Effects of exergames on rehabilitation outcomes in patients with osteoarthritis. A systematic review.

PURPOSE: To analyze the effects of exergames on rehabilitation outcomes in osteoarthritis (OA) patients. MATERIALS AND METHODS: A systematic review was reported according to the PRISMA statement. Randomized controlled trials (RCTs) were searched in Pubmed, Scopus, WoS, CINAHL, and PEDro (inception to November 2023). Studies that applied non-immersive exergames and assessed physical, functional, cognitive, pain, and psychosocial outcomes were included. Comparisons were other exercise modalities and non-intervention. Methodological quality was assessed with PEDro scale, and risk of bias (RoB) was assessed with Cochrane RoB-2 tool. RESULTS: Eight studies were included (total of participants = 401). The mean PEDro score was 6.1, and seven studies had high RoB. Seven studies involved knee OA and one cervical OA. The most frequent duration for interventions was four weeks. Exergames were more effective than controls in at least one outcome in all studies. The outcomes for which exergames were most effective were functional disability, postural balance, muscle strength, proprioception, gait, range of motion, pain, quality of life, depression, and kinesiophobia. CONCLUSION: Non-immersive exergames constitute an effective strategy for optimizing several relevant outcomes in rehabilitation. However, more RCTs with high methodological quality are required to deepen the knowledge about the multidimensional effects of exergames in OA patients.

Osteoarthritis (OA) is one of the leading causes of disability, involving high health costs and a public health problem.Physical exercise has recently been recognized as a first-line treatment in OA to reduce symptomatology and to improve or maintain physical functioning and quality of life.Non-immersive exergames are a safe therapeutic strategy to improve functional disability, postural balance, muscle strength, proprioception, gait performance, range of motion, and pain in OA patients.Similarly, non-immersive virtual reality strategies contribute to the improvement of depression, kinesiophobia, and quality of life in people with OA.

Effect of strength training on knee proprioception in patients with knee osteoarthritis: A systematic review and meta-analysis.

Proprioception is significantly impaired in knee osteoarthritis (KOA), contributing to reduced functionality. Strength training (ST) is essential in KOA by improving muscle strength, although it may also be effective in improving proprioception. The purpose was to determine the effect of ST on knee proprioception in KOA patients. Pubmed, CINAHL, Scopus, WOS, and PEDro were searched for randomized controlled trials (RCTs) (inception to March 2023). Comparisons for ST were physical exercise different from ST, non-exercise-based interventions, and no intervention. Methodological quality was assessed using the PEDro scale, and risk of bias (RoB) using the Cochrane tool. Meta-analyses were performed by comparison groups using the standardized mean difference (SMD) (Hedge's g) with random effects models, also considering subgroups by proprioception tests. Finally, six RCTs were included. The mean PEDro score was 6.3, and the highest proportion of biases corresponds to performance, selection, and detection. The meta-analysis indicated that only when compared with non-intervention, ST significantly improved knee proprioception for the joint position sense (JPS) (active + passive), JPS (passive), and threshold to detect passive motion (TTDPM) subgroups (g â€‹= â€‹-1.33 [-2.33, -0.32], g = â€‹-2.29 [-2.82, -1.75] and g â€‹= â€‹-2.40 [-4.23, -0.58], respectively). However, in the knee JPS (active) subgroup, ST was not significant (g â€‹= â€‹-0.72 [-1.84, 0.40]). In conclusion, ST improves knee proprioception compared to non-intervention. However, due to the paucity of studies and diversity of interventions, more evidence is needed to support the effectiveness of ST. Future RCTs may address the limitations of this review to advance knowledge about proprioceptive responses to ST and contribute to clinical practice.

Exercise-induced hypoalgesia in chronic neck pain: A narrative review.

