Abnormal Motor Behavior Research Articles

A case report on schizophrenia with mild id with genetic disorder the atrophy of the left medial temporal lobe involving the hippocampal amygdala complex

Schizophrenia is a one type of chronic disorder. Schizophrenia is influenced the stigma that is why it is necessary to understand. In the various study concluded the how the schizophrenia is affected in culture. Most of the studied are find out the gender issues, socio-culture factor is related to stigma among the people in India. In the field of medical the main challenge is established genetic association of pathophysiology to understand the concept of schizophrenia. It is the characterized by abnormal motor behavior, feeling sad or worthless. Some time period of manic mood. Impaired occupational academic, delusion, hallucination, speak coherently, when u ask the question, they with the unrelated answer and negative symptoms. In India the the 3/1000 individual prevalence of the disease schizophrenia. The probably rate more chances of schizophrenia are occur in male than female is present etc. The one of the causes of occur schizophrenia abnormalities in the brain. This case report highlights a rare presentation of Atrophy of the Left medial temporal lobe involving the hippocampal amygdala complex.

Motor behavioral abnormalities and histopathological findings in middle aged male Wistar rats inoculated with cerebrospinal fluid from patients with Amyotrophic Lateral Sclerosis

• Middle-aged male rats infused with CSF mimic pathogenic mechanisms observed in ALS. • Infusion of human CSF from patients of ALS causes motor impairment in middle-aged animals. • CSF from patients of ALS is a tool to investigate the characteristics of the disease. Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease associated with loss of upper and lower motor neurons in the primary motor cortex and spinal cord, respectively. Motor deficits are the main clinical features observed in patients with the disease. However, it has been suggested that the presence of neurotoxic factors in the cerebrospinal fluid (CSF) from ALS patients causes loss of motor neurons. The present study investigated the motor and histopathological changes induced by intracerebroventricular (ICV) infusion of CSF from ALS patients in middle aged male Wistar rats. Middle aged male rats were divided into three groups: (1) control group, animals injected with artificial CSF solution; (2) N-ALS group, animals injected with CSF from volunteers without neurological disease; and (3) ALS group, animals inoculated with CFS from a patient with definite ALS. After surgical and infusion procedures, animals were evaluated in different motor tests (grip strength; catalepsy and open field tests). Moreover, animals’ spinal cords were histologically investigated. We observed that ALS-CSF infusion reduced grip strength and led to motor changes and reduction in the number of motor neurons and glial cells in thoracic and lumbar regions of spinal cord. However, CSF N-ALS caused reduction of nerve and glial cells in the thoracic but not in the lumbar region. Our data suggest that ALS-CSF is associated with neurodegenerative mechanisms observed in ALS pathology.

A Two-Phase Machine Learning Approach for Predictive Maintenance of Low Voltage Industrial Motors

Predictive maintenance and sound operating industrial equipment are essential for nearly any production plant. The absence of a systematic maintenance program and data-driven mindset in making manufacturing decisions may result in serious safety risks, unexpected equipment damages, and financial strain. Condition monitoring and predictive maintenance management systems are commonly used in tandem with the Internet of Things, linking sensors on machines and transmitting the data through a wireless network to a data-logging center that will allow further analysis and support decision making. The system described in this paper measures vibrations using sensors attached to low voltage motors and then utilizes a two-phase machine learning approach for predictive maintenance. In the first phase, we conducted an analysis to look for any abnormal behavior, and in the second phase, we attempted to determine the type of specific faults that may occur. The proposed predictive maintenance system aims to reduce the fault detection time and assist with diagnosing the type of fault occurring. We utilized and tested three machine learning algorithms to detect abnormal motor behavior: support vector machine, backpropagation neural network, and random forest. For predicting the type of specific motor faults that may occur, we used a support vector machine. This two-phase machine learning approach demonstrated promising results in detecting abnormal behavior in low voltage motors. Therefore, integrating this machine learning component as a part of a predictive maintenance system can result in high confidence about the motor condition, reduce maintenance cost, and enhance the safety of the operators and the machines.

