Motor Cognitive Function Research Articles

Clinically meaningful improvements after gene therapy for aromatic L-amino acid decarboxylase deficiency (AADCd) in the Peabody Developmental Motor Scale, Second Edition (PDMS-2) and correlation with Bayley-III scores and motor milestones

BackgroundAromatic L-amino acid decarboxylase deficiency (AADCd) is a rare genetic disorder characterized by movement disorders, motor and autonomic dysfunction, and developmental delays. The gene therapy eladocagene exuparvovec has become available in some regions; pooled clinical trial results demonstrate continuous long-term improvement in motor development and cognitive function. We sought to characterize clinically meaningful change in motor function, as measured by Total Peabody Developmental Motor Scales-Second Edition (PDMS-2) score, and assess correlations with cognition and language domains of the Bayley-III and motor milestone (MM) achievement.MethodsData from N = 30 patients from three single-arm clinical studies of eladocagene exuparvovec were analyzed. Anchor-based estimation of the meaningful score difference (MSD) of Total PDMS-2 score was conducted using mean-difference and receiver operating characteristic curve (ROC) approaches. MM achievement served as the anchor defining meaningful change.ResultsAn MSD of 40 points for Total PDMS-2 score was selected for analysis as it yielded specificity > 0.95 using the ROC approach, and generally aligned with the mean-difference approach. Cumulative incidence analysis reflected that 50% of patients treated with eladocagene exuparvovec may achieve the MSD of 40-point change in Total PDMS-2 score at 6 months, and 86% at 18 months. Correlations between measures were of large magnitude and improved over time (Month 6: r = 0.599 [p = 0.0032]; Month 18: r = 0.796 [p = 0.0002]; Month 60: r = 0.861 [p = 0.0007]).ConclusionsThe MSD of 40 points for Total PDMS-2 score enables the interpretation of changes observed in patients with AADCd, and suggests that treatment with eladocagene exuparvovec leads to significant improvements in motor and cognitive function.

Exploring Motor–Cognitive Interference Effects and the Influence of Self-Reported Physical Activity on Dual-Task Walking in Parkinson’s Disease and Healthy Older Adults

Introduction: Parkinson’s disease (PD) is characterized by motor and cognitive impairments that often manifest as distinct motor subtypes: Postural Instability Gait Difficulty (PIGD) and Tremor-Dominant (TD). Motor–cognitive interference, especially under dual-task (DT) walking conditions, may vary by subtype, providing insights into specific impairments. This study explored DT interference effects in PD subtypes, focusing on the potential impact of self-reported physical activity, which may help mitigate subtype-specific impairments and improve motor–cognitive function. Methods: PD patients classified as PIGD or TD and healthy controls completed single-task (ST) and DT walking assessments involving different cognitive tasks (Serial Subtraction, Auditory Stroop, and Clock Task). Physical activity levels were evaluated using the CHAMPS questionnaire, analyzing the self-reported frequency and duration of weekly exercise-related activities. Results: Interference effects were significantly different between PD patients and controls, with the PIGD group showing greater motor impairment under high cognitive load, primarily affecting gait, than the TD and control groups. Performance differences between groups diminished as cognitive load increased. Self-reported physical activity does not significantly moderate motor performance under DT conditions, suggesting that activity levels in this sample are insufficient to offset motor–cognitive interference. However, like group affiliation, physical activity directly influences motor performance during DT conditions, indicating that both factors independently impact motor–cognitive function in PD. Discussion: These findings suggest that DT assessments help differentiate PD motor subtypes, as group differences were minimal in ST conditions. While physical activity is associated with general improvements in motor ST and DT performance in PD and controls, the lack of a significant moderating effect from self-reported exercise-related physical activity indicates that current activity levels may not be high enough to counter motor–cognitive interference. More intensive or DT-specific exercise may be required to reduce interference effects. Future research should examine the role of structured physical activity programs, potentially incorporating DT training, to evaluate their impact on motor–cognitive interference in PD.

