependent manner, making phosphate the brain metabolic booster. Serum phosphate homeostasis is maintained through a complex interaction between intestinal phosphate absorption, renal phosphate handling, and the cellular intake of phosphate. The homeostasis is under the direct hormonal influence of calcitriol, PTH, and phosphatonins, including fibroblast growth factor 23 (FGF-23) . FGF-23 Human energy metabolism is supplemented by several hormonally controlled processes. The integrated energetic processes are controlled by the growth (GH) and thyroid (T4/T3) hormones. T3 acts on most active cells such as neurons and muscle cells, increasing the production of Na/K-ATPase which serves as an ion pump creating an electrochemical gradient across the plasma membrane . In the The secretion of growth hormone (GH) in the pituitary is regulated by the neurosecretory nuclei of the hypothalamus. The growth hormone is secreted in a pulsating manner and the largest GH peak occurs about an hour after the onset of sleep . The relRealization of time-consuming processes such as neuroplastic changes in cortical networks requires the supportive activity of IGF-1, which shares common receptors in the brain with insulin ,53,54. TInsulin receptor substrate 1 (IRS-1) is a signaling protein that plays a key role in transmitting signals from insulin and IGF-1 to intracellular pathways . ImportaSomatostatin regulates the endocrine system and also affects neurotransmission and cell proliferation ,58,59. IA growing body of evidence suggests that peripheral hormones released from the musculoskeletal system may control energy and also cognitive metabolism. One such example of such multi-organ interaction is the pleiotropic effects of the bone-derived hormone, osteocalcin. Osteocalcin is essential to regulate energy metabolism by increasing insulin sensitivity via the stimulation of adiponectin release by adipocytes . The reaSuch involvement of osteocalcin in addition to its progressive decline in midlife may suggest that the hormone is linked with age-related cognitive decline . There hThe essence of life is interaction and adaptation to the environment. To this end, an egocentric representation of the environment is created in the human brain which is constantly being attuned to any environmental changes. To this end, the functional neural networks formed in the cerebral cortex are continuously modified by the streams of sensory stimuli created during interaction with the environment ,63. ImpoCurrent views on brain consciousness are dominated by a holistic view, according to which specialized structures of the brain are assembled in neuronal networks which can be constantly modified by streams of sensory signals. Consequently, the interactions of the functional structures of the brain are established based on a dynamic equilibrium with the environment. In other words, the phenomenon of consciousness consists in selectively capturing relevant information from the environment and saving it in the form of memory traces. However, the output of egocentric control, particularly human motor behavior, seems more complex due to complex interactions between central  and peripheral (executive) control.Brain correlates of cognition are neuronal assemblies that during their entire lifetime are successively modified by perceptive streams. As a consequence, the inscribed in-brain-structure information creates an egocentric representation of ourselves and our surrounding environment that allows for conscious motor activity and social interactions modulated by emotional context. The interactions are sources of sensory signals stimulating brain functional networks. Brain–body–brain interactions are inseparable entities that are responsible for the regulation of both organismal homeostasis and allostasis with the latter being simply the anticipation of needs and preparing to satisfy them before they arise . ImportaCognitive changes in the brain use many different physiological processes with high energy consumption. The dominant role here is synaptogenesis (creating new synaptic connections) as well as pruning and removing unnecessary connections. Since neural connections are particularly loading for cognitive metabolism, their energy efficiency is improved by myelination of the axonal fibers. Both the creation of new permanent synaptic connections, their myelination and the removal of waste products are significant additional energy burdens for the already energy-consuming brain. Therefore, their course is spread over time and most often takes place during sleep. Thus, any sleep disturbance is a significant cause of cognitive metabolism dysfunctions and, consequently, is considered an early prodrome of dementia and neurodegenerative diseases.Cognitive brain functions, including sensory perception and control of behavior, are ascribed to computation in networks of neurons . Brain nIt is commonly accepted that cognitive brain functions, including sensory perception, learning, motor control, and control of behavior, are ascribed to computation by axonal-dendritic chemical synapses in cortical networks . MoreoveThe most numerous neurons found in the cerebral cortex, the hippocampus, and the amygdala, are multipolar pyramidal cells. The complex phenotype of pyramidal cells in the human prefrontal cortex imparts specific biophysical properties and connection patterns that differ from those in other cortical regions . The abiThe high functional plasticity of cortical networks in combination with raised energy supply allows for fast learning  ,70, but It is commonly believed that neuronal energy metabolism could be assessed with the rate of oxidative phosphorylation. The total energy gained in the form of ATP per mole of glucose is around 1159 kJ, while the combustion of 1 mole of glucose releases 2870 kJ . ConsequThe proper course of several physiological processes contributes to the exceptional plasticity of pyramidal neural networks. The primary mechanism of network formation is synaptogenesis, which changes the strength and quality of interneuronal connections . This prA substrate of memory trace within each neuronal network is a specific pattern of synaptic connections and gains, fixed and optimized in the process of learning. Moreover, the interaction of multiple functionally integrated cortical networks, storing various aspects of the given memory trace, ensures distributed and redundant, thus highly reliable, memory. Maintaining such an organized memory requires a lot of energy. Cortical nerve cells interacting within functional networks can create many thousand synaptic connections, and each synapse is the main consumer of energy obtained from oxygen and glucose. As much as 80% of energy consumption in neurons is attributed to synaptic connections . The avaA unique feature of the human brain is its cognitive abilities and the related ability to transform the structure of brain connections in response to any changes in the individual’s environment. Acquiring new skills and behaviors is defined as the learning process, the inseparable form of which is the creation of permanent memory traces. The set of memory traces accumulated during life determines our personality, the creation, and the maintenance of which, due to its size and dynamics, can be called cognitive metabolism. Cognitive metabolism is based on the modification (creating new and removing unnecessary) synaptic connections of the brain’s nerve networks, which represent the temporal-spatial characteristics of the environment as well as the motivational and emotional significance of the stimuli associated with them. Based on this information, patterns of motor responses are created. Thus, we have two components of cognitive metabolism that allow the transformation of streams of environmental stimuli into adequate motor responses. The dynamics of cognitive processes change in the course of individual development, reaching their maximum in the early developmental period and adolescence. In adulthood, these processes stabilize, and then, in the aging period, their intensity and scope gradually decrease. The manifestation of cognitive dysmetabolism is gradually increasing dementia, attention disorders, and a deficit of decision-making processes, as well as a deficit of short-term memory.White matter accounts for more than half of the total brain volume. It is composed firstly of long axonal fibers with varying degrees of myelination ,74 and oBrain development and its longevity are related to the pre-and post-natally accumulated energy metabolites and essential nutrients. At least two of these are recognized recently: nicotinamide riboside and sialic acid. Whereas the first one is directly related to neuronal energy metabolism, the second one is necessary for building and repairing cell membranes and myelin sheaths. Myelination and its plasticity are based on the reciprocal interactions of oligodendrocytes with the axons they ensheath. The integrity of axons depends on the glial supply of metabolites and neurotrophic factors. The relevance of this axoglial interaction can be observed in brain aging as well as in human myelin diseases. It has been well documented that myelination is dependent on the neuronal bioelectrical activity of the neurons and various molecular mediators synthesized and released in response to electrical events . In partAdult neurogenesis and neuronal strongly contribute to the continuous remodeling of the neuronal networks emerging in cognitive processes . SignifiNeurotrophins play pivotal roles in the formation and plasticity of neuronal networks. In particular, the activity of brain-derived neurotrophic factor (BDNF) is vital to the survival, growth, and maintenance of neurons in key brain circuits involved in emotional and cognitive function . OptimizDementia is a disorder that manifests as a set of related symptoms, which involve progressive impairments in memory, thinking, and behavior usually accompanied by emotional problems, difficulties with language, and decreased motivation, which altogether constitute human consciousness. In particular, the main symptoms of Alzheimer’s disease are cognitive malfunctions, particularly memory loss, impaired personality, and judgmental