Neuropsychiatric Symptoms are Related to Blood-biomarkers in Major Neurocognitive Disorders.

BACKGROUND: Neuropsychiatric symptoms (NPS) are highly prevalent among individuals with major neurocognitive disorders (MNCD). OBJECTIVE: Here, we characterized blood biomarkers (metabolic, inflammatory, neurotrophic profiles and total antioxidant), body composition, physical fitness and quality of life (QoL) in individuals with MNCD according to NPS. METHODS: The sample comprised 34 older adults (71.4% women; 74.06±6.03 yrs, with MNCD diagnosis) categorized according to 50th percentile [Low (≤12) or High (≥13)] for NPS (Neuropsychiatric Inventory Questionnaire). Sociodemographic, clinical data, body composition, anthropometric, cognitive assessment (ADAS-Cog), physical fitness (Senior Fitness Test), QoL (QoL-Alzheimer's Disease scale) were evaluated, and blood samples were collected for biochemical analysis. RESULTS: Low compared to high NPS group showed higher levels of IL-6, IGF-1and neurotrophic zscore (composite of IGF-1, VEGF-1, BDNF). Additionally, low compared to high NPS group have higher QoL, aerobic fitness and upper body and lower body strength. CONCLUSION: The severity of NPS seems to be related to modified neurotrophic and inflammatory outcomes, lower physical fitness, and poor QoL. Strategies to counteract NPS development may preserve the physical and mental health of individuals with MNCD.

Portable Digital Monitoring System for Sarcopenia Screening and Diagnosis.

Sarcopenia is a well-known highly prevalent muscle disease that severely impairs overall physical performance in elders, inducing a massive health-related economic burden. The widespread screening, diagnosis and treatment of sarcopenia are pivotal to restrain the disease progression and constrain its societal impact. Simple-to-use, portable, and reliable methods to evaluate sarcopenia are scarce, and sarcopenia-related assessments are typically done in several time-consuming stages. This study presents a portable digital system that enables a simple and intuitive method to evaluate sarcopenia-based on the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) algorithm-including the four Find-Assess-Confirm-Severity (FACS) steps. The system comprises a mobile application (app); two wireless devices: a dynamometer (Gripwise) and a skinfold caliper (Lipowise); and a back-end website. To find cases, the SARC-F questionnaire is applied. To assess sarcopenia, the handgrip strength and the sit-to-stand tests are performed with the Gripwise and an application-embedded stopwatch, respectively. To confirm cases, anthropometric measures are performed, and muscle quantity is estimated with Lipowise. Finally, to assess severity, the app stopwatch grants the gait speed test application, evaluating physical performance. This step-by-step sarcopenia assessment results in a final grading according to the cut-off points of the EWGSOP2 criteria. All data is automatically encrypted and exported into a GDPR-compliant cloud platform, in which healthcare professionals can access and monitor their patients through the internet.

Physical activity and physical fitness according to loneliness levels in adults 50+ / Caraterização da atividade física e aptidão física de acordo com os níveis de solidão em adultos 50+

Loneliness is a perception of dissatisfaction that seems to be the result of a lack of significant re-lationships, with multiple potential causal factors. The current body of research is not conclusive in relation to the link between loneliness and physical activity (PA) and physical fitness (PF) in adults and seniors. The aim of this cross-sectional study is to characterize PA and PF according to levels of loneliness (Social Isolation versus Affinities). The 62 Portuguese individuals (64.68 ± 6.85 years; 68% women) were assessed for loneliness (University of California Los Angeles 16-item Loneliness Scale - UCLA-16). and classified in Social Isolation or Affinities, i.e., presence of significant social rela-tionships. PA was estimated using a questionnaire (International PA Questionnaire - Short Version - IPAQ-SV ) and PF was evaluated using the Senior Fitness Test (upper and lower body strength, upper and lower body flexibility, cardiorespiratory fitness, agility and dynamic balance). Descriptive statistics were used. The comparison between groups was performed using parametric (t-test, AN-COVA adjusted to sex and chi-square) and non-parametric tests (Mann-Whitney). The prevalence of social isolation was 53%. The individuals of the Affinities group spent more minutes per day on moderate and vigorous physical activity (MVPA) than the individuals of the Social Isolation group (0.00 [0.00 ­ 12.86] versus 11.43 [0.00 ­ 17.14] minutes, respectively; p = 0.041). After adjusting for sex, the differences were no longer significant. Loneliness groups were not different in relation to PF. PA appears to contribute to a better mental profile in adults and seniors. The results should be confirmed through studies with larger samples

