The newly discovered glymphatic system: the missing link between physical exercise and brain health?

Dementias are responsible for the most frequent neurodegenerative diseases and the seventh leading cause of death worldwide. As a result, there is a growing effort by the neuroscientific community to understand the physiopathology of neurodegenerative diseases, including how to alleviate the effects of the cognitive decline by means of non-pharmacological therapies (e.g., physical exercise). Studies have shown that exercise can improve aspects of brain health related to cognition. However, there still needs to be more knowledge regarding the mechanisms controlling these relationships, and a newly discovered cleansing system in the brain, named the glymphatic system, can be the missing link in this mechanism. The objective of this paper is to review recent findings regarding the potential impacts of physical exercise on the glymphatic system and its implications for the onset of neurodegenerative diseases. Additionally, considering the close interplay between exercise and sleep quality, we aim to explore how sleep patterns may intersect with exercise-induced effects on glymphatic function, further elucidating the complex relationship between lifestyle factors and brain health.

Diagnosis of Alzheimer's dementia and vehicle driving restriction: a scoping review.

There are doubts about vehicle driving restriction for patients with Alzheimer's disease. A scoping review was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-ScR) methodology. Relevant databases were searched for articles published between 2000 and 2022 in English, Spanish, or Portuguese. Articles were included if they specifically addressed driving, risk of accidents, permission or licence to drive a motor vehicle in a context of important cognitive decline, or if addressed traffic legislation on driving and dementia. Twenty-three articles were selected for full reading, six of which were observational studies and only one with an interventionist method. All articles were carried out in high-income countries such as the UK, the US, and Australia. As a conclusion, there is no psychometric test in the literature sensitive enough to assess vehicle driving competence in older adults with cognitive deficits. Based on selected studies, there is no robust evidence to make recommendation for or against the cessation of vehicular driving for patients with mild cognitive decline or with mild dementia. In some situations, vehicle driving cessation can impact patients and their families. In addition, legal regulations regarding vehicle driving for older adults and people with dementia are scarce worldwide. Despite the scarcity of studies addressing the theme of vehicle driving in the context of dementia, there is some level of consensual reasoning that patients with moderate to severe dementia should halt driving activities, but the same does not apply for patients with mild levels of cognitive impairment, including mild dementia.

Neuropsychological domains and fitness to drive in mild cognitive impairment or Alzheimer's disease.

Cognitive deficits associated with mild cognitive impairment (MCI) or Alzheimer's disease (AD) can impact driving. This integrative review investigated which cognitive domains were associated with poor driving performance or unfitness to drive in studies with outcomes measured in simulator or on-road driving in patients with MCI or AD. The review was conducted by searching for articles published between 2001 and 2020 in the MEDLINE (via PubMed), EMBASE, and SCOPUS databases. Studies addressing patients with other dementias (e.g., vascular or mixed dementia, Lewy body dementia, Parkinson's disease) were excluded. Of 404 articles initially selected, 17 met the eligibility criteria for this review. Based on the findings of this integrative review, attentional capacity, processing speed, executive functions and visuospatial skills were the functions whose declines were most frequently reported in a context of unsafe driving by older adults with MCI or AD. Reports were remarkably heterogeneous in methodological aspects whereas quite limited in cross-cultural coverage and in sample recruited, what prompts for further trials in the field.

Unbalanced networks and disturbed kinetics of serum soluble mediators associated with distinct disease outcomes in severe COVID-19 patients.

