OBJECTIVES:Various exercise strategies have been suggested to address movement deficits in order to improve motor function and quality of life for individuals in the early or moderate stages of Parkinson disease. The purpose is to evaluate the effects of an aquatic Ai Chi intervention on balance, gait speed and quality of life of patients.

DESIGN AND INTERVENTION:Twenty-nine people with Parkinson disease participated in this pilot study. People were randomized into (1) aquatic Ai Chi program (experimental group) and (2) a dry land conventional Western physical therapy intervention (control group). Twenty-two twice-weekly sessions were performed with the 14 patients assigned to the experimental group, during the same period of time as the control group (same number of sessions), who received dry land therapy.

MAIN OUTCOMES MEASURES:Visual Analogue scale (VAS), The Timed Get up and Go test, Five Times Sit-to-Stand test, single leg standing, Yesavage test and Parkinson's Disease Questionnaire (PDQ-39). A descriptive analysis was performed on all study variables.

RESULTS:The results showed a significant effect on time - of a high effect which indicates that the VAS scores (F 1.3; p < 0.001), Five time (F = 1.8; p = 0.001) and Get up and Go (F = 1.7; p < 0.001) significantly decreased in time, independent of the treatment group. In contrast, no significant differences were found in the results shown on the PDQ-39 scale, finding only changes in the section of social support (p < 0.001 F = 18.63).

CONCLUSIONS:The results of this 11-week controlled pilot trial suggest that aquatic Ai Chi applied twice weekly may potentially reduce Parkinsonian symptoms as measured on different motor symptoms, bradykinesia and rigidity.

BACKGROUND:Few studies have examined the association between daily physical activity and cognitive function among older adults with Parkinson's disease (PD).

OBJECTIVE:Here we evaluate the association between accelerometer-assessed physical activity and cognition among older patients with PD.

METHODS:Cognition assessed via the Montreal Cognitive Assessment (MoCA). Moderate-to-vigorous physical activity (MVPA) was assessed via accelerometry over a 1-2 week monitoring period.

RESULTS:After adjusting for motor impairment severity, for every 1 min/day increase in MVPA, participants had a 0.09 unit increase in MoCA-determined cognitive function (β = 0.09; 95% CI: -0.003-0.19; P = 0.05). When further adjusting for motor impairment, age and gender, results were unchanged (β = 0.09; 95% CI: 0.004-0.19; P = 0.04).

CONCLUSION:The present study provides suggestive evidence of a favorable association between daily physical activity behavior and cognitive function among adults with PD.

OBJECTIVES:The purpose of this study was to examine the effectiveness and safety of combined treatment using acupuncture and bee venom acupuncture (BVA) as an adjunctive treatment for idiopathic Parkinson's disease (PD).

METHODS:Eleven patients (7 men and 4 women) with idiopathic PD who had been receiving a stable dose of anti-parkinsonian medication for at least 4 weeks. Participants received conventional treatment for 12 weeks. Subsequently, they received additional treatment with acupuncture and BVA twice weekly for 12 weeks while still maintaining conventional treatment. All participants were assessed at baseline, 12 weeks, and 24 weeks by using the Unified Parkinson's Disease Rating Scale (UPDRS), the Parkinson's Disease Quality of Life Questionnaire (PDQL), the speed and number of steps required to walk 20 m, and the Beck Depression Inventory (BDI). Maximum excursion and directional control, measured by computerized dynamic posturography (Balance Master(®) System, NeuroCom, San Carlos, CA), were used to assess postural stability.

RESULTS:Patients who underwent 12 weeks of twice-weekly combined treatment with acupuncture and BVA showed significant improvements in gait speed, PDQL score, activities of daily living (UPDRS part II), motor symptoms (UPDRS part III), and combined UPDRS part II+III scores compared with assessments after conventional treatment.

CONCLUSIONS:Combined treatment with acupuncture and BVA showed promising results as a safe adjunctive therapy for PD.

OBJECTIVES:The purpose of this study was to examine the effectiveness and safety of combined treatment using acupuncture and bee venom acupuncture (BVA) as an adjunctive treatment for idiopathic Parkinson's disease (PD).

METHODS:Eleven patients (7 men and 4 women) with idiopathic PD who had been receiving a stable dose of anti-parkinsonian medication for at least 4 weeks. Participants received conventional treatment for 12 weeks. Subsequently, they received additional treatment with acupuncture and BVA twice weekly for 12 weeks while still maintaining conventional treatment. All participants were assessed at baseline, 12 weeks, and 24 weeks by using the Unified Parkinson's Disease Rating Scale (UPDRS), the Parkinson's Disease Quality of Life Questionnaire (PDQL), the speed and number of steps required to walk 20 m, and the Beck Depression Inventory (BDI). Maximum excursion and directional control, measured by computerized dynamic posturography (Balance Master(®) System, NeuroCom, San Carlos, CA), were used to assess postural stability.