A solidão é uma percepção de insatisfação que parece resultar da carência de relacionamentos significativos, sendo múltiplos os seus potenciais fatores causais. A atual evidência não é robusta no que diz respeito à associação da solidão com a atividade física (AF) e aptidão física (ApF) em adultos 50+. O objetivo deste estudo transversal é caracterizar a AF e ApF de acordo com a solidão. Os 62 indivíduos portugueses (64,68 ± 6,85 anos; 68% mulheres) foram avaliados para solidão (Escala de Solidão de 16 itens da Universidade da Califórnia em Los Angeles - UCLA-16) e classificados como Isolamento Social ou Afinidades, i.e., presença de relações socias significativas. A AF foi estimada por questionário (Questionário Internacional de AF - Versão Curta - IPAQ-SV ) e a ApF medida pela bateria Senior Fitness Test (força de membros superiores e inferiores, flexibilidade de membros superiores e membros inferiores, aptidão cardiorrespiratória e agilidade e equilíbrio dinâmico. Foram utilizadas estatísticas descritivas. A comparação entre grupos foi realizada através de testes paramétricos (teste-t, ANCOVA ajustada ao sexo e qui-quadrado) e não paramétricos (Mann-Whitney). A prevalência de isolamento social foi de 53%. O grupo Afinidades apresentou mais AF moderada a vigorosa comparativamente ao grupo Isolamento Social (11,43 [0,00 ­ 17,14] vs (0,00 [0,00 ­ 12,86], respetivamente; p = 0,041). Após ajuste para o sexo, as diferenças deixaram de ser significativas. Os grupos de solidão não foram diferentes relativamente à ApF. A AF parece contribuir para um melhor perfil mental de adultos e idosos, contudo, os resultados devem ser confirmados em estudos com amostras maiores

Wearable Devices for Physical Activity and Healthcare Monitoring in Elderly People: A Critical Review.

The availability of wearable devices (WDs) to collect biometric information and their use during activities of daily living is significantly increasing in the general population. These small electronic devices, which record fitness and health-related outcomes, have been broadly utilized in industries such as medicine, healthcare, and fitness. Since they are simple to use and progressively cheaper, they have also been used for numerous research purposes. However, despite their increasing popularity, most of these WDs do not accurately measure the proclaimed outcomes. In fact, research is equivocal about whether they are valid and reliable methods to specifically evaluate physical activity and health-related outcomes in older adults, since they are mostly designed and produced considering younger subjects' physical and mental characteristics. Additionally, their constant evolution through continuous upgrades and redesigned versions, suggests the need for constant up-to-date reviews and research. Accordingly, this article aims to scrutinize the state-of-the-art scientific evidence about the usefulness of WDs, specifically on older adults, to monitor physical activity and health-related outcomes. This critical review not only aims to inform older consumers but also aid researchers in study design when selecting physical activity and healthcare monitoring devices for elderly people.

"Body & Brain": effects of a multicomponent exercise intervention on physical and cognitive function of adults with dementia - study protocol for a quasi-experimental controlled trial.

