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The review describes correlations between impaired functioning of chaperones and co-chaperones in Alzheimer's disease (AD) pathogenesis. The study aims to highlight significant lines of research in this field. Chaperones like Hsp90 or Hsp70 are critical agents in regulating cell homeostasis. Due to some conditions, like aging, their activity is damaged, resulting in ß-amyloid and tau aggregation. This leads to the development of neurocognitive impairment. Dysregulation of co-chaperones is one of the causes of this condition. Disorders in the functioning of molecules like PP5, Cdc37, CacyBP/SIPTRAP1, CHIP protein, FKBP52, or STIP1 play a key role in AD pathogenesis. PP5, Cdc37, CacyBP/SIPTRAP1, and FKBP52 are Hsp90 co-chaperones. CHIP protein is a co-chaperone that switches Hsp70/Hsp90 complexes, and STIP1 binds to Hsp70. Recognition of precise processes allows for the invention of effective treatment methods. Potential drugs may either reduce tau levels or inhibit tau accumulation and aggregation. Some substances neuroprotect from Aß toxicity. Further studies on chaperones and co-chaperones are required to understand the fundamental tenets of this topic more entirely and improve the prevention and treatment of AD.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/metabolismo , Chaperonas Moleculares/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas de Choque Térmico HSP70 , Peptídeos beta-AmiloidesRESUMO
This editorial investigates chronic traumatic encephalopathy (CTE) as a course of Alzheimer's disease (AD). CTE is a debilitating neurodegenerative disease that is the result of repeated mild traumatic brain injury (TBI). Many epidemiological studies show that experiencing a TBI in early or middle life is associated with an increased risk of dementia later in life. Chronic traumatic encephalopathy (CTE) and Alzheimer's disease (AD) present a series of similar neuropathological features that were investigated in this work like recombinant tau into filaments or the accumulation and aggregation of Aß protein. However, these two conditions differ from each other in brain-blood barrier damage. The purpose of this review was to evaluate information about CTE and AD from various articles, focusing especially on new therapeutic possibilities for the improvement in cognitive skills.
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Doença de Alzheimer , Encefalopatia Traumática Crônica , Humanos , Doença de Alzheimer/complicações , Doença de Alzheimer/patologia , Doença de Alzheimer/etiologia , Encefalopatia Traumática Crônica/patologia , Encefalopatia Traumática Crônica/complicações , Proteínas tau/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologiaRESUMO
This review describes associations between dementia and loneliness on the neurobiological and epidemiological levels according to the recent body of literature. The aim of this study was to highlight major lines of research in this field. Sociocognitive skills and social interactions present complex interdependencies with dementia which may be explained by two theories. According to the first one, not sufficiently engaging in social or cognitive activities results in brain atrophy. The second one claims that brain neurogenesis and synaptic density are being increased by social connections. The relationship between loneliness and dementia could be mediated by sensory loss, including hearing and visual impairment, as well as depression and psychotic symptoms. Loneliness itself might cause a depletion in sensory and cognitive stimulation which results in a decrease in neural reserve. Certain changes in the structures of the brain caused by loneliness were found in imaging examination. Loneliness appears to be a crucial risk factor for dementia in recent times due to the modern lifestyle and consequences of the outbreak of COVID-19. Additional studies are required to understand more completely the key tenets of this topic and therefore to improve the prevention and treatment of dementia.
