Onset and mortality of Parkinson's disease in relation to type II diabetes.

OBJECTIVES: There is growing evidence that Parkinson's disease and diabetes are partially related diseases; however, the association between the two, and the impact of specific treatments, are still unclear. We evaluated the effect of T2D and antidiabetic treatment on age at PD onset and on all-cause mortality. RESEARCH DESIGN AND METHODS: The standardized rate of T2D was calculated for PD patients using the direct method and compared with subjects with essential tremor (ET) and the general Italian population. Age at onset and survival were also compared between patients without T2D (PD-noT2D), patients who developed T2D before PD onset (PD-preT2D) and patients who developed T2D after PD onset (PD-postT2D). RESULTS: We designed a retrospective and prospective study. The T2D standardized ratio of PD (N = 8380) and ET (N = 1032) patients was 3.8% and 6.1%, respectively, while in the Italian general population, the overall prevalence was 5.3%. In PD-preT2D patients, on antidiabetic treatment, the onset of PD was associated with a + 6.2 year delay (p < 0.001) while no difference was observed in PD-postT2D. Occurrence of T2D before PD onset negatively affected prognosis (adjusted hazard ratio = 1.64 [95% CI 1.33-2.02]; p < 0.001), while no effect on survival was found in PD-postT2D subjects (hazard ratio = 0.86, [95% CI 0.53-1.39]; p = 0.54). CONCLUSIONS: T2D, treated with any antidiabetic therapy before PD, is associated with a delay in its onset. Duration of diabetes increases mortality in PD-preT2D, but not in PD-postT2D. These findings prompt further studies on antidiabetic drugs as a potential disease-modifying therapy for PD.

Clinical correlates of serum 25-hydroxyvitamin D in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) patients have lower levels of serum 25-hydroxyvitamin D (25(OH)D) than the general population. Previous studies have suggested a negative association between 25(OH)D and clinical features of PD, but the data are inconsistent. MATERIALS AND METHODS: We conducted a cross-sectional, observational study. Serum 25(OH)D, disease (Hoehn-Yahr stage [HY]) and clinical symptom (Unified Parkinson Disease Rating Scale [UPDRS]) severity and global cognitive functions (Mini-Mental State Examination [MMSE]) were studied in 500 consecutive PD patients not using vitamin D supplements. Information on sunlight exposure and dietary intakes (using a 66-item food frequency questionnaire) were also collected. A convenient sample of age and sex-matched community healthy controls (N = 100) was included as a control group. RESULTS: PD patients had lower 25(OH)D serum levels than controls. Deficiency status (<20 ng/mL) was found in 65.6% of patients. 25(OH)D levels were independently correlated to sunlight exposure (P = .002) and vitamin D intake (P = .009). In multivariate models, using a Mendelian randomization approach, lower serum 25(OH)D was associated with more severe disease (HY, P = .035), worse clinical symptoms (UPDRS Part-III total score [P = .006] and dopaminergic [P = .033] and non-dopaminergic subscores [P = .001]) and greater global cognitive function impairment (P = .041). Neither cognitive functions nor clinical features were associated with reduced intake of vitamin D and sunlight exposure. CONCLUSION: : Serum 25(OH)D was negatively correlated with disease and symptoms severity, as well as with global cognitive functions. Our study adds to the evidence that low 25(OH)D may affect the progression of PD negatively. Intervention studies in this area are required.

Resting energy expenditure in Parkinson's disease patients under dopaminergic treatment.

Background: Weight homeostasis is complex in Parkinson's disease (PD) and body weight changes substantially throughout the course of the disease. We designed a case-control study to (i) investigate whether PD is associated with changes in resting energy expenditure (REE), (ii) to assess how accurately REE could be predicted for individuals with PD utilizing the equations constructed for healthy individuals, and (iii) to eventually construct a new equation.Materials & Methods: Measured REE (mREE) was compared between 122 PD patients and 122 gender and body mass index (BMI)-matched controls. The accuracy of estimated REE by 5 common equations (Harris/Benedict-1919, Roza/Shizgal-1984, Mifflin St. Jeor, WHO/FAO and aggregate formula) was investigated in PD using Bland-Altman analysis and reported as the frequency of accurate predictions (±10%). Concordance correlation coefficients (CCC) were also calculated. Then, we regressed a new REE equation - using gender, age, weight, height and Hoehn-Yahr stage - and validated it in an independent sample (N = 100).Results: No significant difference in mREE was recorded between the whole PD sample and healthy controls. However, mREE was increased in patients with BMI ≥ 30 kg/m2 and Hoehn-Yahr stage ≥ 3. Limited accuracy was present in the available REE equations (accurate prediction [±10%] frequency, <60% for all). For the new equation, the proportion of accurate prediction was 67.0% (overestimation, 24.0%) and CCC was 0.77.Conclusion: PD patients are not commonly characterized by an increase in REE. This is limited to patients suffering from obesity and more severe disease. Common REE equations appear to be inaccurate. The new predictive equation proposed in this study provided better REE estimates.