Chronic neck pain (CNP) is a worldwide health problem with several risk factors. One of the most widely used treatments for managing this condition is therapeutic exercise, which could generate a response called exercise-induced hypoalgesia (EIH). There is no consensus on the best exercise modality to induce hypoalgesia. Therefore, this review aims to analyze and synthesize the state-of-the-art about the hypoalgesic effect of exercise in subjects with CNP. We included articles on EIH and CNP in patients older than 18 years, with pain for more than three months, where the EIH response was measured. Articles that studied CNP associated with comorbidities or measured the response to treatments other than exercise were excluded. The studies reviewed reported variable results. Exercise in healthy subjects has been shown to reduce indicators of pain sensitivity; however, in people with chronic pain, the response is variable. Some investigations reported adverse effects with increased pain intensity and decreased pain sensitivity, others found no clinical response, and some even reported EIH with decreased pain and increased sensitivity. EIH is an identifiable, stimulable, and helpful therapeutic response in people with pain. More research is still needed on subjects with CNP to clarify the protocols and therapeutic variables that facilitate the EIH phenomenon. In addition, it is necessary to deepen the knowledge of the intrinsic and extrinsic factors that influence EIH in people with CNP.

Nicotinic acetylcholine receptors and learning and memory deficits in Neuroinflammatory diseases.

Animal survival depends on cognitive abilities such as learning and memory to adapt to environmental changes. Memory functions require an enhanced activity and connectivity of a particular arrangement of engram neurons, supported by the concerted action of neurons, glia, and vascular cells. The deterioration of the cholinergic system is a common occurrence in neurological conditions exacerbated by aging such as traumatic brain injury (TBI), posttraumatic stress disorder (PTSD), Alzheimer's disease (AD), and Parkinson's disease (PD). Cotinine is a cholinergic modulator with neuroprotective, antidepressant, anti-inflammatory, antioxidant, and memory-enhancing effects. Current evidence suggests Cotinine's beneficial effects on cognition results from the positive modulation of the α7-nicotinic acetylcholine receptors (nAChRs) and the inhibition of the toll-like receptors (TLRs). The α7nAChR affects brain functions by modulating the function of neurons, glia, endothelial, immune, and dendritic cells and regulates inhibitory and excitatory neurotransmission throughout the GABA interneurons. In addition, Cotinine acting on the α7 nAChRs and TLR reduces neuroinflammation by inhibiting the release of pro-inflammatory cytokines by the immune cells. Also, α7nAChRs stimulate signaling pathways supporting structural, biochemical, electrochemical, and cellular changes in the Central nervous system during the cognitive processes, including Neurogenesis. Here, the mechanisms of memory formation as well as potential mechanisms of action of Cotinine on memory preservation in aging and neurological diseases are discussed.

Self-perceived cognitive function and neuropsychological performance in women with fibromyalgia

BACKGROUND: Cognitive dysfunction is a common complain in patients with fibromyalgia (FM). Aim: To assess the perceived cognitive function and cognitive performance in women with FM. MATERIAL AND METHODS: Cross-sectional study including 100 women with FM (FMG) and 100 healthy controls (CG). Self-perceived cognitive functioning was evaluated using the Functional Assessment of Cancer Therapy Cognition scale (FACT-Cogv3). The neuropsychological performance was assessed with the Trail Making Test (TMT-A, TMT-B), Digit Span test (DS), Barcelona test (DS-F/B) and the Frontal Assessment Battery (FAB-E), Spanish version test. Results: The mean scores of all cognitive self-perception factors and all neuropsychological tests were lower in the FMG (p < 0.001). Over 90% of the FMG took longer than the population mean (P50) to complete the TMT-A and TMT-B tests, while in the CG, 1/3 took longer than the P50 in both tests. The minimum expected scores for the DS-F and DS-B tests were not achieved by 40 and 9% of FMG participants, respectively. According to FAB-E, 54% and 24% of FMG were categorized as fronto-subcortical deficit and fronto-subcortical dementia, respectively. CONCLUSIONS: Women with FM have a higher perception of cognitive dysfunction and lower cognitive performance in objective tests than healthy women. More research is needed to explore the clinical, psychosocial, and sociodemographic characteristics that predispose to cognitive deficits in this group of patients.

