The presence of a caregiver is associated with patient outcomes in patients with Parkinson's disease and atypical parkinsonisms.

INTRODUCTION: Approximately 88% of men and 79% of women with Parkinson's disease (PD) identify an informal caregiver. Although caregivers can play a key role in supporting patients, little is known about how and whether PD patients with and without caregivers differ in terms of physical, cognitive, and mood outcomes. This study explored whether caregiver presence was associated with variations in patient presentation and outcomes in a palliative PD and atypical PD population. METHODS: Secondary data on individuals with PD and their caregivers came from baseline data of a 3-site randomized controlled trial of outpatient palliative care for PD in the US and Canada. Measures included: MDS UPDRS III, Montreal Cognitive Assessment, quality of life (QOL) measures, depression, prolonged grief, spirituality (FACIT SP-12) and Palliative Performance Scale. RESULTS: Of 210 participants, 175 (83%) had a caregiver. Patients with caregivers had greater motor difficulty, lower cognitive scores, and greater palliative needs as measured by the Palliative Performance Scale. Despite poorer cognitive and motor function, those with caregivers had higher QOL as measured by the Quality of Life in Alzheimer Disease and less spiritual distress. There were no group differences on anxiety, depression, or grief. Caregiver presence moderated the association between lower MoCA score and worse motor symptoms. CONCLUSION: Findings of the present study highlight the influence of caregiver engagement on PD patient outcomes. These findings have implications for clinical practice and suggest that presence of a caregiver may be an important modifying variable on patient outcomes to examine in future research.

Naringin Exhibits Neuroprotection Against Rotenone-Induced Neurotoxicity in Experimental Rodents.

Parkinson's disease (PD) is a neurodegenerative disease that is accompanied with the loss of dopaminergic neurons in the substantia nigra pars compacta which subsequently leads to a reduction in the dopamine level in the striatum. The flavonoids are gaining critical attention in the management of PD due to the toxic effects of the synthetic drugs. Naringin, a potent flavonoid, exerts neuroprotective activity against experimental animal models of PD. It also exhibits protective activity against rotenone-induced neurotoxicity in cell line studies. Therefore, the present study was designed to evaluate the therapeutic potential of naringin against rotenone-induced animal model of PD. The rotenone was injected through intracerebroventricular route into substantia nigra pars compacta (SNpc) to induce PD-like manifestations in the male rats. The behavioral deficits of the animals due to dopaminergic toxicity were evaluated in actophotometer, OFT, bar catalepsy, narrow beam walk, rota-rod, grip strength and foot print analysis. Naringin-attenuated rotenone-induced behavioral abnormalities in the experimental rats. Further, naringin reduced the rotenone-induced dopaminergic toxicity in striatum and SNpc the animals. At the sub-cellular level, naringin attenuated the rotenone-induced decrease in the mitochondrial function, integrity and bioenergetics in the SNpc of the animals. Furthermore, naringin reduced the rotenone-induced mitochondria-dependent apoptosis in the rat SNpc. However, Trigonelline significantly abolished the therapeutic effects of naringin on behavioral, biochemical and molecular observations in rotenone-induced PD-like animals. These observations indicate that naringin may exert neuroprotective activity against rotenone-induced toxicity in the animals possibly through Nrf2-mediated pathway. Thus, it can be presumed that naringin could be an alternative option in the management of PD.

Deferiprone Rescues Behavioral Deficits Induced by Mild Iron Exposure in a Mouse Model of Alpha-Synuclein Aggregation.

Parkinson's disease (PD) is the most common neurodegenerative movement disorder, and its causes remain unknown. A major hallmark of the disease is the increasing presence of aggregated alpha-synuclein (aSyn). Furthermore, there is a solid consensus on iron (Fe) accumulation in several regions of PD brains during disease progression. In our study, we focused on the interaction of Fe and aggregating aSyn in vivo in a transgenic mouse model overexpressing human aSyn bearing the A53T mutation (prnp.aSyn.A53T). We utilized a neonatal iron-feeding model to exacerbate the motor phenotype of the transgenic mouse model. Beginning from day 100, mice were treated with deferiprone (DFP), a ferric chelator that is able to cross the blood-brain barrier and is currently used in clinics as treatment for hemosiderosis. Our paradigm resulted in an impairment of the learning abilities in the rotarod task and the novel object recognition test. DFP treatment significantly improved the performance in both tasks. Although this was not accompanied by alterations in aSyn aggregation, our results support DFP as possible therapeutic option in PD.

Dietary Supplementation of Walnut Partially Reverses 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Induced Neurodegeneration in a Mouse Model of Parkinson's Disease.

