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Purpose: The objective of this research was to develop a musical digital game for rehabilitation of upper limb and to verify its usability and user experience with professionals in the field (physical therapists). Materials and Methods: Thirty working professionals were recruited to evaluate the system. The usability was evaluated with the System Usability Scale (SUS) and the user experience was verified with the Game Flow scale. Results: The overall score of the SUS scale was 88.67 (±9.129); this score is interpreted as "Best Imaginable" (86-100). The user experience rating had most of its domains equal or higher than 4, which indicates that all the requirements for a good user experience were present in the game. Conclusions: The Moniz Game proved to be a game with good usability and can be a tool for application in clinical practice regarding motor coordination. However, further studies are needed to evaluate the effect of the Moniz Game on motor coordination in patients with neurological dysfunctions.
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Música , Jogos de Vídeo , Humanos , Jogos de Vídeo/psicologia , Jogos de Vídeo/normas , Jogos de Vídeo/estatística & dados numéricos , Adulto , Feminino , Masculino , Música/psicologia , Interface Usuário-Computador , Extremidade Superior/fisiologia , Pessoa de Meia-Idade , Destreza Motora/fisiologiaRESUMO
BACKGROUND: Spinocerebellar ataxia 17 (SCA17) is a rare autosomal dominant form of inherited ataxia, caused by heterozygous trinucleotide repeat expansions encoding glutamine in the TATA box-binding protein (TBP) gene. CASE DESCRIPTION: We describe the clinical history, neuropsychological, and neuroimaging findings of a 42-year-old patient who presented for medical attention showing prevalent behavioral and cognitive problems along with progressively worsening gait disturbances. The patient's family history indicated the presence of SCA17 in the maternal lineage. Genetic analysis confirmed a heterozygous 52-CAG pathological expansion repeat in TBP (normal interval, 25-40 CAG. Brain 18-fluorodeoxyglucose positron emission tomography (FDG-PET) showed bilateral hypometabolism in the sensorimotor cortex, with a slight predominance on the right, as well as in the striatal nuclei and thalamic hypermetabolism, a finding similar to what is observed in Huntington's disease. The patient also underwent neuropsychological evaluation, which revealed mild cognitive impairment and difficulties in social interaction and understanding other's emotions (Faux Pas Test and Reading the Mind in the Eyes Test). CONCLUSION: Our report emphasizes the importance of considering SCA17 as a possible diagnosis in patients with a prevalent progressive cognitive and behavioral disorders, even with a pattern of FDG-PET hypometabolism not primarily indicative of this disease.
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Disfunção Cognitiva , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons , Ataxias Espinocerebelares , Adulto , Humanos , Encéfalo/diagnóstico por imagem , Ataxia Cerebelar/diagnóstico por imagem , Ataxia Cerebelar/genética , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/genética , Disfunção Cognitiva/etiologia , Testes Neuropsicológicos , Transtornos do Comportamento Social/diagnóstico por imagem , Transtornos do Comportamento Social/etiologia , Ataxias Espinocerebelares/diagnóstico por imagem , Ataxias Espinocerebelares/genética , Proteína de Ligação a TATA-Box/genéticaRESUMO
OBJECTIVE: In this systematic review and meta-analysis, we critically evaluate available evidence regarding the association between primary headaches and subsequent decline of cognitive function and dementia. BACKGROUND: Recent studies suggested that headache disorders may increase the risk for dementia. However, available studies are conflicting. METHODS: To identify qualifying studies, we searched scientific databases, including Pubmed, Scopus, Web of Science, Science Direct and BMC, screening for relevant papers. In order to reduce the heterogeneity between different studies, the analyses were further subdivided according to the clinical diagnoses and the study methodologies. RESULTS: We identified 23 studies investigating the association between primary headaches and the risk of dementia. Of these, 18 met our inclusion criteria for meta-analysis (covering 924.140 individuals). Overall effect-size shows that primary headaches were associated with a small increase in dementia risk (OR = 1,15; CI 95%: 1,03-1,28; p = 0,02). Analyzing subgroups, we found that migraine was associated with both a moderate increased risk of all-cause dementia (OR = 1,26; p = 0,00; 95% CI: 1,13-1,40) as well as a moderate increased risk of Alzheimer's disease (OR = 2,00; p = 0,00; 95% CI: 1,46-2,75). This association was significant in both case-control and retrospective cohort studies but not in prospective studies. CONCLUSIONS: Our study supports the presence of a link between primary headaches and dementia. However, in the subgroup analysis, only patients with migraine showed a moderate increase risk for all-cause dementia and for Alzheimer's disease. Additional rigorous studies are needed to elucidate the possible role of primary headaches on the risk of developing cognitive impairment and dementia.