Does Gut Microbiota Influence the Course of Parkinson's Disease? A 3-Year Prospective Exploratory Study in de novo Patients.

BACKGROUND: Although abnormalities in gut microbiota are hypothesized to influence the pathogenesis and clinical phenotype of Parkinson's disease (PD), prospective studies on de novo patients are lacking. OBJECTIVE: To preliminarily investigate whether gut microbiota in early untreated PD may predict motor and non-motor features progression over a 3-year period. METHODS: 16S ribosomal RNA gene amplicons were sequenced on fecal samples of 39 de novo PD patients. Multiple confounders were taken into account, including dietary habits. Motor and non-motor symptoms were assessed using validated scales at baseline and followed-up yearly for 3 years. At last follow-up, a detailed neuropsychological assessment was additionally performed. A general linear model for repeated measurements- adjusted by dopaminergic therapy at follow-up- was used to investigate the relationship between bacterial taxa abundance at baseline (stratified by the median of distribution at baseline) and outcome variables. RESULTS: Twenty-five patients were included (11 refused, 2 lost at follow-up, 1 died). Lower abundance of Roseburia (Firmicutes phylum) at baseline was associated with worse evolution of motor, non-motor and cognitive functions at 3-year follow-up. Similarly, lower abundance of Ruminococcaceae and Actinobacteria at baseline was associated with faster worsening of global cognitive functions. At follow-up, frontal lobe functions were the features most robustly associated with baseline microbial abnormalities. CONCLUSION: In the present exploratory study on de novo PD, we found an association between abnormal distribution of specific bacterial taxa and the progression of motor and non-motor features over a 3-year period. This proof-of-principle study supports the design of a larger observational study aiming to determine whether these differences survive multiple-comparison correction and define microbiota-specific subgroups suitable for therapeutic targeting.

COVID-19 in Parkinson's Disease Patients Living in Lombardy, Italy.

BACKGROUND: It is unknown whether patients with PD are at greater risk of COVID-19, what their risk factors are, and whether their clinical manifestations differ from the general population. OBJECTIVES: The study aimed to address all these issues. METHODS: In a case-controlled survey, we interviewed 1,486 PD patients attending a single tertiary center in Lombardy, Italy and 1,207 family members (controls). RESULTS: One hundred five (7.1%) and 92 controls (7.6%) were identified as COVID-19 cases. COVID-19 patients were younger, more likely to suffer from chronic obstructive pulmonary disease, to be obese, and vitamin D nonsupplemented than unaffected patients. Six patients (5.7%) and 7 family members (7.6%) died from COVID-19. Patients were less likely to report shortness of breath and require hospitalization. CONCLUSIONS: In an unselected large cohort of nonadvanced PD patients, COVID-19 risk and mortality did not differ from the general population, but symptoms appeared to be milder. The possible protective role of vitamin D supplementation warrants future studies. © 2020 International Parkinson and Movement Disorder Society.

α-Synuclein oligomers in skin biopsy of idiopathic and monozygotic twin patients with Parkinson's disease.

A variety of cellular processes, including vesicle clustering in the presynaptic compartment, are impaired in Parkinson's disease and have been closely associated with α-synuclein oligomerization. Emerging evidence proves the existence of α-synuclein-related pathology in the peripheral nervous system, even though the presence of α-synuclein oligomers in situ in living patients remains poorly investigated. In this case-control study, we show previously undetected α-synuclein oligomers within synaptic terminals of autonomic fibres in skin biopsies by means of the proximity ligation assay and propose a procedure for their quantification (proximity ligation assay score). Our study revealed a significant increase in α-synuclein oligomers in consecutive patients with Parkinson's disease compared to consecutive healthy controls (P < 0.001). Proximity ligation assay score (threshold value > 96 using receiver operating characteristic) was found to have good sensitivity, specificity and positive predictive value (82%, 86% and 89%, respectively). Furthermore, to disclose the role of putative genetic predisposition in Parkinson's disease aetiology, we evaluated the differential accumulation of oligomers in a unique cohort of 19 monozygotic twins discordant for Parkinson's disease. The significant difference between patients and healthy subjects was confirmed in twins. Intriguingly, although no difference in median values was detected between consecutive healthy controls and healthy twins, the prevalence of healthy subjects positive for proximity ligation assay score was significantly greater in twins than in the consecutive cohort (47% versus 14%, P = 0.019). This suggests that genetic predisposition is important, but not sufficient, in the aetiology of the disease and strengthens the contribution of environmental factors. In conclusion, our data provide evidence that α-synuclein oligomers accumulate within synaptic terminals of autonomic fibres of the skin in Parkinson's disease for the first time. This finding endorses the hypothesis that α-synuclein oligomers could be used as a reliable diagnostic biomarker for Parkinson's disease. It also offers novel insights into the physiological and pathological roles of α-synuclein in the peripheral nervous system.

