Association Between Depressive Symptoms, Cognitive Status, and the Dual-Task Performance Index in Older Adults: A Cross-Sectional Study.

The Performance Index (P-Index) is a measure for evaluating mobility-related dual-task performance in older adults. The identification of specific clinicodemographic factors predictive of P-Index scores, however, remains unclear. This cross-sectional study analyzed data from 120 community-dwelling older adults (average age 71.3 ± 11.23 years) to explore clinicodemographic variables that influence P-Index scores during the instrumented timed up and go test. Unadjusted analyses suggested several factors, including age, gender, body mass index, Mini-Mental Status Examination scores, functional reach test performance, history of falls, ethnicity, Geriatric Depression Scale scores, alcohol consumption, and educational levels, as potential predictors of P-Index. However, adjusted multinomial multiple regression analysis revealed Geriatric Depression Scale and Mini-Mental Status Examination scores as the exclusive independent predictors of P-Index classifications, segmented into high, intermediate, or low (percentiles ≤ 25, 26-74, or ≥ 75, respectively). A significant association was observed between the manifestation of depressive symptoms, lower Mini-Mental Status Examination scores, and reduced cognitive-motor performance. The findings implicate depressive symptoms and low cognitive performance as substantial impediments to optimal dual-task mobility within this cohort. Further studies are warranted to examine the efficacy of cognitive stimulation and antidepressant therapy, in augmenting mobility-related dual-task performance among older adults.

The 180° Turn Phase of the Timed Up and Go Test Better Predicts History of Falls in the Oldest-Old When Compared With the Full Test: A Case-Control Study.

The 180° turn phase of the test may better differentiate the oldest-old regarding their history of falls. This is a case-control study designed to detect the ability of the 180° turn timed up and go (TUG) phase to detect a history of falls in the oldest-old. Sixty people aged 85 years and older were assessed in their homes. The single-task and dual-task TUG tests were performed using an inertial sensor (G-Walk). Sociodemographic data, physical activity levels, mental status, depressive symptoms, concern for falls occurrence, number of medicines in use, self-perception of balance, and the functional reach test were also assessed. The logistic regressions revealed the 180° turn phase of both the single-task and dual-task TUG was almost three times better than the full TUG test to detect a history of falls, thus providing insights that can be used to better assess functional mobility in the oldest-old.

Influence of Different Dual-Task Conditions During Straight or Curved Walking on Gait Performance of Physically Active Older Women With Cognitive Decline.

Real-world walking requires shifting attention from different cognitive demands to adapt gait. This study aims to evaluate the effect of dual tasking on spatiotemporal gait parameters of older adults. Participants were asked to perform a primary complex single-walking task, consisting of a fast-paced linear and a curved gait. Primary task was performed separately and simultaneously with different motor and cognitive secondary tasks. Spatiotemporal gait parameters, walk ratio, and walk stability ratio were measured. Apart from stride length, which stood relatively unchanged, gait speed and cadence were strongly affected by cognitive dual tasking. Cadence seems to be the most impacted by dual tasking during curved gait as it combines challenges of both primary and secondary tasks. Also, during curved phase, walking ratio was significantly lower and stability ratio was greater demonstrating that participants adopted a cautious gait where maintenance of stability took preference over efficiency.

Experimental Post-traumatic Stress Disorder Decreases Astrocyte Density and Changes Astrocytic Polarity in the CA1 Hippocampus of Male Rats.

Post-traumatic stress disorder (PTSD) is a psychiatric condition resulting from exposure to a traumatic event. It is characterized by several debilitating symptoms including re-experiencing the past trauma, avoidance behavior, increased fear, and hyperarousal. Key roles in the neuropathology of PTSD and its symptomatology have been attributed to the hippocampus and amygdala. These regions are involved in explicit memory processes and context encoding during fear conditioning. The aim of our study was to investigate whether PTSD is capable of altering the morphology, density and expression of glial fibrillary acidic protein (GFAP) in astrocytes from the CA1 region of the hippocampus and the medial amygdala and correlate the data obtained with the orientation index of the polarity of astrocytes. Thirty male rats were divided in two groups: control (n = 15) and PTSD (n = 15). The inescapable shock protocol, in which the animals are exposed to a single episode of footshock, was used to induce PTSD. Our results show that, in the hippocampus, PTSD is capable of decreasing the density of GFAP+ astrocytes as well as altering astrocytic morphology, as shown by the reductions observed in the total number of primary processes, in the number of primary processes in the lateral quadrants, and the degree of branching in the lateral quadrants. The analysis of the orientation index indicates that PTSD alters the polarity of hippocampal astrocytes. No alterations were observed in the amygdala astrocytes. Therefore, this study demonstrates notable changes in hippocampal astrocytes, supporting the concept that these cells play an important role in PTSD symptomatology.