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Doença de Alzheimer , Disfunção Cognitiva , Transtornos de Enxaqueca , Humanos , Doença de Alzheimer/complicações , Estudos Retrospectivos , Estudos Prospectivos , Cefaleia/epidemiologia , Cefaleia/complicações , Disfunção Cognitiva/complicações , Fatores de Risco , Transtornos de Enxaqueca/complicaçõesRESUMO
We describe a 52-year-old patient with a progressive visuospatial disorder and apraxia. Neuropsychological assessment, neuroradiological findings, and Alzheimer's disease (AD) core biomarker assay on cerebrospinal fluid led to a diagnosis of posterior cortical atrophy due to AD. We performed a next generation sequencing dementia-gene panel and found the c.1301âC>T p.(Ala434Val) variant in the Presenilin1 (PSEN1) gene. The missense change affects the PAL (Pro433-Ala434-Leu435) motif critical for catalytic activity of the macromolecular γ-secretase complex. Evolutionary and integrated bioinformatic tools predicted a deleterious effect of the variant supporting its role in the AD pathogenesis.
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The objectives of this study were to develop and validate a computerized device to measure joint flexibility; to measure flexibility in children in elementary school aged 8 to 10 years using the Wells bank; to compare the data obtained by the Wells bank and the computerized device developed in the present study and evaluate the usability of the device. 215 volunteers participated in this research, aged between 8 and 10 years, 63.72% (137) were female and 36.28% (78) were male, duly enrolled in an educational institution in the Alto Tietê region. For data collection, the volunteers performed the flexibility test using the Wells bank and the computerized device developed in this research to assess flexibility. The computerized device it was made on a 3D printing technology printer. A usability evaluation was carried out with 15 Physical Education teachers for the product developed through a usability questionnaire based on the System Usability Scale (SUS) form, which contains 10 multiple-choice questions. The data obtained by the objective measures determined were evaluated in terms of frequency, mean and standard deviation. The arithmetic means of the three measurements performed at each stage were calculated. Mann-Whitney and Kruskal-Wallis tests and Spearman's correlation were performed for the investigation. For all analyses, significant differences were considered p<0.05. It is concluded that the computerized device to measure joint flexibility is capable of evaluating the range of motion in degrees, and was qualified as easy to handle by professionals in the field of physical education.
Los objetivos de este estudio fueron desarrollar y validar un dispositivo computarizado para medir la flexibilidad articular; medir la flexibilidad en niños en la escuela primaria de 8 a 10 años a través del banco Wells; comparar los datos obtenidos por la base de datos Wells y el dispositivo computarizado desarrollado en el presente estudio y evaluar la usabilidad del dispositivo. Un total de 215 voluntarios participaron en esta investigación, con edades de 8 a 10 años, 63,72% (137) mujeres y 36,28% (78) hombres, debidamente matriculados en una institución educativa de la región del Alto Tietê. Para la recolección de datos, los voluntarios realizaron la prueba de flexibilidad utilizando la base de datos Wells y el dispositivo computarizado desarrollado en esta investigación para evaluar la flexibilidad. El dispositivo fue hecho de una impresora de tecnología de impresión 3D. Se realizó una evaluación de usabilidad con 15 profesores de Educación Física para el producto desarrollado a través del cuestionario de usabilidad basado en el formulario System Usability Scale (SUS) que contiene 10 preguntas de opción múltiple. Los datos obtenidos por las mediciones objetivas determinadas fueron evaluados para la frecuencia, media y desviación estándar. Se calcularon las medias aritméticas de las tres mediciones realizadas en cada etapa. Las pruebas de Mann-Whitney y Kruskal-Wallis y la correlación de Spearman se realizaron para la investigación. Para todos los análisis, se consideraron diferencias significativas p<0,05. Se concluye que el dispositivo computarizado para medir la flexibilidad articular es capaz de evaluar el rango de movimiento en grados, y fue calificado fácil de manejar por profesionales de la educación física.