RESULTS:Patients who underwent 12 weeks of twice-weekly combined treatment with acupuncture and BVA showed significant improvements in gait speed, PDQL score, activities of daily living (UPDRS part II), motor symptoms (UPDRS part III), and combined UPDRS part II+III scores compared with assessments after conventional treatment.

CONCLUSIONS:Combined treatment with acupuncture and BVA showed promising results as a safe adjunctive therapy for PD.

Ginseng, a perennial plant belonging to the Panax genus of the Araliaceae family, has been used in China, Korea, and Japan as a traditional herbal medicine for thousands of years. Ginseng is recorded to have exhibited a wide variety of beneficial pharmacological effects and has become a popular and worldwide known health supplement and drug. The protective effects of ginseng on central nervous system are discussed in this review. Ginseng species and ginsenosides and their intestinal metabolism and bioavailability are concisely introduced. The molecular mechanisms of the effects of ginseng on central nervous system, mainly focused on the neuroprotection properties of ginseng, memory, and learning enhanced properties, and the effects on neurodegenerative disorders are presented. Thus, ginseng and its constituents are of potential merits in the treatment of cerebral disorders.

Motor learning is impaired in Parkinson's disease (PD), with patients demonstrating deficits in skill acquisition (online learning) and consolidation (offline learning) compared to healthy adults of similar age. Recent studies in young adults suggest that single bouts of aerobic exercise (AEX), performed in close temporal proximity to practicing a new motor task, may facilitate motor skill learning. Thus, we aimed at investigating the effects of a single bout of aerobic cycling on online and offline learning in PD patients.17 PD patients (Hoehn and Yahr 1 - 2.5, age: 64.4± 6.2) participated in this crossover study. Immediately prior to practicing a novel balance task, patients either performed 30 min of (i) moderate intensity (60-70% VO) aerobic cycling, or (ii) seated rest (order counterbalanced). The task required patients to stabilize a balance platform (stabilometer) in a horizontal position for 30 s. For each experimental condition, patients performed 15 acquisition trials, followed by a retention test 24 h later. We calculated time in balance (platform within± 5° from horizontal) for each trial, and analyzed within- and between-subjects differences in skill acquisition (online learning) and skill retention (offline learning) using mixed repeated-measures ANOVA.We found that the exercise bout had no effect on performance level or online gains during acquisition, despite affecting the time course of skill improvements (larger initial and reduced late skill gains). Aerobic cycling significantly improved offline learning, as reflected by larger 24-h skill retention compared to the rest condition.Our results suggest that a single bout of moderate-intensity AEX is effective in improving motor skill consolidation in PD patients. Thus, acute exercise may represent an effective strategy to enhance motor memory formation in this population. More work is necessary to understand the underlying mechanisms, the optimal scheduling of exercise, and the applicability to other motor tasks. Further, the potential for patients in later disease stages need to be investigated. The study was a priori registered at ClinicalTrials.gov (NCT03245216).

Motor learning is impaired in Parkinson's disease (PD), with patients demonstrating deficits in skill acquisition (online learning) and consolidation (offline learning) compared to healthy adults of similar age. Recent studies in young adults suggest that single bouts of aerobic exercise (AEX), performed in close temporal proximity to practicing a new motor task, may facilitate motor skill learning. Thus, we aimed at investigating the effects of a single bout of aerobic cycling on online and offline learning in PD patients.17 PD patients (Hoehn and Yahr 1 - 2.5, age: 64.4± 6.2) participated in this crossover study. Immediately prior to practicing a novel balance task, patients either performed 30 min of (i) moderate intensity (60-70% VO) aerobic cycling, or (ii) seated rest (order counterbalanced). The task required patients to stabilize a balance platform (stabilometer) in a horizontal position for 30 s. For each experimental condition, patients performed 15 acquisition trials, followed by a retention test 24 h later. We calculated time in balance (platform within± 5° from horizontal) for each trial, and analyzed within- and between-subjects differences in skill acquisition (online learning) and skill retention (offline learning) using mixed repeated-measures ANOVA.We found that the exercise bout had no effect on performance level or online gains during acquisition, despite affecting the time course of skill improvements (larger initial and reduced late skill gains). Aerobic cycling significantly improved offline learning, as reflected by larger 24-h skill retention compared to the rest condition.Our results suggest that a single bout of moderate-intensity AEX is effective in improving motor skill consolidation in PD patients. Thus, acute exercise may represent an effective strategy to enhance motor memory formation in this population. More work is necessary to understand the underlying mechanisms, the optimal scheduling of exercise, and the applicability to other motor tasks. Further, the potential for patients in later disease stages need to be investigated. The study was a priori registered at ClinicalTrials.gov (NCT03245216).