The present study applied distinct models of descriptive analysis to explore the integrative networks and the kinetic timeline of serum soluble mediators to select a set of systemic biomarkers applicable for the clinical management of COVID-19 patients. For this purpose, a total of 246 participants (82 COVID-19 and 164 healthy controls - HC) were enrolled in a prospective observational study. Serum soluble mediators were quantified by high-throughput microbeads array on hospital admission (D0) and at consecutive timepoints (D1-6 and D7-20). The results reinforce that the COVID-19 group exhibited a massive storm of serum soluble mediators. While increased levels of CCL3 and G-CSF were associated with the favorable prognosis of non-mechanical ventilation (nMV) or discharge, high levels of CXCL10 and IL-6 were observed in patients progressing to mechanical ventilation (MV) or death. At the time of admission, COVID-19 patients presented a complex and robust serum soluble mediator network, with a higher number of strong correlations involving IFN-γ, IL-1Ra and IL-9 observed in patients progressing to MV or death. Multivariate regression analysis demonstrates the ability of serum soluble mediators to cluster COVID-19 from HC. Ascendant fold change signatures and the kinetic timeline analysis further confirmed that the pairs "CCL3 and G-CSF" and "CXCL10 and IL-6" were associated with favorable or poor prognosis, respectively. A selected set of systemic mediators (IL-6, IFN-γ, IL-1Ra, IL-13, PDGF and IL-7) were identified as putative laboratory markers, applicable as complementary records for the clinical management of patients with severe COVID-19.

Structural equation modelling provides insights to understand the construct of chronic pain in women with rheumatoid arthritis.

OBJECTIVES: We aimed to adopt a multidimensional approach and investigate the interconnections between biomarkers (cytokines, matrix metalloproteinases, and cortisol) and psychosocial aspects considering pain acceptance, the individual construct of pain perception in terms of blood inflammation biomarkers, anxiety, self-efficacy, and functional performance and to define the quality of life (QoL) in women with rheumatoid arthritis (RA). METHODS: An observational cross-sectional study with a total of 42-RA participants, with chronic pain and 42-women without rheumatic diseases or chronic pain were included. A structural equation model was used to investigate the association between independent variables. RESULTS: Women with RA presented high blood biomarker levels, representing an intense inflammatory process. The participants with RA reported moderate pain most of the time, a worsening QoL, functionality, engagement in activities, and a willingness to live with pain and self-efficacy. It was found that the higher the chronic pain, the greater the intensity of pain perceived by these women with RA, as well as, the worse the functionality, the higher the perceived pain. CONCLUSIONS: The exacerbation of pain perception leads to worsening of the experience of chronic pain. The new construct of pain experience should include functionality as a crucial factor in understanding the mechanisms underlying pain.

Lower risk of car crashes among older drivers compared with younger drivers: analysis of 10 years of data / Menor risco de acidentes de automóvel entre motoristas idosos comparado a jovens: resultado de um estudo de 10 anos

Objective: Traffic crashes are a significant cause of health expenditure, mainly considering disability and death. Driving skills are key when it comes to traffic crashes, and older drivers may be unfit to drive. The statistics of traffic crashes involving older drivers can contribute to planning actions that reduce accidents. This study aimed to present statistical data on traffic crashes among older adults in a Brazilian state. Methods: This is an epidemiological study performed with data from the Traffic Accident Information System of the Federal District Traffic Department, Brazil, ranging from 2008 to 2017 and comparing the incidence of injury crashes between older drivers and adult drivers. Results: Although the system recorded 60 705 drivers involved in injury crashes, a 24% reduction was seen in the overall crash incidence during the studied period (2008 ­ 2017); within the older drivers group, this reduction was two times smaller (12%). Despite the smaller drop in incidence, older car drivers presented around three times less risk of crashes when compared to adult drivers, along with a lower risk of accidents on urban, low-speed streets, and were mostly involved in collisions during the day. Conclusion: We found that the risk of older drivers being involved in injury crashes was three times smaller than that of adult drivers. The behavior of older drivers can influence the occurrence of accidents.