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COVID-19 , Terapia Cognitivo-Comportamental , Demência , Humanos , Solidão , Encéfalo , Demência/epidemiologiaRESUMO
Early and premature menopause, or premature ovarian insufficiency (POI), affects 1% of women under the age of 40 years. This paper reviews the main aspects of early and premature menopause and their impact on cognitive decline. Based on the literature, cognitive complaints are more common near menopause: a phase marked by a decrease in hormone levels, especially estrogen. A premature reduction in estrogen puts women at a higher risk for cardiovascular disease, parkinsonism, depression, osteoporosis, hypertension, weight gain, midlife diabetes, as well as cognitive disorders and dementia, such as Alzheimer's disease (AD). Experimental and epidemiological studies suggest that female sex hormones have long-lasting neuroprotective and anti-aging properties. Estrogens seem to prevent cognitive disorders arising from a cholinergic deficit in women and female animals in middle age premature menopause that affects the central nervous system (CNS) directly and indirectly, both transiently and in the long term, leads to cognitive impairment or even dementia, mainly due to the decrease in estrogen levels and comorbidity with cardiovascular risk factors, autoimmune diseases, and aging. Menopausal hormone therapy from menopause to the age of 60 years may provide a "window of opportunity" to reduce the risk of mild cognitive impairment (MCI) and AD in later life. Women with earlier menopause should be taken care of by various specialists such as gynecologists, endocrinologists, neurologists, and psychiatrists in order to maintain their mental health at the highest possible level.
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Doença de Alzheimer , Disfunção Cognitiva , Menopausa Precoce , Humanos , Animais , Feminino , Terapia de Reposição de Estrogênios/efeitos adversos , Menopausa , Disfunção Cognitiva/etiologia , Doença de Alzheimer/etiologia , EstrogêniosRESUMO
Central nervous system (CNS) diseases are the leading causes of death and disabilities in the world. It is quite challenging to treat CNS diseases efficiently because of the blood-brain barrier (BBB). It is a physical barrier with tight junction proteins and high selectivity to limit the substance transportation between the blood and neural tissues. Thus, it is important to understand BBB transport mechanisms for developing novel drug carriers to overcome the BBB. This paper introduces the structure of the BBB and its physiological transport mechanisms. Meanwhile, different strategies for crossing the BBB by using nanomaterial-based drug carriers are reviewed, including carrier-mediated, adsorptive-mediated, and receptor-mediated transcytosis. Since the viral-induced CNS diseases are associated with BBB breakdown, various neurotropic viruses and their mechanisms on BBB disruption are reviewed and discussed, which are considered as an alternative solution to overcome the BBB. Therefore, most recent studies on virus-mimicking nanocarriers for drug delivery to cross the BBB are also reviewed and discussed. On the other hand, the routes of administration of drug-loaded nanocarriers to the CNS have been reviewed. In sum, this paper reviews and discusses various strategies and routes of nano-formulated drug delivery systems across the BBB to the brain, which will contribute to the advanced diagnosis and treatment of CNS diseases.
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Barreira Hematoencefálica/metabolismo , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Nanoestruturas/química , Animais , Transporte Biológico , HumanosRESUMO
BACKGROUND: The lack of effective treatment for Alzheimer's disease (AD) stems mainly from the incomplete understanding of AD causes. Neuroinflammation has emerged as an important component of AD pathology, and a vast number of experimental and clinical data indicated a crucial role for the activation of the innate immune system in disease promotion and symptom progression. METHODS: Clinical examinations of AD patients in a different stage of disease severity in correlation with the measurement of two innate immune reactions, i.e., peripheral blood leukocyte (PBLs) resistance to viral infection (vesicular stomatitis virus, VSV) ex vivo, and cytokines: TNF-α, IFN-γ, IL-1ß, and IL-10, production with enzyme-linked immunosorbent assay (ELISA), have been investigated during this preliminary study before and after 4 weeks of oral treatment with dietary supplement proline-rich polypeptide complex (PRP) (120 µg of PRP/day). The potential effect of PRP on the distribution of PBLs' subpopulations has been specified. RESULTS: We have found a deficiency in innate immune response in AD patients. It was demonstrated for the first time that the degree of PBLs resistance to VSV infection was closely related to the stage of clinical severity of AD. Our study showed significant differences in cytokine production which pointed that in AD patients innate immune mechanisms are impaired. Administration of PRP to our patients increased innate immune response of PBLs and declined pro- and anti-inflammatory cytokine production, thus subduing the excessively developed inflammatory response, especially among patients with high severity of AD. PRP did not exhibit a pro-proliferative activity. It was showed, however, significant influence of PRP on the distribution of PBLs' subpopulations. CONCLUSION: The findings mentioned above might be crucial in the context of potential application of immunomodulatory therapy in AD patients and indicated PRP as a potential target for future treatments in neuroinflammatory diseases like AD.