Muscle-targeted nutritional support for rehabilitation in patients with parkinsonian syndrome.

OBJECTIVE: We evaluated the efficacy of muscle-targeted nutritional support on the functional outcomes of multidisciplinary intensive rehabilitation treatment (MIRT) in patients with Parkinson disease (PD) or parkinsonism. METHODS: We conducted a pragmatic, bicentric, randomized (1:1), assessor-blind controlled trial (Protein, Leucine and Vitamin D Enhancing Rehabilitation [PRO-LEADER]; April 2017 to January 2018) in cognitively intact patients with PD or parkinsonism and undergoing a 30-day MIRT. Patients (n = 150) received a standard hospital diet with or without a whey protein-based nutritional supplement enriched with leucine and vitamin D twice daily. The primary efficacy endpoint was the increase in the distance walked during a 6-minute walking test (6MWT). Secondary endpoints were changes in 4-meter walking speed, Timed Up and Go test (TUG), Berg balance scale, handgrip strength, Self-assessment Parkinson's Disease Disability Scale, body weight, and skeletal muscle mass (SMM). RESULTS: Nutritional support resulted in greater increase in the distance walked during 6MWT (mean 69.6 meters [95% confidence interval (CI) 60.7-78.6]) than no support (51.8 meters [95% CI 37.0-66.7]): center-adjusted mean difference, 18.1 meters (95% CI 0.9-35.3) (p = 0.039). Further adjustment for changes in dopaminergic therapy and SMM yielded consistent results: mean difference, 18.0 meters (95% CI 0.7-35.2) (p = 0.043). A meaningful effect was also found for the following secondary endpoints: 4-meter walking speed (p = 0.032), TUG (p = 0.046), SMM, and SMM index (p = 0.029). Six patients discontinued the nutritional therapy due to mild side effects. CONCLUSION: The consumption of a whey protein-based nutritional formula enriched with leucine and vitamin D with MIRT improved lower extremity function and preserved muscle mass in patients with PD or parkinsonism.Clinicaltrials.gov IDENTIFIER: NCT03124277. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with parkinsonism undergoing intensive rehabilitation, a whey protein-based nutritional formula enriched with leucine and vitamin D increased distance walked on the 6MWT.

Nutritional characterisation of Zambian Moringa oleifera: acceptability and safety of short-term daily supplementation in a group of malnourished girls.

In Zambia, chronic malnutrition still is one of the most common problem among children. To fight against malnutrition, the easiest short-term solution could be to combine specific types of food with affordable local plants. A large variety of natural food resources grow in Zambia, such as Moringa oleifera (MO), whose leaves are known for their health benefits, but are not consumed much by local populations. We analysed Zambian MO powder obtained from dried leaves and found that it contains large amounts of protein, minerals and vitamins, such as iron, calcium and carotenoids. These characteristics make MO a good and sustainable complementary solution to malnutrition. We also evaluated the acceptability and the safety of dietary supplementation with MO powder in malnourished children for 30 days. A daily dose of 14 g daily was safe and well accepted. Its regular use in the menu of local populations may be viable proposition.

Unraveling gut microbiota in Parkinson's disease and atypical parkinsonism.