Objetivo: Os acidentes de trânsito são causa significativa de gasto em saúde com incapacidades e mortes. Habilidades de condução veicular são elementos-chave para a ocorrência de acidentes de trânsito, e o motorista idoso pode ser incapaz para dirigir. As estatísticas de acidentes de trânsito com motoristas idosos podem contribuir para o planejamento de ações que reduzam os acidentes. Este estudo teve como objetivo apresentar dados estatísticos sobre acidentes de trânsito entre idosos em um estado brasileiro. Metodologia: Estudo epidemiológico com dados do Sistema de Informações de Acidentes de Trânsito do Departamento de Trânsito do Distrito Federal, Brasil, no período de 2008 a 2017, comparando a incidência de acidentes com vitima entre motoristas de automóveis idosos e não idosos. Resultados: De 2008 a 2017, apesar de o sistema contabilizar 60 705 motoristas envolvidos em acidentes de automóveis com vítimas, houve uma redução de 24% na incidência geral nos anos avaliados, sendo essa redução duas vezes menor no grupo de motoristas idosos (12%). A despeito da menor queda na incidência, os motoristas idosos condutores de automóveis tiveram cerca de três vezes menos risco de acidentes comparados a motoristas não idosos; menor risco para acidentes em vias urbanas, as de velocidade mais baixa; e maior predominância de acidentes tipo colisão no período diurno. Conclusões: Encontrou-se risco três vezes menor de motoristas idosos se envolverem em acidentes de automóveis com vitima quando comparados a não idosos. O comportamento dos motoristas idosos pode influenciar na ocorrência de acidentes.

Paternal Resistance Exercise Modulates Skeletal Muscle Remodeling Pathways in Fathers and Male Offspring Submitted to a High-Fat Diet.

Although some studies have shown that a high-fat diet (HFD) adversely affects muscle extracellular matrix remodeling, the mechanisms involved in muscle trophism, inflammation, and adipogenesis have not been fully investigated. Thus, we investigated the effects of 8 weeks of paternal resistance training (RT) on gene and protein expression/activity of critical factors involved in muscle inflammation and remodeling of fathers and offspring (offspring exposed to standard chow or HFD). Animals were randomly distributed to constitute sedentary fathers (SF; n = 7; did not perform RT) or trained fathers (TF n = 7; performed RT), with offspring from mating with sedentary females. After birth, 28 male pups were divided into four groups (n = 7 per group): offspring from sedentary father submitted either to control diet (SFO-C) or high-fat diet (SFO-HF) and offspring from trained father submitted to control diet (TFO-C) or high-fat diet (TFO-HF). Our results show that an HFD downregulated collagen mRNA levels and upregulated inflammatory and atrophy pathways and adipogenic transcription factor mRNA levels in offspring gastrocnemius muscle. In contrast, paternal RT increased MMP-2 activity and decreased IL-6 levels in offspring exposed to a control diet. Paternal RT upregulated P70s6k and Ppara mRNA levels and downregulated Atrogin1 mRNA levels, while decreasing NFκ-B, IL-1ß, and IL-8 protein levels in offspring exposed to an HFD. Paternal physical training influences key skeletal muscle remodeling pathways and inflammatory profiles relevant for muscle homeostasis maintenance in offspring submitted to different diets.

Older drivers are at increased risk of fatal crash involvement: Results of a systematic review and meta-analysis.

Older adults have become a larger part of the driving population, but whether they are at increased risk of being involved in fatal crashes remains unclear. METHODS: We performed a systematic review of studies investigating fatal crash involvement of older vs non-older drivers by searching the following databases: PubMed, Cochrane Library, Embase, LILACS, SciELO, Web of Science, and ProQuest. Studies that used fatal crash involvement rates per distance driven as a measure of frequency were selected for meta-analysis. RESULTS: We analyzed 14 studies published between 2001 and 2018. Of these, 12 reported a higher rate of fatal crashes involving older drivers than non-older drivers; 9 of them used involvement rates per distance driven, which is considered the most appropriate metric. The meta-analysis revealed high heterogeneity between studies. The meta-regression attributed 40% of the heterogeneity to age (older vs non-older drivers) (p<0.005). CONCLUSION: Age appears to be associated with higher driver involvement rates for fatal crashes among older persons.

Evaluation of depression and anxiety symptoms, alcohol consumption, and binge eating in older adults undergoing bariatric surgery: a 6-year follow-up / Avaliação dos sintomas de depressão e ansiedade, consumo de álcool e compulsão alimentar em idosos submetidos à cirurgia bariátrica: seguimento de 6 anos