Neuropsychological Sequelae, Quality of Life and Adaptive Behavior in Children and Adolescents with Anti-NMDAR Encephalitis: A Narrative Review.

Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is a rare autoimmune illness characterized by a constellation of often severe, but treatable, psychiatric and neurological symptoms. Whereas symptoms such as psychosis and bizarre and abnormal motor behavior are common in adults, pediatric patients typically present with behavioral changes, irritability and sleep dysfunction. The recovery phase is usually slow and may be associated with longstanding adaptive, behavioral and neuropsychological problems. Very few studies explored the cognitive and adaptive sequelae in children with anti-NMDAR encephalitis. The present review article suggests that, although most children and adolescents return to their daily life and previous activities, they may have a low quality of life and show neuropsychological sequelae involving language, memory, especially verbal memory, and attentional resources, even after several months from the hospital discharge. In particular, the available results reveal difficulties in cognitive skills involving executive functions. This impairment is considered the “core” of the cognitive profile of young patients with anti-NMDAR encephalitis. On the other hand, some cognitive skills, such as general intelligence, show good overall recovery over time. Additional neuropsychological research evaluating larger samples, more homogenous methods and longitudinal studies is required.

Biallelic variants in HPDL cause pure and complicated hereditary spastic paraplegia.

Human 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) is a putative iron-containing non-heme oxygenase of unknown specificity and biological significance. We report 25 families containing 34 individuals with neurological disease associated with biallelic HPDL variants. Phenotypes ranged from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spasticity and global developmental delays, sometimes complicated by episodes of neurological and respiratory decompensation. Variants included bona fide pathogenic truncating changes, although most were missense substitutions. Functionality of variants could not be determined directly as the enzymatic specificity of HPDL is unknown; however, when HPDL missense substitutions were introduced into 4-hydroxyphenylpyruvate dioxygenase (HPPD, an HPDL orthologue), they impaired the ability of HPPD to convert 4-hydroxyphenylpyruvate into homogentisate. Moreover, three additional sets of experiments provided evidence for a role of HPDL in the nervous system and further supported its link to neurological disease: (i) HPDL was expressed in the nervous system and expression increased during neural differentiation; (ii) knockdown of zebrafish hpdl led to abnormal motor behaviour, replicating aspects of the human disease; and (iii) HPDL localized to mitochondria, consistent with mitochondrial disease that is often associated with neurological manifestations. Our findings suggest that biallelic HPDL variants cause a syndrome varying from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spastic tetraplegia associated with global developmental delays.

Motor development of infants (6-12 months) with low birth weight.

The aim of this study was to describe the motor development (MD) and growth of infants born with low birth weight (LBW) versus adequate birth weight (ABW) by using the Alberta Infant Motor Scale (AIMS). The cross-sectional study including LBW infants (aged 6-12 months) followed at an outpatient clinic from a University Hospital in Brazil and a group of infants of the same age with ABW. The variables were recorded as maternal, birth, and infant conditions. The infants were assessed for MD using the AIMS. In total, 98 infants (38 LBW versus 60 ABW) were evaluated and no statistically significant differences were found in demographic characteristics and in the AIMS results. The AIMS results of the total sample were suspicious or abnormal MD in 44 (45%) of total infants. Higher frequency of suspected or abnormal motor behavior was found in the age group between 9 and 12 (54.6%) months. A frequency of 45% of suspected or abnormal behavior was observed in the evaluated infants, with a higher frequency of occurrence in those aged 9-12 months (54.6%).

Deletion of Mea6 in Cerebellar Granule Cells Impairs Synaptic Development and Motor Performance.