ANTECEDENTESA: La disfunción cognitiva es una queja común en pacientes con fibromialgia (FM). Objetivo: Investigar la función cognitiva percibida y el desempeño cognitivo en mujeres chilenas con FM. MATERIAL Y MÉTODOS: Estudio transversal incluyendo a 100 mujeres con FM (GFM) y 100 mujeres como controles sanos (GC). El funcionamiento cognitivo autopercibido se evaluó mediante la prueba Functional Assessment of Cancer Therapy Cognition scale (FACT-Cogv3). El rendimiento neuropsicológico se evaluó mediante las pruebas Trail Making Test (TMT-A, TMT-B) y Digit Span test (DS), Barcelona test (DS-F/B) y la prueba Frontal Assessment Battery, versión española (FAB-E). RESULTADOS: Las puntuaciones medias de todos los factores de autopercepción cognitiva y todas las pruebas neuropsicológicas fueron significativamente menores en el GFM. Para TMT-A y TMT-B, más del 90% del GFM tardó más que la media poblacional (P50) para completar las pruebas, mientras que en el GC aproximadamente 1/3 requirió más tiempo que el P50 en ambas pruebas. Un 40 y 9% del GFM no obtuvo la puntuación mínima esperada para las pruebas DS-F y DS-B, respectivamente. Según FAB-E, el 54% y 24% del GFM se clasificó como déficit fronto-subcortical y demencia fronto-subcortical, respectivamente. Conclusiones: Las mujeres con FM tienen una mayor percepción de disfunción cognitiva y menor rendimiento cognitivo en pruebas objetivas que mujeres sanas. Se necesita más investigación para explorar las características clínicas, psicosociales y sociodemográficas que predisponen a los déficits cognitivos en este grupo de pacientes.

Self-perceived cognitive function and neuropsychological performance in women with fibromyalgia.

BACKGROUND: Cognitive dysfunction is a common complain in patients with fibromyalgia (FM). AIM: To assess the perceived cognitive function and cognitive performance in women with FM. MATERIAL AND METHODS: Cross-sectional study including 100 women with FM (FMG) and 100 healthy controls (CG). Self-perceived cognitive functioning was evaluated using the Functional Assessment of Cancer Therapy Cognition scale (FACT-Cogv3). The neuropsychological performance was assessed with the Trail Making Test (TMT-A, TMT-B), Digit Span test (DS), Barcelona test (DS-F/B) and the Frontal Assessment Battery (FAB-E), Spanish version test. RESULTS: The mean scores of all cognitive self-perception factors and all neuropsychological tests were lower in the FMG (p < 0.001). Over 90% of the FMG took longer than the population mean (P50) to complete the TMT-A and TMT-B tests, while in the CG, 1/3 took longer than the P50 in both tests. The minimum expected scores for the DS-F and DS-B tests were not achieved by 40 and 9% of FMG participants, respectively. According to FAB-E, 54% and 24% of FMG were categorized as fronto-subcortical deficit and fronto-subcortical dementia, respectively. CONCLUSIONS: Women with FM have a higher perception of cognitive dysfunction and lower cognitive performance in objective tests than healthy women. More research is needed to explore the clinical, psychosocial, and sociodemographic characteristics that predispose to cognitive deficits in this group of patients.