disorders. At least two pathogenic causes have been documented in the aging brain. The first is aging-related dysfunction of energy metabolism leading to neurodegeneration and massive death of neuronal cells. The second is a progressive involution of the brain in aging due to reduced cognitive and motor activity. Up to date, all attempts to treat dementias by removing their symptoms rather than their causes have failed.Two fundamental factors are responsible for the aging and death of neurons that must be kept in mind when developing prevention strategies. Neurons are among the unique long-lived cells that have only one life. Throughout life, the number of neurons that make up the brain continues to decline, and the total number of synaptic connections changes. The second important factor is the optimization of energy expenditure, essential for life, by removing unnecessary or inefficient nerve cells. However, the ability to modify the structures of neural networks through cognitive processes remains throughout life. For the sake of simplicity, it can be assumed that the energy metabolism of the brain has two components: functional, related to the structure and maintenance of brain tissue, and cognitive, related to modification of the brain structure by learning and memory, emotions, and decision-making processes.The energy crisis in the aging brain and the mass death of malfunctioning and unnecessary neurons impede the formation of new memory traces. The functional and trophic interaction inherent in the functioning of the brain has a particularly destructive effect on the functioning of the old and the formation of new functional networks in the elderly. This interaction ensures the correct energy supply and the necessary metabolites only of highly active neurons. It intensifies dysmetabolism, disturbs homeostasis, and accelerates the aging and death of nerve cells. The manifestation of these dysfunctions is late-onset neurodegenerative diseases. These diseases are preceded by prodromes signaling early metabolic brain dysfunctions such as arterial hypertension, type 2 diabetes, sleep disorders, anosmia, and mental changes with a characteristic increase in the level of anxiety. Later on, depending on the size and location of areas of the brain damaged, a set of quite specific symptoms appears. Since the effects of brain aging may appear rather late and usually concern different areas at the same time, the observed symptoms can be very diverse, which in the case of neurodegenerative diseases makes diagnosis and treatment extremely complicated. For instance, early clinical symptoms of Parkinson’s disease appear after 5–10 years after prodromes when almost 80% of dopaminergic neurons of the substantia niagra are dead .2+ fluxes, permeability transition pore opening, and perhaps secretion of specific proteins/peptides [Mitochondrial dysfunction has been implicated in the pathophysiology of cellular aging and neurodegeneration. Mitochondria signal stress by alterations in adenine nucleotide levels, reactive oxygen species(ROS) production, Capeptides . Oxidatipeptides .The correlation of pathological changes in the brain with accompanying symptoms allows for a better understanding of the pathophysiology of dementia. The most common feature of dementia is the loss of the ability to form new memory traces. This implies that brain aging and the resulting progressive degradation of cortical functional networks of the cerebral cortex and the hippocampus are the primary loci of dementia development. The neurodegenerative processes may be then spread to the limbic system, especially the amygdala as well as the entorhinal and cingulate cortex . The alsMisfolded proteins have been widely considered to be the triggering factors in Alzheimer’s disease . Indeed,The APP is an integral membrane protein involved in synapse formation and neural plasticity. During cognitive processes, APP moves from the endoplasmic reticulum (ER) to the plasma membrane, where it is endocytosed by endosomes and lysosomes . In physSimilarly, alpha-synuclein is a neuronal protein that normally regulates synaptic vesicle trafficking and subsequent neurotransmitter release . It is fAn increase in metabolic demand will lead to an increase in cerebral blood flow (CBF) . The CBFBrain activity and its energy metabolism are determined by specific, very complex interactions between neurons and glial cells. Particularly, astrocyte reactivity is triggered by any alteration in brain homeostasis ,95,96. AThe brain is considered to be autonomous in lipid synthesis with astrocytes producing lipids far more efficiently than neurons . AstrocyNeurons alone are unable to synthesize from glucose either the glutamate or the inhibitory GABA, and thus, they are fully dependent on astrocytes’ metabolic cycle of the glutamate/GABA-glutamine ,97,98. FMyelin, formed by oligodendrocytes, is a lipid-rich material that surrounds axonal fibers to insulate them and increases the rate and energetic efficiency of neuronal transmission. Besides that, the oligodendrocytes support axons metabolically by providing lactate as a nutrient . The maiThe myelination process is triggered and intensified in response to learning and new experiences leading to the formation of new memory traces. The myelinated fiber tracts integrate multiple brain areas associated with various cognitive, emotional, and motor functions. In young adulthood, when the individual level of accumulated experiences reaches its maximum, the white matter structure is relatively stable. Next, cognitive brain functioning and structure decline steadily. The common factor in older adults is decreased motor and cognitive activity that impacts neuronal brain networks. The process of demyelination strikes redundant and poorly functioning neuronal networks first.The theory of retrogenesis claims that late-maturing brain tissue is particularly vulnerable during aging and that tissue degeneration in the aging brain follows the reverse sequence of tissue maturation ,76. AccoThe regulation and coordination of complex cellular processes such as adult neurogenesis, cell migration, differentiation, and apoptosis depend on communication between neuronal and glial cells. The primary mediators of such physiological cell responses are receptor tyrosine kinases (RTKs). Additionally, insulin-like growth factor-1 (IGF-1) supports neuronal and glial differentiation, migration, and positioning in the brain . AstrocyThe brain is one of the greatest beneficiaries of energy processes and at the same time the most sensitive to energy deficit. Short-lasting energy deficiency usually causes a temporary decrease in motivation for physical activity, with increased signaling of energy nutritional needs. The changes are manifested in both motivation and mood. The problem of energy deficit begins to complicate the situation of elderly people, in whom the positive reinforcement systems (serotonergic and oxytocin) are malfunctioning, and fear and anxiety become dominant. The related stress disrupts the functioning of the whole organism, which consequently comes down to avoiding all activities and preferring a sedentary lifestyle. In such conditions, most of the cortical networks become poorly used and consequently deprived of energy. This opens the vicious circle of dementia. Decreasing metabolism in the aging brain combined with hypoactivity escalates muscle loss (sarcopenia) which in turn substantially reduces the capacity of striatal muscle to store and use glucose . AdditioThe first and most relevant for brain aging are energy metabolism-related changes, autonomic disturbances, deficient glucose metabolism (type II diabetes), and hypertension . They arThe formation of memory networks and their modeling requires extraordinary energy inputs ,108. TheSleep disorders negatively affect a wide range of cognitive functions, including memory, learning, attention, and emotional reactivity . ConsequSleep has a critical function in ensuring metabolic homeostasis . Sleep iSleep disorders cause an accumulation of waste products that additionally intensify brain dysmetabolism by impairing the functioning of the entire glymphatic system and, additionally, the process of adult neurogenesis which is another key mechanism in brain neuroplasticity and memory. Neurogenesis in the adult brain is limited to olfactory bulbs, hippocampus, and striatum, and the efficiency of the process relies on the migration of progenitor cells from the subventricular zone area via the rostral migratory stream to the target places . AccumulThe age-related impairment in sleep quality may cause the increasing impairment of glymphatic waste product clearance. Amyloid-β plaque formation is usually associated with an inflammatory response, including reactive micro- and astrogliosis . ConsequPhysiological sleep plays a vital role in the control of brain energy metabolism. Chronic sleep disorders can lead to impaired glucose metabolism . After oPoor sleep quality and circadian dysfunction can exacerbate neurodegeneration . Sleep dAlzheimer’s disease is the most common form of dementia in the elderly . AmyloidCortical atrophy dominates in dementia with Lewy bodies with an additional, concentrated area of atrophy in the subcortical brain, including the midbrain, hypothalamus, thalamus, basal ganglia, and substantia innominate ,127. It The pathological changes may appear locally or cover larger cortical areas. Growing evidence suggests that neurodegenerative diseases are caused by cortical network dysfunction rather than the dysregulation of an isolated brain region ,13. LocaThe long lifespan of neurons makes intracellular maintenance an important challenge . Active Neuropathologies and dementias are frequently linked with tau proteins that have become hyperphosphorylated insoluble aggregates called neurofibrillary tangles . The tauVascular inflammation in the context of an altered blood–brain barrier (BBB) has been implicated in the pathogenesis of AD. Recent studies have shown that demented patients lose significant numbers of pericytes in the cortex and hippocampus leading to BBB damage, increased Aβ deposition, and tau pathology, culminating in severe cognitive impairment . AstrocyMicroglia acts as