The cerebellum is conceptualized as a processor of complex movements. Many diseases with gene-targeted mutations, including Fahr’s disease associated with the loss-of-function mutation of meningioma expressed antigen 6 (Mea6), exhibit cerebellar malformations, and abnormal motor behaviors. We previously reported that the defects in cerebellar development and motor performance of Nestin-Cre;Mea6F/F mice are severer than those of Purkinje cell-targeted pCP2-Cre;Mea6F/F mice, suggesting that Mea6 acts on other types of cerebellar cells. Hence, we investigated the function of Mea6 in cerebellar granule cells. We found that mutant mice with the specific deletion of Mea6 in granule cells displayed abnormal posture, balance, and motor learning, as indicated in footprint, head inclination, balanced beam, and rotarod tests. We further showed that Math1-Cre;Mea6F/F mice exhibited disrupted migration of granule cell progenitors and damaged parallel fiber-Purkinje cell synapses, which may be related to impaired intracellular transport of vesicular glutamate transporter 1 and brain-derived neurotrophic factor. The present findings extend our previous work and may help to better understand the pathogenesis of Fahr’s disease.

Abnormal Gray Matter Volume and Functional Connectivity in Parkinson's Disease with Rapid Eye Movement Sleep Behavior Disorder.

Objective Rapid eye movement (REM) sleep behavior disorder (RBD) is a common symptom in Parkinson's disease (PD), and patients with PD-RBD tend to have an increased risk of cognitive decline and have the tendency to be akinetic/rigidity predominant. At the same time, the mechanisms of RBD in patients with PD remain unclear. Therefore, this study aimed to detect the structural and functional differences in patients with PD-RBD and PD without RBD (PD-nRBD). Methods Twenty-four polysomnography-confirmed patients with PD-RBD, 26 patients with PD-nRBD, and 26 healthy controls were enrolled. Structural and functional patterns were analyzed based on voxel-based morphometry and seed-based functional connectivity (FC). Correlations between altered gray matter volume (GMV)/FC values and cognitive scores and motor impairment scores in PD subgroups were assessed. Results Compared with patients with PD-nRBD, patients with PD-RBD showed relatively high GMV in the cerebellar vermis IV/V and low GMV in the right superior occipital gyrus (SOG). For the FC, patients with PD-RBD displayed lower FC between the right SOG and the posterior regions (left fusiform gyrus, left calcarine sulcus, and left superior parietal gyrus) compared with the patients with PD-nRBD. The GMV values in the right SOG were negatively correlated with the Unified PD Rating Scale-III scores in patients with PD-RBD but positively correlated with delayed memory scores. The GMV values in the cerebellar vermis IV/V were positively correlated with the tonic chin EMG density scores. There were positive correlations between the FC values in the right SOG-left superior parietal gyrus and MoCA and visuospatial skills/executive function scores and in the right SOG-left calcarine sulcus and delayed memory scores. Conclusion Higher GMV in the cerebellum may be linked with the abnormal motor behaviors during REM sleep in patients with PD-RBD, and lower GMV and FC in the posterior regions may indicate that PD-RBD correspond to more serious neurodegeneration, especially the visuospatial–executive function impairment and delayed memory impairment. These findings provided new insights to learn more about the complicated characteristics in patients with PD-RBD.

EEG Gamma Band Alterations and REM-like Traits Underpin the Acute Effect of the Atypical Psychedelic Ibogaine in the Rat.

Ibogaine is a psychedelic alkaloid that has attracted large scientific interest because of its antiaddictive properties in observational studies in humans as well as in animal models. Its subjective effect has been described as intense, vivid dream-like experiences occurring while awake; hence, ibogaine is often referred to as an oneirogenic psychedelic. While this unique dream-like profile has been hypothesized to aid the antiaddictive effects, the electrophysiological signatures of this psychedelic state remain unknown. We previously showed in rats that ibogaine promotes a waking state with abnormal motor behavior along with a decrease in NREM and REM sleep. Here, we performed an in-depth analysis of the intracranial electroencephalogram during "ibogaine wakefulness". We found that ibogaine induces gamma oscillations that, despite having larger power than control levels, are less coherent and less complex. Further analysis revealed that this profile of gamma activity compares to that of natural REM sleep. Thus, our results provide novel biological evidence for the association between the psychedelic state and REM sleep, contributing to the understanding of the brain mechanisms associated with the oneirogenic psychedelic effect of ibogaine.