The impact of sociodemographic, psychological, and quality of life factors on dual-task performance in elderly individuals: a cross-sectional study in Iraq

Objective This study aims to explore how sociodemographic, psychological, and quality of life factors impact dual-task performance among elderly individuals in Iraq. Methods This cross-sectional study included 384 healthy community-dwelling participants aged 60 years and over, recruited from Najaf, Iraq. Data were collected using the Depression Anxiety Stress Scales-21 (DASS-21), Mindful Attention Awareness Scale (MAAS), and the World Health Organization Quality of Life Brief Form (WHOQOL-BREF). Dual-task performance was assessed using the Nine-Hole Peg Test (NHPT) combined with a cognitive task of counting backward by threes. Correlation and multivariate regression analyses were conducted to determine the predictors of cognitive dual-task performance. Results Among the WHOQOL domains, only physical health significantly predicted dual-task performance for both dominant and non-dominant hands (β = 0.234, p = 0.041; β = 0.263, p = 0.025, respectively), underscoring the importance of physical well-being in cognitive-motor functions. Psychological factors (depression, anxiety, and stress) measured by DASS-21 did not significantly predict dual-task performance. The model explained a small part of the variance in dual-task performance, suggesting that other factors may influence these abilities in elderly individuals. Conclusion While psychological factors measured by DASS-21 did not significantly impact dual-task performance, the overall quality of life remained essential. These insights can inform the design of elderly care programs.

Key shifts in frontoparietal network activity in Parkinson’s disease

We aimed to study the effect of Parkinson’s disease (PD) and motor-cognitive load on the interplay between activation level and spatial complexity. To that end, 68 PD patients and 30 controls underwent electroencephalography (EEG) recording while executing visual single- and dual- Go/No-go tasks. The EEG underwent source localization, followed by parcellation of the neural activity into 116 regions of interest. We observed alterations in activity within a distributed network of brain areas associated with attention and inhibition operations, including a circuit pathway connecting frontal and temporal/parietal regions and the limbic network. The alterations in activity were associated with task complexity (single- or dual- task) and group (PD or controls) and encompassed spatial, temporal and spectral dimensions. These results elucidate electrophysiological alterations in four core aspects of brain activity associated with motor-cognitive function in PD patients and hold potential implications for future studies involving adaptive electrical interventions.

Effect of Therapeutic Diet Along with Special Physiotherapy Program on Gross Motor Development and Cognitive Function in Autistic Children: A Randomized Controlled Trial

Children with autism spectrum disorder (ASD) experience negative effects on their everyday activities due to cognitive and motor disabilities. Physiotherapy treatment plans aim to reduce body structure and function impairments, promote developmental sequence, and facilitate milestones, while gluten-free casein-free (GFCF) diets have been proven effective in improving autism symptoms. So, the purpose of this study was to investigate the effect of a combined GFCF diet and neurodevelopmental (NDT) physical therapy program on the gross motor development and cognition of children with ASDs. Eighty children with ASD were distributed into four groups: A, for diet intervention; B, for physical therapy; C, for combined diet and physical therapy; and D was the control group. The evaluation was performed using gross motor functional measures and Stanford–Binet V5 before and after intervention. Intervention continued for 3 months for the children with ASD in the Jazan region, Kingdom of Saudi Arabia. Group A showed non-significant change for both gross motor (P = 0.89) and cognition (P = 0.53) functions, Groups B and C revealed significant improvement for both gross motor [mean difference (MD) = −12.77, 14.61] and cognition (MD = −14.2, 14.55), respectively, with (P = 0.001), and finally Group D showed no significant change for both gross motor (P = 0.65) and cognition (P = 0.16). Gross motor development and cognitive function of children with ASD significantly improved with the combination of the GFCF diet and NDT physical therapy program, with significant improvement with the NDT physical therapy alone on gross motor development and cognition, while using the GFCF diet alone had no change.

Correlation between motor symptoms, cognitive function, and optical coherence tomography findings in Parkinson's disease.