the primary immune response in the central nervous system ,133. ForAstrogliosis  and micrThe increasing population of Europe coupled with the aging demographics in many European countries provides a clear indication that the overall number of people with dementia is likely to continue to increase significantly. Up to date all attempts to treat neurodegenerative diseases by removing their symptoms rather than their causes have failed. Therefore, in the presented narrative review, I attempt to explain the etiology of dementia and Alzheimer’s disease from the perspective of energy and cognitive metabolism dysfunction in an aging brain. I hope that this perspective, though perhaps too simplified, will bring us closer to the essence of neurodegenerative disorders and will soon allow us to develop new preventive/therapeutic strategies in our struggle with dementia.The knowledge gathered so far allows us to posit that the basic cause of brain aging is the loss of control over glucose metabolism, resulting in the loss of energy balance. Homeostasis is ensured by balancing the processes of glucose intake and accumulation in skeletal muscles, the liver, and adipose tissue, and then their activity-dependent redistribution within the organism. While glucose intake and storage is a short-term process controlled by insulin, the use of this energy fuel is controlled by the growth hormone/IGF-1 cycle, whose long-term activity allows for the continuation of the cognitive brain activity during sleep. Three key factors responsible for brain aging and dementia are (1) the loss of the brain’s ability to sense blood glucose levels, (2) decreased IGF1 activity and (3) sleep disorders. The implemented-by-brain compensatory processes, including type 2 diabetes and hypertension, occur to be more pathogenic. Increased glucose levels that cannot be utilized by the brain and muscles result in hypoactivity which dramatically restricts cognitive processes. The unused neuronal networks are systematically reduced, which triggers the development of dementia. Moreover, almost all the most energy-consuming nervous structures are reduced. Besides cortical pyramidal neurons, age-related neurodegeneration also strikes the brain pyramidal pathways including the nigrostriatal control system and other long and unmyelinated axons of the autonomic nervous system.The glucose/energy crisis also impacts emotional control. Chronic stress accompanying energy dysmetabolism potentiates sleep disorders and additionally triggers the process of gluconeogenesis contributing strongly to hypoactivity-dependent sarcopenia. Simultaneously, sleep disorders devastate the functioning of the glymphatic system with its two major physiological functions: waste product removal and adult neurogenesis. Taken together, all pathophysiological and behavioral processes cumulate, progressively reaching the critical point of microglia deficiency and uncontrolled neurodegeneration. This is the final act of conscious brain self-destruction. If it is the case, how we can help people suffering from dementia?Massive death of cortical neurons ultimately terminates the functioning of the cognitive brain. The dead neurons will never recover, but early intervention may slow down or even reverse the cascade of neurodegeneration. Intensified cognitive metabolism supplemented by essential energy nutrients such as NAD, IGF-1, and probably vitamin D and phosphate should improve the functioning of the cortical networks. If we combine it with a low-fat diet and physical activity, we can anticipate better functioning and maintenance of the cognitive networks in good shape until a late age. This opens a window of opportunity to treat or slow down the process of dementia before it reaches a critical point with no return.In this context, it is worth mentioning the NAD and phosphate contribution to brain aging and neurodegeneration. There is rapidly growing research on the role of vitamin B3 precursors  in supporting neuronal viability. In the case of senile neurons, the curing properties may occur rather limited. Supplementation of vitamin B3 precursors may, however, slow down the aging process in cortical neurons and their cognitive networks. At the same time, it should be remembered that only neuronal cells cognitively stimulated show increased activity and may finally benefit from NAD supplementation and improved energy metabolism. Similarly, there is an underrated problem of phosphate/calcium (Ca/P) homeostasis and its impact on brain energy metabolism. An increasing body of evidence suggests that the physiology of the brain depends strongly on bone-controlled calcium and phosphate homeostasis. Age-related dysfunction of Ca/P homeostasis strongly impacts the functioning of neural and muscular cells. The dysfunction is initially observed as a fatigue syndrome. Phosphate plays an important role in brain energy metabolism. Its inflow to neurons allows for glucose phosphorylation which is the initial step of oxidative phosphorylation and ATP production. A combination of hypophosphatemia and elevated glucose level may be devastating for elderly subjects. Therefore, recovery of Ca/P homeostasis is the second main target in the treatment of neurodegenerative diseases. Recent studies on the pathogenic effect of hypophosphatemia suggest that vitamin D supplementation may improve energy metabolism while removing symptoms of chronic fatigue. This gives new hope to elderly people suffering from neurodegenerative diseases.


Mouth breathing is one of the most common deleterious oral habits in children. It often results from upper airway obstruction, making the air enter completely or partially through oral cavity. In addition to nasal obstruction caused by various kinds of nasal diseases, the pathological hypertrophy of adenoids and/or tonsils is often the main etiologic factor of mouth breathing in children. Uncorrected mouth breathing can result in abnormal dental and maxillofacial development and affect the health of dentofacial system. Mouth breathers may present various types of growth patterns and malocclusion, depending on the exact etiology of mouth breathing. Furthermore, breathing through the oral cavity can negatively affect oral health, increasing the risk of caries and periodontal diseases. This review aims to provide a summary of recent publications with regard to the impact of mouth breathing on dentofacial development, describe their consistencies and differences, and briefly discuss potential reasons behind inconsistent findings. Mouth breathing is one of the most common deleterious oral habits in children and a symptom of sleep disordered breathing (SDB). Its prevalence ranges from 11 to 56% in children . As withDefined as over 25%−30% of the air passing through the mouth instead of the nose , 8, moutThis review provides a succinct summary of recent publications regarding the impact of mouth breathing on dentofacial development, describes their consistencies and differences, in order to help dental practitioners and clinicians in other related specialties perform evidence-informed decision-making, and to improve the awareness of currently available evidence and key research findings among investigators and postgraduate students working in relevant fields.Mouth breathing can result from obstruction at any site of upper airway. Upper airway can be divided into four sections: nasal cavity, nasopharynx, oropharynx, and laryngopharynx . DiffereNasal obstruction can be attributed to nasal inflammation in children, including allergic rhinitis, chronic rhinitis, and sinusitis. In recent years, environmental degradation and air pollution have led to an increased prevalence of nasal allergic diseases, and therefore allergic rhinitis related nasal obstruction has become more common. In addition, morphological deformities of the nose which affect nasal ventilation and reduce nasal airflow, such as the deviated nasal septum, turbinate hypertrophy, nasal polyps, and nasal trauma, can also lead to mouth breathing –18.Adenotonsillar hypertrophy is the most common cause of mouth breathing in children , 19. TheThe function and morphology of the orofacial system are unified. The habitual position of muscles inside and outside the mouth will affect dental development . MalocclMouth breathing results in muscle imbalance, which may lead to oral and craniofacial alterations. Mouth-breathing children have a significant decrease in tongue pressure , 25. ChiThe clinical features of malocclusion can vary with etiological factors  of mouth breathing . PosteriHowever, several studies on mouth breathing with adenoids and/or tonsils hypertrophy have also shown different conclusions. A previous study found that tonsillar hypertrophy in different degrees was associated with an increased risk of large overjet and Class II malocclusion, whereas adenoid hypertrophy was not significantly associated with malocclusion in children around 6 years of age . A possiIn 1981, Harvold et al.  carried Similar to the malocclusion, skeletal patterns present dissimilarly with different etiological factors. The obstruction resulting from tonsillar hypertrophy often exhibits a Class III skeletal pattern, which is distinguished by maxillary sagittal dysplasia and mandibular protrusion –53. IwasHowever, some publications have stated different conclusions. It has also been suggested that mouth breathing has no impact on sagittal parameters but is significantly associated with lower anterior facial height in the vertical direction. Furthermore, the removal of hypertrophic adenoids improves vertical skeletal growth . A systeWhen air flows through the mouth, saliva evaporates and causes a decrease in the humidity in oral cavity. As an important agent for immune defense, antibacterial action, lubrication, and dissolution of inorganic substances, saliva contributes to the stability of PH in the oral environment and the prevention of dental caries . Many stIn an intermittent nasal congestion rat model, there was a significant reduction in the thickness of the hyperplasia layer as well as the hypertrophic layer of condylar joint, which suggested that the development of the temporomandibular joint was also influenced by oral breathing habits . A previMouth