BACKGROUND: Dementia is a leading cause of death and disability that was declared as one of the greatest health and social care challenges of the twenty-first century. Regular physical activity and exercise have been proposed as a non-pharmacological strategy in disease prevention and management. Multicomponent Training (MT) combines aerobic, strength, balance and postural exercises and might be an effective training to improve both functional capacity and cognitive function in individuals with dementia (IwD). Nevertheless, data on the effects of MT in IwD are still limited and the extent to which IwD can retain improvements after an exercise intervention still needs to be elucidated. The aim of "Body & Brain" study is to investigate the effects of a 6-month MT intervention and 3-month detraining on the physical and cognitive function of IwD. Additionally, we aim to explore the impact of this intervention on psychosocial factors and physiologic markers related to dementia. METHODS: This study is a quasi-experimental controlled trial using a parallel-group design. The study sample consists of community-dwelling individuals aged ≥60 years who are clinically diagnosed with dementia or major neurocognitive disorder. Participants will be either allocated into the intervention group or the control group. The intervention group will participate in MT biweekly exercise sessions, whereas the control group will receive monthly sessions regarding physical activity and health-related topics for 6 months. The main outcomes will be physical function as measured by the Short Physical Performance Battery (SPPB) and cognitive function evaluated using the Alzheimer Disease Assessment Scale - Cognitive (ADAS-Cog) at baseline, after 6-months and 3-months after the end of intervention. Secondary outcomes will be body composition, physical fitness, daily functionality, quality of life, neuropsychiatric symptoms and caregiver's burden. Cardiovascular, inflammatory and neurotrophic blood-based biomarkers, and arterial stiffness will also be evaluated in subsamples. DISCUSSION: If our hypothesis is correct, this project will provide evidence regarding the efficacy of MT training in improving physical and cognitive function and give insights about its impact on novel molecular biomarkers related to dementia. This project may also contribute to provide guidelines on exercise prescription for IwD. TRIAL REGISTRATION: ClinicalTrials.gov - identifier number NCT04095962 ; retrospectively registered on 19 September 2019.

Preventive and Therapeutic Potential of Physical Exercise in Neurodegenerative Diseases.

Significance: The prevalence and incidence of age-related neurodegenerative diseases (NDDs) tend to increase along with the enhanced average of the world life expectancy. NDDs are a major cause of morbidity and disability, affecting the health care, social and economic systems with a significant impact. Critical Issues and Recent Advances: Despite the worldwide burden of NDDs and the ongoing research efforts to increase the underlying molecular mechanisms involved in NDD pathophysiologies, pharmacological therapies have been presenting merely narrow benefits. On the contrary, absent of detrimental side effects but growing merits, regular physical exercise (PE) has been considered a prone pleiotropic nonpharmacological alternative able to modulate brain structure and function, thereby stimulating a healthier and "fitness" neurological phenotype. Future Directions: This review summarizes the state of the art of some peripheral and central-related mechanisms that underlie the impact of PE on brain plasticity as well as its relevance for the prevention and/or treatment of NDDs. Nevertheless, further studies are needed to better clarify the molecular signaling pathways associated with muscle contractions-related myokines release and its plausible positive effects in the brain. In addition, particular focus of research should address the role of PE in the modulation of mitochondrial metabolism and oxidative stress in the context of NDDs.

Physical exercise positively modulates DOX-induced hepatic oxidative stress, mitochondrial dysfunction and quality control signaling.