Antidepressant Effects of Ketamine Are Not Related to ¹8F-FDG Metabolism or Tyrosine Hydroxylase Immunoreactivity in the Ventral Tegmental Area of Wistar Rats.

Major depressive disorder (MDD) is an important health problem that is often associated to stress. One of the main brain regions related to MDD is the ventral tegmental area (VTA), a dopaminergic center, part of the reward and motivation circuitry. Recent studies show that changes to VTA dopaminergic neurons are associated with depression and treatment. Ketamine has recently shown a fast, potent antidepressant effect in acute, sub-anesthetic doses. Thus, our aims were to elucidate if ketamine would be able to revert depression-like behaviors induced by a chronic unpredictable stress (CUS) protocol and if it could cause alterations to metabolism and tyrosine hydroxylase (TH)-immunoreactivity in VTA. For this, 48 Wistar rats were divided into four groups: control + saline (CTRL + SAL), control + ketamine (CTRL + KET), CUS + saline (CUS + SAL), CUS + ketamine (CUS + KET). The CUS groups underwent 28 days of CUS protocol. Saline or ketamine (10 mg/kg) was administered intraperitonially once on day 28. The behavior was assessed by the sucrose preference test, the open field test, and the forced swim test. Glucose brain metabolism was assessed and quantified with microPET. TH-immunoreactivity was assessed by estimating neuronal density and regional and cellular optical densities. A decrease in sucrose intake in the CUS groups and an increase in immobility was rapidly reverted by ketamine (p < 0.05). No difference was observed in the open field test. There was no alteration to VTA metabolism and TH-immunoreaction. These results suggest that the depressive-like behavior induced by CUS and the antidepressant effects of ketamine are unrelated to changes in neuronal metabolism or dopamine production in VTA.

Neural underpinnings of fine motor skills under stress and anxiety: A review.

This review offers a comprehensive examination of how stress and anxiety affect motor behavior, particularly focusing on fine motor skills and gait adaptability. We explore the role of several neurochemicals, including brain-derived neurotrophic factor (BDNF) and dopamine, in modulating neural plasticity and motor control under these affective states. The review highlights the importance of developing therapeutic strategies that enhance motor performance by leveraging the interactions between key neurochemicals. Additionally, we investigate the complex interplay between emotional-cognitive states and sensorimotor behaviors, showing how stress and anxiety disrupt neural integration, leading to impairments in skilled movements and negatively impacting quality of life. Synthesizing evidence from human and rodent studies, we provide a detailed understanding of the relationships among stress, anxiety, and motor behavior. Our findings reveal neurophysiological pathways, behavioral outcomes, and potential therapeutic targets, emphasizing the intricate connections between neurobiological mechanisms, environmental factors, and motor performance.

Environmental Enrichment in Stroke Research: an Update.

Environmental enrichment (EE) refers to different forms of stimulation, where the environment is designed to improve the levels of sensory, cognitive, and motor stimuli, inducing stroke recovery in animal models. Stroke is a leading cause of mortality and neurological disability among older adults, hence the importance of developing strategies to improve recovery for such patients. This review provides an update on recent findings, compiling information regarding the parameters affected by EE exposure in both preclinical and clinical studies. During stroke recovery, EE exposure has been shown to improve both the cognitive and locomotor aspects, inducing important neuroplastic alterations, increased angiogenesis and neurogenesis, and modified gene expression, among other effects. There is a need for further research in this field, particularly in those aspects where the evidence is inconclusive. Moreover, it is necessary refine and adapt the EE paradigms for application in human patients.

The Stroke Self-Efficacy Questionnaire Brazil (SSEQ-B): a structural validity analysis.