breathing is a common deleterious oral habit among children. During the growth period, mouth breathing may negatively affect dentofacial development if not corrected in time. Consequences resulting from mouth breathing habits include malocclusion, the deterioration of oral hygiene, increased prevalence of caries, periodontal diseases, and abnormal maxillofacial growth. Therefore, the early diagnosis and intervention of mouth breathing, based on a thorough analysis of its exact etiology, is of paramount importance .Adenotonsillar hypertrophy is the most common cause of mouth breathing in children. Adenoids and palatine tonsils are located in different sites of upper airway. During the growth period, the obstruction occurring in different locations and times may result in corresponding facial patterns. Thus, the dentofacial development of children with both tonsillar hypertrophy and adenoid hypertrophy presents great complexity. Adenotonsillectomy may promote the normalization of breathing patterns and inhibit or even reverse the development of dentofacial deformity during the growth period , 74. It This review aims to provide a summary of recent publications with regard to the impact of mouth breathing on dentofacial development, describe their consistencies and differences, and briefly discuss potential reasons behind inconsistent findings. Actually, for more than 100 years since mouth breathing was proposed, its influence on the malocclusion and morphological and functional development of the maxillofacial region has been controversial. What remains unknown is the precise contribution of genetic and environmental factors. In recent years, new relevant studies elaborate their findings and offer different opinions. What counts is that there is no high-quality evidence elucidating the effects of mouth breathing on dentofacial development and health, which is also due to the lack of well-designed clinical studies. The mechanism of mouth-breathing impact on the development of the dental and craniofacial region is still unclear.Many studies have relied on questionnaires, inspection, simple screening tests (such as water holding test and mirror test), and the diagnosis of nasal endoscopy used by otolaryngologists to identify mouth-breathing patients. To our knowledge, there are no strict criteria for the diagnosis of mouth breathing, and the subjective assessment of mouth breathing may be one of the reasons why the findings are difficult to achieve agreement. The lack of diagnostic criteria makes the research on the association between mouth breathing and dentofacial development limited as well. In the future, more comprehensive studies should also be devoted to the establishment of a unified guideline of mouth breathing diagnostic criteria, as well as improvement of research methods, and further exploration of the effects and mechanisms of mouth breathing. The aim is to advance the knowledge of clinical dentists and pediatricians about mouth breathing and its influences, furthermore, to provide them with a more evidence-based diagnostic paradigm. Early screening of children's potential mouth breathing habits can help to interrupt it before their growth spurt, thus avoiding possible adverse impacts.LL and TZ: manuscript drafting. LL: visualization. DQ, FH, and HH: critical revision of the manuscript. All authors: approval of the final version.This work was supported by the Wuhan Knowledge Innovation Project (No. 2022020801020502), the CSA Orthodontic Clinical Research Project for Central and West China (No. CSA-MWO2021-01), the Fundamental Research Funds for the Central Universities , and the Wuhan University School & Hospital of Stomatology Clinical Research Project (No. LYZX202101).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


In order to improve the dynamic evaluation ability of medical image multimedia courseware-assisted teaching effect, the evaluation of medical image multimedia courseware-assisted teaching effect based on a deep learning algorithm is proposed. The statistical data analysis model of medical image multimedia courseware-assisted teaching effect is established to estimate its utilization rate and scale parameters. Based on the prediction of spatial attribute parameters, the classification big data mining model of medical image multimedia courseware-assisted teaching is constructed by using the deep learning algorithm, mining association rules and frequent item sets that can dynamically reflect the quality of medical image multimedia courseware-assisted teaching, and extracting the statistical feature of the dataset of constraint indicators of medical image multimedia courseware-assisted teaching effect to improve the teaching quality of medical imaging course. The simulation results show that this method has a better precision delivery effect, higher dynamic matching degree of teaching evaluation parameters, more than 90% reliability, and better clustering of statistical eigenvalues. Through the evaluation of the effect of medical image multimedia courseware-assisted teaching, combined with the analysis of the use characteristics of medical image multimedia courseware-assisted teaching, it is necessary to evaluate the effect of medical image multimedia courseware-assisted teaching under the multisource information resource as a service (miraas) mode so as to improve the intelligent service level of medical image multimedia courseware-assisted teaching , 2.The research on the evaluation of the effect of medical image multimedia courseware-assisted instruction is realized by analyzing the utilization state characteristics of medical image multimedia courseware-assisted instruction , 4 and aIn view of the above problems, this paper proposes an evaluation method of medical image multimedia courseware assistant teaching effect based on the deep learning algorithm. It shows the superiority of this method in improving the evaluation ability of medical image multimedia courseware. Finally, the simulation test analysis shows the superiority of this method in improving the teaching effect of medical image multimedia courseware.Deep learning is to learn the inherent rules and representation levels of sample data. The information obtained in the learning process is of great help to the interpretation of data such as words, images, and sounds , 8. The Each node in the deep learning model represents a basic calculation and a calculated value, and the calculated result is applied to the values of the child nodes of this node. We consider a computational set, which can be allowed in every node and possible graph structure, and define a family of functions. The input node has no parent node, and the output node has no child nodes. Through layer-by-layer feature transformation, the feature representation of the sample in the original space is transformed into a new feature space, thus making classification or prediction easier. Compared with the method of constructing features by artificial rules, using big data to learn features can better depict the rich internal information of data.The design of medical image multimedia courseware-aided teaching system is to apply the system method to study and explore the essential relationship between each element in the teaching and learning system and between the element and the whole and comprehensively consider and coordinate their relations in the design so that each element can be organically combined to complete the function of the teaching system. If we do not consider the various elements that affect the implementation of the solution and the relationship between them, the designed solution will not achieve its expected goals.The research object of teaching system design is the system of learning and teaching at different levels. This system includes the contents, conditions, resources, methods, and activities to promote students' learning. The process of teaching system design is the process of making specific plans for these elements that affect the teaching effect.The purpose of teaching system design is to transform the principles and methods of basic theories such as learning theory and teaching theory into solutions to practical teaching problems. It is to creatively solve problems in teaching by using known teaching laws. The results or products of teaching system design are verified teaching system implementation plans that can achieve the expected functions, including teaching objectives, teaching activities, and implementation plans required to achieve certain teaching objectives and relevant supporting materials.The networked control technology of the Internet of things is used to realize the networked control of the process of medical image multimedia courseware-assisted teaching effect evaluation. The constructed medical image multimedia courseware-assisted teaching effect evaluation system includes an information collection module, a data analysis module, and a resource scheduling module. The data bus development platform of the medical image multimedia courseware-assisted teaching effect evaluation system is established. The utilization rate and scale parameters of the medical image multimedia courseware-assisted teaching effect are estimated , 14. TheBased on the principles of intensive construction, coconstruction and sharing, overall planning and promotion, the evaluation system of medical image multimedia courseware-assisted teaching effect is constructed. The overall structure of the system is shown in The web framework system is adopted to evaluate and optimize the effect of medical image multimedia courseware-assisted teaching under multimedia technology. The image teaching is the main content, the advanced client-server system is selected, the switching fast Ethernet technology and the relevant supporting network equipment are applied, and the star topology structure and integrated wiring technology are adopted to realize the automatic control of the evaluation of medical image multimedia courseware-assisted teaching effect, The network design of the system is shown in In order to evaluate the teaching effect of medical image multimedia courseware based on the deep learning algorithm, first, a statistical data analysis model