Brain Injury in Critical Illness and a Note on the Virus

Brain Injury in Critical Illness and a Note on the Virus

Spontaneous motor-behavior abnormalities in two Drosophila models of neurodevelopmental disorders

Mutations in hundreds of genes cause neurodevelopmental disorders with abnormal motor behavior alongside cognitive deficits. Boys with fragile X syndrome (FXS), a leading monogenic cause of intellectual disability, often display repetitive behaviors, a core feature of autism. By direct observation and manual analysis, we characterized spontaneous-motor-behavior phenotypes of Drosophila dfmr1 mutants, an established model for FXS. We recorded individual 1-day-old adult flies, with mature nervous systems and prior to the onset of aging, in small arenas. We scored behavior using open-source video-annotation software to generate continuous activity timelines, which were represented graphically and quantitatively. Young dfmr1 mutants spent excessive time grooming, with increased bout number and duration; both were rescued by transgenic wild-type dfmr1+ . By two grooming-pattern measures, dfmr1-mutant flies showed elevated repetitions consistent with perseveration, which is common in FXS. In addition, the mutant flies display a preference for grooming posterior body structures, and an increased rate of grooming transitions from one site to another. We raise the possibility that courtship and circadian rhythm defects, previously reported for dfmr1 mutants, are complicated by excessive grooming. We also observed significantly increased grooming in CASK mutants, despite their dramatically decreased walking phenotype. The mutant flies, a model for human CASK-related neurodevelopmental disorders, displayed consistently elevated grooming indices throughout the assay, but transient locomotory activation immediately after placement in the arena. Based on published data identifying FMRP-target transcripts and functional analyses of mutations causing human genetic neurodevelopmental disorders, we propose the following proteins as candidate mediators of excessive repetitive behaviors in FXS: CaMKIIα, NMDA receptor subunits 2A and 2B, NLGN3, and SHANK3. Together, these fly-mutant phenotypes and mechanistic insights provide starting points for drug discovery to identify compounds that reduce dysfunctional repetitive behaviors.

Neuroprotective Effect of Curcumin on the Nigrostriatal Pathway in a 6-Hydroxydopmine-Induced Rat Model of Parkinson's Disease is Mediated by α7-Nicotinic Receptors.

Parkinson’s disease (PD) is a common neurodegenerative disorder, characterized by selective degeneration of dopaminergic nigrostriatal neurons. Most of the existing pharmacological approaches in PD consider replenishing striatal dopamine. It has been reported that activation of the cholinergic system has neuroprotective effects on dopaminergic neurons, and human α7-nicotinic acetylcholine receptor (α7-nAChR) stimulation may offer a potential therapeutic approach in PD. Our recent in-vitro studies demonstrated that curcumin causes significant potentiation of the function of α7-nAChRs expressed in Xenopus oocytes. In this study, we conducted in vivo experiments to assess the role of the α7-nAChR on the protective effects of curcumin in an animal model of PD. Intra-striatal injection of 6-hydroxydopmine (6-OHDA) was used to induce Parkinsonism in rats. Our results demonstrated that intragastric curcumin treatment (200 mg/kg) significantly improved the abnormal motor behavior and offered neuroprotection against the reduction of dopaminergic neurons, as determined by tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra and caudoputamen. The intraperitoneal administration of the α7-nAChR-selective antagonist methyllycaconitine (1 µg/kg) reversed the neuroprotective effects of curcumin in terms of both animal behavior and TH immunoreactivity. In conclusion, this study demonstrates that curcumin has a neuroprotective effect in a 6-hydroxydopmine (6-OHDA) rat model of PD via an α7-nAChR-mediated mechanism.