This study aimed to evaluate the total macular thickness as well as the thickness of the inner and outer retinal layers in patients with Parkinson's disease. It also aimed to verify the correlation of these parameters with motor symptoms and cognitive function. A total of 46 eyes of 23 patients with Parkinson's disease and 40 eyes of 20 healthy controls were included in the study. The patients' cognitive, functional, and nonmotor symptoms were evaluated using the Katz Index of Independence and Pfeffer's Activities of Daily Living, Mini-Mental State Examination, Frontal Assessment Battery, Schwab and England Staging Scales, and Movement Disorders Society Nonmotor Symptoms Scale. The macular thickness measurements obtained via total, inner, and outer optical coherence tomography were recorded. Furthermore, the correlation of the parameters of optical coherence tomography with cognitive, functional, and nonmotor symptoms was assessed. The scores of the Katz Index of Independence and Pfeffer's Activities of Daily Living as well as the Movement Disorders Society Nonmotor Symptoms Scale were significantly lower in patients with Parkinson's disease than in healthy controls. Moreover, the former had greater total macular thickness. The temporal and inferior outer sectors were significantly greater for the ganglion cell complex thickness in patients. A significant correlation was observed between the total macular thickness and the Movement Disorder Society-Unified Parkinson's Disease Rating Scale, Parte III (MDS-UPDRS-III) values. Contrarily, there was a negative correlation between the outer macular thickness and the MDS-UPDRS-III values. Meanwhile, the total macular thickness and ganglion cell complex thickness were significantly correlated with the scores of the Mini-Mental State Examination, Schwab and England Staging Scale, Frontal Assessment Battery, and Katz Index of Independence and Pfeffer's Activities of Daily Living. In addition, the Schwab and England scale was correlated with the outer macular thickness. The total and inner macular thicknesses at the temporal and inferior outer sectors were greater in patients with Parkinson's disease than in the control group. These findings indicate that macular thickness may be greater in those with Parkinson's disease, particularly when associated with mild motor symptoms. In addition, the parameters of the total, inner, and outer optical coherence tomography were significantly associated with motor and nonmotor symptoms as well as cognitive function impairment.

Effectiveness of Distant/Remote Blessing Treatment on Cognitive-motor Function: A Randomized Double-blind Placebo-controlled Trial.

Biofield therapies can be administered in person (hands-on treatment) or remotely, and this study focuses on the latter. A literature review did not find any reports on the effectiveness of remote biofield energy /blessing therapy in enhancing cognition and motor function performance in adults. The aim of this study was to examine the effect of distant/remote blessing (biofield energy) therapy on the cognitive and motor functions in adults with self-reported neuropsychological impairments using NIH Toolbox®. The present study was a randomized, double-blind clinical trial involving 117 participants with self-reported neuropsychological impairments. These participants were stratified into three distinct groups: control, sham control, and blessing/biofield treatment as the intervention. At baseline (day 0), day 90, and day 180, NIH Toolbox® was employed to evaluate all participants' cognitive and motor function scores. In the blessing treatment group, language function score (p <0.01), working memory (p <0.0001), and episodic memory (p <0.0001) scores exhibited statistically significant differences compared to both the naïve control and sham control groups. Moreover, in the blessing intervention group, a substantial improvement was observed in locomotion (p <0.0001), standing balance (p <0.01), dexterity (p <0.01), grip strength (p <0.05), and muscle endurance (p <0.05) compared to the naïve control and sham control groups. Importantly, no adverse effects were reported during the study period. The study outcomes revealed that distant/remote blessing/biofield energy therapy is safe, non-invasive, and less expensive. It enhances cognitive-motor functions in adults with perceived neuropsychological impairments. CTRI/2022/07/043736.