Doxorubicin (DOX), a widely used and efficient antineoplastic agent, is mainly limited by cardiotoxicity, although other tissues including liver are also affected. The effects of exercise to cope with DOX side-effects has already been studied in the heart and brain, demonstrating successful results. However, the benefits of this non-pharmacological strategy have not been so extensively checked in the liver. We here aimed to ascertain whether exercise could mitigate DOX-induced liver harmful effects using mitochondria as a model for evaluating toxicity. Twenty-four male rats were divided into four groups: SED + SAL (sedentary with saline administration), SED + DOX (sedentary with DOX administration), ET + DOX (endurance-trained with DOX administration) and VPA + DOX (voluntary physical activity with DOX administration). Isolated liver mitochondria were obtained for evaluation of their respiratory activity and transmembrane electrical potential endpoints. Molecular markers of oxidative damage (carbonyls, MDA, aconitase, MnSOD), mitochondrial dynamics (PGC-1α, TFAM, OPA1, DRP1, MFN1) and auto(mito)phagy signaling (p62, LC3, Beclin1, Bcl-2, PINK, Parkin) were measured. Transmission electron microscopy evaluation was used to analyze mitochondrial morphological alterations. When compared to SED + SAL, respiratory function of SED + DOX was compromised. Decreased SOD and aconitase activities and increased MDA content, decreases in PGC-1α, TFAM, OPA1 and MFN1 expressions, and increases in DRP1 and LC3II/LC3I ratio were also observed after DOX administration. However, these alterations were reverted or mitigated in the ET + DOX group. Semi-quantitative and qualitative analyses from microphotographs showed that liver mitochondria of SED + DOX animals were more circular and had lower density, whereas the animals with exercise showed a tendency to revert this phenotype and increase the mitochondrial density. Taken together, our results suggest that physical exercise, particularly ET, positively reversed the deleterious effects caused by DOX administration, such as oxidative damage, mitochondrial dysfunction, and altered mitochondrial dynamics toward fission, thus contributing to increase liver resistance against DOX administration.

Feasibility and Impact of a Multicomponent Exercise Intervention in Patients With Alzheimer's Disease: A Pilot Study.

This quasi-experimental, nonrandomized study examined the feasibility and impact of a multicomponent (MT) intervention on 7 community-dwelling individuals diagnosed with probable Alzheimer's disease (AD) at mild to moderate stage. During 6 months, patients with AD and their caregivers were submitted to a biweekly exercise program, including muscle strengthening, aerobics, balance, and postural exercises. The following tests were used: Senior Fitness Test and Incremental Treadmill Test, Disability Assessment for Dementia Scale, Alzheimer Disease Assessment Scale-Cognitive, and Quality of Life-Alzheimer's. Attendance and retention mean rates were high (86% and 78%, respectively). No adverse events occurred. Results revealed a significant beneficial effect on cardiorespiratory fitness ( P = .028), upper ( P = .018) and lower ( P = .026) body muscle strength, agility ( P = .018), and ability to perform daily activities ( P = .018). Data suggest that a biweekly MT intervention is feasible to conduct in patients with AD. Findings also suggest a potential positive effect on mitigating cognitive decline and in positively influencing quality of life.

Physical exercise prior and during treatment reduces sub-chronic doxorubicin-induced mitochondrial toxicity and oxidative stress.

Doxorubicin (DOX) is an anti-cancer agent whose clinical usage results in a cumulative and dose-dependent cardiotoxicity. We have previously shown that exercise performed prior to DOX treatment reduces the resulting cardiac(mito) toxicity. We sought to determine the effects on cardiac mitochondrial toxicity of two distinct chronic exercise models (endurance treadmill training-TM and voluntary free-wheel activity-FW) when used prior and during DOX treatment. Male-young Sprague-Dawley rats were divided into six groups (n=6 per group): SAL+SED (saline sedentary), SAL+TM (12-weeks TM), SAL+FW (12-weeks FW), DOX+SED (7-weeks of chronic DOX treatment 2mg/kg per week), DOX+TM and DOX+FW. DOX administration started 5weeks after the beginning of the exercise protocol. Heart mitochondrial ultrastructural alterations, mitochondrial function (oxygen consumption and membrane potential), semi-quantification of oxidative phosphorylation (OXPHOS) proteins and their in-gel activity, as well as proteins involved in mitochondrial oxidative stress (SIRT3, p66shc and UCP2), biogenesis (PGC1α and TFAM), acetylation and markers for oxidative damage (carbonyl groups, MDA,SH, aconitase, Mn-SOD activity) were evaluated. DOX treatment resulted in ultrastructural and functional alterations and decreased OXPHOS. Moreover, DOX decreased complex I activity and content, mitochondrial biogenesis (TFAM), increased acetylation and oxidative stress. TM and FW prevented DOX-induced alteration in OXPHOS, the increase in oxidative stress, the decrease in complex V activity and in complex I activity and content. DOX-induced decreases in TFAM and SIRT3 content were prevented by TM only. Both chronic models of physical exercise performed before and during the course of sub-chronic DOX treatment translated into an improved mitochondrial bioenergetic fitness, which may result in part from the prevention of mitochondrial oxidative stress and damage.