Maternal alcohol and drug use during pregnancy affects the motor behaviour and general movements of infants aged 3–4 months

BackgroundExposure of alcohol and/or other addictive drugs in pregnancy is a documented risk factor for later neurological impairment. AimsThe aim of the study was to determine whether infants suffering from prenatal exposure to addictive drugs and alcohol develop an abnormal motor behaviour at three to four months of age. Study designControlled cohort study of infants exposed to alcohol and/or other addictive drugs in pregnancy who were recruited from a hospital follow-up programme. The control group consisted of healthy, unexposed infants. SubjectsThe study group of 108 infants exposed to alcohol and/or addictive drugs in pregnancy were enrolled based on referrals from primary health care. The control group included 106 infants who had not been exposed to the aforementioned substances. Outcome measuresWe assessed the general movements (Prechtl’s General-Movement-Assessment, GMA), the motor repertoire (Assessment-of-Motor-Repertoire, AMR), and the Alberta-Infant Motor-Scale (AIMS) in all infants at three to four months of age. ResultsNone of the infants in either group had absent fidgety movements (FMs). In the study group 5(5%) had exaggerated FMs and 5(5%) had sporadic FMs; and 68(63%) infants in the study group displayed an abnormal movement character, compared to 23(22%) in the control group (p<0.001). On the AIMS, 46(44%) infants in the study group scored below the 10th percentile, compared to 2(3%) controls (p< 0.001). ConclusionThe study describes an abnormal movement character of infants exposed to alcohol and/or addictive drugs in pregnancy when their motor repertoire was assessed at three to four months of age. The AIMS also showed negative effects on their motor behaviour.

Reduced Interhemispheric Coherence after Cerebellar Vermis Output Perturbation.

Motor coordination and motor learning are well-known roles of the cerebellum. Recent evidence also supports the contribution of the cerebellum to the oscillatory activity of brain networks involved in a wide range of disorders. Kainate, a potent analog of the excitatory neurotransmitter glutamate, can be used to induce dystonia, a neurological movement disorder syndrome consisting of sustained or repetitive involuntary muscle contractions, when applied on the surface of the cerebellum. This research aims to study the interhemispheric cortical communication between the primary motor cortices after repeated kainate application on cerebellar vermis for five consecutive days, in mice. We recorded left and right primary motor cortices electrocorticograms and neck muscle electromyograms, and quantified the motor behavior abnormalities. The results indicated a reduced coherence between left and right motor cortices in low-frequency bands. In addition, we observed a phenomenon of long-lasting adaptation with a modification of the baseline interhemispheric coherence. Our research provides evidence that the cerebellum can control the flow of information along the cerebello-thalamo-cortical neural pathways and can influence interhemispheric communication. This phenomenon could function as a compensatory mechanism for impaired regional networks.

Clinical Manifestation Differences of Schizophrenia Patients Based on Gender

Background: Schizophrenia is yet to be deeply understood, despite being one of the most common mental illnesses in the world. Male and female schizophrenic patients may show different clinical presentations. The differences have been studied extensively globally, but there has yet many reports in regards of this in Indonesia.Aims: Knowing the differences of clinical manifestation on schizophrenia patients based on gender.Method: This research is analytic study in retrospective design. The data is taken from medical records of male and female schizophrenic inpatients of Psychiatric Ward of Dr. Soetomo General Hospital Surabaya on January 1st to December 31st, 2018, in total of 75 samples included. Data is processed with ANOVA statistic method.Result: The prevalence of male schizophrenic inpatients is 65,3% and 34,7% for female inpatients, with the ratio of 1,88:1. The differences of clinical presentations are not significant for the following clinical manifestations; abnormal motor behaviour (P=0,281), delusion (P=0,240), disorganized thinking (P=0,306), diminished emotional expression (P=0,295), and avolition (P=0,633) clinical manifestations. There is a significant difference in hallucination clinical manifestation between male and female inpatients (P=0,037).Conclusion: There is a significant difference in schizophrenia’s clinical manifestation of hallucination between male and female inpatients.