BACKGROUND: Self-efficacy has been shown to play an important role in rehabilitation outcomes of stroke patients. The Stroke Self-Efficacy Questionnaire Brazil (SSEQ-B) is designed to assess self-efficacy of functional performance after stroke. OBJECTIVE: This research sought to address the structural validity of the SSEQ-B using exploratory and confirmatory factorial analyses. METHODS: This is a cross-sectional study. We performed a reliability assessment and structural validation of the SSEQ-B in 115 Brazilian stroke survivors living in Rio Grande do Sul or São Paulo. Results: Sample mean age was 62.7 ± 14.2 years. Internal consistency presents a Cronbach's Alpha (αC) of 0.829. Exploratory factorial analysis using the scree plot method revealed a bifactorial structure, consisting of activity and self-management domains. While confirmatory factorial analysis suggested a trifactorial structure, the loading ranges between factors 1 and 3 were very similar, suggesting they could be collapsed - resulting in the same factors found in the scree plot analysis. Both structures with subscales showed good construct validity. CONCLUSION: SSEQ-B is a valid and reliable measure of stroke self-efficacy. The preferred structure of the SSEQ-B is bifactorial and includes the domains activity and self-management.

Can anxiety-like behavior and spatial memory predict the extremes of skilled walking performance in mice? An exploratory, preliminary study.

Introduction: Skilled walking is influenced by memory, stress, and anxiety. While this is evident in cases of neurological disorders, memory, and anxiety traits may predict skilled walking performance even in normal functioning. Here, we address whether spatial memory and anxiety-like behavior can predict skilled walking performance in mice. Methods: A cohort of 60 adult mice underwent a behavioral assessment including general exploration (open field), anxiety-like behavior (elevated plus maze), working and spatial memory (Y-maze and Barnes maze), and skilled walking performance (ladder walking test). Three groups were established based on their skilled walking performance: superior (SP, percentiles ≥75), regular (RP, percentiles 74-26), and inferior (IP, percentiles ≤25) performers. Results: Animals from the SP and IP groups spent more time in the elevated plus maze closed arms compared to the RP group. With every second spent in the elevated plus maze closed arms, the probability of the animal exhibiting extreme percentiles in the ladder walking test increased by 1.4%. Moreover, animals that spent 219 s (73% of the total time of the test) or more in those arms were 4.67 times more likely to exhibit either higher or lower percentiles of skilled walking performance. Discussion: We discuss and conclude anxiety traits may influence skilled walking performance in facility-reared mice.

Conventional Mirror Therapy versus Immersive Virtual Reality Mirror Therapy: The Perceived Usability after Stroke.

Background: Stroke is a widespread and complex health issue, with many survivors requiring long-term rehabilitation due to upper-limb impairment. This study is aimed at comparing the perceived usability of two feedback-based stroke therapies: conventional mirror therapy (MT) and immersive virtual reality mirror therapy (VR). Methods: The study involved 45 participants, divided into three groups: the stroke survivors (n = 15), stroke-free older adults (n = 15), and young controls (n = 15). Participants performed two tasks using both MT and VR in a semirandom sequence. Usability instruments (SUS and NASA-TLX) were applied at the end of the activities, along with two experience-related questions. Results: The results indicated that both MT and VR had similar levels of perceived usability, with MT being more adaptable and causing less overall discomfort. Conversely, VR increased the perception of task difficulty and prevented participants from diverting their attention from the mirror-based feedback. Conclusion: While VR was found to be less comfortable than MT, both systems exhibited similar perceived usability. The comfort levels of the goggles may play a crucial role in determining the usability of VR for upper limb rehabilitation after stroke.

The Foot Fault Scoring System to Assess Skilled Walking in Rodents: A Reliability Study.