Exercise mitigates diclofenac-induced liver mitochondrial dysfunction.

BACKGROUND: Several strategies have been developed to counteract liver injury as a consequence of nonsteroid anti-inflammatory drugs toxicity. Here, we aimed to determine whether physical exercise results in liver mitochondrial protection against in vitro diclofenac toxicity. MATERIAL AND METHODS: Male adult Sprague-Dawley rats were divided into sedentary, 12-week endurance training (ET) and voluntary activity (VPA). In vitro liver mitochondrial function as assessed by oxygen consumption, transmembrane electric potential (ΔΨ) and susceptibility to the mitochondrial permeability transition pore (MPTP) was evaluated in the absence and presence of diclofenac. Mitochondrial oxidative stress markers [MnSOD, aconitase, -SH and MDA, SIRT3, p66shc(Ser36)/p66shc ratio] and apoptotic signalling (caspases 3, 8 and 9, Bax, Bcl-2 and CypD) were assessed. Content of OXPHOS components and qualitative liver morphological evaluation were assessed. RESULTS: Despite no effects of ET and VPA on basal liver mitochondrial oxygen consumption or ΔΨ endpoints, exercised animals showed lower susceptibility to MPTP. Diclofenac-induced decrease in ΔΨ, increased state 4 respiration and susceptibility to MPTP opening were all prevented by exercise. Under untreated conditions, VPA group showed higher aconitase activity, while ET decreased MDA and increased Bax content. VPA decreased p66shc(Ser36), complex III and V OXPHOS subunits. Both ET and VPA increased complex IV OXPHOS subunit, and SIRT3 and Bcl-2 content and decreased caspase 9 activity. Unexpectedly, ET and VPA decreased ANT. CONCLUSIONS: Both chronic physical exercise models augmented the resistance to in vitro diclofenac-induced mitochondrial alterations, including increased MPTP susceptibility, possibly by modulating oxidative stress and MPTP regulators.

Physical exercise prevents and mitigates non-alcoholic steatohepatitis-induced liver mitochondrial structural and bioenergetics impairments.

Exercise is considered a non-pharmacological tool against several lifestyle disorders in which mitochondrial dysfunction is involved. The present study aimed to analyze the preventive (voluntary physical activity-VPA) and therapeutic (endurance training-ET) role of exercise against non-alcoholic steatohepatitis (NASH)-induced liver mitochondrial dysfunction. Sixty male Sprague-Dawley rats were divided into standard-diet sedentary (SS, n=20), standard-diet VPA (SVPA, n=10), high-fat diet sedentary (HS, n=20) and high-fat diet VPA (HVPA, n=10). After 9weeks of diet-treatment, half of SS and HS animals were engaged in an ET program (SET and HET) for 8weeks, 5days/week and 60min/day. Liver mitochondrial oxygen consumption and transmembrane-electric potential (ΔΨ) were evaluated in the presence of glutamate-malate (G/M), palmitoyl-malate (P/M) and succinate (S/R). Mitochondrial enzymes activity, lipid and protein oxidation, oxidative phosphorylation (OXPHOS) subunits, cytochrome c, adenine nucleotide translocator (ANT) and uncoupling protein-2 (UCP2) content were assessed. HS groups show the histological features of NASH in parallel with decreased ΔΨ and respiratory control (RCR) and ADP/O ratios (G/M and P/M). A state 3 decrease (G/M and S/R), FCCP-induced uncoupling respiration (S/R) and ANT content were also observed. Both exercise types counteracted oxygen consumption (RCR, ADP/O and FCCP-uncoupling state) impairments and improved ΔΨ (lag-phase). In conclusion, exercise prevented or reverted (VPA and ET, respectively) the bioenergetic impairment induced by NASH, but only ET positively remodeled NASH-induced liver structural damage and abnormal mitochondria. It is possible that alterations in inner membrane integrity and fatty acid oxidation may be related to the observed phenotypes induced by exercise.