Pro-BDNF Knockout Causes Abnormal Motor Behaviours and Early Death in Mice

Brain derived neurotrophic factor (BDNF) is a member of the neurotrophin family, best characterized for its survival and differentiative effects in the central nervous system. Pro-BDNF, known as the precursor of BDNF, is believed to have opposite functions to mature BDNF (mBDNF). The opposing effects of Pro-BDNF and mBDNF have led researchers to propose a ‘yin’ (Pro-BDNF) and ‘yang’ (mBDNF) model of which, the specific mechanism of its opposing functions is unclear and requires further investigation. In order to elucidate pro-BDNF’s explicit role, we established a pro-BDNF knockout (KO) mouse model. This BDNF pro-domain KO mouse model showed significant weight loss, impaired righting reflex, abnormal motor behaviours and short lifespan (less than 22 days), mimicking a Huntington’s disease (HD)-like phenotype. ELISA results showed BDNF pro-domain KO not only blocked pro-BDNF, but also significantly affected the level of mBDNF. Abnormal morphologic changes were found in the dentate gyrus (DG) of the hippocampus in pro-BDNF KO mice, and western blot confirmed significant cell apoptosis in pro-BDNF KO mice brains. Furthermore, the expression of glutamic acid decarboxylase 65/67 (GAD65/67) was significantly reduced in pro-BDNF KO mice, indicating impaired inhibitory neurotransmission. Heterozygous (Het) mice showed impaired learning and memory capability and depressive-like behaviours, compared with wild type (WT) mice. Overall, these results support that pro-domain of BDNF is an indispensable part of the BDNF gene; without the proper formation of pro-BDNF, mBDNF cannot be produced successfully and function correctly on its own. Our study also supports the BDNF hypothesis in the pathogenesis of HD.

Calbindin-D9k is a Novel Risk Gene for Neurodegenerative Disease.

Calcium homeostasis plays a crucial role in neuronal development and disease. Calbindin-D9k (CaBP-9k) acts as calcium modulators and sensors in various tissues. However, the neurobiological functions of CaBP-9k are unknown. We used CaBP-9k knockout (KO) mice to investigate the roles of these gene in neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. We used anatomical and biochemical approaches to characterize functional abnormalities of the brain in the CaBP-9k KO mice. We found that the brains of CaBP-9k KO mice have increased APP/β-amyloid, Tau, and α-synuclein accumulation and endoplasmic reticulum (ER) stress-induced apoptosis. Neurons deficient for these CaBP-9k had abnormal intracellular calcium levels and responses. ER stress inhibitor TUDCA reduced ER stress-induced apoptosis and restored ER stress- and apoptosis-related proteins expression to wild-type levels in CaBP-9k KO mice. Furthermore, treatment with TUDCA rescued the abnormal memory and motor behaviors exhibited by older CaBP-9k KO mice. Our results suggest that a loss of CaBP-9k may contribute to the onset and progression of neurodegenerative diseases.

Correlates of Normal and Abnormal General Movements in Infancy and Long-Term Neurodevelopment of Preterm Infants: Insights from Functional Connectivity Studies at Term Equivalence.

Preterm infants born before 32 weeks gestation have increased risks for neurodevelopmental impairment at two years of age. How brain function differs between preterm infants with normal or impaired development is unknown. However, abnormal spontaneous motor behavior at 12–15 weeks post-term age is associated with neurodevelopmental impairment. We imaged brain blood oxygen level-dependent signals at term-equivalent age in 62 infants born at <32 weeks gestation and explored whether resting state functional connectivity (rsFC) differed with performances on the General Movement Assessment (GMA) at 12–15 weeks, and Bayley III scores at two years of corrected age. Infants with aberrant general movements exhibited decreased rsFC between the basal ganglia and regions in parietal and frontotemporal lobes. Infants with normal Bayley III cognitive scores exhibited increased rsFC between the basal ganglia and association cortices in parietal and occipital lobes compared with cognitively impaired children. Infants with normal motor scores exhibited increased rsFC between the basal ganglia and visual cortices, compared with children with motor impairment. Thus, the presence of abnormal general movements is associated with region-specific differences in rsFC at term. The association of abnormal long-term neurodevelopmental outcomes with decreased rsFC between basal ganglia and sub-score specific cortical regions may provide biomarkers of neurodevelopmental trajectory and outcome.