The Effect of a Video‐Based Game Exercise Program on Motor Skills, Proprioception, and Cognitive Functions in Individuals With Intellectual Disabilities

Background: Individuals with intellectual disability (ID) exhibit various problems, such as attention, learning, and physical–motor difficulties. The study is aimed at investigating the effects of video game–based therapy programs on cognitive and physical functions in individuals with ID.Methods: The study, conducted through a three‐arm randomized trial, involved 45 adults aged 18–30 with mild to moderate ID. Participants were divided into three groups: Group 1 received home‐based video game–based therapy, supervised video game–based therapy, and occupational therapy–based activity training. Group 2 received video game–based therapy supervised by a therapist and an occupational therapy–based activity training program. Group 3 received occupational therapy–based activity training only. MOXO d‐CPT was used to evaluate attention; sit‐to‐stand test, joint position sense, and nine‐hole peg test were used to assess physical–motor functionality.Results: Results showed significant improvements in attention, functional performance, proprioception, and fine motor skills in all groups (p &lt; 0.05). Group 1 was superior to Group 3 in nondominant JPS‐flexion, sit‐to‐stand test, and nondominant JPS‐abduction parameters (p &lt; 0.017). When comparing Group 1 and Group 2, Group 1 was found to be more effective in the sit‐to‐stand test parameter compared to Group 2 (p &lt; 0.017), while the other parameters of the two groups were similar to each other (p &gt; 0.017). There were no significant differences between groups for different outcome measures (p &gt; 0.017).Conclusion: The study suggests that video‐based game exercises combined with occupational therapy interventions can effectively enhance cognitive functions, functional performance, proprioception, and fine motor skills in adults with ID.Trial Registration: ClinicalTrials.gov identifier: NCT06097819

Fahr's Syndrome With Hypoparathyroidism in a Patient With Schizophrenia and Iron Deficiency Anemia: A Case Report

ABSTRACTFahr's syndrome is a rare neurological disorder that shows up as calcium deposits in the brain, affecting motor control and cognitive functions. In this case report, a 45‐year‐old woman with schizophrenia was diagnosed with Fahr's syndrome, which can be challenging to diagnose due to coexisting neurological comorbidity.

RESILIENCE COMPONENTS, POSTOPERATIVE COMPLICATIONS, AND QUALITY OF LIFE DETERIORATION AFTER PANCREATECTOMY

Abstract Background Resilience, the ability to adapt positively to adversity, remains a multisystemic process with no standardized objective measurement methods. The aim of this study was to identify the association between resilience components and frailty, postoperative complications, and quality of life changes after pancreatectomy in older patients. Methods This study evaluated older patients (aged ≥ 65) scheduled for pancreatectomy between August 2020 and December 2023. Patients who underwent a Comprehensive Geriatric Assessment and signed informed consent were included. Frailty was determined by multidimensional frailty score more than 5. Neurohumoral resilience was measured using the ACTH stimulation test, cardiovascular autonomic function using orthostatic blood pressure measurement, and cognitive-motor function using dual-task gait tests. The primary outcome was postoperative complications, and the secondary outcome was the deterioration in quality of life one year after pancreatectomy. Results A total of 57 patients were included in the analysis. Among them, 17 (29.8%) were classified as frail, 10 patients (17.5%) experienced postoperative complications, and 12 patients (24.5%) had worsened quality of life after one year. Low blood pressure and slow usual gait speed was associated with frailty. Diminished cortisol responsiveness correlated with frailty and postoperative complications. Quality of life deterioration was associated with differences between dual-task (serial 7) gait speed and fast gait speed. Conclusion This study highlights the potential association between multidomain resilience components, frailty, and clinical outcomes in older patients undergoing pancreatectomy. Future research should focus on developing robust, objective, and reliable resilience metrics for clinical use.

