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.

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.

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.

Body Adiposity Index, but not Visceral Adiposity Index, Correlates with Inflammatory Markers in Sarcopenic Obese Elderly Women.

Background/Study Context: The association of body adiposity index (BAI) and visceral adiposity index (VAI) with inflammatory markers has yet to be understood. The aim of this work was to investigate the association of BAI and VAI with inflammatory markers in elderly women with sarcopenic obesity (SO). METHODS: A total of 130 women (age: 66.7 ± 5.2 years) underwent body composition analysis by dual-energy x-ray absorptiometry (DEXA). Volunteers were classified according to SO definition. BAI, VAI, and waist-to-hip ratio (WHR) were calculated. Blood samples were collected for C-reactive protein (CRP), tumor necrosis factor, and interleukin-6 (IL-6) measurements. RESULTS: SO prevalence was 20.8%. BAI correlated with the DEXA-derived body fat content (rS = .90), CRP (rS = .55), and IL-6 (rS = .53), whereas WHR correlated with CRP (rS = .60) only (all p < .01). VAI did not correlate with any of the inflammatory variables. CONCLUSION: Simple and cheap anthropometric indices such as BAI and WHR may be better predictors of low-grade inflammation than VAI in elderly women with SO.

Habitual dietary intake and mediators of the inflammaging process in Brazilian older women.

AIM: This study aimed to assess whether the habitual intake of macronutrients by older women associates with circulating levels of important inflammaging mediators by means of a cross-sectional design with 229 Brazilian elderly women. METHODS: Laboratory tests determined serum IL1α, IL1ß, IL6, IL8, IL10, IL12 and TNFα by specific immunoassays. Food records of three alternate days were decomposed into usual intake of carbohydrates, proteins and lipids (and fractions), as well as total energy value (TEV) per patient. Moreover, the study has identified and controlled results for metabolic conditions known to influence the inflammatory profile: hypercholesterolemia, hypertension and diabetes. RESULTS AND DISCUSSION: Pearson's correlation test revealed that log10IL8 expressed a positive association with levels of saturated fatty acid (FA) (r = 0.173; p = 0.009) and total cholesterol intake (r = 0.223; p = 0.001). Similar analysis of the other mediators revealed no association with dietary intake. CONCLUSION: Higher intakes of total cholesterol and saturated FA seem to correlate with increased serum IL8 levels, being a possible mechanism by which this pro-atherogenic intake pattern may increase the risk of age-related chronic diseases with important inflammatory contribution.

Serum Immune Mediators Independently Associate with Atherosclerosis in the Left (But Not Right) Carotid Territory of Older Individuals.

BACKGROUND AND AIM: Disturbance in the carotid arteries strongly predicts cerebrovascular events and correlates with a systemic inflammatory milieu. We investigated the relationship of a profile of 10 circulating inflammatory mediators with measures of carotid intima-media thickness (cIMT) in elderly subjects, taking traditional risk factors into account. METHODS: Clinical inspection for present and past chronic conditions and events, as well as biochemical and anthropometric measurements, was performed for patients in ambulatory setting. Scores of cIMT were obtained bilaterally in the distal common carotid artery wall. Serum concentrations of cytokines were assessed by bead-based, multiplexed flow cytometry immunoassays. RESULTS: Correlation analysis between log-transformed cytokines levels implicated the mediators interleukin-1ß (IL1ß), IL6, IL8, IL10, and tumor necrosis factor-α (TNFα) (P ≤ .005) with scores of the left cIMT. Stepwise multivariate regression showed that TNFα, IL1ß, and IL6 levels accounted for most of the variance in the cIMT scores. Comparison of cytokine levels across increasing tertiles of the left cIMT reproduced the positive association with TNFα and IL1ß levels. CONCLUSION: Five out of ten immune mediators independently correlated with cIMT of older subjects in a territory-sensitive manner. This possible contribution of immune mediators to an atherosclerotic process probably relates to the inflammaging process.

Lack of association between apolipoprotein E genotypes and cognitive performance in the non-demented elderly.

AIM: The ε4 alelle of the apolipoprotein E gene is known to be a key genetic risk factor for Alzheimer's disease and possibly for other neurological disorders. Some evidence in the literature indicates that the ε4 allele interferes with human cognition independently of chronological age and diagnosis of Alzheimer's disease. The present study investigated the correlation of allelic variants of apolipoprotein E with the cognitive performance of elderly individuals without apparent cognitive impairment. METHODS: This was a cross-sectional analysis that included 213 non-demented elderly individuals (age ≥60 years) from the Brazilian Federal District. The analysis assessed the subjects for cognitive domains including short- and long-term episodic memory, processing speed, and attention and executive functions. Sociodemographic and other clinical characteristics were gathered and analyzed as covariates. RESULTS: Being sufficiently powered, the present study did not identify differential performance across apolipoprotein E genotypes. There was no influence of age, gender, marital status, schooling, depressive symptoms or use of central nervous system depressants when the analyses were controlled for such factors. CONCLUSIONS: Our findings suggest that the ε4 allele does not contribute to detectable cognitive decline within the context of non-dementia.

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.

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.

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.

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.

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.

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.

Neuromuscular electrical stimulation in critically ill traumatic brain injury patients attenuates muscle atrophy, neurophysiological disorders, and weakness: a randomized controlled trial.

BACKGROUND: Critically ill traumatic brain injury (TBI) patients experience extensive muscle damage during their stay in the intensive care unit. Neuromuscular electrical stimulation (NMES) has been considered a promising treatment to reduce the functional and clinical impacts of this. However, the time needed for NMES to produce effects over the muscles is still unclear. This study primarily aimed to assess the time needed and effects of an NMES protocol on muscle architecture, neuromuscular electrophysiological disorder (NED), and muscle strength, and secondarily, to evaluate the effects on plasma systemic inflammation, catabolic responses, and clinical outcomes. METHODS: We performed a randomized clinical trial in critically ill TBI patients. The control group received only conventional physiotherapy, while the NMES group additionally underwent daily NMES for 14 days in the lower limb muscles. Participants were assessed at baseline and on days 3, 7, and 14 of their stay in the intensive care unit. The primary outcomes were assessed with muscle ultrasound, neuromuscular electrophysiology, and evoked peak force, and the secondary outcomes with plasma cytokines, matrix metalloproteinases, and clinical outcomes. RESULTS: Sixty participants were randomized, and twenty completed the trial from each group. After 14 days, the control group presented a significant reduction in muscle thickness of tibialis anterior and rectus femoris, mean of - 0.33 mm (- 14%) and - 0.49 mm (- 21%), p < 0.0001, respectively, while muscle thickness was preserved in the NMES group. The control group presented a higher incidence of NED: 47% vs. 0% in the NMES group, p < 0.0001, risk ratio of 16, and the NMES group demonstrated an increase in the evoked peak force (2.34 kg/f, p < 0.0001), in contrast to the control group (- 1.55 kg/f, p < 0.0001). The time needed for the NMES protocol to prevent muscle architecture disorders and treat weakness was at least 7 days, and 14 days to treat NED. The secondary outcomes exhibited less precise results, with confidence intervals that spanned worthwhile or trivial effects. CONCLUSIONS: NMES applied daily for fourteen consecutive days reduced muscle atrophy, the incidence of NED, and muscle weakness in critically ill TBI patients. At least 7 days of NMES were required to elicit the first significant results. TRIAL REGISTRATION: The trial was registered at ensaiosclinicos.gov.br under protocol RBR-8kdrbz on 17 January 2016.