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Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/imunologia , Imunidade Inata/efeitos dos fármacos , Receptores de Peptídeos/administração & dosagem , Receptores de Peptídeos/imunologia , Adulto , Idoso , Doença de Alzheimer/metabolismo , Animais , Linhagem Celular , Citocinas/antagonistas & inibidores , Citocinas/imunologia , Citocinas/metabolismo , Feminino , Humanos , Imunidade Inata/fisiologia , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Leucócitos/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Domínios Proteicos Ricos em Prolina/efeitos dos fármacos , Domínios Proteicos Ricos em Prolina/fisiologia , Receptores de Peptídeos/metabolismoRESUMO
The prevalence of both Alzheimer's disease (AD) and vascular dementia (VaD) is increasing with the aging of the population. Studies from the last several years have shown that people with diabetes have an increased risk for dementia and cognitive impairment. Therefore, the authors of this consensus review tried to elaborate on the role of diabetes, especially diabetes type 2 (T2DM) in both AD and VaD. Based on the clinical and experimental work of scientists from 18 countries participating in the International Congress on Vascular Disorders and on literature search using PUBMED, it can be concluded that T2DM is a risk factor for both, AD and VaD, based on a pathology of glucose utilization. This pathology is the consequence of a disturbance of insulin-related mechanisms leading to brain insulin resistance. Although the underlying pathological mechanisms for AD and VaD are different in many aspects, the contribution of T2DM and insulin resistant brain state (IRBS) to cerebrovascular disturbances in both disorders cannot be neglected. Therefore, early diagnosis of metabolic parameters including those relevant for T2DM is required. Moreover, it is possible that therapeutic options utilized today for diabetes treatment may also have an effect on the risk for dementia. T2DM/IRBS contribute to pathological processes in AD and VaD.
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Encéfalo/patologia , Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/etiologia , Doença de Alzheimer/patologia , Encéfalo/metabolismo , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/patologia , HumanosRESUMO
A molecular test for Alzheimer's disease could lead to better treatment and therapies. We found 18 signaling proteins in blood plasma that can be used to classify blinded samples from Alzheimer's and control subjects with close to 90% accuracy and to identify patients who had mild cognitive impairment that progressed to Alzheimer's disease 2-6 years later. Biological analysis of the 18 proteins points to systemic dysregulation of hematopoiesis, immune responses, apoptosis and neuronal support in presymptomatic Alzheimer's disease.
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Doença de Alzheimer/classificação , Doença de Alzheimer/diagnóstico , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Doença de Alzheimer/sangue , Biomarcadores/sangue , Transtornos Cognitivos/sangue , Transtornos Cognitivos/classificação , Transtornos Cognitivos/diagnóstico , Humanos , Fenótipo , Valor Preditivo dos TestesRESUMO
Introduction: Down syndrome (DS) stands out as one of the most prevalent genetic disorders, imposing a significant burden on both society and the healthcare system. Scientists are making efforts to understand the neural mechanisms behind the pathophysiology of this disorder. Among the valuable methods for studying these mechanisms is electroencephalography (EEG), a non-invasive technique that measures the brain's electrical activity, characterised by its excellent temporal resolution. This review aims to consolidate studies examining EEG usage in individuals with DS. The objective was to identify shared elements of disrupted EEG activity and, crucially, to elucidate the neural mechanisms underpinning these deviations. Searches were conducted on Pubmed/Medline, Research Gate, and Cochrane databases. Results: The literature search yielded 17 relevant articles. Despite the significant time span, small sample size, and overall heterogeneity of the included studies, three common features of aberrant EEG activity in people with DS were found. Potential mechanisms for this altered activity were delineated. Conclusions: The studies included in this review show altered EEG activity in people with DS compared to the control group. To bolster these current findings, future investigations with larger sample sizes are imperative.