Numerous studies indicating that natural plant sources and their active phytochemicals offer protection to the pathological processes related to the development of neurogenerative diseases including Parkinson's disease (PD). In the present study, the neuro protective efficacy of dietary supplementation of walnut (6 %) for 28 days was examined in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (i.p., 20 mg/kg body weight/day) for last four consecutive days. MPTP injection diminished the levels of GSH, dopamine and metabolites along with decreased activities of GPx and mitochondrial complex I. Further, the levels of TBARS and enzymatic antioxidants such as SOD and catalase, MAO-B activities were enhanced by MPTP treatment. Behavioral deficits and lowered TH expression are also proved MPTP induced neurotoxicity. Dietary supplementation of walnut attenuated MPTP-induced impairment in PD mice might be by its MAO-B inhibitory, antioxidant and mitochondrial protective actions. To find out the exact mechanism of action walnut on PD mice warrants further extensive studies.

Protective effects of Althaea officinalis L. extract in 6-hydroxydopamine-induced hemi-Parkinsonism model: behavioral, biochemical and histochemical evidence.

It is well known that Parkinson's disease (PD) is the second most common neurodegenerative disorder in humans. In this regard, the neuroprotective effect of Althaea officinalis (AO) has already been reported. Therefore, this study examined whether administration of AO extract would improve behavioral, biochemical and structural abnormalities in an experimental animal model of PD in rats. For this purpose, we induced hemi-Parkinsonism by unilateral intranigral injection of 6-hydroxydopamine (6-OHDA, 8 µg/5 µl saline-ascorbate). The rats were pretreated i.p. with AO extract (10 mg/kg) started 6 days before surgery and continued until the 3rd day post-surgery. Regarding oxidative stress, brain MDA concentration (as a lipid peroxidation marker) increased significantly in the 6-OHDA-administered group in comparison with rats pretreated with AO extract. It was found that AO treatment attenuated rotational behavior in the 6-OHDA-administered group and protected the neurons of substantia nigra pars compacta against 6-OHDA toxicity. Overall, AO extract administration indicated neuroprotective effects against 6-OHDA-induced hemi-Parkinsonism in rats.

Neuroprotective effects of curcumin on 6-hydroxydopamine-induced Parkinsonism in rats: behavioral, neurochemical and immunohistochemical studies.

Curcumin, the active principle of turmeric used in Indian curry is known for its antitumor, antioxidant, antiarthritic, anti-ischemic and anti-inflammatory properties and might inhibit the accumulation of destructive beta-amyloid in the brains of Alzheimer's disease patients. A Parkinsonian model in rats was developed by giving 6-hydroxydopamine (10 µg/2 µl in 0.1% ascorbic acid-saline) in the right striatum. After 3 weeks of lesioning, the behavior activities (rotarod, narrow beam test, grip test and contra-lateral rotations) were increased in a lesioned group as compared to a sham group and these activities were protected significantly with the pretreatment of curcumin. A significant protection on lipid peroxidation, glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase, tyrosine hydroxylase and D(2) receptor binding was observed in the striatum of lesioned group animals pretreated with 80 mg/kg body weight of curcumin for 21 days as compared to lesion group animals. No significant alterations on behavior and biochemical parameters were observed in sham group animals and the animals of sham group pretreated with curcumin. This study indicates that curcumin, which is an important ingredient of diet in India and also used in various systems of indigenous medicine, is helpful in preventing Parkinsonism and has therapeutic potential in combating this devastating neurologic disorder.

Methanolic extract of Hibiscus asper leaves improves spatial memory deficits in the 6-hydroxydopamine-lesion rodent model of Parkinson's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: While the Hibiscus asper Hook.f. (Malvaceae) is a traditional herb largely used in tropical region of the Africa as vegetable, potent sedative, tonic and restorative, anti-inflammatory and antidepressive drug, there is very little scientific data concerning the efficacy of this. AIM OF THE STUDY: We investigated antioxidant activity and the effects of methanolic extract of Hibiscus asper leaves on neurological capacity of male Wistar rats subjected to unilateral 6-hydroxydopamine (6-OHDA)-lesion. MATERIALS AND METHODS: Two model systems: 2,4-dinitrophenyl-1-picryl hydrazyl (DPPH) radical scavenging activity and ß-carotene bleaching inhibition assay were used to measure the antioxidant activities of the plan extract. We also investigated the neuroprotective effect of methanolic extract of Hibiscus asper leaves (50 and 100 mg/kg) in male Wistar rats subjected to unilateral 6-hydroxydopamine (6-OHDA)-lesion rat model. RESULTS: Methanolic extract of Hibiscus asper leaves showed potent antioxidant and free radical scavenging activity. Chronic administration of methanolic extract (50 and 100 mg/kg, i.p., daily, for 7 days) significantly reduce anxiety-like behavior and inhibit depression in elevated plus-maze and forced swimming tests, suggesting anxiolytic and antidepressant activity. Also, spatial memory performance in Y-maze and radial arm-maze tasks was improved, suggesting positive effects on memory formation. CONCLUSIONS: Taken together, our results suggest that the methanolic extract of Hibiscus asper leaves have antioxidant effects and might provide an opportunity to management neurological abnormalities in Parkinson's disease conditions.