Parkinson's disease, a progressive neurodegenerative disease, is caused by the loss of dopaminergic neurons in the substantia nigra (SN). It is characterized by the formation of intracytoplasmic Lewy bodies that are primarily composed of the protein alpha-synuclein (α-syn), along with dystrophic neurites. Acupuncture stimulation results in an enhanced survival of dopaminergic neurons in the SN in Parkinsonism animal models. We investigated the role of acupuncture in inhibiting the increase in α-syn expression that is related to dopaminergic cell loss in the SN in a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Parkinsonism mouse model. In this model, acupuncture stimulation at GB34 and LR3 attenuated the decrease in tyrosine hydroxylase in the SN. Moreover, acupuncture stimulation attenuated the increase in α-syn in SN. Acupuncture stimulation also maintained the phosphorylated α-syn on serine 129 at levels similar to the control group. Our findings indicate that the MPTP-mediated increase in α-syn, and the acupuncture-mediated inhibition of the increase in α-syn, may be responsible for the neuroprotective effects of acupuncturein the SN following damage induced by MPTP.

Ketogenic diet has been used in treating epilepsy for more than 80 years. It is based on a drastic change of proportions in the consumption of carbohydrates, proteins and fats. In everyday diet we consume approximately 34 per cent of fats, 50 per cent of carbohydrates and 14 per cent of proteins. While ketogenic diet consists in 80-90 per cent of fats and in 10-20 per cents of carbohydrates and proteins together. Despite its indisputable effectiveness, the functioning of the ketogenic diet has not been explained. It seems that its functioning mechanism is unique and results from a number of chronic metabolic changes as well as the adaptation in the cenral nervous system that occurs during its long-term application. The most recent clinical and experimental data suggest that the ketogenic diet also has neuroprotective properties, which makes it a useful alternative therapeutic method in the modification of the natural history of the diseases related with neurodegeneration processes.

ETHNOPHARMACOLOGICAL RELEVANCE:Withania somnifera (Family: Solanaceae), commonly known as Ashwagandha or Indian ginseng is distributed widely in India, Nepal, China and Yemen. The roots of plant consist of active phytoconstituents mainly withanolides, alkaloids and sitoindosides and are conventionally used for the treatment of multiple brain disorders.

AIM OF THE REVIEW:This review aims to critically assess and summarize the current state and implication of Ashwagandha in brain disorders. We have mainly focussed on the reported neuroactive phytoconstituents, available marketed products, pharmacological studies, mechanism of action and recent patents published related to neuroprotective effects of Ashwagandha in brain disorders.

MATERIALS AND METHODS:All the information and data was collected on Ashwagandha using keywords"Ashwagandha"along with"Phytoconstituents","Ayurvedic, Unani and Homeopathy marketed formulation","Brain disorders","Mechanism"and"Patents". Following sources were searched for data collection: electronic scientific databases such as Science Direct, Google Scholar, Elsevier, PubMed, Wiley On-line Library, Taylor and Francis, Springer; books such as AYUSH Pharmacopoeia; authentic textbooks and formularies.

RESULTS:Identified neuroprotective phytoconstituents of Ashwagandha are sitoindosides VII-X, withaferin A, withanosides IV, withanols, withanolide A, withanolide B, anaferine, beta-sitosterol, withanolide D with key pharmacological effects in brain disorders mainly anxiety, Alzheimer's, Parkinson's, Schizophrenia, Huntington's disease, dyslexia, depression, autism, addiction, amyotrophic lateral sclerosis, attention deficit hyperactivity disorder and bipolar disorders. The literature survey does not highlight any toxic effects of Ashwagandha. Further, multiple available marketed products and patents recognized its beneficial role in various brain disorders; however, very few data is available on mechanistic pathway and clinical studies of Ashwagandha for various brain disorders is scarce and not promising.