The foot fault scoring system of the ladder rung walking test (LRWT) is used to assess skilled walking in rodents. However, the reliability of the LRWT foot fault score has not been properly addressed. This study was designed to address this issue. Two independent and blinded raters analyzed 20 rats and 20 mice videos. Each video was analyzed twice by the same rater (80 analyses per rater). The intraclass correlation coefficient (ICC) and the Kappa coefficient were employed to check the accuracy of agreement and reliability in the intra- and inter-rater analyses of the LRWT outcomes. Excellent intra- and inter-rater agreements were found for the forelimb, hindlimb, and both limbs combined in rats and mice. The agreement level was also excellent for total crossing time, total time stopped, and the number of stops during the walking path. Rating individual scores in the foot fault score system (0-6) ranged from satisfactory to excellent, in terms of the intraclass correlation indexes. Moreover, we showed that experienced and inexperienced raters can obtain reliable results if supervised training is provided. We concluded that the LRWT is a reliable and useful tool to study skilled walking in rodents and can help researchers address walking-related neurobiological questions.

Contagious depression: Automatic mimicry and the mirror neuron system - A review.

Contagious depression is a theory proposing that depression can be induced or triggered by our social environment. This theory is based on emotional contagion, the idea that affective states can be transferred during social interaction, since humans can use emotional contagion to communicate feelings and emotions in conscious and unconscious ways. This review presents behavioral, physiological, and neuroanatomical aspects of two essential contagious depression mechanisms, automatic mimicry and the mirror neuron system.

History of falls alters movement smoothness and time taken to complete a functional mobility task in the oldest-old: A case-control study.

BACKGROUND: Mobility smoothness assessed by the spectral arc length (SPARC) may reflect the complex biomechanical alterations that occur with aging and may help detect functional mobility changes after experiencing falls. Here, we sought to explore whether smoothness of angular velocities of the trunk measured using SPARC metrics in the instrumented timed-up-and-go (iTUG) test are assoacited with a history of falls in the oldest-old. METHODS: A case-control study. The sample consisted of 64 community-dwelling oldest-old individuals who underwent the following assessments: clinical and sociodemographic questionnaire, Mini Mental State Examination (MMSE), Falls Efficacy-questionnaire International (FESI), the Activities-specific Balance Confidence (ABC), Functional Reaching Test (FRT), and the iTUG test. We used an inertial measurement unit (IMU) to obtain trunk angular velocities from the IMU's gyroscope, which was used to calculate mobility smoothness (SPARC). RESULTS: Standard deviation of the mobility smoothness around the anteroposterior axis of rotation (SPARC roll SD) (OR: 6.15 / CI 95 % = 1.58-23.94) and duration (OR: 1.11 / CI 95 % = 1.09-1.22) in the full iTUG test were associated with a history of falls in oldest-old. Using solely the full iTUG duration (59.19 ± 2.18) or SPARC (61.87 ± 2.40) resulted in lower probability to detect a history of falls in comparison with the combined measurement (66.21 ± 2.50). CONCLUSION: SPARC roll SD in the full iTUG may be a relevant biomarker to detect mobility smoothness changes in the oldest-old. This study provides evidence the oldest-old with a history of falls may change their functional mobility, in terms of movement duration and smoothness.

Age-related tolerance to paraquat-induced parkinsonism in Drosophila melanogaster.

Paraquat (PQ) is a widely used herbicide that can cross the dopaminergic neuronal membrane, accumulate in mitochondria and damage complex I of the electron transport chain, leading to neuronal death. In Drosophila melanogaster, PQ exposure leads to the development of parkinsonism and is a classical model for studying Parkinson's Disease (PD). Muscle mitochondrial dysfunction, affecting survival and locomotion, is described in familial PD in D. melanogaster mutants. However, no study has shown the effects of PQ-induced parkinsonism in D. melanogaster regarding muscle ultrastructure and locomotor behavior at different ages. Thus, we evaluated survival, locomotion, and morphological parameters of mitochondria and myofibrils using transmission electron microscopy in 2 and 15-day-old D. melanogaster, treated with different PQ doses: control, 10, 50, 100, 150, and 200 mM. PQ100mM presented 100% lethality in 15-day-old D. melanogaster, while in 2-day-old animals PQ150mM produced 20% lethality. Bradykinesia was only observed in 15-day-old D. melanogaster treated with PQ10 mM and PQ50 mM. However, these results are unlikely to be associated with changes to morphology. Taken together, our data indicate pathophysiological differences between PQ-induced parkinsonism and familial parkinsonism in D. melanogaster (resultant from gene mutations), demonstrating for the first time a differential susceptibility to PQ in two developmental stages.

The Performance Index Identifies Changes Across the Dual Task Timed Up and Go Test Phases and Impacts Task-Cost Estimation in the Oldest-Old.