BACKGROUND: Although several studies have suggested that abnormalities in gut microbiota may play a critical role in the pathogenesis of PD, data are still extremely heterogeneous. METHODS: 16S gene ribosomal RNA sequencing was performed on fecal samples of 350 individuals, subdivided into idiopathic PD (n = 193, of whom 39 were drug naïve) stratified by disease duration, PSP (n = 22), MSA (n = 22), and healthy controls (HC; n = 113). Several confounders were taken into account, including dietary habits. RESULTS: Despite the fact that unadjusted comparison of PD and HC showed several differences in relative taxa abundances, the significant results were greatly reduced after adjusting for confounders. Although most of these differences were associated with disease duration, lower abundance in Lachnospiraceae was the only difference between de novo PD and HC (remaining lower across almost all PD duration strata). Decreased Lachnospiraceae and increased Lactobacillaceae and Christensenellaceae were associated with a worse clinical profile, including higher frequencies of cognitive impairment, gait disturbances, and postural instability. When compared with HC, MSA and PSP patients shared the changes in PD, with a few exceptions: in MSA, Lachnospiraceae were not lower, and Prevotellaceae were reduced; in PSP, Lactobacillaceae were similar, and Streptococcaceae were reduced. CONCLUSIONS: Gut microbiota may be an environmental modulator of the pathogenesis of PD and contribute to the interindividual variability of clinical features. Data are influenced by PD duration and several confounders that need to be taken into account in future studies. Prospective studies in de novo PD patients are needed to elucidate the net effect of dysbiosis on the progression of the disease. © 2018 International Parkinson and Movement Disorder Society.

Daily intake of Mucuna pruriens in advanced Parkinson's disease: A 16-week, noninferiority, randomized, crossover, pilot study.

BACKGROUND: Thousands of individuals with Parkinson's disease (PD) in low-income countries have limited access to marketed levodopa preparations. Mucuna pruriens (MP), a levodopa-containing leguminous plant growing in tropical areas, may be a sustainable alternative therapy for indigent patients. Single-dose intake of MP proved noninferior to marketed levodopa preparations. METHODS: Fourteen PD patients with motor fluctuations and dyskinesias received MP powder (obtained from roasted seeds) and marketed levodopa/carbidopa (LD/CD) in a randomized order and crossover design over a 16-week period. Efficacy measures were changes in quality of life, motor and non-motor symptoms, and time with good mobility without troublesome dyskinesias. Safety measures included tolerability, frequency of adverse events, changes in laboratory indices and electrocardiogram. RESULTS: Daily intake of MP was associated with a variable clinical response, especially in terms of tolerability. Seven patients (50%) discontinued MP prematurely due to either gastrointestinal side-effects (n = 4) or progressive worsening of motor performance (n = 3), while nobody discontinued during the LD/CD phase. In those who tolerated MP, clinical response to MP was similar to LD/CD on all efficacy outcome measures. Patients who dropped out entered a study extension using MP supernatant water (median[IQR], 16 [7-20] weeks), which was well tolerated. CONCLUSIONS: The overall benefit provided by MP on the clinical outcome was limited by tolerability issues, as one could expect by the relatively rapid switch from LD/CD to levodopa alone in advanced PD. Larger parallel-group studies are needed to identify appropriate MP formulation (e.g. supernatant water), titration scheme and maintenance dose to minimize side-effects in the long-term. CLINICAL TRIALS. GOV IDENTIFIER: NCT02680977.

Mucuna pruriens in Parkinson disease: A double-blind, randomized, controlled, crossover study.

OBJECTIVE: To investigate whether Mucuna pruriens (MP), a levodopa-containing leguminous plant growing in all tropical areas worldwide, may be used as alternative source of levodopa for indigent individuals with Parkinson disease (PD) who cannot afford long-term therapy with marketed levodopa preparations. METHODS: We investigated efficacy and safety of single-dose intake of MP powder from roasted seeds obtained without any pharmacologic processing. Eighteen patients with advanced PD received the following treatments, whose sequence was randomized: (1) dispersible levodopa at 3.5 mg/kg combined with the dopa-decarboxylase inhibitor benserazide (LD+DDCI; the reference treatment); (2) high-dose MP (MP-Hd; 17.5 mg/kg); (3) low-dose MP (MP-Ld; 12.5 mg/kg); (4) pharmaceutical preparation of LD without DDCI (LD-DDCI; 17.5 mg/kg); (5) MP plus benserazide (MP+DDCI; 3.5 mg/kg); (6) placebo. Efficacy outcomes were the change in motor response at 90 and 180 minutes and the duration of on state. Safety measures included any adverse event (AE), changes in blood pressure and heart rate, and the severity of dyskinesias. RESULTS: When compared to LD+DDCI, MP-Ld showed similar motor response with fewer dyskinesias and AEs, while MP-Hd induced greater motor improvement at 90 and 180 minutes, longer ON duration, and fewer dyskinesias. MP-Hd induced less AEs than LD+DDCI and LD-DDCI. No differences in cardiovascular response were recorded. CONCLUSION: Single-dose MP intake met all noninferiority efficacy and safety outcome measures in comparison to dispersible levodopa/benserazide. Clinical effects of high-dose MP were similar to levodopa alone at the same dose, with a more favorable tolerability profile. CLINICALTRIALSGOV IDENTIFIER: NCT02680977.