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INTRODUCTION: Depression is the most prevalent comorbid neuropsychiatric condition in individuals with Parkinson's disease (PD), and its underlying mechanisms are not yet fully understood. Current treatment methods are characterised by moderate effectiveness and possible side effects, prompting the search for new non-invasive and safe treatment methods. METHODS: This narrative review explores the use of transcranial direct current stimulation (tDCS) in the treatment of depression in PD, based on neuropsychological measures. Searches were conducted in the PubMed/Medline, Research Gate, and Cochrane databases. RESULTS: Nine relevant studies were identified, where depression scores served as either primary or secondary outcomes. Stimulation protocols displayed heterogeneity, especially concerning choice of stimulation site. Patient samples were also heterogeneous. The majority of the studies incorporated anodal stimulation targeting the left dorsolateral prefrontal cortex (DLPFC). The results revealed a reduction in depression scores among PD patients following tDCS. Potential mechanisms through which tDCS may alleviate depression in PD were discussed and recommendations for future research were made. CONCLUSIONS: Preliminary evidence suggests that tDCS applied anodally to the left DLPFC reduces depression scores in people with PD; however, due to the heterogeneity of the studies analysed, the use of tDCS in this field should be approached with caution and warrants further validation and confirmation.
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Alzheimer's disease is the most common cause of dementia globally. The pathogenesis is multifactorial and includes deposition of amyloid-ß in the central nervous system, presence of intraneuronal neurofibrillary tangles and a decreased amount of synapses. It remains uncertain what causes the progression of the disease. Nowadays, it is suggested that the brain is connected to the gastrointestinal tract, especially the enteric nervous system and gut microbiome. Studies have found a positive association between AD and gastrointestinal diseases such as periodontitis, Helicobacter pylori infection, inflammatory bowel disease and microbiome disorders. H. pylori and its metabolites can enter the CNS via the oropharyngeal olfactory pathway and may predispose to the onset and progression of AD. Periodontitis may cause systemic inflammation of low severity with high levels of pro-inflammatory cytokines and neutrophils. Moreover, lipopolysaccharide from oral bacteria accompanies beta-amyloid in plaques that form in the brain. Increased intestinal permeability in IBS leads to neuronal inflammation from transference. Chronic inflammation may lead to beta-amyloid plaque formation in the intestinal tract that spreads to the brain via the vagus nerve. The microbiome plays an important role in many bodily functions, such as nutrient absorption and vitamin production, but it is also an important factor in the development of many diseases, including Alzheimer's disease. Both the quantity and diversity of the microbiome change significantly in patients with AD and even in people in the preclinical stage of the disease, when symptoms are not yet present. The microbiome influences the functioning of the central nervous system through, among other things, the microbiota-gut-brain axis. Given the involvement of the microbiome in the pathogenesis of AD, antibiotic therapy, probiotics and prebiotics, and faecal transplantation are being considered as possible therapeutic options.