Neuroprotective activity of alcoholic extract of Operculina turpethum roots in aluminum chloride-induced Alzheimer’s disease in rats

Alzheimer’s disease (AD) involves complex pathways leading to neuronal damage. Neurotoxicity, resulting from exposure to harmful agents such as chemotherapeutic drugs, heavy metals, dietary additives, illicit substances, and radiation, contributes to conditions like AD. This study explored the neuroprotective potential of an ethanolic extract of Operculina turpethum (EEOT) roots in rats subjected to AD induced by aluminum chloride. Wistar rats weighing between 230 to 250 g were used to investigate neuroprotective effects. Disease induction was achieved through AlCl3 treatment, while therapeutic intervention was provided with EEOT root at low and high doses. The extract was administered orally once daily, mirroring the dosing schedule of the conventional AD medication, rivastigmine. Neuroprotective outcomes were evaluated through multiple parameters, including antioxidant enzyme levels (Catalase, SOD, LPO), total brain protein content, acetylcholinesterase activity, and behavioral assessments of motor learning, spatial learning, exploratory behavior, and cognitive function. The results demonstrated that EEOT root enhanced muscle strength (rotarod test) and improved learning ability (Morri’s water maze test). Additionally, the EEOT root reduced anxiolytic-like exploration in the Hole board test. The results suggest that EEOT roots may help protect neurons, possibly mitigating the damage caused by aluminum chloride by lowering oxidative stress. This protective effect is likely linked to the preservation of normal acetylcholinesterase activity, which helps maintain cholinergic function. According to this study, EEOT roots may have applications as neuroprotective agents.

Machine Learning and Statistical Analyses of Sensor Data Reveal Variability Between Repeated Trials in Parkinson's Disease Mobility Assessments.

Mobility tasks like the Timed Up and Go test (TUG), cognitive TUG (cogTUG), and walking with turns provide insights into the impact of Parkinson's disease (PD) on motor control, balance, and cognitive function. We assess the test-retest reliability of these tasks in 262 PD participants and 50 controls by evaluating machine learning models based on wearable-sensor-derived measures and statistical metrics. This evaluation examines total duration, subtask duration, and other quantitative measures across two trials. We show that the diagnostic accuracy for distinguishing PD from controls decreases by a mean of 1.8% between the first and the second trial, suggesting that task repetition may not be necessary for accurate diagnosis. Although the total duration remains relatively consistent between trials (intraclass correlation coefficient (ICC) = 0.62 to 0.95), greater variability is seen in subtask duration and sensor-derived measures, reflected in machine learning performance and statistical differences. Our findings also show that this variability differs not only between controls and PD participants but also among groups with varying levels of PD severity, indicating the need to consider population characteristics. Relying solely on total task duration and conventional statistical metrics to gauge the reliability of mobility tasks may fail to reveal nuanced variations in movement.

Neurobehavioral Performance in Preschool Children Exposed Postnatally to Organophosphates in Agricultural Regions, Northern Thailand.

Evidence of the effects of postnatal exposure to organophosphates (OPs) on children's neurodevelopment remains limited but crucial. This cross-sectional study evaluated exposure to OPs and neurobehavioral performance in 172 preschool children. Urinary dialkyl phosphate (DAP) metabolites, biomarkers for exposure to OPs, were measured. The neurobehavioral assessments included motor skills, memory, and cognitive function, measured using the Purdue pegboard test, digit span test, object memory test, and visual-motor integration. Multiple linear regression models were employed to explore the associations between urinary DAP metabolite levels and neurobehavioral performance, adjusting for potential confounders. Findings revealed that children of farming parents had higher urinary levels of dimethylphosphate (DMP) (Beta = 0.730, 95% CI = 0.138, 1.322, p value = 0.016) and diethylphosphate (DEP) (Beta = 0.668, 95% CI = 0.044, 1.291, p value = 0.036). Additionally, high fruit consumption correlated with increased urinary DEP levels (Beta = 0.398, 95% CI = 0.063, 0.733, p value = 0.020). Critically, elevated urinary DEP was associated with poorer fine motor coordination, affecting performance in the Purdue pegboard test for the dominant hand (Beta = -0.428, 95% CI = -0.661, -0.194, p value < 0.001), the preferred hand (Beta = -0.376, 95% CI = -0.603, -0.149, p value = 0.001), and both hands (Beta = -0.524, 95% CI = -0.773, -0.276, p value < 0.001). These findings highlight the role of parental occupation and diet in children's OP exposure and suggest that OP exposure negatively impacts fine motor coordination. Targeted interventions, such as promoting organic diets, enhancing workplace safety, and ongoing biomonitoring, are vital to reduce neurodevelopmental risks for vulnerable populations.