Os objetivos deste estudo foram desenvolver e validar um dispositivo computadorizado para mensurar a flexibilidade articular; mensurar a flexibilidade em crianças no ensino fundamental de 8 a 10 anos por meio do banco de Wells; comparar os dados alcançados pelo banco de Wells e o dispositivo computadorizado desenvolvido no presente estudo e avaliar a usabilidade do dispositivo. Participaram desta pesquisa 215 voluntários, com idade de 8 a 10 anos, sendo 63,72% (137) do sexo feminino e 36,28% (78) do sexo masculino, devidamente matriculados em uma instituição de ensino na região do Alto Tietê. Para coleta de dados, os voluntários realizaram o teste de flexibilidade utilizando o banco de Wells e o dispositivo computadorizado desenvolvido nessa pesquisa para avaliar a flexibilidade.O dispositivo foi confeccionado numa impressora de tecnologia de impressão 3D. Foi realizada uma avaliação da usabilidade com 15 professores de Educação Física para o produto desenvolvido através da interação de usabilidade baseada no formulário System Sustainability Scale (SUS) que contém 10 questões de múltipla-escolha. Os dados obtidos por medidas objetivas determinadas foram avaliadas quanto à frequência, média e desvio padrão. Foram seguidas como médias aritméticas das três medidas realizadas em cada etapa. Para investigar realizou-se os testes de Mann-Whitney e de Kruskal-Wallis e a tradução de Spearman. Para todas as análises foram consideradas diferenças significativas p<0,05.Conclui-se que o dispositivo computadorizado para medir a flexibilidade articular é capaz de avaliar em graus a amplitude de movimento,
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BACKGROUND: The HeartMate 3 (HM 3; Abbott) left ventricular assist device (LVAD) has improved hemocompatibility-related adverse outcomes. In sporadic cases, external compression of the outflow graft causing obstruction (eOGO) can result from substance accumulation between the outflow graft and its bend relief. We sought to evaluate the prevalence, course, and clinical implications of eOGO in an international study. METHODS: A multicenter retrospective analysis of HM 3 LVADs implanted between November 2014 and April 2021 (n = 2108) was conducted across 17 cardiac centers in 8 countries. We defined eOGO as obstruction >25% in the cross-sectional area in imaging (percutaneous angiography, computed tomography, or intravascular ultrasound). The prevalence and annual incidence were calculated. Serious adverse events and outcomes (death, transplantation, or device exchange) were analyzed for eOGO cases. RESULTS: Of 2108 patients, 62 were diagnosed with eOGO at a median LVAD support duration of 953 (interquartile range, 600-1267) days. The prevalence of eOGO was 3.0% and the incidence at 1, 2, 3, 4, and 5 years of support was 0.6%, 2.8%, 4.0%, 5.2%, and 9.1%, respectively. Of 62 patients, 9 were observed, 27 underwent surgical revision, 15 underwent percutaneous stent implantation, 8 received a heart transplant, and 2 died before intervention. One patient underwent surgical revision and later stent implantation. The mortality with therapeutic intervention was 9/53 (17.0%). CONCLUSIONS: Although uncommon, HM 3 LVAD-supported patients might develop eOGO with an increasing incidence after 1 year of support. Although engineering efforts to reduce this complication are under way, clinicians must maintain a focus on early detection and remain vigilant.