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Doença de Alzheimer , Gastroenteropatias , Microbioma Gastrointestinal , Humanos , Doença de Alzheimer/microbiologia , Gastroenteropatias/microbiologia , Eixo Encéfalo-Intestino/fisiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Periodontite/microbiologia , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/metabolismo , Helicobacter pylori , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/metabolismo , Encéfalo/metabolismoRESUMO
Introduction: HIV is a severe and incurable disease that has a devastating impact worldwide. It affects the immune system and negatively affects the nervous system, leading to various cognitive and behavioral problems. Scientists are actively exploring different therapeutic approaches to combat these issues. One promising method is transcranial direct current stimulation (tDCS), a non-invasive technique that stimulates the brain. Methods: This review aims to examine how tDCS can help HIV patients. Searches were conducted in the Pubmed/Medline, Research Gate, and Cochrane databases. Results: The literature search resulted in six articles focusing on the effects of tDCS on cognitive and behavioral measures in people with HIV. In some cases, tDCS showed positive improvements in the measures assessed, improving executive functions, depression, attention, reaction time, psychomotor speed, speed of processing, verbal learning and memory, and cognitive functioning. Furthermore, the stimulation was safe with no severe side effects. However, the included studies were of low quality, had small sample sizes, and did not use any relevant biomarkers that would help to understand the mechanisms of action of tDCS in HIV. Conclusions: tDCS may help patients with HIV; however, due to the limited number of studies and the diversity of protocols used, caution should be exercised when recommending this treatment option in clinical settings. More high-quality research, preferably involving neurophysiological and neuroimaging measurements, is necessary to better understand how tDCS works in individuals with HIV.
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INTRODUCTION: Binge eating disorder (BED) is the most common eating disorder among those contributing to the development of obesity, and thus acts as a significant burden on the lives and health of patients. It is characterized by complex neurobiology, which includes changes in brain activity and neurotransmitter secretion. Existing treatments are moderately effective, and so the search for new therapies that are effective and safe is ongoing. AIM AND METHODS: This review examines the use of transcranial direct current stimulation (tDCS) in the treatment of binge eating disorder. Searches were conducted on the PubMed/Medline, Research Gate, and Cochrane databases. RESULTS: Six studies were found that matched the review topic. All of them used the anodal stimulation of the right dorsolateral prefrontal cortex (DLPFC) in BED patients. tDCS proved effective in reducing food cravings, the desire to binge eat, the number of binging episodes, and food intake. It also improved the outcomes of inhibitory control and the treatment of eating disorder psychopathology. The potential mechanisms of action of tDCS in BED are explained, limitations in current research are outlined, and recommendations for future research are provided. CONCLUSIONS: Preliminary evidence suggests that the anodal application of tDCS to the right DLPFC reduces the symptoms of BED. However, caution should be exercised in the broader use of tDCS in this context due to the small number of studies performed and the small number of patients included. Future studies should incorporate neuroimaging and neurophysiological measurements to elucidate the potential mechanisms of action of tDCS in BED.
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Transtorno da Compulsão Alimentar , Estimulação Transcraniana por Corrente Contínua , Feminino , Humanos , Transtorno da Compulsão Alimentar/terapia , Transtorno da Compulsão Alimentar/psicologia , Fissura/fisiologia , Córtex Pré-Frontal Dorsolateral , Córtex Pré-Frontal , Estimulação Transcraniana por Corrente Contínua/métodos , Resultado do Tratamento , MasculinoRESUMO
INTRODUCTION: Methamphetamine is a highly stimulating psychoactive drug that causes life-threatening addictions and affects millions of people around the world. Its effects on the brain are complex and include disturbances in the neurotransmitter systems and neurotoxicity. There are several known treatment methods, but their effectiveness is moderate. It must be emphasised that no drugs have been approved for treatment. For this reason, there is an urgent need to develop new, effective, and safe treatments for methamphetamine. One of the potential treatments is mindfulness meditation. In recent years, this technique has been researched extensively in the context of many neurological and psychiatric disorders. METHODS: This review explores the use of mindfulness in the treatment of methamphetamine addiction. Searches were conducted in the PubMed/Medline, Research Gate, and Cochrane databases. RESULTS: Ten studies were identified that used mindfulness-based interventions in the treatment of methamphetamine addiction. The results show that mindfulness is an effective form of reducing hunger, risk of relapses, stress indicators, depression, and aggression, alone or in combination with transcranial direct current stimulation (tDCS). Mindfulness also improved the cognitive function in addicts. The included studies used only behavioural measures. The potential mechanisms of mindfulness in addiction were explained, and it was proposed that it can induce neuroplasticity, alleviating the symptoms of addiction. CONCLUSIONS: Evidence from the studies suggest that mindfulness may be an effective treatment option for methamphetamine addiction, used alone or in combination with tDCS. However, further high-quality research is required to establish the role of this treatment option in this field. The use of neuroimaging and neurophysiological measures is fundamental to understand the mechanisms of mindfulness.