NaHS alters synaptic plasticity proteins and enhances dendritic arborization to improve cognitive and motor deficits after traumatic brain injury in mice.

Traumatic brain injury (TBI) is a complex medical condition affecting people globally. Hydrogen sulfide (H2S) is a recently discovered gaseous mediator and is dysregulated in the brain after TBI. Sodium hydrogen sulfide (NaHS), a known donor of H2S, is beneficial in various biological processes involving aging and diseases, including injury. It is neuroprotective against oxidative stress, neuroinflammation, and other secondary injury processes. However, the NaHS-H2S system has not been investigated as a regulator of injury-mediated synaptic plasticity proteins and the underlying mechanisms after TBI. We developed a model of TBI in Swiss albino mice to study the effects of exogenous H2S, administered as NaHS. We assessed cognitive function (Barnes maze and novel object recognition) and motor function (rotarod). Brain tissue was analysed with ELISA, qRT-PCR, immunoblotting, Golgi-cox staining, and immunofluorescence. NaHS administration restored the injury-caused decline in H2S levels. Injury-mediated oxidative stress parameters were improved following NaHS. It down-regulated TBI biomarkers, ameliorated the synaptic marker proteins, and improved cognitive and motor deficits. These changes were accompanied by enhanced dendritic arborization and spine number. Restoration of N-methyl D-aspartate receptor subunits and diminished glutamate and calcium levels, along with marked changes in microtubule-associated protein 2 A and calcium/calmodulin-dependent protein kinase II, formed the basis of the underlying mechanism(s). Our findings suggest that NaHS could have therapeutic activity against TBI, as it ameliorated cognitive and motor deficits caused by changes in synaptic plasticity proteins and dendritic arborisation, in our model.

Neurodevelopment at Age 9 Years Among Children Born at 32 to 36 Weeks’ Gestation

Although children born moderate to late preterm (MLP; 32-36 weeks' gestation) have more neurodevelopmental problems compared with children born early term or later (≥37 weeks' gestation), detailed understanding of affected domains at school age is lacking. Little is known of risk factors for poorer development. To examine whether being born MLP compared with being born early term or later is associated with neurodevelopmental outcomes at age 9 years and to describe factors associated with poorer neurodevelopment in children born MLP. This prospective, longitudinal cohort study recruited children born MLP and children born early term or later with healthy birth weight (≥2500 g) at a single tertiary hospital in Melbourne, Victoria, Australia, between December 7, 2009, and March 26, 2014. Nine-year follow-up occurred between June 20, 2019, and February 27, 2024. Moderate to late preterm birth. Cognitive ability, academic performance, motor function, behavior, and social communication skills, assessed at 9-year follow-up. Group differences were estimated using linear, logistic, or quantile regression adjusted for multiple birth and socioeconomic risk. Multiple imputation was used to account for missing data. Associations of antenatal and neonatal factors and developmental delay at 2 years with poorer 9-year neurodevelopment were explored using univariable regression. Of 201 recruited children born MLP and 201 born early term or later, 159 born MLP (79.1%; 72 [45.3%] male) and 137 born early term or later (68.2%; 75 [54.7%] male) were assessed. Compared with children born early term or later, children born MLP had lower mean (SD) full-scale IQ scores (105.2 [13.6] vs 110.1 [13.0]; adjusted mean difference, -4.4 [95% CI, -7.7 to -1.0]) and poorer performance for cognitive domains, including verbal comprehension, visuospatial, and working memory. They also had poorer academic performance: pseudoword decoding (mean [SD] score, 103.0 [11.3] vs 107.3 [10.5]; adjusted mean difference, -4.0 [95% CI, -7.0 to -1.1]) and mathematics (mean [SD] score, 96.6 [14.7] vs 101.5 [14.5]; adjusted mean difference, -5.0 [95% CI, -8.8 to -1.2]). Children born MLP had similar manual dexterity to those born early term or later (mean [SD] score, 8.4 [3.5] vs 9.1 [3.4]; adjusted mean difference, -0.9 [95% CI, -1.8 to 0.04]) but more behavioral difficulties (50 of 158 [31.7%] vs 29 of 135 [21.5%]; adjusted risk ratio, 1.57 [95% CI, 1.06-2.33]). Developmental delay at 2 years was associated with poorer 9-year neurodevelopment across multiple domains. In this longitudinal cohort study of children born MLP, neurodevelopmental challenges persisted into school age. An assessment at age 2 years may assist in identifying children born MLP who are at risk of school-age impairments.