Dietary habits in Parkinson's disease: Adherence to Mediterranean diet.

INTRODUCTION: Our objective is to describe the dietary habits, food preferences and adherence to Mediterranean diet (MeDi) of a large sample of Italian Parkinson's Disease (PD) patients compared to a group of controls. METHODS: Dietary habits of 600 PD patients from throughout Italy and 600 controls matched by gender, age, education, physical activity level and geographical residence, were collected using the ON-GP Food Frequency Questionnaire. Then, we compared patients by disease duration and the presence of swallowing disturbances. RESULTS: Overall, adherence of PD patients (males, 53.8%; mean disease duration, 9.2 ± 7.0 years) to MeDi was similar to controls (score, 4.8 ± 1.7 vs. 4.9 ± 1.6; P = 0.294). Patients consumed less alcohol and fish and drank significantly less water, coffee, and milk which resulted also in lower total fluids intake. On the contrary, they ate more fruit, cooked vegetables, cereals and baked items, more dressings and more sweets in general. Disease duration was associated with increased intake of several food groups but it was not associated with changes in MeDi score (P = 0.721). Patients with swallowing disturbances (n = 72) preferred softer and more viscous food but preferences did not result in differences in dietary pattern. However, patients with dysphagia drank less fluids (P = 0.043). DISCUSSION: PD patients presented different dietary habits and food preferences compared to the general population and adherence to MeDi was not associated with disease duration. Self-reported dysphagia was associated with reduced intake of fluids. These aspects may be amenable to change in order to improve the management of nutritional issues in this patient population.

Dietary habits and neurological features of Parkinson's disease patients: Implications for practice.

BACKGROUND & AIMS: Parkinson's disease (PD) patients can benefit considerably from appropriate nutritional care, particularly from diet. However, there is limited evidence on the eating habits of PD patients and their relationship with the features of the disease. METHODS: We conducted a large case-control study. Consecutive PD patients (N = 600) receiving systematic nutritional care and healthy controls (N = 600) matched (1:1) for age, gender, education, physical activity level and residence were studied using a 66-item food frequency questionnaire. The relationship between dietary habits and the following features of PD were investigated in patients: body weight, energy balance, constipation, and levodopa therapy (dose) and its related motor complications. RESULTS: PD patients had lower BMI and reported higher food intake than controls. BMI was found to be inversely associated with disease duration and severity, and levodopa-related motor complications, whereas energy intake was positively associated with these variables. An increase in protein intake by 10 g over physiological requirements (0.8 g/kg/day) corresponded to a mean increase in levodopa dose of 0.7 mg/kg/day. Constipation was also associated with higher levodopa requirements. Finally, protein intake and its distribution throughout the day influenced levodopa-related motor complications. CONCLUSION: The management of protein intake and the treatment of constipation should be considered to be an integral part of the care of PD patients. Attention should always be focused on energy intake also. This would result in the maintenance of nutritional status, the optimization of levodopa-therapy and the minimization of its related motor complications.

Probiotics and prebiotic fiber for constipation associated with Parkinson disease: An RCT.

OBJECTIVES: Our objective was to evaluate the efficacy of probiotics and prebiotics in patients with Parkinson disease (PD) and constipation. METHODS: We conducted a tertiary setting, randomized, double-blind, placebo-controlled trial in patients with PD with Rome III-confirmed constipation based on 2-week stool diary data at baseline. Patients (n = 120) were randomly assigned (2:1) to either a fermented milk, containing multiple probiotic strains and prebiotic fiber, or placebo, once daily for 4 weeks. The primary efficacy endpoint was the increase in the number of complete bowel movements (CBMs) per week. The key secondary endpoints were 3 or more CBMs and an increase by one or more CBMs per week during weeks 3 and 4. RESULTS: For the primary endpoint, the consumption of a fermented milk containing probiotics and prebiotics resulted in a higher increase in the number of CBMs (mean 1.2, 95% confidence interval [CI] 0.8-1.6) than placebo (0.1, 95% CI -0.4% to 0.6%) (mean difference 1.1, 95% CI 0.4-1.8; p = 0.002). For the key secondary endpoints, a higher number of patients in the probiotics-prebiotics group vs the placebo group reported 3 or more CBMs (p = 0.030; 58.8% vs 37.5%; odds ratio = 2.4, 95% CI 1.1-5.2) and an increase by one or more CBMs (p = 0.004; 53.8% vs 25.0%; odds ratio = 3.5, 95% CI 1.8-8.1) during weeks 3 and 4. CONCLUSIONS: The consumption of a fermented milk containing multiple probiotic strains and prebiotic fiber was superior to placebo in improving constipation in patients with PD. CLINICALTRIALSGOV IDENTIFIER: NCT02459717. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with PD who have constipation, fermented milk containing probiotics and prebiotics increases the frequency of CBMs.