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Two multidimensional problems of recent times - Alzheimer's disease and light pollution - seem to be more interrelated than previously expected. A series of studies in years explore the pathogenesis and the course of Alzheimer's disease, yet the mechanisms underlying this pathology remain not fully discovered and understood. Artificial lights which accompany civilization on a daily basis appear to have more detrimental effects on both environment and human health than previously anticipated. Circadian rhythm is affected by inappropriate lighting conditions in particular. The consequences are dysregulation of the sleep-wake cycle, gene expression, neuronal restructuring, brain's electricity, blood flow, metabolites' turnover, and gut microbiota as well. All these phenomena may contribute to neurodegeneration and consequently Alzheimer's disease. There is an increasing number of research underlining the complexity of the correlation between light pollution and Alzheimer's disease; however, additional studies to enhance the key tenets are required for a better understanding of this relationship.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/etiologia , Poluição Luminosa , Ritmo Circadiano/fisiologiaRESUMO
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and is the most common cause of dementia. The pathogenesis of AD still remains unclear, including two main hypotheses: amyloid cascade and tau hyperphosphorylation. The hallmark neuropathological changes of AD are extracellular deposits of amyloid-ß (Aß) plaques and intracellular neurofibrillary tangles (NFTs). Endocytosis plays an important role in a number of cellular processes including communication with the extracellular environment, nutrient uptake, and signaling by the cell surface receptors. Based on the results of genetic and biochemical studies, there is a link between neuronal endosomal function and AD pathology. Taking this into account, we can state that in the results of previous research, endolysosomal abnormality is an important cause of neuronal lesions in the brain. Endocytosis is a central pathway involved in the regulation of the degradation of amyloidogenic components. The results of the studies suggest that a correlation between alteration in the endocytosis process and associated protein expression progresses AD. In this article, we discuss the current knowledge about endosomal abnormalities in AD.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Emaranhados Neurofibrilares/metabolismo , Emaranhados Neurofibrilares/patologia , EndocitoseRESUMO
The long COVID (coronavirus disease), a multisystemic condition following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, is one of the widespread problems. Some of its symptoms affect the nervous system and resemble symptoms of Alzheimer's disease (AD)-a neurodegenerative condition caused by the accumulation of amyloid beta and hyperphosphorylation of tau proteins. Multiple studies have found dependence between these two conditions. Patients with Alzheimer's disease have a greater risk of SARS-CoV-2 infection due to increased levels of angiotensin-converting enzyme 2 (ACE2), and the infection itself promotes amyloid beta generation which enhances the risk of AD. Also, the molecular pathways are alike-misregulations in folate-mediated one-carbon metabolism, a deficit of Cq10, and disease-associated microglia. Medical imaging in both of these diseases shows a decrease in the volume of gray matter, global brain size reduction, and hypometabolism in the parahippocampal gyrus, thalamus, and cingulate cortex. In some studies, a similar approach to applied medication can be seen, including the use of amino adamantanes and phenolic compounds of rosemary. The significance of these connections and their possible application in medical practice still needs further study but there is a possibility that they will help to better understand long COVID.