A systematic review: enhancing stroke recovery through complementary interventions-Clinical outcomes and neural activity insights.

http://www.crd.york.ac.uk/PROSPERO, identifier (ID: CRD42023455192).

Brain-computer interface applications in the aging population with Alzheimers and Parkinsons disease

Abstract. The rapidly aging population faces increasing prevalence of neurodegenerative conditions like Alzheimer's Disease (AD) and Parkinson's Disease (PD), which significantly impair cognitive and motor functions. There is an urgent need for increased research, awareness, and development of effective treatments to mitigate their impact on the affected individuals and their families. This paper delves into the history, mechanisms, and applications of brain-computer interfaces (BCIs) as innovative solutions to mitigate these impacts. BCIs enable direct brain-to-device communication, circumventing conventional neuromuscular routes. We highlight how neurofeedback and neuroplasticity facilitated by BCIs not only restore motor skills and cognitive functions but also enhance the overall quality of life for sufferers. Through applications in cognitive training, motor assistance, and advanced communication aids, BCIs present a significant promise despite the ethical and practical challenges they pose. The continual advancement of this technology promises to a future when its incorporation into treatment plans will be widely used and provide significant advantages for those with PD and AD.

Correlation between fall experience and life functions among community-dwelling older adults in Japan

This study investigated the correlation between the risk of falls and life functions, including motor function, cognitive function, and urinary disorders, among older adults residing in small cities in the metropolitan areas of Japan and evaluated the contents of fall prevention instructions. Sixty-nine older adults residing at home participated in this case-control study conducted between September and October 2019. The survey items included questions pertaining to the history of falls; grip strength; the 30-s Chair Stand Test (CS-30), Functional Reach Test (FRT), and Timed Up and Go Test (TUG) scores; mental and cognitive functions [Test Your Memory-Japanese version test (TYM-J)]; living conditions; and urination status [Core Lower Urinary Tract Symptom Score (CLSS)]. Participants with a history of falls had significantly lower CS-30 and FRT scores, and significantly higher TUG scores and CLSS than those with no history of falls. Grip strength bore significant correlations with the CS-30 and TUG scores. The CS-30 scores were correlated with the FRT and TUG scores. The FRT scores were correlated with the TUG and French State Activity Index (FAI) scores. The TUG scores were correlated with the TYM-J and FAI scores. The CLSS showed no significant correlations with the remaining items. The FRT scores and CLSS exerted a significant effect on the risk of experiencing falls. Both balancing ability and micturition status affect fall risk and should be considered in treatment strategies for urinary disorders in fall prevention programs for older adults.