of medical image multimedia courseware teaching effect is established by using the multidimensional spatial hierarchical depth information mining method. Combined with spatial resolution parameter analysis, the image data feature detection method and the pixel division method are adopted to analyze the object model of medical image multimedia courseware teaching effect . Then, wAccording to the component design of Based on the prediction of spatial attribute parameters, the classification big data mining model of medical image multimedia courseware-assisted teaching is constructed by using the deep learning algorithm with constraint index parameters such as courseware design appreciation, multimedia courseware theory, diversity of teaching methods, and discipline construction requirements, and the association rules and frequent item sets that can dynamically reflect the quality of medical image multimedia courseware-assisted teaching are mined , 18. Accs represents the comprehensive semivariance distribution neighborhood. j quantitative evaluation point, l represents the characteristic value of the attribute space control variable, p is the local variance of the multimedia image. Based on the constraint index parameters such as courseware design appreciation, multimedia courseware theory, diversity of teaching methods, and discipline construction requirements, a threshold analysis model of medical image multimedia courseware-assisted teaching is established by using image regional feature analysis , which indicates the recommendation degree of medical image multimedia courseware-assisted teaching information resources, and the semantic similarity is obtained as follows:In formula , C1 and α is a constant, and In formula , θ^ inditeaching .A = {a1, a2,…, an} and b = {b1, b2,…, bm}. According to the above, the standard function of the teaching constraint index parameter is obtained as follows:Based on the method of spatial and attribute parameter prediction, a dynamic constraint parameter model of medical image multimedia courseware-assisted teaching effect evaluation is established. Combined with subspace fusion cluster analysis, the maximum tree bifurcation method is adopted to conduct data-driven and segmentation scale adaptive estimation in the process of medical image multimedia courseware-assisted teaching effect evaluation. According to the spatial characteristics and attribute characteristics, the estimated construction effect of medical image multimedia courseware-assisted teaching is obtained, x represents the lateral component of the constraint index parameters of medical image multimedia courseware, Y represents the central component of the constraint index parameters of medical image multimedia courseware, Z represents the three-dimensional characteristic quantity of the constraint index parameters of medical image multimedia courseware, and σ represents the fuzzy membership parameter. Based on the machine learning algorithm, data from multiple data sources are merged together to obtain the grouping detection model as follows:In formula , x reprexi is the integration parameter of the i-th medical image multimedia courseware-assisted teaching distribution block, yi is the auto-correlation characteristic matching coefficient of medical image multimedia courseware-assisted teaching, and zi2 is the fuzzy dynamic detection parameter. The entropy evaluation model of medical image multimedia courseware-assisted teaching effect evaluation is established, and the maximum information entropy distribution is as follows:In formula , xi is tEint(vi) represents the self-adaptive estimation parameter value of multimedia courseware-assisted teaching effect construction of medical images, Eext(vi) represents the local equation of multimedia courseware-assisted teaching images of medical images, and N represents the sample number of segmented patches. By using the method of fuzzy information fusion, the fuzzy clustering function of multimedia courseware-assisted teaching effect evaluation of medical images is expressed as follows:In formula , Eint(viX represents the level residual error of the utilization efficiency of multimedia courseware for medical images; Y represents the frequency quantization characteristic parameter value. Then, we calculate the variation function value of the medical image multimedia courseware-assisted teaching subblock, extract the statistical feature quantity of the medical image multimedia courseware-assisted teaching effect constraint index dataset by inverse feature analysis, and get the clustering model of medical image multimedia courseware-assisted teaching effect evaluation by fuzzy clustering maximum tree algorithm analysis. Under the optimized control rules, we establish the sparse scattered point parameter fusion model of medical image multimedia courseware-assisted teaching constraint index parameters, combining the analysis of generalized association rules and periodic association rules to realize the item set analysis of medical image multimedia courseware, and the statistical characteristic quantity of dynamic evaluation effectiveness is as follows:In formula , x⟶=x1,xσ is the root mean square error of minimum support, δkmis the regression steady-state parameter of medical image multimedia courseware aided teaching evaluation, and it is the joint detection probability density. The transaction database is transformed into a transaction matrix, and the fuzzy retrieval and information clustering analysis of constraint index parameters of medical image multimedia courseware are carried out through the feature extraction results [In formula , σ is th results , 25. To  results , 27. TheAccording to In order to verify the classification guidance and teaching evaluation of medical image multimedia courseware, this paper analyzes and tests the parameters of medical image multimedia courseware with SPSS 22.0 Chinese version statistical analysis software and MATLAB simulation tools. First, the minimum confidence of medical image multimedia courseware classification is set at 43%, and the sample sequence size is 2400, and the rationality of course content design, classroom atmosphere, diversity of teaching methods, penetration of subject theory, and feedback benefit of classroom teaching are taken as explanatory variables. The low point of constraint dynamic frequency of medical multimedia courseware is 54 Hz, the sampling rate of association rules is 26 kHz, and the length of classification data of medical multimedia courseware is 12,000 cm. Thus, the distribution of big data statistical characteristics of medical multimedia courseware is shown in Taking the data of According to the analysis of According to the analysis of This method has important significance in improving the quality of medical image multimedia courseware-assisted teachingThe effect evaluation of medical image multimedia courseware based on the deep learning algorithm can achieve effective clustering outputIn this paper, the reliability of medical image multimedia courseware-assisted teaching evaluation was compared, and the results were above 90%This paper presents a method of evaluating the effect of medical image multimedia courseware based on the deep learning algorithm to realize the quantitative evaluation of the teaching effect of medical image multimedia courseware and to improve the teaching quality of medical image courses. The simulation test shows the superior performance of this method in improving the evaluation ability of medical image multimedia courseware-assisted teaching, which is shown in the following aspects:


High urban density, land scarcity, rapid population growth, and traffic congestion have restricted urban development. In response, selected multiple functions have increasingly been integrated into the underground public space (UPS) to maximize the 3D utilization of precious urban space. The accelerated intensity of UPS use has alerted safety concerns. UPS with enclosed and confined natures, complex building structures, locations usually in cramped areas, and limited emergency exits are potentially more prone to heavy casualties and losses in natural or human-made disasters. As research on UPS safety is limited and focused on single risks, we attempted to fill the knowledge gap by developing an integrated risk analysis of UPS to understand risk resilience and improve risk management. From the perspective of the UPS system, four latent factors were identified: natural environment, economic environment, facilities and equipment, and physical structure. Seventeen resilience indicators subsumed under the factors were selected based on resilience concepts. A questionnaire was designed to gather opinions on the relative importance rating of the resilience indicators. SPSS and AMOS software were enlisted to build a structural equation model (SEM), validate the data and model, and calculate the path coefficients and index weights to test four hypotheses. The SEM model results were employed to develop a holistic resilience enhancement strategy under a four-phase framework: before, during, after, and long-term, and under four latent factors. The resilience enhancements can optimize UPS disaster prevention, rescue and evacuation, mitigation, and response management. Urban development in high-density areas often necessitates using underground spaces. They include mainly subways (underground railways) and underground shopping venues. The increasingly heavy use of such underground public space (UPS) has engendered common and acute safety problems ,2. CompaUPS usually has a complex system with unique internal and inter facial traits requiring different safety management. They include enclosed space, built structures densely packed in a limited volume of space, diverse and closely juxtaposed functions, complicated networks of pedestrian passages with multiple nodes and segments, considerable vertical distances between some levels, crowded and highly mobile people flow, and a limited number of entrances and exits ,5. Many The safety concerns in UPS with the potential to develop into mass casualty incidents demand meticulous management and research on risks and their prevention. The critical concerns are