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The identification of reliable biomarkers in biological fluids is paramount to optimizing the diagnosis of Alzheimer's disease (AD). Measurement of Aß42, t-tau, and p-tau in cerebrospinal fluid (CSF) is the most accepted method to support the diagnosis of AD. However, lumbar puncture represents an invasive investigation, whereas saliva is one of the most accessible body fluids. The aim of our study was to investigate salivary concentrations in AD and evaluate the correlation between salivary and CSF Aß42 concentrations in AD patients, patients with non-AD dementias, and controls. We recruited 100 subjects: 18 AD patients, 64 patients with non-AD dementias, and 18 controls. The mean saliva Aß42 concentrations in AD patients were higher than in controls (p < 0.001), and to patients with non-AD dementias (p = 0.001). A significant negative correlation between salivary and CSF Aß42 concentrations was found in the overall group (r = −0.562, p < 0.001) and in non-AD patients (r = −0.443, p < 0.001). Salivary Aß42 concentrations positively correlated with CSF t-tau (r = 0.321, p = 0.001) and p-tau (r = 0.297, p = 0.001). Our study showed that in AD patients' saliva, Aß42 concentrations are specifically increased, and we found an interesting negative correlation between CSF and salivary Aß42 concentrations that warrants further investigation.
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Previous studies suggested a role for adipokines in ageing and in several age-related diseases. The purpose of our study was to further elucidate adipokines involvement in neurodegeneration, investigating adiponectin, leptin and resistin in Alzheimer's disease (AD) and Frontotemporal Dementia (FTD). We enrolled for the study 70 subjects: 26 AD, 21 FTD, and 23 with other neurological (but not neurodegenerative) conditions (CTR, control group). According to a standardized protocol, we measured adipokines plasmatic levels, blood parameters of glucidic and lipidic metabolism, ESR, cerebrospinal fluid (CSF) markers of neurodegeneration (beta-amyloid, total-Tau, phosphorylated-Tau) and anthropometric parameters. In comparison with control group, we found lower resistin concentrations in patients with dementia, and in particular in AD (p < 0.001). In multivariate analysis, AD relative risk was reduced by resistin, when controlling for sex, age and anthropometric/metabolic parameters (RR = 0.71, P < 0.0001). Considering CSF biomarkers, we found a direct correlation between resistin and Aß1-42 CSF concentration in patients (p < 0.001, r = 0.50). Lower resistin characterized AD patients in our study and AD, but not FTD, diagnosis risk was found to be inversely associated with resistin when controlling for confounders. We hypothesize that resistin-linked metabolic profile has to be reconsidered and further investigated in AD.
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BACKGROUND: Synaptic disruption precedes neuronal death and correlates with clinical features of Alzheimer's disease (AD). The identification of fluid biomarkers of synaptic damage is emerging as a goal for early and accurate diagnosis of the disease. OBJECTIVE: To perform a systematic review and meta-analysis to determine whether fluid biomarkers of synaptic damage are impaired in AD. METHODS: PubMed, Scopus, EMBASE, and Web of Science were searched for articles reporting synaptic proteins as fluid biomarkers in AD and cognitively unimpaired (CU) individuals. Pooled effect sizes were determined using the Hedge G method with random effects. Questions adapted from the Quality Assessment of Diagnostic Accuracy Studies were applied for quality assessment. A protocol for this study has been previously registered in PROSPERO (registration number: CRD42021277487). RESULTS: The search strategy identified 204 articles that were assessed for eligibility. A total of 23 studies were included in the systematic review and 15 were included in the meta-analysis. For Neurogranin, 827 AD and 1,237 CU subjects were included in the meta-analysis, showing a significant increase in cerebrospinal fluid of patients with AD compared to CU individuals, with an effect size of 1.01 (pâ<â0.001). A significant increase in SNAP-25 and GAP-43 levels in CSF of patients with AD was observed. CONCLUSION: Neurogranin, SNAP-25, and GAP-43 are possible biomarkers of synaptic damage in AD, and other potential synaptic biomarkers are emerging. This meta-analysis also revealed that there are still relatively few studies investigating these biomarkers in patients with AD or other dementias and showed wide heterogeneity in literature.