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Doença de Alzheimer , COVID-19 , Humanos , Doença de Alzheimer/metabolismo , SARS-CoV-2 , Síndrome de COVID-19 Pós-Aguda , Peptídeos beta-Amiloides , Doença CrônicaRESUMO
Alzheimer's disease (AD) is a neurodegenerative disorder and the most common cause of dementia globally. The pathogenesis of AD remains still unclear. The three main features of AD are extracellular deposits of amyloid beta (Aß) plaque, accumulation of abnormal formation hyper-phosphorylated tau protein, and neuronal loss. Mitochondrial impairment plays an important role in the pathogenesis of AD. There are problems with decreased activity of multiple complexes, disturbed mitochondrial fusion, and fission or formation of reactive oxygen species (ROS). Moreover, mitochondrial transport is impaired in AD. Mouse models in many research show disruptions in anterograde and retrograde transport. Both mitochondrial transportation and network impairment have a huge impact on synapse loss and, as a result, cognitive impairment. One of the very serious problems in AD is also disruption of insulin signaling which impairs mitochondrial Aß removal.Discovering precise mechanisms leading to AD enables us to find new treatment possibilities. Recent studies indicate the positive influence of metformin or antioxidants such as MitoQ, SS-31, SkQ, MitoApo, MitoTEMPO, and MitoVitE on mitochondrial functioning and hence prevent cognitive decline. Impairments in mitochondrial fission may be treated with mitochondrial division inhibitor-1 or ceramide.
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Doença de Alzheimer , Doenças Mitocondriais , Camundongos , Animais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/etiologia , Doença de Alzheimer/terapia , Peptídeos beta-Amiloides/metabolismo , Doenças Mitocondriais/metabolismo , Mitocôndrias/metabolismo , AntioxidantesRESUMO
Women have an over 50% greater risk of dementia than men, which is a main topic of much research. This review aims to investigate the impact of a woman's reproductive history on dementia risk. The consequences of stillbirth are long-term health and psychosocial problems for women. Because of the awareness of an endangered pregnancy, many parents experience deep anxiety and stress in subsequent pregnancies. There are contradictory conclusions from research about abortion and the risk of dementia correlation. When it comes to the late age of first birth, which is said to be above 35 years old, it was observed that older mothers have a decreased risk of dementia compared to those who gave birth in their 20s; however, being a child of the older mother is connected with a higher risk of developing dementia. Using hormonal contraception can result in decreased risk of dementia as estrogen stimulates microglia-related Aß removal and reduces tau hyperphosphorylation. The influence of postmenopausal hormonal therapy and the duration of the reproductive period on developing dementia remains unclear. Although female disorders like endometriosis and polycystic ovary syndrome are reported to increase the risk of dementia, the research on this topic is very limited, especially when it comes to endometriosis, and needs further investigation. Interestingly, there is no conclusion on whether hypertensive disorders of pregnancy increase the risk of dementia, but most articles seem to confirm this theory.
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BACKGROUND: The aim of this study was to evaluate atrophy rates, perfusion, and diffusion disturbances within the hippocampus, which is the site of characteristic changes in Alzheimer's disease (AD) and mild cognitive impairment (MCI). MATERIAL AND METHODS: Thirty patients with AD (mean age 71.2 yrs) - 34 with MCI (mean age 67.7 yrs) and 20 healthy controls (mean age 68.1 yrs) - underwent structural MR examination followed by perfusion and diffusion-weighted imaging on a 1.5 T scanner. Visual rating of hippocampal atrophy, planimetric measurements of hippocampal formation (HF) and perihippocampal fluid spaces (PFSs), and values of relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) were assessed. The results were correlated with the MMSE scores. RESULTS: In AD we found decreased size of HF and increased diameters of PFSs and ADC values, compared to MCI and control group. Compared to normal controls, the MCI group showed decreased HF size and increased diameters of only medial PFS. There were no differences in rCBV values among all the subject groups. Planimetric measurements of hippocampal atrophy showed the highest accuracy in diagnosing AD and MCI. In all patients, the increased rates of hippocampal atrophy correlated with the increased ADC values. In MCI, MMSE scores correlated with the HF size and ADC values. CONCLUSIONS: In AD and MCI, hippocampal atrophy is associated with decreased tissue integrity without coexisting perfusion disturbances. Of all evaluated hippocampal measurements, atrophy rates seem to be the most useful parameters in detecting changes among AD, MCI, and control subjects.