INTRODUCTION: The literature remains scarce on the late effects of bariatric surgery on the general health of patients who underwent such procedures at an older age. The present study aimed to evaluate depression and anxiety symptoms, risky alcohol consumption, and binge eating in older adults undergoing bariatric surgery. METHODS: This study used current data (from medical records and tests) to conduct a cross-sectional study. A total of 74 individuals aged 60 years and older who underwent bariatric surgery after 55 years of age at a specialist center for obesity management located in Brazil were included and evaluated by the Beck Depression Inventory, Beck Anxiety Inventory, Alcohol Use Disorders Identification Test, and Binge Eating Scale. Demographic and clinical data related to the surgical procedure (weight loss) were also collected. The Cochran-Armitage trend test, Pearson's χ2 test, and a multiple linear regression model were used as needed. A p < 0.05 was considered significant. RESULTS: The individuals were white (65.70%) and women (78.30%), with a mean age of 65.8 (SD 3.90) years. The mean time elapsed from surgery to evaluation was 75.70 (SD 43.70) months; 10.80% of the participants had moderate to severe depression, 8.10% moderate to severe anxiety, and 5.40% risky or high-risk alcohol consumption. None of the participants had binge eating problems. Weight regain was not associated with depressive symptom severity or risky alcohol consumption, but it was significantly associated (p = 0.034) with few or neither anxiety symptoms. Excess weight loss was not associated with any study variable. CONCLUSION: The results show a low prevalence of mental symptoms in older adults undergoing bariatric surgery compared to data from the literature on younger adults undergoing the same procedure.

INTRODUÇÃO: A literatura ainda é escassa sobre os efeitos tardios na saúde geral de pacientes idosos submetidos à cirurgia bariátrica. O presente estudo teve como objetivo avaliar os sintomas de depressão e ansiedade, consumo de álcool de risco e compulsão alimentar em idosos submetidos à cirurgia bariátrica. METODOLOGIA: Este estudo utilizou dados atuais (de prontuários e exames) para realizar um estudo transversal. Um total de 74 indivíduos com 60 anos ou mais que se submeteram à cirurgia bariátrica após os 55 anos em um centro especializado em tratamento da obesidade localizado no Brasil foram incluídos e avaliados pelo Inventário de Depressão e Ansiedade de Beck, Alcohol Use Disorders Identification e Escala de compulsão alimentar. Dados demográficos e clínicos relacionados ao procedimento cirúrgico (perda de peso) também foram coletados. O teste de tendência Cochran-Armitage, o teste do χ2 de Pearson e um modelo de regressão linear múltipla foram usados conforme necessidade. Um p < 0,05 foi considerado significativo. RESULTADOS: Os indivíduos em sua maioria eram brancos (65,70%) e mulheres (78,30%), com média de idade de 65,8 (DP 3,90) anos. O tempo médio decorrido desde a cirurgia até a avaliação foi de 75,70 (DP 43,70) meses; 10,80% dos participantes tinham depressão moderada a grave, 8,10% ansiedade moderada a grave e 5,40% consumo de álcool de risco ou alto risco. Nenhum dos participantes teve problemas de compulsão alimentar. O ganho de peso não foi associado à gravidade dos sintomas depressivos ou consumo de álcool de risco, mas foi significativamente associado (p = 0,034) com poucos ou nenhum sintoma de ansiedade. A perda de excesso de peso não se associou a nenhuma variável do estudo. CONCLUSÕES: Os resultados mostram baixa prevalência de sintomas mentais em idosos submetidos à cirurgia bariátrica em comparação com dados da literatura em adultos jovens submetidos ao mesmo procedimento.

A cirurgia bariátrica como intervenção segura e eficaz para o controle de comorbidades em idosos / Bariatric surgery as a safe and effective intervention for the control of comorbidities in older adults