Successful treatment with Yokukansan for behavioral and psychological symptoms of Parkinsonian dementia.

OBJECTIVE: To evaluate the efficacy and safety of Yokukansan, a traditional Chinese herbal medicine, for treating behavioral and psychological symptoms of dementia (BPSD) in patients with Parkinson disease (PD; n=7) and those with PD with dementia (PDD; n=7). BACKGROUND: BPSD are often seen in patients with senile dementia and have serious deleterious effects on the lives of patients and caregivers. Recent studies indicate that the traditional Chinese herbal medicine Yokukansan may be safe and beneficial for the treatment of BPSD patients. METHODS: We treated 7 PD and 7 PDD patients for 4 weeks with Yokukansan and observed them without Yokukansan for 4 weeks. Changes in behavioral and psychological symptoms were evaluated every 4 weeks according to the Neuropsychiatric Inventory (NPI) scale. RESULTS: Significant improvements in behavioral and psychological symptoms, particularly in the incidence and duration of hallucinations, were observed in most PD and PDD patients after 4 weeks of Yokukansan treatment. No significant changes were observed in the laboratory tests, cognitive function, activities of daily living, or parkinsonism. CONCLUSION: Our results suggest that Yokukansan improves BPSD in both PD and PDD patients without worsening their cognitive function, ability to perform activities of daily living, or parkinsonism.

Preventive effects of soy meal (+/- isoflavone) on spatial cognitive deficiency and body weight in an ovariectomized animal model of Parkinson's disease.

The aim of the present study was to investigate the preventive effect of 4 weeks soy meal (+/- isoflavone) on post-menopausal cognitive deficiency and body weight alteration in ovariectomized (OVX)-6-hydroxy dopamine (6-OHDA)-induced animal model of Parkinson's Disease (PD) which mimics status in menopause women. Female Wistar rats (250-300 g, 5-6 months old) were divided into 2 main groups. (1) Control; (2) OVX; included 5 subgroups that were pre-treated with 10 or 20 g soy with isoflavone in 30 g daily diet (10 and 20 groups, respectively), 10 or 20 g soy without isoflavone in 30 g daily diet (-10 and -20 groups, respectively) and 0 g soy (sham treated group) during 4 weeks after OVX. To induce animal model ofPD in main second group (OVX rats) the substantia nigra pars compacta (SNpc) was lesioned by 6-hydroxydopamine (6-OHDA) (8 microg kg(-1) 4 microL(-1) normal saline contains 0.1% ascorbate). All animals were trained in Morris water maze for evaluating the spatial learning and memory. The results indicated that pre-treatment of Parkinsonian rats with different doses of dietary soy meal (+/- isoflavone) improved the spatial learning and memory and prevents increasing the body weight after menopause significantly. Our data show that, long-duration dietary soy meal may have the potential neuroprotective effect against post-menopausal cognitive deficiency induced by degeneration of nigrostriatal dopaminergic system and constant body weight during post-menopausal life cycle.

[The nursing experience of a patient with parkinsonian type of multiple system atrophy].

This article describes the nursing experience of a patient with multiple system atrophy-parkinsonian type (MSA-P). The writer collected subjective and objective information using observation, interviews, and nursing care during the time period May 22 to June 3, 2006. A holistic nursing assessment and nursing problems were established as body image disturbance, risk for aspiration, constipation and family support, self-care deficit and risk for fall. Through individual nursing intervention and family support, the patient accommodated himself to the physical activities and mental situation. We hope that this complete nursing experience can in future serve as a reference for other nurses in the MSA-P field as they assist similar patients.

Prefrontal cortex dysfunction and depression in atypical parkinsonian syndromes.