CONCLUSION:The review concludes the results of recent studies on Ashwagandha suggesting its extensive potential as neuroprotective in various brain disorders as supported by preclinical studies, clinical trials and published patents. However vague understanding of the mechanistic pathways involved in imparting the neuroprotective effect of Ashwagandha warrants further study to promote it as a promising drug candidate.

Avocados have a high content of phytochemicals especially antioxidants with potential neuroprotective effect. Aging is the major risk factor for neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. A large body of evidence indicates that oxidative stress is involved in the pathophysiology of these diseases. Oxidative stress can induce neuronal damages and modulate intracellular signaling, ultimately leading to neuronal death by apoptosis or necrosis. There is evidence for increased oxidative damage to macromolecules in amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, and Alzheimer's disease. Thus, antioxidants have been used for their effectiveness in reducing these deleterious effects and neuronal death in many in vitro and in vivo studies. The critical review results indicate that compounds in avocado are unique antioxidants, preferentially suppressing radical generation, and thus may be promising as effective neuropreventive agents. The diverse array of bioactive nutrients present in avocado plays a pivotal role in the prevention and cure of various neurodegenerative diseases.

Curcumin is widely consumed in Asia either as turmeric directly or as one of the culinary ingredients in food recipes. The benefits of curcumin in different organ systems have been reported extensively in several neurological diseases and cancer. Curcumin has got its global recognition because of its strong antioxidant, anti-inflammatory, anti-cancer, and antimicrobial activities. Additionally, it is used in diabetes and arthritis as well as in hepatic, renal, and cardiovascular diseases. Recently, there is growing attention on usage of curcumin to prevent or delay the onset of neurodegenerative diseases. This review summarizes available data from several recent studies on curcumin in various neurological diseases such as Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, Huntington's disease, Prions disease, stroke, Down's syndrome, autism, Amyotrophic lateral sclerosis, anxiety, depression, and aging. Recent advancements toward increasing the therapeutic efficacy of curcuma/curcumin formulation and the novel delivery strategies employed to overcome its minimal bioavailability and toxicity studies have also been discussed. This review also summarizes the ongoing clinical trials on curcumin for different neurodegenerative diseases and patent details of curcuma/curcumin in India.

Recent developments in brain research and in the field of music therapy have led to the development of music-based methods specifically aimed at relieving symptoms of Parkinson's disease and other neurologic disorders. Rhythmic auditory stimulation uses external rhythmic auditory cues from song, music or metronome to aid patients improving their walking functioning and has been shown to be effective both within sessions and as a result of training over time. Melodic intonation therapy and related vocal techniques can improve expressive dysphasia and aid rehabilitation of neurologic disorders, particularly Parkinson's disease, stroke and developmental disorders.

This study explored whether reflexology could improve or sustain the wellbeing of people with Parkinosn's Disease [PD] using the PDQ39 wellbeing tool designed specifically for use with people with PD. The treatmnt protocal involved giving 8 therapy sessions to 16 people with varying derees of PD in a cross-over design to enable a longitudinal survey of impact. Whilst the results reflected the progressive nature of PD deterioration over time there was an improvement in wellbeing over the active therapy phase. These results suggest that continuous two- three weekly reflexology may limit further deteroration or maintain improvement of wellbeing. A further study is indicated to study this hypothesis.

The complexity of the endocannabinoid (eCB) system is becoming better understood and new drivers of eCB signaling are emerging. Modulation of the activities of the eCB system can be therapeutic in a number of diseases. Research into the eCB system has been paralleled by the development of agents that interact with cannabinoid receptors. In this regard it should be remembered that herbal cannabis contains a myriad of active ingredients, and the individual cannabinoids have quite distinct biological activities requiring independent studies. Areas covered: This article reviews the most important current data involving the eCB system in relation to human diseases, to reflect the present (based mainly on the most used prescription cannabinoid medicine, THC/CBD oromucosal spray) and potential future uses of cannabinoid-based therapy. Expert commentary: From the different therapeutic possibilities, THC/CBD oromucosal spray has been in clinical use for approximately five years in numerous countries world-wide for the management of multiple sclerosis (MS)-related moderate to severe resistant spasticity. Clinical trials have confirmed its efficacy and tolerability. Other diseases in which different cannabinoids are currently being investigated include various pain states, Alzheimer's disease, Parkinson's disease, Huntington's disease and epilepsy. The continued characterization of individual cannabinoids in different diseases remains important.