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Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/líquido cefalorraquidiano , Proteína GAP-43 , Neurogranina/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Disfunção Cognitiva/diagnósticoRESUMO
Several studies have revealed defects in autophagy in neurodegenerative disorders including Alzheimer's disease (AD) and frontotemporal dementia (FTD). SQSTM1/p62 plays a key role in the autophagic machinery and may serve as a marker for autophagic flux in vivo. We investigated the role of p62 in neurodegeneration, analyzing its concentrations in the CSF of AD and FTD patients. We recruited 76 participants: 22 patients with AD, 28 patients with FTD, and 26 controls. CSF p62 concentrations were significantly increased in AD and FTD patients when compared to controls, which persisted after adjusting for age (p = 0.01 and p = 0.008, respectively). In female FTD patients, p62 positively correlated with the neurodegenerative biomarkers t-Tau and p-Tau. A significant correlation between CSF p62 concentrations and several clinical features of AD was found. Our data show that p62 is increased in CSF of AD and FTD patients, suggesting a key role of autophagy in these two disorders. The levels of p62 in CSF may reflect an altered autophagic flux, and p62 could represent a potential biomarker of neurodegeneration.
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Recent studies suggested that epigenetic mechanisms, including DNA methylation, may be involved in migraine pathogenesis. The calcitonin gene-related peptide (CGRP), encoded by calcitonin gene-related peptide 1 (CALCA) gene, plays a key role in the disease. The aim of the study was to evaluate DNA methylation of CALCA gene in patients with episodic migraine. 22 patients with episodic migraine (F/M 15/7, mean age 39.7 ± 13.4 years) and 20 controls (F/M 12/8, mean age 40.5 ± 14.8 years) were recruited. Genomic DNA was extracted from peripheral blood. Cytosine-to-thymine conversion was obtained with sodium bisulfite. The methylation pattern of two CpG islands in the promoter region of CALCA gene was analyzed. No difference of methylation of the 30 CpG sites at the distal region of CALCA promoter was observed between migraineurs and controls. Interestingly, in patients with episodic migraine the methylation level was lower in 2 CpG sites at the proximal promoter region (CpG -1461, p = 0.037, and -1415, p = 0.035, respectively). Furthermore, DNA methylation level at different CpG sites correlates with several clinical characteristics of the disease, as age at onset, presence of nausea/vomiting, depression and anxiety (p < 0.05). In conclusion, we found that DNA methylation profile in two CpG sites at the proximal promoter region of CALCA is lower in migraineurs when compared to controls. Intriguingly, the -1415 hypomethylated unit is located at the CREB binding site, a nuclear transcription factor. In addition, we found a correlation between the level of CALCA methylation and several clinical features of migraine. Further studies with larger sample size are needed to confirm these results.
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BACKGROUND AND PURPOSE: Hand grip strength (HGS) is a simple test to evaluate the upper limb strength function in patients with different diseases. The purpose of this review was to investigate HGS in patients who have been implanted with left ventricular assist devices (LVADs) or waiting for implantation. The objectives were: (1) defining if HGS can predict rehabilitative outcomes such as the walked distance at the 6-minute walking test, and (2) identifying specific HGS cut-off values. METHODS: We searched eight primary databases for English-language studies published from their inception until April 2021. We excluded editorials, letters to the editor, and studies that did not describe HGS assessment procedures. RESULTS: A total of 30 articles were identified. We ultimately included 5 publications, and 217 patients constituted the cohort of the present study. In three studies, HGS was evaluated before implantation. Two studies were conducted during the postoperative course, and HGS measurements were taken before and after rehabilitation. In two studies, HGS has correlated with a significant increase of the 6-MWT passing from 300.1 to 404.8 m and 56.6 to 83.8 m, respectively. HGS in patients with LVADs ranges between (1) ca.18 and ca.33 Kg at the preoperative stage, (2) ca.24 and >40 Kg postoperatively, and (3) ca.33 and >36 Kg after having attended a postoperative rehabilitation program. CONCLUSION: HGS appears to be a simple and reliable measure to correlate rehabilitative outcomes, such as the 6-MWT, in patients receiving or awaiting LVADs.