Cholinergic Receptor Modulation as a Target for Preventing Dementia in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative condition characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) in the midbrain resulting in progressive impairment in cognitive and motor abilities. The physiological and molecular mechanisms triggering dopaminergic neuronal loss are not entirely defined. PD occurrence is associated with various genetic and environmental factors causing inflammation and mitochondrial dysfunction in the brain, leading to oxidative stress, proteinopathy, and reduced viability of dopaminergic neurons. Oxidative stress affects the conformation and function of ions, proteins, and lipids, provoking mitochondrial DNA (mtDNA) mutation and dysfunction. The disruption of protein homeostasis induces the aggregation of alpha-synuclein (α-SYN) and parkin and a deficit in proteasome degradation. Also, oxidative stress affects dopamine release by activating ATP-sensitive potassium channels. The cholinergic system is essential in modulating the striatal cells regulating cognitive and motor functions. Several muscarinic acetylcholine receptors (mAChR) and nicotinic acetylcholine receptors (nAChRs) are expressed in the striatum. The nAChRs signaling reduces neuroinflammation and facilitates neuronal survival, neurotransmitter release, and synaptic plasticity. Since there is a deficit in the nAChRs in PD, inhibiting nAChRs loss in the striatum may help prevent dopaminergic neurons loss in the striatum and its pathological consequences. The nAChRs can also stimulate other brain cells supporting cognitive and motor functions. This review discusses the cholinergic system as a therapeutic target of cotinine to prevent cognitive symptoms and transition to dementia in PD.

Estrogenic Plants: to Prevent Neurodegeneration and Memory Loss and Other Symptoms in Women After Menopause.

In mammals, sexual hormones such as estrogens play an essential role in maintaining brain homeostasis and function. Estrogen deficit in the brain induces many undesirable symptoms such as learning and memory impairment, sleep and mood disorders, hot flushes, and fatigue. These symptoms are frequent in women who reached menopausal age or have had ovariectomy and in men and women subjected to anti-estrogen therapy. Hormone replacement therapy alleviates menopause symptoms; however, it can increase cardiovascular and cancer diseases. In the search for therapeutic alternatives, medicinal plants and specific synthetic and natural molecules with estrogenic effects have attracted widespread attention between the public and the scientific community. Various plants have been used for centuries to alleviate menstrual and menopause symptoms, such as Cranberry, Ginger, Hops, Milk Thistle, Red clover, Salvia officinalis, Soy, Black cohosh, Turnera diffusa, Ushuva, and Vitex. This review aims to highlight current evidence about estrogenic medicinal plants and their pharmacological effects on cognitive deficits induced by estrogen deficiency during menopause and aging.

Correction to: Intranasal Cotinine Plus Krill Oil Facilitates Fear Extinction, Decreases Depressive-Like Behavior, and Increases Hippocampal Calcineurin A Levels in Mice.

The original version of this article unfortunately contained mistake in its Funding inforation.

Correction to: Cotinine: A Therapy for Memory Extinction in Post-traumatic Stress Disorder.

The original version of this article unfortunately contained mistake in its Funding inforation. That is, the Grant Number has an error currently read as "This work was supported by the Fondo de Ciencia y Tecnología (FONDECYT) de Chile, Grant #1150149".

Intranasal Cotinine Plus Krill Oil Facilitates Fear Extinction, Decreases Depressive-Like Behavior, and Increases Hippocampal Calcineurin A Levels in Mice.

Failure in fear extinction is one of the more troublesome characteristics of posttraumatic stress disorder (PTSD). Cotinine facilitates fear memory extinction and reduces depressive-like behavior when administered 24 h after fear conditioning in mice. In this study, it was investigated the behavioral and molecular effects of cotinine, and other antidepressant preparations infused intranasally. Intranasal (IN) cotinine, IN krill oil, IN cotinine plus krill oil, and oral sertraline were evaluated on depressive-like behavior and fear retention and extinction after fear conditioning in C57BL/6 mice. Since calcineurin A has been involved in facilitating fear extinction in rodents, we also investigated changes of calcineurin in the hippocampus, a region key on contextual fear extinction. Short-term treatment with cotinine formulations was superior to krill oil and oral sertraline in reducing depressive-like behavior and fear consolidation and enhancing contextual fear memory extinction in mice. IN krill oil slowed the extinction of fear. IN cotinine preparations increased the levels of calcineurin A in the hippocampus of conditioned mice. In the light of the results, the future investigation of the use of IN cotinine preparations for the extinction of contextual fear memory and treatment of treatment-resistant depression (TRD) in PTSD is discussed.