Depressive symptoms are common in patients with neurodegenerative disorders. Imaging studies suggest that a disruption of frontal-subcortical pathways may underlie depression associated with basal ganglia disease. This pilot study tested the hypothesis that frontal dysfunction contributes to depression associated with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Depressed patients with MSA (n = 11), PSP (n = 9), and age-matched controls (n = 25) underwent measures of cerebral glucose metabolism applying positron emission tomography with (18)F-fluorodeoxyglucose. Regional metabolism in the patient groups was compared to the normal subjects using the voxel-based statistical parametric mapping. Depressive symptom severity (Hamilton Depression Rating) and degree of locomotor disability (Hoehn & Yahr) were assessed in the patient groups. The association between prefrontal metabolism and the occurrence of depressive symptoms and the degree of locomotor disability was investigated. When compared to controls, MSA patients revealed significant metabolic decreases in bilateral frontal, parietal, and cerebellar cortex and in the left putamen. In PSP patients, significant hypometabolism was demonstrated in bilateral frontal cortex, right thalamus, and midbrain. Depression severity but not the patients' functional condition was significantly associated with dorsolateral prefrontal glucose metabolism in both patient groups. The findings of this pilot study support the hypothesis that depressive symptoms in MSA and PSP are associated with prefrontal dysfunction.

DHEA improves symptomatic treatment of moderately and severely impaired MPTP monkeys.

The steroid dehydroepiandrosterone (DHEA) is abundant in men and women and decreases rapidly during aging. Parkinson's disease (PD) is the second most common neurodegenerative disorder just behind Alzheimer. l-3,4-Dihydroxyphenylalanine (l-Dopa) therapy remains the most effective treatment but many patients develop motor complications. This study investigated the acute effect of DHEA alone and with l-Dopa in 12 females monkeys lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to model PD. DHEA administration alone improved the mean parkinsonian score at 1, 5 and 15mg/kg in moderately and severely impaired MPTP monkeys and increased blood DHEA concentrations. DHEA with a low dose of l-Dopa increased the l-Dopa effect in moderately and severely impaired MPTP monkeys. DHEA lengthened duration of the effect of the low dose of l-Dopa by 15-45min. DHEA at 1, 5 and 15mg/kg combined with a high dose of l-Dopa did not increase dyskinesias. DHEA could act by reducing inhibitory GABAergic activity in the striatal output pathways. DHEA could also be metabolized into estradiol in the brain and increase acutely dopamine activity.

Effect of sesamin in Acanthopanax senticosus HARMS on behavioral dysfunction in rotenone-induced parkinsonian rats.

The aim of this study was to determine whether sesamin, a component from Acanthopanax senticosus HARMS (ASH) pharmacologically offers protection against Parkinson's disease (PD) and its related depressive behavior in rats administered rotenone. We also examined how sesamin affected the rotenone-induced loss of tyrosine hydroxylase (TH) or glial cell line-derived neurotrophic factor (GDNF)-positive neurons in the midbrain of rats. Rats were orally administered sesamin (3, 30 mg/kg) once a day for 2 weeks before an intraperitoneal injection of rotenone (2.5 mg/kg). The pole test and catalepsy test were used to evaluate the effects of sesamin administration on bradykinesia and depressive behaviors in the PD model of rats given rotenone for 5 weeks. Those effects were compared with the ASH administrated group (250 mg/kg). Treatment with sesamin for seven weeks resulted in prophylactic effects on rotenone-induced parkinsonian bradykinesia and catalepsy, and the effects were equivalent to ASH effects. Immunohistochemistical analysis using TH or GDNF antibody showed that sesamin provided cytoprotective effects against rotenone-induced loss of DA cells. The results suggest that it may be possible to use the ASH and sesamin for the prevention of nigral degenerative disorders, e.g., PD with depression, caused by exposure to pesticide or environmental neurotoxins in general.

Pallidal stimulation for parkinsonism: improved brain activation during sequence learning.

We used (15)O-labeled water and positron emission tomography to assess the effect of deep brain stimulation of the internal globus pallidus on motor sequence learning in Parkinson's disease. Seven right-handed patients were scanned on and off stimulation while they were performing a motor sequence learning task and a kinematically matched motor execution reference task. The scans were performed after a 12-hour medication washout. Stimulation parameters were adjusted for maximal motor improvement; experimental task parameters were held constant across stimulation conditions. Internal globus pallidus stimulation improved motor ratings by 37% (p < 0.01). During the sequence learning task, stimulation improved performance as measured by several correct anticipatory movements (p < 0.01) and by verbal report (p < 0.001). Concurrent positron emission tomography imaging during learning demonstrated significant (p < 0.01) increases in brain activation with stimulation in the left dorsolateral prefrontal cortex, bilaterally in premotor cortex, and in posterior parietal and occipital association areas. Stimulation did not affect the activity of these regions during the performance of the motor execution reference task. These findings suggest that internal globus pallidus deep brain stimulation can enhance the activity of prefrontal cortico-striato-pallidothalamic loops and related transcortical pathways. Improved sequence learning with stimulation may be directly related to these functional changes.