identifying and evaluating the risks, developing suitable preventive measures and emergency responses, and striking a balance between operation and regulation ,9. Due tThe application of the resilience theory  to underA resilience evaluation system and evaluation indicators can provide the basis for quantification and implementation. Xu et al.  developeMost research applied the resilience theory to urban development, rail transportation, and other safety fields ,24. The Therefore, the purpose of this study is to identify and analyze the possible risk factors of UPS, establish a model to measure the risk level of UPS, and propose resilience enhancement strategies for UPS in combination with resilience theory to improve the safety of UPS. The focus of the next section is to identify the main risk factors of the UPS based on the literature.We consulted the risk management processes in the ISO 31000:2018 Risk Management Standard . The dynThe risks of the UPS system are different from above ground public spaces due to a limited space environment and a certain degree of confinement. It can be affected by economic, environmental, management, technical, organizational, and other factors, with a bearing on safety accidents and human and economic losses . Human lResilience is an inherent ability of a system to resist and adapt to external risks. Based on the studies of disasters in UPS, the system resilience can be defined as the ability to continuously and dynamically adjust and resist external disturbances and ensure the normal operation of functions soon after the disruptive event ,28. WhenThe study started from the perspective of system resilience and conducted response research at the system level concerning risk events in UPS. The resilience analysis covered four dimensions: natural environment, economic environment, facilities and equipment, and physical structure. The selection of these four latent factors was based on the Design Code for the Internal Environment of Urban Underground Space  and rela(1) Natural environment factorNatural disasters are important UPS risk factors, so eliminating or responding to the effects brought by them can improve the safety level ,35. The (2) Economic environment factorFrom the perspective of the economic environment, the impacts of safety accidents on UPS cover three main aspects: prevention before the risk event, support when the risk occurs, and recovery after the risk . Therefo(3) Facilities and equipment factorThe effectiveness of facilities and equipment furnishes the material basis of UPS. Based on previous studies, the four indicators shaping UPS resilience are included in (4) Physical structure factorThe physical structure’s functional integrity constitutes the foundation for UPS’s safety and security and an essential prerequisite to preventing and tackling risk events. The UPS system is more vulnerable to disaster impacts if the physical structure is unstable or poorly configured, which can increase the probability of risk and severity of its consequences . The relThe SEM model for UPS system resilience was divided into the measurements of sub-model and structural sub-model. They were then combined to build the complete SEM . Based on the findings in the literature on the resilience of urban underground spaces, four hypotheses were developed corresponding to the four latent factors: natural environment, economic environment, facilities and equipment, and physical structure .The questionnaire survey method was applied to evaluate the resilience of the UPS system. The questionnaire contains two parts . The firFour kinds of respondents were targeted: (a) the professionals in the construction and transportation industries; (b) pedestrians in the shopping venues and subway train passengers; (c) students and faculty members in the College of Architecture and Transportation; and (d) staff of the commercial concerns and subway railway staff in the UPS. Of the 250 distributed questionnaires including for living laboratories, 224 were collected, denoting a response rate of 89.6%. They were scrutinized to exclude those with wrong or missing answers, leaving 208 valid questionnaires representing a success rate of 92.8%, which met the SEM sample-size requirement . The SPS(1) Running reliability analysisThe reliability of the questionnaire data can reflect the validity of the measured factors . With siThe reliability analysis was carried out by the alpha reliability coefficient method . Common to questionnaire analyses, the alpha coefficient was calculated by the SPSS 26.0 software to obtain Cronbach’s alpha coefficients . The alp(2) Conducting structural validity analysisThe questionnaire data were subjected to a validity analysis to detect the correlation between the sample and actual data. A strong correlation denotes high validity. The validation factor analysis was used to assess the structural validity of the model. The results were obtained by SPSS statistical data calculation, analysis-dimensional reduction-factor analysis, and calculation. Principal components were extracted employing the maximum variance rotation. The KMO appropriateness parameter test and Bartlett’s sphericity test determined the validity, indicating that the sample was suitable for factor analysis.The KMO value range and significance grading scale are shown in p < 0.001, further signifying that the data were suitable for factor analysis.To further examine the reliability of the grading scale, the bias coefficient was added, which is the coefficient obtained by eliminating one of the measured items. The overall reliability can be improved by excluding items that do not meet the requirements. The validity analysis of the resilience indicators was calculated by SPSS using the analysis-dimensional reduction-factor program, and the results are shown in (3) Performing convergent validity analysisThe convergent validity analysis can measure whether the questionnaire results correspond to the latent factors. The convergent validity analysis can measure whether the questionnaire results correspond to the latent factors. The validation factor analysis was conducted by the AMOS 23.0 software using the confirmatory factor analysis (CFA). The scale was analyzed for convergent validity using combined reliability (CR) and average variance extracted (AVE). The test results are shown in The maximum likelihood estimation method of the structural equation model was applied to the questionnaire data using AMOS. The method tested the significance of the path coefficients calculated by the model. The path diagram and path coefficients of the first-order structural equation model were calculated . The modp < 0.05, indicating that the model is fit. Based on the theoretical and UPS first-order CFA model estimation results  Running path analysisTo further explore the influence of resilience indicators on the UPS system, a second-order structural equation model was constructed in AMOS. The computed path coefficients are given in (2) Conducting model fitting testThe results of parameter estimation for the second-order structural equation model and fitness test are compiled in The overall fitness calculations of the second-order structural equation model for UPS system resilience are listed in p < 0.05. These results satisfied the requirements of statistical significance and acceptance.We adopted Cohen’s criteria to judge the effect of path coefficients . A valueThe four hypotheses paraphrased in Most research in China on urban disaster prevention and mitigation focused on the aboveground urban public space, with few on the UPS. Moreover, most studies investigated a single-risk type, such as fire and flood, with few exploring the system resilience and disaster management from a holistic perspective. UPS system resilience is principally a time-dimensional issue. The core consideration is improving the resilience level to implement the whole-cycle management. It ranges from pre-disaster prevention and control, to mid-disaster emergency response, post-disaster recovery and reconstruction, and long-term development of UPS resilience. The full spectrum of resilience enhancement strategy of UPS systems can be assessed in four stages  with reference to four dimensions . It is based on the analysis of UPS risks and the driving factors of UPS system resilience.Enhancing system resilience involves strengthening the adaptive and resistance capacity to coexist with risks. The risk management adaptive cycle covers the “before, during, after, and long-term development” phases . It emphEnhancing the resilience strategy of the UPS system revolves around the four-stage framework of ex-ante, in-event, post-event, and long-term development. The following strategy packages contain measures to prevent or mitigate disaster risks.Preventing and controlling beforehand is a crucial risk management step. The occurrence of UPS safety accidents reflects risk factors breaching the safety protection system and propagating under the single-risk scenario or multi-risk coupling with mutual influence and interaction. The UPS suffers damage and loss with the disruption of overall stability. To reduce risks and enhance resilience for UPS, targeted control and suppression of risk factors should be implemented before events occurrence. The goal is reducing the probability of risk occurrence from the source, thus enhancing system resilience. The proposed actions for the ex-ante resilience enhancement of UPS are expressed in The identification of the risk sources of UPS due to natural disasters has been widely realized. The top priority after risk recognition is preventing specific risk factors. The measures should be implemented in good time. Firstly, it is necessary to strengthen disaster early warning management, improve the ability to perceive natural-disaster risks and achieve early detection and prevention. After receiving disaster warnings, some urgent actions should forthwith be taken, including preparing emergency resources, protective measures, and other emergency actions. Arrangements should be made promptly to control and evacuate people and minimize impacts on the UPS. The hidden dangers should be investigated. Potential risks and secondary accidents