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Coração Auxiliar , Estudos de Coortes , Força da Mão , Humanos , Resultado do Tratamento , Extremidade SuperiorRESUMO
Migraine is a common neurovascular disorder characterized by recurrent episodes of headache and associated neurological symptoms. At present, a significant portion of patients do not obtain a satisfactory response to acute pain-relieving therapies, including NSAIDs and triptans. In this context, pharmacogenetics plays a key role in the understanding of such a diverse response. In order to investigate whether functional polymorphisms in proinflammatory cytokine genes (IL-1α, IL-1ß, IL-1RN; IL-6 and TNF-α) may influence the response to acute treatment, 313 consecutive patients with episodic migraine without aura were enrolled. Pain relief by administration of NSAIDs or triptans for three consecutive migraine attacks was evaluated. We found a significant association between A allele of the TNF-α promoter (−308 A/G) and a lack of efficacy after NSAID administration (p < 0.01, OR 2.51, 95% CI: 1.33 < OR < 4.75 compared to the G allele). Remaining polymorphisms had no significant effect on pain relief. Our study showed that a functional polymorphism in the TNF-α gene significantly modulates the clinical response to NSAID administration in acute attacks. Patients with higher production of the active cytokine during stress showed a significantly lower anti-migraine effect. Our results further support a role for TNF-α in the pathophysiological mechanisms of migraine attack.
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Anti-Inflamatórios não Esteroides , Transtornos de Enxaqueca , Triptaminas , Humanos , Anti-Inflamatórios não Esteroides/uso terapêutico , Cefaleia/tratamento farmacológico , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/genética , Triptaminas/uso terapêutico , Fator de Necrose Tumoral alfa/genéticaRESUMO
Left ventricular assist device (LVAD) support in donors may contribute in preserving proper haemodynamics and systemic perfusion during organ retrieval thus decreasing the risk of multiple organ injury. This is an option to expand the current organ supply. We report on intra-abdominal organs procurement strategy in a selected LVAD recipient who suffered a fatal cerebrovascular accident at the time of COVID-19 pandemic outbreak. The liver and kidneys grafts have been successfully transplanted.
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COVID-19 , Coração Auxiliar , Morte Encefálica , Humanos , Pandemias , Coleta de Tecidos e ÓrgãosRESUMO
Orexins are hypothalamic neuropeptides that regulate several physiological functions, such as appetite, arousal, cognition, stress, sleep and metabolism. Emerging pieces of evidence suggest an orexinergic dysfunction in several neuropsychiatric disorders, including depression, anxiety and addiction. A syndromic overlap between behavioural variant frontotemporal dementia (bvFTD) and several psychiatric disorders was recently demonstrated. Therefore, we analysed cerebrospinal fluid (CSF) orexin A concentrations of 40 bvFTD and 32 non-demented patients, correlating neuropeptide concentrations with several clinical characteristics. A significant increase of orexin A concentrations was found in bvFTD patients when compared to controls (p<0.001). CSF orexin A concentration showed a correlation with Mini-Mental State Examination scores, drug assumption, history of compulsive behaviour and extrapyramidal signs. Moreover, we found a relationship between CSF markers of neurodegeneration, total tau and Aß1-42 and CSF orexin A concentrations. Our study provides evidence of an orexinergic dysfunction in bvFTD, correlating with several clinical symptoms. Further larger studies are needed to confirm our data.