INTRODUÇÃO: A obesidade no idoso, além de estar associada à piora de doenças relacionadas à síndrome metabólica e a distúrbios osteoarticulares, aumenta o risco de quedas, síndrome de fragilidade, depressão e demência, com consequente perda de funcionalidade. Entre todos os tratamentos disponíveis, a cirurgia bariátrica é uma alternativa em pacientes elegíveis. OBJETIVOS: Discutir aspectos relacionados à segurança e aos benefícios da cirurgia bariátrica para o controle ou a remissão de comorbidades no idoso. METODOLOGIA: Foi realizada revisão de literatura em bases de dados utilizando os seguintes descritores: bariatric surgery and elderly or aged or older adult and comorbidities or safety. Foram incluídos ensaios clínicos, estudos observacionais, estudos comparativos e revisões que avaliaram o efeito da cirurgia bariátrica no controle ou na remissão de comorbidades em idosos. RESULTADOS: Nos últimos anos, vários estudos têm demonstrado não apenas controle ou remissão de comorbidades como diabetes, hipertensão e síndrome da apneia do sono, mas também reduzida taxa de complicações, semelhante à observada em jovens. CONCLUSÕES: Com base nos resultados desses estudos, há espaço para que procedimentos de cirurgia bariátrica sejam indicados a idosos elegíveis, sem limite de idade, considerando também aspectos funcionais e de expectativa de vida.

INTRODUCTION: In addition to being associated with worsening of diseases related to metabolic syndrome and musculoskeletal disorders, obesity in older adults increases the risk of falls, frailty syndrome, depression, and dementia, with consequent functional loss. Among all treatments available, bariatric surgery is an option for eligible patients. OBJECTIVES: To discuss aspects related to the safety and benefits of bariatric surgery for the control or remission of comorbidities in older adults. METHODS: This literature review was carried out in databases, using the following keywords: bariatric surgery and elderly or aged or older adult and comorbidities or safety. We included clinical trials, observational studies, comparative studies, and reviews that evaluated the effect of bariatric surgery on the control or remission of comorbidities in older adults. RESULTS: In recent years, several studies have evidenced not only control or remission of comorbidities, such as diabetes, hypertension, and sleep apnea syndrome, but also a low rate of complications, similar to those observed in young people. CONCLUSIONS: Based on the results of these studies, bariatric surgical procedures can be indicated for eligible older adults, without age restriction, taking into account functional and life expectancy aspects.

Serum Levels of Matrix Metalloproteinase-1 in Brazilian Patients with Benign Prostatic Hyperplasia or Prostate Cancer.

Metalloproteinases (MMPs) are involved in metastatic tumor processes, with changes in circulating levels detected in several cancer types. Here, we compare serum concentrations of metalloproteinase-1 (MMP-1) across individuals clinically diagnosed with prostate cancer (PCa) or benign prostatic hyperplasia (BPH), correcting results for the rs495366 single nucleotide polymorphism (SNP) that predisposes to differential MMP-1 levels. 196 men aged ≥50 years were followed at a university hospital urology outpatient clinic, with clinical, anthropometric, and rectal examinations performed by one urologist. Blood samples obtained prior to any clinical intervention provided baseline MMP-1 and total/free PSA levels as well as metabolic, hormonal, and inflammatory markers. The SNP was genotyped by real-time PCR. Participants with medical and/or laboratory profile compatible with malignancy composed the PCa group when confirmed by the Gleason scale. As expected, A-allele homozygotes showed reduced levels of MMP-1. Genotype-adjusted analyses revealed the mean MMP-1 level as 2-fold higher in PCa carriers compared to BPH patients. No other differences were found according to the prostatic condition or genotypic distribution, except for the expected raise in total and free PSA levels in PCa. In conclusion, increased serum levels of MMP-1 were observed in this context of prostatic malignancy compared to a benign phenotype, regardless of a genetic influence.

Whole-Blood Levels of MicroRNA-9 Are Decreased in Patients With Late-Onset Alzheimer Disease.

Recent evidence suggests changes in circulating microRNA levels may be promising biomarkers for the clinical diagnosis of Alzheimer disease (AD). We hypothesized that whole-blood microRNAs may be useful to identify individuals with established AD. For this purpose, a sample of community-dwelling women (≥55 years old) carrying the ApoE ∊4 allele were clinically evaluated using the American Psychiatric Association/Diagnostic and Statistical Manual of Mental Disorders, Fourth edition and the Alzheimer Disease Assessment Scale-Cognitive Subscale criteria to diagnose probable AD, and the Clinical Dementia Rating scale to stage the dementia. A set of 25 mature microRNAs was rationally selected for evaluation based on experimental evidence of interaction with genes linked to the late-onset AD neuropathology. Whole-blood concentrations were determined by quantitative real-time polymerase chain reaction. Compared to patients without dementia, a median 3-fold decrease in miR-9 levels was found among patients with AD (P = .001). Our findings support blood-borne miR-9 as a candidate biomarker for probable AD, embodied by evidence from the literature of its implication in amyloidogenesis.