must be prevented. The emergency plan for natural disasters should be continually improved in response to changing circumstances, mainly by relevant local government departments. Unlike other urban risks, natural disasters are characterized by inevitable occurrence, not being amenable to elimination, and incurring severe consequences. A holistic plan encompasses the medical, technical, economic, and other particular emergency aspects. The disaster response measures should include orderly public space management and procedures to calm, comfort, and help affected people.From the economic environment dimension, resilience enhancement refers to adjusting the organization of disaster prevention and mitigation measures from the economic perspective to respond effectively to UPS risks. The government and the private sector have to improve resource allocation to tackle accidents and disasters and response capabilities. The local government and UPS management units have to continually review and upgrade the emergency rescue system and capacity, emergency rescue plans, and prevention and control measures. Adequate funding should be allocated to acquire emergency supplies and reserves and implement rescue operations. It is essential to develop emergency evacuation plans, optimize emergency evacuation routes, and conduct regular evacuation drills. Sound measures to facilitate recovery can be included in a commercial response plan to reduce economic loss.Facilities and equipment are the cornerstone of smooth and safe UPS operation. The complex and inter-related components per se can become the risk sources. Faulty, defective, worn-out, aging, and poorly maintained equipment items could incur safety accidents. As such, they are vulnerable to impacts and failures induced by natural disasters, human-made disasters, terrorist attacks, and other safety incidents. It is necessary to strengthen the upkeep and protection of facilities and equipment to minimize breakdowns and associated losses. Their resilience is related to physical location, exposure, and vulnerability to impacts in the underground milieu. They should be installed at places that can be shielded from disaster impingements and include defensive or protective means to withstand or tolerate risk impacts. In addition, standardizing the operation and maintenance of facility and equipment operators could contribute to risk control. A stable and solid underground building structure can significantly reduce the impacts of external forces on the UPS, thus reducing the consequences of impacts. The building structure and space can be designed or modified to resist or alleviate accident or disaster impacts. The capacity and network layout of the passages could be rationalized for normal use and emergency evacuation. The 3D spatial configuration of horizontal and vertical flow paths and floor connections can be evaluated in detail in devising the rescue and evacuation plans. It is pertinent to ensure adequate and effective emergency shelters, passages, and exits. In-event control constitutes the core of risk management. In-event resilience enhancement can shorten the impact duration of the risk event and reduce losses. Risk occurrence can be divided into five states: optimal, basic operable, recoverable, can-be-mitigated, and failure , as depiThe development of the risk should be accurately judged, and the risk source should be ascertained. The risk must be intervened or blocked to reduce the speed of risk development and contain the risk propagation. The risk source must be stopped from coupling with other potential risk factors, which may aggravate the harmful impacts. Second, once an emergency event occurs, a swift response mechanism is needed. For example, accidents and disasters can lead to blocked passages in the UPS. If the number of usable emergency exits is inadequate, it could incur a chain of disastrous congestion, pile-up, and stampede accidents. Therefore, it is necessary to mobilize rapidly alternative emergency rescue channels. The rescue materials should be made available at appropriate locations or conveyed to the incident sites in time. The crisis plan should allow speedy deployment of emergency personnel, evacuation of the disaster site, and dispatch of ambulances, doctors, and other medical and health services. Meanwhile, the social work organizations should be well prepared and primed to provide shelter and sustenance when necessary.The UPS post-incident resilience mainly includes space recovery and reconstruction. Recovery refers to the return to normal operation. Reconstruction refers to repairing or replacing structures, facilities, and equipment damaged by accident, to be accomplished in the shortest possible time after effectively controlling the incident and the site. A key goal in the post-event phase is eliminating the root cause of the accident backlash and forestalling the lingering negative impacts.The restoration and reconstruction of the material aspects of UPS allow resumption of regular operation and productive activities. Damaged structures and physical facilities can be repaired or rebuilt expeditiously. They may include power, water, drainage, escalators, elevators, gates, etc. If appropriate, the reprovisioned items should be rendered more resistant to damage. The ability of all facilities and equipment to cope with risks could be holistically reviewed to assess the ability to resist risks, with more attention to the more seriously affected areas. The ability to evacuate and respond could be strengthened in a targeted manner.Safety accidents in UPS often result in economic impacts such as damage to facilities, disruption and suspension of rail transport service, and closure of underground businesses. Many resources, such as medical and health, rescue materials, and disaster relief funds, would have been consumed. The priority is restoring underground commercial activities and the operation of underground transportation. The disaster relief funds should be carefully managed and disbursed to maximize their utilities and relief functions. Scientific evaluation of disaster relief resources and emergency plans can identify the shortcomings and inform improvement and effectiveness.Safety accidents in UPS, especially those causing heavy casualties, often trigger psychological trauma in victims and reduce people’s general sense of security in the UPS. Therefore, in the aftermath, psychological rehabilitation care and support can provide relief to distressed people and restore their mental health. To enhance users’ understanding of the safe, harmonious, and stable UPS environment, safety education, awareness, and literacy can be transmitted to passengers, customers, managers, and transport staff. A public education campaign can disseminate UPS safety knowledge and emergency measures to reduce casualties and losses. To prevent the recurrence of similar accidents and contain the losses, it is necessary to review the disaster’s causes, losses, and rescue procedures to enhance UPS system resilience. The administration should evaluate the technical, economic, environmental, and personnel domains, learn from event experiences, and distill improvement measures. In particular, for extraordinary risk incidents, more effective prevention and protection strategies should be devised. The training of emergency rescue teams and the provision of rescue resources can be strengthened. Public safety education and social awareness of UPS risks and countering measures could be stepped up and more assiduously implemented to reach more citizens. The science and technology of UPS safety and resilience could be more actively studied, and the research findings could be translated into enhanced practices. Information technology can be judiciously enlisted to improve risk monitoring, advocacy, and management.Studies of risk resilience of cities in China and abroad are focused on the aboveground realm. This project was conceived to fill the knowledge gap, the bottleneck in UPS safety governance, by applying the relevant resilience concepts and practice. We aimed to develop a new approach to enhance the risk management of the increasingly patronized and expanding urban UPS.The UPS system was analyzed by the 17 selected resilience indicators in the four dimensions of latent factors: natural environment, facilities and equipment, economic environment, and physical structure. Our primary data were obtained by a questionnaire tailor-made to match the research objectives. Computational software of SPSS and AMOS were employed to construct the structural equation models, test the model fitting, and evaluate model validity and applicability.The results showed that the economic environment and physical structure factors influenced UPS system resilience more than natural environment and facilities and equipment factors. The computed relative importance of the resilience indicators allowed the development of a package of resilience enhancement measures. The resilience enhancement strategy of the UPS system was developed by combining our results with the findings of cognate risk assessments. The practical recommendations could be realized in four stages: before, during, after, and long-term development, under the four dimensions of latent factors. The improved strategy can suppress impacts during the disaster event, facilitate rescue and evacuation operations, reduce casualties and losses, and permit prompt recovery after the event. Thus, it can enhance the practice of UPS disaster response and provide theoretical guidance for risk control and management in China.However, limitations also exist in this study. First, the selection of the UPS resilience indicators could be expanded to include more factors to strengthen the predictive power and utility of the model. For example, public safety education, related social awareness, social environment, ecological environment, institutions, spatial structure and other indicators to continue the study. Second, the criteria and questionnaire data selected for this study are from China, so the findings are only applicable to the Chinese region, and further investigation of other regions in future studies is recommended to apply to a wider area.