Experimental model of convulsive syndrome based on phenylcarbamate

Introduction. Carbamates are widely used in the pharmaceutical industry, agriculture, and household chemicals. Being reversible cholinesterase inhibitors, carbamates can cause the development of generalized convulsive syndrome. Untimely treatment contributes to the emergence of persistent neurological disorders. In order to develop and adequately assess in preclinical studies the specific activity of new drugs for the relief of convulsive syndrome in acute intoxication with this group of substances, an easily reproducible experimental model of convulsive carbamate-induced syndrome is required.Objective. Development of an experimental model of generalized convulsive syndrome in rats using phenylcarbamate as a model toxicant for testing in preclinical studies of therapies for poisoning with cholinesterase inhibitors.Materials and methods. The study was performed using mongrel sexually mature male rats, aged 3 months (80 animals), divided into 4 groups (3 experimental and 1 control). At the first stage, the parameters of convulsive syndrome caused by model toxicants were compared: phenylcarbamate 1 mg/kg bw, corazol 65 mg/kg bw, and thiosemicarbazide 8 mg/kg bw. The following parameters were studied: motor activity (open field test), neuromotor functions (grip strength test), cognitive functions (conditioned avoidance responses, CAR), and cardiovascular indicators (ECG and cardiac rhythmogram assessment). The severity of the convulsive syndrome was identified by Racine stages. Additionally, the structure of brain tissues was evaluated by histological methods. second stage, biochemical parameters were studied in three experimental (with toxicants) and control groups. Some biochemical parameters were studied in the blood serum, assessing the function of the liver, kidneys, prooxidant and antioxidant systems. At the third stage, the activity of cholinesterase in the blood and brain was studied in 30 control and 30 experimental rats after phenylcarbamate exposure. Statistical processing of the results was carried out using Statistica v.10.Results. When modeling convulsive syndrome in rats, phenylcarbamate is comparable to corazol in terms of the onset of the latency period, duration and intensity of seizures. When implementing the model, a significant decrease in heart rate was recorded 48 h after administration. The CAR test found that the introduced substance increases the time of the first entry into the dark compartment before training. Significant changes in markers of liver function (ALT, bilirubin, cholesterol, triglycerides), lipid peroxidation and the antioxidant system (MDA, GPx) confirm the complexity of mechanisms responsible for the development of seizures and neurological disorders. The results of histological examination of brain tissues indicate that phenylcarbamate induces pronounced disorders of the brain structure in an experiment on rats.Conclusions. The developed experimental model of phenylcarbamate-based convulsive syndrome in rats is easy to reproduce, thus being recommended for preclinical studies of new drugs for the relief of convulsive syndrome in poisoning with cholinesterase inhibitors.

In Vivo Expression of an SCA27A-linked FGF14 Mutation Results in Haploinsufficiency and Impaired Firing of Cerebellar Purkinje Neurons.

Autosomal dominant mutations in FGF14 , which encodes intracellular fibroblast growth factor 14 (iFGF14), underlie spinocerebellar ataxia type 27A (SCA27A), a devastating multisystem disorder resulting in progressive deficits in motor coordination and cognitive function. Mice lacking iFGF14 ( Fgf14 -/- ) exhibit similar phenotypes, which have been linked to iFGF14-mediated modulation of the voltage-gated sodium (Nav) channels that control the high frequency repetitive firing of Purkinje neurons, the main output neurons of the cerebellar cortex. To investigate the pathophysiological mechanisms underlying SCA27A, we developed a targeted knock-in strategy to introduce the first point mutation identified in FGF14 into the mouse Fgf14 locus ( Fgf14 F145S ), we determined the impact of in vivo expression of the mutant Fgf14 F145S allele on the motor performance of adult animals and on the firing properties of mature Purkinje neurons in acute cerebellar slices. Electrophysiological experiments revealed that repetitive firing rates are attenuated in adult Fgf14 F145S/+ cerebellar Purkinje neurons, attributed to a hyperpolarizing shift in the voltage-dependence of steady-state inactivation of Nav channels. More severe effects on firing properties and Nav channel inactivation were observed in homozygous Fgf14 F145S/F145S Purkinje neurons. Interestingly, the electrophysiological phenotypes identified in adult Fgf14 F145S/+ and Fgf14 F145S/F145S cerebellar Purkinje neurons mirror those observed in heterozygous Fgf14 +/- and homozygous Fgf14 -/- Purkinje neurons, respectively, suggesting that the mutation results in the loss of the iFGF14 protein. Western blot analysis of lysates from adult heterozygous Fgf14 F145S/+ and homozygous Fgf14 F145S/F145S animals revealed reduced or undetectable, respectively, iFGF14 expression, supporting the hypothesis that the mutant allele results in loss of the iFGF14 protein and that haploinsufficiency underlies SCA27A neurological phenotypes.