Resistance Training Modulates the Humoral Inflammatory (but Not the DNA Methylation) Profile of Diabetic Older Adults Using Metformin.

BACKGROUND AND AIM: Inflammatory and methylation imbalances occur in patients with type 2 diabetes mellitus (T2DM). The aim of the present study was to analyze the effect of acute resistance exercise on the inflammatory profile and on DNA methylation of elderly patients with T2DM using metformin. METHODS: For this purpose, we enrolled 22 male and female older adults (68.2 ± 5.3 years), of whom 13 had controlled T2DM (D) under metformin use and 9 were nondiabetics (ND). All subjects underwent a neuromuscular circuit (8 exercises in 40 min, with each exercise performed in 3 sets of 40 s each and a 20-s interval between repetitions). RESULTS: The main results indicated a significant difference between groups for baseline interleukin (IL)-10, with a higher concentration in the D group compared to the ND group (p = 0.019). An increase in IL-6 concentration after intervention was observed in group D (p = 0.035). No effect was observed in total DNA methylation within or between groups. CONCLUSIONS: The resistance training protocol applied in this study modulates the IL-10 and IL-6 concentrations in elderly people with T2DM and under metformin use, possibly as a result of physiological adaptations, with no effect on nondiabetic elderly. No effects on absolute levels of DNA methylation were observed.

Frailty syndrome in older adults from the community and long-term care institutions: an exploratory analysis / Síndrome da fragilidade em idosos da comunidade e de instituições de longa permanência: uma análise exploratória

OBJECTIVES: To investigate the association between Frailty syndrome, lipid profile, anthropometric variables, and the functional capacity of older adults; and to analyze an explanatory model of variables with higher predictive capacity for Frailty syndrome. METHODS: This cross-sectional study included 36 and 86 older adults residing in long-term care facilities and in their households, respectively. Anamnesis was followed by evaluation of anthropometric data, risk of falls, functional tests, and biochemical tests. Frailty syndrome was determined according to the criteria suggested by Fried et al. RESULTS: Geriatric patients classified as frail were older; had higher medication consumption; and presented lower performance in handgrip strength, sit-to-stand, and gait speed tests as compared to pre- and non-frail older adults. CONCLUSION: Gait speed and sit-to-stand tests were significant predictors of Frailty syndrome. Specifically, a good performance in these tests represents a protection factor against Frailty syndrome. Furthermore, gait speed performance was explained by age, handgrip strength performance, and frailty status, while sit-to-stand performance was explained by risk of falls and muscular strength.

OBJETIVOS: Investigar a associação entre síndrome da fragilidade, perfil lipídico, variáveis antropométricas e capacidade funcional de idosos; e analisar um modelo explicativo de variáveis com maior capacidade preditiva para síndrome da fragilidade. MÉTODOS: Este estudo transversal incluiu 36 e 86 idosos residentes em instituições de longa permanência e em suas residências, respectivamente. A anamnese foi seguida pela avaliação dos dados antropométricos, risco de quedas, testes funcionais e testes bioquímicos. A síndrome da fragilidade foi determinada de acordo com os critérios sugeridos por Fried et al. RESULTADOS: Os idosos classificados como frágeis eram mais idosos; tiveram maior consumo de medicação; e apresentaram menor desempenho nos testes de força de preensão palmar, levantar e sentar e velocidade da marcha quando comparados aos idosos pré e não frágeis. CONCLUSÕES: Os testes velocidade da marcha e levantar e sentar foram preditores significativos de síndrome da fragilidade. Especificamente, um bom desempenho nesses testes representa um fator de proteção contra a síndrome da fragilidade. Além disso, o desempenho da velocidade da marcha foi explicado pela idade, desempenho da força de preensão palmar e estado de fragilidade, enquanto o desempenho do levantar e sentar foi explicado pelo risco de quedas e força muscular.