Neuropsychiatric Symptoms and Risk Factors in Mild Cognitive Impairment: A Cohort Investigation of Elderly Patients.

Neuropsychiatric symptoms (NPS) have been shown to affect the progression and development of Alzheimer's disease (AD) in the elderly. However, the published data are still controversial and limited in large cohort-based NPS study. To explore the potential relationship between NPS and mild cognitive impairment (MCI) among the elderly of Chinese community. A total of 465 Chinese community-dwelling elderly (age ≥ 60 years) with mild cognitive impairment (MCI) were recruited into this investigation. At baseline, enrolled participants were assessed for Clinical Dementia Rating (CDR), mini-psychiatric examination. They were also subjected to categorical language fluency test, list learning and delayed recall. We assessed the NPS severity by Neuropsychological Inventory (NPI). The global cognitive status (GCS) of the participants at the end of the 3-year study period were measured with the CDR. Approximately 41.6% of subjects had 1 or more NPS (total NPI score ≥ 1) at baseline. The most common NPSs were nocturnal behavior (20.8%), depression (17.3%), apathy (12.7%) and anxiety (13.2%). At the end of 3-year follow-up, 26.9% of baseline depressed patients developed AD, while 15.2% of baseline non-depressed patients developed AD (χ2 = 4.86, P=0. 04). Abnormal motor behavior was significantly correlated with cognitive deterioration as well (χ2 = 5.75, P=0. 03). Logistic regression analysis revealed that depression was considered as a risk factor for AD progression at baseline (95% CI: 1.12-5.67, OR=2.37, P=0.03). Depression may be an independent factor representing early neurodegeneration in elder patients with MCI. Further studies are warranted to assess whether effective management of NPS promotes the cognitive functions.

Inhibitory potential of plant secondary metabolites on anti-Parkinsonian drug targets: Relevance to pathophysiology, and motor and non-motor behavioural abnormalities

Parkinson’s disease (PD), a progressive neurodegenerative motor disorder, is caused due to the loss of dopaminergic neurons in the substantia nigra pars compacta region of mid-brain and the resultant depletion of the levels of the neurotransmitter dopamine. Although the pathophysiology of the disease is least understood, studies in animal models revealed oxidative stress, mitochondrial dysfunction and inflammation to be the major contributors. Dopamine replenishment therapy by oral administration of L-DOPA, the precursor of dopamine remains to be the therapeutic gold-standard for symptomatic treatment of PD. In addition, use of inhibitors of dopamine metabolizing enzymes (viz. monoamine oxidase-B: MAO-B; and catechol-O-methyltransferase: COMT) are the other strategies for amelioration of the motor abnormalities. Further, PD is associated with non-motor behavioural abnormalities as well, including cognitive impairment and mood disorders, which are caused due to cholinergic neurodegeneration, and thus inhibition of Acetylcholinesterase (AChE) is suggested. However, the currently used drugs against the three crucial enzymes (MAO-B, COMT and AChE) elicit several side effects, and thus the search for novel compounds continues, and plant-based compounds have promising potential in this regard. In the present study, we have used computational modeling to determine the efficiency of 40 plant-based natural products in inhibiting the three anti-Parkinsonian drug targets. Further, statistical analysis was performed to identify the properties of the compounds which are crucial for inhibition of the enzymes. While all the phytochemicals showed potential in inhibiting the enzymes, Rutin, Demethoxycurcumin and Acteoside were found to be most effective inhibitors of MAO-B, COMT and AChE respectively. Since most of the compounds are established anti-oxidant and anti-inflammatory molecules, they are surmised to confer neuroprotection in PD, and prevent progression of the disease.