Cotinine: A Therapy for Memory Extinction in Post-traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) is a mental disorder that may develop after exposure to exceptionally threatening or unescapable horrifying events. Actual therapies fail to alleviate the emotional suffering and cognitive impairment associated with this disorder, mostly because they are ineffective in treating the failure to extinguish trauma memories in a great percentage of those affected. In this review, current behavioral, cellular, and molecular evidence supporting the use of cotinine for treating PTSD are reviewed. The role of the positive modulation by cotinine of the nicotinic acetylcholine receptors (nAChRs) and their downstream effectors, the protection of astroglia, and the inhibition of microglia in the PTSD brain are also discussed.

Cotinine Plus Krill Oil Decreased Depressive Behavior, and Increased Astrocytes Survival in the Hippocampus of Mice Subjected to Restraint Stress.

Restraint stress (RS) is a condition affecting millions of people worldwide. The investigation of new therapies to alleviate the consequences of prolonged RS is much needed. Cotinine, a nicotine-derivative, has shown to prevent the decrease in cerebral synaptic density, working memory deficits, anxiety, and depressive-like behavior after prolonged restraint stress (RS) in mice. Furthermore, post-treatment with cotinine reduced the adverse effects of chronic RS on astrocyte survival and architecture. On the other hand, the nutritional supplement krill oil (KO), has shown to be beneficial in decreasing depressive-like behavior and oxidative stress. In this study, in the search for effective preventative treatments to be used in people subjected to reduced mobility, the effect of co-treatment with cotinine plus KO in mice subjected to prolonged RS was investigated. The results show that cotinine plus KO prevented the loss of astrocytes, the appearance of depressive-like behavior and cognitive impairment induced by RS. The use of the combination of cotinine plus KO was more effective than cotinine alone in preventing the depressive-like behavior in the restrained mice. The potential use of this combination to alleviate the psychological effects of reduced mobility is discussed.

Intranasal cotinine improves memory, and reduces depressive-like behavior, and GFAP+ cells loss induced by restraint stress in mice.

Posttraumatic stress disorder (PTSD), chronic psychological stress, and major depressive disorder have been found to be associated with a significant decrease in glial fibrillary acidic protein (GFAP) immunoreactivity in the hippocampus of rodents. Cotinine is an alkaloid that prevents memory impairment, depressive-like behavior and synaptic loss when co-administered during restraint stress, a model of PTSD and stress-induced depression, in mice. Here, we investigated the effects of post-treatment with intranasal cotinine on depressive- and anxiety-like behaviors, visual recognition memory as well as the number and morphology of GFAP+ immunoreactive cells, in the hippocampus and frontal cortex of mice subjected to prolonged restraint stress. The results revealed that in addition to the mood and cognitive impairments, restraint stress induced a significant decrease in the number and arborization of GFAP+ cells in the brain of mice. Intranasal cotinine prevented these stress-derived symptoms and the morphological abnormalities GFAP+ cells in both of these brain regions which are critical to resilience to stress. The significance of these findings for the therapy of PTSD and depression is discussed.

Role of neuroinflammation and sex hormones in war-related PTSD.

The susceptibility to develop posttraumatic stress disorder (PTSD) is greatly influenced by both innate and environmental risk factors. One of these factors is gender, with women showing higher incidence of trauma-related mental health disorders than their male counterparts. The evidence so far links these differences in susceptibility or resilience to trauma to the neuroprotective actions of sex hormones in reducing neuroinflammation after severe stress exposure. In this review, we discuss the impact of war-related trauma on the incidence of PTSD in civilian and military populations as well as differences associated to gender in the incidence and recovery from PTSD. In addition, the mutually influencing role of inflammation, genetic, and sex hormones in modulating the consequences derived from exposure to traumatic events are discussed in light of current evidence.