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Demência Frontotemporal , Orexinas/líquido cefalorraquidiano , Estudos de Casos e Controles , Demência Frontotemporal/líquido cefalorraquidiano , HumanosRESUMO
BACKGROUND: Headache is a frequent symptom of the novel coronavirus 19 disease (COVID-19). To date, there are limited information on how COVID-19 affects migraine and its treatment. CASE DESCRIPTION: A 47-year-old patient, suffering from chronic migraine and medication-overuse headache, in September 2020 started erenumab at 70 mg once monthly. Two months later, monthly migraine days decreased from 20 to 5. On the third month, the patient developed mild COVID-19 symptoms, experiencing extreme fatigue, hyposmia, and attention deficit, resulting positive for SARS-Cov-2 RNA. A significant increase in migraine attacks frequency was reported. Brain MRI and EEG were normal. Erenumab was increased to 140 mg/month, and attacks decreased to 3 monthly migraine days and remained stable. All the headaches experienced by our patient during the infection fulfilled the criteria of the migraine attacks, without tensive-like features. CONCLUSION: We report the first case showing the effects of SARS-CoV-2 infection in a patient with chronic migraine and medication-overuse headache treated with erenumab. Our case description suggests that inflammatory processes induced by SARS-CoV-2 infection may increase the frequency of migraine attacks, probably through an activation of the trigeminovascular system. Whether treatment with CGRP receptor antagonist may influence COVID is still debated. Additional studies regarding anti-CGRP monoclonal antibodies in COVID-19 patients are warranted.
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COVID-19 , Transtornos de Enxaqueca , Anticorpos Monoclonais Humanizados , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina , Humanos , Pessoa de Meia-Idade , Transtornos de Enxaqueca/tratamento farmacológico , RNA Viral , SARS-CoV-2RESUMO
Proper functioning of all organs, including the brain, requires iron. It is present in different forms in biological fluids, and alterations in its distribution can induce oxidative stress and neurodegeneration. However, the clinical parameters normally used for monitoring iron concentration in biological fluids (i.e., serum and cerebrospinal fluid) can hardly detect the quantity of circulating iron, while indirect measurements, e.g., magnetic resonance imaging, require further validation. This review summarizes the mechanisms involved in brain iron metabolism, homeostasis, and iron imbalance caused by alterations detectable by standard and non-standard indicators of iron status. These indicators for iron transport, storage, and metabolism can help to understand which biomarkers can better detect iron imbalances responsible for neurodegenerative diseases.
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Doença de Alzheimer/diagnóstico , Biomarcadores/sangue , Encéfalo/metabolismo , Ferroptose/fisiologia , Ferro/metabolismo , Doença de Alzheimer/metabolismo , Biomarcadores/líquido cefalorraquidiano , Encéfalo/patologia , Ceruloplasmina/deficiência , Ceruloplasmina/metabolismo , Ferritinas/sangue , Ferritinas/líquido cefalorraquidiano , Ferritinas/metabolismo , Humanos , Ferro/sangue , Ferro/líquido cefalorraquidiano , Distúrbios do Metabolismo do Ferro/metabolismo , Imageamento por Ressonância Magnética , Doenças Neurodegenerativas/metabolismo , Estresse Oxidativo/fisiologia , Transferrina/líquido cefalorraquidiano , Transferrina/metabolismoRESUMO
Alzheimer's disease (AD) is the most common form of dementia, characterized by a complex etiology that makes therapeutic strategies still not effective. A true understanding of key pathological mechanisms and new biomarkers are needed, to identify alternative disease-modifying therapies counteracting the disease progression. Iron is an essential element for brain metabolism and its imbalance is implicated in neurodegeneration, due to its potential neurotoxic effect. However, the role of iron in different stages of dementia is not clearly established. This study aimed to investigate the potential impact of iron both in cerebrospinal fluid (CSF) and in serum to improve early diagnosis and the related therapeutic possibility. In addition to standard clinical method to detect iron in serum, a precise quantification of total iron in CSF was performed using graphite-furnace atomic absorption spectrometry in patients affected by AD, mild cognitive impairment, frontotemporal dementia, and non-demented neurological controls. The application of machine learning techniques, such as clustering analysis and multiclassification algorithms, showed a new potential stratification of patients exploiting iron-related data. The results support the involvement of iron dysregulation and its potential interaction with biomarkers (Tau protein and Amyloid-beta) in the pathophysiology and progression of dementia.