Introduction: Dual tasking is common in activities of daily living (ADLs) and the ability to perform them usually declines with age. While cognitive aspects influence dual task (DT) performance, most DT-cost (DT-C) related metrics include only time- or speed- delta without weighting the accuracy of cognitive replies involved in the task. Objectives: The primary study goal was to weight the accuracy of cognitive replies as a contributing factor when estimating DT-C using a new index of DT-C that considers the accuracy of cognitive replies (P-index) in the instrumented timed up and go test (iTUG). Secondarily, to correlate the novel P-index with domains of the Mini-Mental State Examination (MMSE). Methods: Sixty-three participants (≥85 years old) took part in this study. The single task (ST) and DT iTUG tests were performed in a semi-random order. Both the time taken to complete the task measured utilizing an inertial measurement unit (IMU), and the accuracy of the cognitive replies were used to create the novel P-index. Clinical and sociodemographic data were collected. Results: The accuracy of the cognitive replies changed across the iTUG phases, particularly between the walk 1 and walk 2 phases. Moreover, weighting 0.6 for delta-time (W1) and 0.4 for cognitive replies (W2) into the P-index enhanced the prediction of the MMSE score. The novel P-index was able to explain 37% of the scores obtained by the fallers in the "spatial orientation" and "attention" domains of the MMSE. The ability of the P-index to predict MMSE scores was not significantly influenced by age, schooling, and number of medicines in use. The Bland-Altman analysis indicated a substantial difference between the time-delta-based DT-C and P-index methods, which was within the limits of agreement. Conclusions: The P-index incorporates the accuracy of cognitive replies when calculating the DT-C and better reflects the variance of the MMSE in comparison with the traditional time- or speed-delta approaches, thus providing an improved method to estimate the DT-C.

Early environmental enrichment rescues memory impairments provoked by mild neonatal hypoxia-ischemia in adolescent mice.

Hypoxia-ischemia (HI) is a consequence of a lack of oxygen and glucose support to the developing brain, which causes several neurodevelopmental impairments. Environmental enrichment (EE) is considered an option to recover the alterations observed in rodents exposed to HI. The aim of this study was to investigate the impact of early EE on memory, hippocampal volume and brain-derived neurotrophic factor (Bbnf) and glucocorticoid receptor (Nr3c1) gene expression of mice exposed to HI. At P10, pups underwent right carotid artery permanent occlusion followed by 35 min of 8% O2 hypoxic environment. Starting at P11, animals were reared in EE or in standard cage (HI-SC or SHAM-SC) conditions until behavioral testing (P45). SHAM pups did not undergo carotid ligation and hypoxic exposure. Memory performance was assessed in the Y-maze, Novel object recognition, and Barnes maze. Animals were then sacrificed for analysis of hippocampal volume and Bdnf and Nr3c1 gene expression. We observed that animals exposed to HI performed worse in all three tests compared to SHAM animals. Furthermore, HI animals exposed to EE did not differ from SHAM animals in all tasks. Moreover, HI decreased hippocampal volume, while animals reared in early EE were not different compared to SHAM animals. Animals exposed to HI also showed upregulated hippocampal Bdnf expression compared to SHAM animals. We conclude that early EE from P11 to P45 proved to be effective in recovering memory impairments and hippocampal volume loss elicited by HI. Nevertheless, Bdnf expression was not associated with the improvements in memory performance observed in animals exposed to EE after a hypoxic-ischemic event.

[Dance as an intervention to improve mobility and balance in elderly: a literature review]. / Dança como uma intervenção para melhorar a mobilidade e o equilíbrio em idosos: uma revisão de literatura.

The aim of the present review was to identify whether dance protocols can benefit mobility and balance in elderly. A literature review was conducted in which 927 potentially relevant studies were identified (published in Portuguese, English, French, German, Spanish or Italian). There was no publication period restriction. After reading the titles, abstracts and review of the exclusion criteria, 15 randomized controlled trials were included. Most of the studies evaluated female subjects, using heterogeneous protocols of intervention and unspecific control groups. In addition, the period of exposure to dance was generally short: 2.6 weekly practices, of 59.1 minutes each, performed through 12.1 weeks. Dance was shown to be beneficial in 77.6% of the evaluated outcomes, exhibiting a moderate effect size for static balance and functional balance; and small effect size for mobility and strength/resistance of the lower limbs. However, future studies with the use of specific control groups and adoption of longer lasting protocols are necessary to evaluate the actual size effect that dance has on the maintenance of mobility and balance in elderly.