Combined effects of aging and in vitro non-steroid anti-inflammatory drugs on kidney and liver mitochondrial physiology.

AIMS: Aging and drug-induced side effects may contribute to deteriorate mitochondrial bioenergetics in many tissues, including kidney and liver. One possibility is that the combination of both aging and drug toxicity accelerates the process of mitochondrial degradation, leading to progressive bioenergetic disruption. We therefore analyzed in vitro kidney (KM) and liver (LM) mitochondrial response to salicylate and diclofenac in old and adult animals. MAIN METHODS: Male-Wistar adult (19-wks) and aged (106-wks) rats were used. In vitro endpoints of oxygen consumption and membrane potential were evaluated in non-treated conditions (vehicle) and in the presence of salicylate (0.5mM) and diclofenac (50µM). The susceptibility to calcium-induced permeability transition pore (MPTP) was assessed. Aconitase and C, -SH and MDA contents were measured. Apoptotic signaling was followed by measuring caspase 3, 8 and 9 activities, Bax, Bcl2 and CypD expression. ANT content was semi-quantified. KEY FINDINGS: In general, animal age alone compromised KM state 3 and LM ADP lag phase while resulting in decreased resistance to the MPTP. Aging decreased LM CypD and increased Mn-SOD. Kidney caspase 9-like activity was lower in aged group. Salicylate and diclofenac induced KM and LM dysfunction. ADP lag phase in KM was further increased in the aged group in the presence of diclofenac. No further impairments were observed regarding drug toxicity adding to the aging process. SIGNIFICANCE: Aging impaired KM and LM function despite no detected alterations on oxidative stress and apoptosis. However, aging did not further exacerbate KM and LM frailty induced by salicylate and diclofenac.

Intracyclic velocity variation and arm coordination assessment in swimmers with Down syndrome.

This study examined the differences in intracycle velocity variation and arm coordination in front crawl in swimmers with Down syndrome in three breathing conditions. International swimmers with Down syndrome (N = 16) performed 3 × 20 m front crawl at 50 m race speed: without breathing, breathing to the preferred side, and breathing to the nonpreferred side. A two dimensional video movement analysis was performed using the APASystem. Breathing conditions were compared using Repeated Measures ANOVA. Swimming velocity was higher without breathing and intracyclic velocity variation was higher while breathing. Swimmers tended to a catch up arm coordination mode for both breathing conditions and a superposition mode when not breathing. These data reflect arm coordination compromising swimming performance, particularly when comparing with non disabled swimmers in literature. The physical and perhaps cognitive impairment associated with Down syndrome may result in a disadvantage in both propulsion and drag, more evident when breathing.

Physical exercise as a possible strategy for brain protection: evidence from mitochondrial-mediated mechanisms.

Aging and neurodegenerative conditions such as Alzheimer and Parkinson diseases are characterized by tissue and mitochondrial changes that compromise brain function. Alterations can include increased reactive oxygen species production and impaired antioxidant capacity with a consequent increase in oxidative damage, mitochondrial dysfunction that compromises brain ATP production, and ultimately increased apoptotic signaling and neuronal death. Among several non-pharmacological strategies to prevent brain degeneration, physical exercise is a surprisingly effective strategy, which antagonizes brain tissue and mitochondrial dysfunction. The present review aims to discuss the role of physical exercise in the modulation of the mechanisms involved in neuroprotection including the activation of signaling pathways underlying brain protection.