Although individuals with agenesis of corpus callosum (ACC) possess intelligence coefficients within regular parameters, current studies have demonstrated decision-making compromise and potential negative social consequences. Furthermore, alternative pathways regarding brain connectivity in acallosal patients combined with cognitive therapy that would potentially mitigate such difficulties. Therefore, this study aimed to examine the current state of the art regarding brain foundations in the role of neuroplasticity by improving the decision-making quality in ACC.A systematic revision of literature was performed including studies conducted on non-syndromic ACC individuals and analyzing the impact of the potential role of neuroplasticity on the decision-making published to date. Studies with patients who underwent callosotomy were excluded. Experimental studies performed on animal models were included.During this period, 849 studies were identified; among them, 11 were eligible for qualitative analysis. Despite the paucity of evidence on this matter, patients with ACC present considerable decision-making difficulties mainly due to the functional connectivity impairment in the frontal lobes. Moreover, neuroplasticity was characterized by increased anterior commissure width as compared with controls. Notwithstanding, no studies were conducted on cognitive therapists managing this type of disease.Although the reorganization of inter-hemispheric bundles on anterior commissure has demonstrated the main natural neuroanatomic strategy in ACC, further evidence will be needed to clarify whether cognitive stimulus could improve the decision-making quality. Congenital abnormalities of the corpus callosum (CC) are brain malformations including a partial or complete absence of CC and hypoplasia, with incidence ranging from 1.47 per 10,000 in the general population according to the Emilia Romagna Italy report, i.e., 1 of 4,000 live births in agenesis of the corpus callosum (ACC) in other studies . FurtherThe decision-making behavior has been considered one of the main pillars of neurocognition and is important during daily choices or taking resolutions demanding more sophisticated skills, such as planning and reasoning . NeuroanThe brain’s functional connectivity associated with the CC could be compromised by iatrogenic or congenital situations, such as callosotomy and ACC, respectively, and these have been converted into valuable models to understand the physiology of this commissure and the potential effects of rehabilitative interventions. Interestingly, as serious neurological consequences occurred if complete callosotomy is performed, which would evoke the so-called split-brain condition, lesser neurological compromise is normally observed on the ACC.Although the importance of the CC on the brain’s connectivity was proven, some controversies remained because individuals who underwent partial callosotomy displayed no differences in inter-hemispheric neuronal synchronicity , and an Given that the decision-making of patients with ACC was compromised, a valid correlation should be established between neuroplasticity’s improvement and neurocognition in these patients. To our knowledge, this could be converted as a valuable guide for pediatric neurosurgeons and neurologists by talking to their fathers on how to proceed in a long-term plan in children diagnosed with ACC and the potential impact of early cognitive stimulation in improving high-level functions of the brain. Therefore, this study aimed to examine the current state-of-the-art effects of neuroplasticity on patients with ACC focusing on decision-making, and shedding light on further studies.MethodsA systematic literature revision was performed by searching the data bank available on the PubMed and Web of Science and retrieving studies focusing on the ACC and its relationship with neuroplasticity and decision-making. The research process followed the Prisma protocol .Inclusion CriteriaThis systematic review considered all studies focusing on the pediatric population affecting the ACC in which the functional connectivity was examined using imaging strategies, such as functional magnetic resonance imaging (fMRI) and/or MRI with diffusion tensor imaging, neuroplasticity, and decision-making of individuals with ACC.Moreover, were included the experimental studies in which ACC animal models were adopted and the brain structure using imaging or microscopic techniques was examined.Clinical and experimental studies conducted to date were considered in this study. Furthermore, studies deemed for analysis were those published exclusively in the English language.Behavioral tests, intelligence scales, and other types of neurocognitive assessments were performed. However, they were not considered inclusion criteria.Exclusion CriteriaHuman studies conducted neurocognitive tests alone without brain imaging or examining the brain structure were excluded from this review. Furthermore, genetic studies on animal models that examined the relationship between genes and ACC were also excluded. In addition, studies including patients who underwent surgical disconnection of the CC, case reviews, and syndromic cases were excluded. Therein, studies conducted on patients with primary ACC preferred for analysis over dysgenesis and hypoplasia of CC despite such malformations were considered.Intervention or Exposure and OutcomesRehabilitative interventions if available in the literature were included in the analysis to improve decision-making in patients with primary ACC. The primary outcome was the functional impact of neuroplasticity on ACC, and secondary outcomes were neuroanatomic adaptations.Search Strategy and Data ExtractionAn electronic literature search was performed by two independent researchers who compiled the papers. The PubMed and Web of Science databases were used in this study using the following constructs: 'agenesis of corpus callosum' and 'decision-making'; 'agenesis of corpus callosum' and 'neuroplasticity'; 'corpus callosum' and 'decision-making'; and 'corpus callosum' and 'neuroplasticity'.ResultsAfter applying the aforementioned criteria, 849 studies were identified. Moreover, the following results were achieved from the constructs on PubMed: 'corpus callosum' and 'decision-making' (165 studies); 'corpus callosum' and 'neuroplasticity' (350 studies); 'agenesis of corpus callosum' and 'decision-making' (24 studies); and 'agenesis of corpus callosum' and 'neuroplasticity' (30 studies). On the Web of Science, the following results were observed: 'corpus callosum' and 'decision-making' (157 studies); 'corpus callosum' and 'neuroplasticity' (101 studies); 'agenesis of corpus callosum' and 'decision-making' (13 studies); and 'agenesis of corpus callosum' and 'neuroplasticity' (9 studies).Duplications and exclusions were performed, and finally, 11 studies were considered for qualitative analysis (Figure DiscussionFoundations of NeuroplasticityIndividuals who presented with stroke, brain trauma injuries, or were born with connectivity impairments have the potential to develop multifactorial adaptative changes allowing them to replace the compromised brain function -21. The Decision-Making and ACCOne of the major neurocognitive decision-making aspects is the ability to predict the future reward and choose a low gain in a short term, which is recognized as a delayed reward discount . IndividUndoubtedly, a study on pathological conditions aids in the awareness of several complex brain functions, and the decision-making quality is better appreciated in selecting patients with punctual deficiencies in specific brain regions such as ACC. Furthermore, the assessment of these individuals shows alternative pathways of neuroplasticity. Overall, they have regular intelligence scores besides the decision-making difficulty, suggesting the major role of interconnectivity instead of the gray matter during this process. Interestingly, animal studies have contributed to the best understanding of CC function and in some instances, different species separated for millions of years demonstrated a curious decision-making process. Therefore, CC is a mammalian structure that increases as an evolutionary jump , and, thOwen et al.  analyzedAlthough patients with ACC have been demonstrated to have acceptable cognitive performance and can execute social tasks that demand reasoning or manual capacity, alterations associated with the anterior region of the insula could affect social behaviors requiring leadership. Such a statement is corroborated by Edelson et al.  who usedOne of the limitations of the studies was the method used to assess the connectivity in patients with ACC using resting-state functional MRI, in which the brain activity is not evaluated during the high demand and, therefore, just reveals the baseline brain activity based on fluctuations of blood oxygen consumption. Imaging studies were applied during tasks.Brown et al.  studied Perspectives of High-Order Brain ImprovementThe difficulty of solving new problems and making the right decisions while balancing the pros and cons is likely related with the deal with excess information of the environment correctly. One plausible explanation is anatomic and associated with a smaller diameter of the anterior commissure, with the main path to neuroplasticity for this case, allowing the performance and processing of all information between the frontal hemispheres. Moreover, the lack of flexible thought attributed to patients with ACC and autism is related to the difficulty in processing different information for different decision-making, becoming more likely to choose based on the rigid mental process. Therefore, two possible strategies are required for this hypothesis: offering problems in a slow form and cognitive training to ameliorate the brain capacity for integration. To date, leadership specifically in the field of decision-making is still not evident. However, indirect evidence reinforced this impression of optimization of inter-hemispheric connectivity in the brain. For instance, the excess of social media use could worsen the integration between hemispheres mainly in the forceps minor of CC, whereas the stress experience with the application of tough tasks has proven to improve this integration , 37. NowOne goal of the rehabilitative approach was proposed by the international classification of Functioning, Disability, and Heath considering the bio-psychosocial aspect of these patients, stimulating general functions and improving social integration, not only a specific function associated with CC has given more importance to the environment as a facilitator. Moreover, monitoring neuropsychological disturbances during school age is mandatory to explore the best neuroplasticity  Tables  and 2.LimitationsAlthough this systematic review has compiled a wide range of studies regarding congenital aberrations affecting the CC in experimental and clinical studies to obtain an in-depth understanding of how neuroplasticity works in these patients, some limitations were observed. Only a few studies have focused on neuroplasticity in these patients, and only one study showed compromised decision-making in a well-delineated study. Furthermore, studies including primary acallosal patients are quite rare, making it impossible to draw a reliable meta-analysis. Nonetheless, this study shed light on important nuances regarding neuroplasticity, which should be considered by patients and physicians to stimulate the affected children early.Parents of children diagnosed with ACC should be informed of the expected decision-making difficulty and potential negative consequences during adulthood, despite normal levels of intelligence. Furthermore, an immediate recommendation from the cognitive therapist remains a theoretical potential benefit for the improvement of neuroplasticity.Although the augmented size of anterior commissure constitutes the major neuroplasticity anatomical event in acallosal patients, no current evidence is available to recommend an efficient cognitive therapy to improve the decision-making quality by explaining the heterogeneity among patients. Further experimental studies will be needed especially in employing molecular markers to clarify this field of knowledge.