SPARC Metrics Provide Mobility Smoothness Assessment in Oldest-Old With and Without a History of Falls: A Case Control Study.

Aging-related neuromuscular and neurocognitive decline induces unsmooth movements in daily functional mobility. Here, we used a robust analysis of linear and angular spectral arc length (SPARC) in the single and dual task instrumented timed up-and-go (iTUG) test to compare functional mobility smoothness in fallers and non-fallers aged 85 and older. 64 participants aged 85 and older took part in this case control study. The case group (fallers, n = 32) had experienced falls to the ground in the 6 months prior to the assessment. SPARC analyses were conducted in all phases of the single and dual task iTUGs. We also performed correlation mapping to test the relation of socio-demographic and clinical features on SPARC metrics. The magnitude of between-group differences was calculated using D-Cohen effect size (ES). SPARC was able to distinguish fallers during the single iTUG (ES ≈ 4.18). Turning while walking in the iTUG induced pronounced unsmooth movements in the fallers (SPARC ≈ -13; ES = 3.52) and was associated with the ability to maintain balance in the functional reach task. This information is of importance in the study of functional mobility in the oldest-old and to assess the efficacy of fall-prevention programs.

Neuroprotective effect of ACTH on collagenase-induced peri-intraventricular hemorrhage in newborn male rats.

Peri-intraventricular hemorrhage (PIVH) is a common and serious prematurity-related complication in neonates. Adrenocorticotropic hormone (ACTH) has neuroprotective actions and is a candidate to ameliorate brain damage following PIVH. Here, we tested the efficacy of ACTH1-24 on a collagenase-induced lesion of the germinal matrix (GM) in newborn male rats. Animals received microinjection of the vehicle (PBS, 2 µl) or collagenase type VII (0.3 IU) into the GM/periventricular tissue on postnatal day (PN) 2. Twelve hours later pups received microinjection of either the agonist ACTH1-24 (0.048 mg/kg), or the antagonist SHU9119 (antagonist of MCR3/MCR4 receptors, 0.01 mg/kg), or their combination. Morphological outcomes included striatal injury extension, neuronal and glial cells counting, and immunohistochemical expression of brain lesion biomarkers ipsilateral and contralateral to the hemorrhagic site. Data were evaluated on PN 8. Collagenase induced PIVH and severe ipsilateral striatal lesion. ACTH1-24 dampened the deleterious effects of collagenase-induced hemorrhage in significantly reducing the extension of the damaged area, the striatal neuronal and glial losses, and the immunoreactive expression of the GFAP, S100ß, and NG2-glia biomarkers in the affected periventricular area. SHU9119 blocked the glial density rescuing effect of ACTH1-24. ACTH1-24 could be further evaluated to determine its suitability for preclinical models of PVH in premature infants.

Does Angiotensin II Peak in Response to SARS-CoV-2?

Human infection by the SARS-CoV-2 is causing the current COVID-19 pandemic. With the growing numbers of cases and deaths, there is an urgent need to explore pathophysiological hypotheses in an attempt to better understand the factors determining the course of the disease. Here, we hypothesize that COVID-19 severity and its symptoms could be related to transmembrane and soluble Angiotensin-converting enzyme 2 (tACE2 and sACE2); Angiotensin II (ANG II); Angiotensin 1-7 (ANG 1-7) and angiotensin receptor 1 (AT1R) activation levels. Additionally, we hypothesize that an early peak in ANG II and ADAM-17 might represent a physiological attempt to reduce viral infection via tACE2. This viewpoint presents: (1) a brief introduction regarding the renin-angiotensin-aldosterone system (RAAS), detailing its receptors, molecular synthesis, and degradation routes; (2) a description of the proposed early changes in the RAAS in response to SARS-CoV-2 infection, including biological scenarios for the best and worst prognoses; and (3) the physiological pathways and reasoning for changes in the RAAS following SARS-CoV-2 infection.