Carnosic acid (CA; C20H28O4), a phenolic diterpene characterized as an ortho-dihydroquinone-type molecule, is a pro-electrophile agent that becomes an electrophile after reacting with free radicals. The electrophile generated from CA interacts with and activates the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor, which is a major modulator of redox biology in mammalian cells. CA induces antioxidant and anti-inflammatory effects in several cell types, as observed in both in vitro and in vivo experimental models. In this context, CA has been viewed as a neuroprotective agent by activating signaling pathways associated with cell survival during stressful conditions. Indeed, CA exhibits the ability to promote mitochondrial protection in neural cells. Mitochondria are the main source of both ATP and reactive species in animal cells. Mitochondrial dysfunction plays a central role in the start and development of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, among others. Therefore, the study of strategies aiming to reduce mitochondrial impairment in the case of neurodegeneration is of pharmacological interest. In the present review, it is described and discussed the effects of CA on brain mitochondria in experimental models of neural lesion. Based on the data discussed here, CA is a potential candidate to be listed as a neuroprotective agent by acting on the mitochondria of neural cells.

Coenzyme Q(10) (CoQ(10)) and creatine are promising agents for neuroprotection in neurodegenerative diseases via their effects on improving mitochondrial function and cellular bioenergetics and their properties as antioxidants. We examined whether a combination of CoQ(10) with creatine can exert additive neuroprotective effects in a MPTP mouse model of Parkinson's disease, a 3-NP rat model of Huntington's disease (HD) and the R6/2 transgenic mouse model of HD. The combination of the two agents produced additive neuroprotective effects against dopamine depletion in the striatum and loss of tyrosine hydroxylase neurons in the substantia nigra pars compacta (SNpc) following chronic subcutaneous administration of MPTP. The combination treatment resulted in significant reduction in lipid peroxidation and pathologic alpha-synuclein accumulation in the SNpc neurons of the MPTP-treated mice. We also observed additive neuroprotective effects in reducing striatal lesion volumes produced by chronic subcutaneous administration of 3-NP to rats. The combination treatment showed significant effects on blocking 3-NP-induced impairment of glutathione homeostasis and reducing lipid peroxidation and DNA oxidative damage in the striatum. Lastly, the combination of CoQ(10) and creatine produced additive neuroprotective effects on improving motor performance and extending survival in the transgenic R6/2 HD mice. These findings suggest that combination therapy using CoQ(10) and creatine may be useful in the treatment of neurodegenerative diseases such as Parkinson's disease and HD.

We used positron emission tomography (PET) and the 18-flourodeoxyglucose tracer to study cerebral effects of complementary acupuncture in Parkinson's disease. Five patients received scalp-acupuncture and Madopa, while the other five had Madopa only. PET scans before and after 5 weeks of complementary acupuncture treatment show increased glucose metabolisms in parietal, temporal, occipital lobes, the thalamus, and the cerebellum in the light-diseased hemisphere, and in parietal and occipital lobes of the severe-diseased hemisphere. No changes were observed in the Madopa-only group. Acupuncture in combination with Madopa may improve cerebral glucose metabolism in Parkinson's disease.

We used positron emission tomography (PET) and the 18-flourodeoxyglucose tracer to study cerebral effects of complementary acupuncture in Parkinson's disease. Five patients received scalp-acupuncture and Madopa, while the other five had Madopa only. PET scans before and after 5 weeks of complementary acupuncture treatment show increased glucose metabolisms in parietal, temporal, occipital lobes, the thalamus, and the cerebellum in the light-diseased hemisphere, and in parietal and occipital lobes of the severe-diseased hemisphere. No changes were observed in the Madopa-only group. Acupuncture in combination with Madopa may improve cerebral glucose metabolism in Parkinson's disease.

Curcumin as a hydrophobic polyphenol is extracted from the rhizome of. Curcumin is widely used as a dietary spice and a topical medication for the treatment of inflammatory disorders in Asia. This compound also possesses remarkable anti-inflammatory and neuroprotective effects with the ability to pass from the blood brain barrier. Based on several pharmacological activities of curcumin, it has been introduced as an ideal candidate for different neurological disorders. Despite the pleiotropic activities of curcumin, poor solubility, rapid clearance and low stability have limited its clinical application. In recent years, nano-based drug delivery system has effectively improved the aqueous solubility and bioavailability of curcumin. In this review article, the effects of curcumin nanoparticles and their possible mechanism/s of action has been elucidated in various central nervous system (CNS)-related diseases including Parkinson's disease, Huntington disease, Alzheimer's disease, Multiple sclerosis, epilepsy and Amyotrophic Lateral Sclerosis. Furthermore, recent evidences about administration of nano-curcumin in the clinical trial phase have been described in the present review article.