Sarcopenia and Dynapenia in Patients With Parkinsonism.

OBJECTIVES: To estimate prevalence of sarcopenia and dynapenia in outpatients with Parkinson disease (PD) and to investigate their association with the features of the disease. DESIGN: Cross-sectional study. SETTING: A specialized tertiary care center. PARTICIPANTS: Consecutive patients (n = 364) aged 65 years or older, affected by parkinsonian syndromes. MEASUREMENTS: Skeletal muscle mass (SMM), as well as strength and gait speed (GS) were assessed by bioimpedence analysis, handgrip dynamometry, and the 4-meter walking test, respectively. Based on these assessments, sarcopenia was diagnosed using the European Working Group on Sarcopenia in Older People criteria. Dynapenia was defined as handgrip strength less than 30 kg in men and less than 20 kg in women. RESULTS: In total, 235 patients (64.6%) had a diagnosis of idiopathic PD. Low SMM index was recorded in 27 patients. Due to gait disturbances and postural instability, GS could not be measured in 98 patients and was found to be reduced in 61.3% of those assessed. Prevalence of sarcopenia and dynapenia was 6.6% (95% confidence interval [CI] 4.3-9.7) and 75.5% (95% CI 70.8-79.9), respectively. Sarcopenia tended to be higher in patients unable to perform GS assessment and was unrelated to the type of parkinsonian syndrome. It was associated with older age, longer disease duration, more severe disease, and higher disability in activities of daily living, as assessed by disease-specific clinical rating scale. Dynapenia was directly associated with parkinsonism other than PD, older age, and disability, whereas regular physical therapy appeared to be a preventive factor. However, it was unrelated to disease duration and severity. Finally, the disability score of activities of daily living was inversely correlated with handgrip strength and GS, whereas no association was found with SMM index. CONCLUSION: Being primarily motor disorders, parkinsonian syndromes are characterized by progressive disability in performing activities of daily living. Impaired functional status is a prominent feature of this patient population, independently of disease duration and severity. Sarcopenia is mainly related to advancing disease and, due to a significant sparing of SMM, is an infrequent condition, likely to play a minor role in disability. Several factors could be responsible for this favorable body composition (eg, motor symptoms, levodopa therapy) and deserve further investigation. The prognostic impact of sarcopenia also needs to be addressed.

Mucuna pruriens for Parkinson's disease: Low-cost preparation method, laboratory measures and pharmacokinetics profile.

BACKGROUND: Parkinson's disease (PD) is a progressive neurological condition. Levodopa (LD) is the gold standard therapy for PD patients. Most PD patients in low-income areas cannot afford long-term daily Levodopa therapy. The aim of our study was to investigate if Mucuna pruriens (MP), a legume with high LD content that grows in tropical regions worldwide, might be potential alternative for poor PD patients. METHODS: We analyzed 25 samples of MP from Africa, Latin America and Asia. We measured the content in LD in various MP preparations (dried, roasted, boiled). LD pharmacokinetics and motor response were recorded in four PD patients, comparing MP vs. LD+Dopa-Decarboxylase Inhibitor (DDCI) formulations. RESULTS: Median LD concentration in dried MP seeds was 5.29%; similar results were obtained in roasted powder samples (5.3%), while boiling reduced LD content up to 70%. Compared to LD+DDCI, MP extract at similar LD dose provided less clinical benefit, with a 3.5-fold lower median AUC. CONCLUSION: Considering the lack of a DDCI, MP therapy may provide clinical benefit only when content of LD is at least 3.5-fold the standard LD+DDCI. If long-term MP proves to be safe and effective in controlled clinical trials, it may be a sustainable alternative therapy for PD in low-income countries.

Dementia in Parkinson's disease: Is male gender a risk factor?

BACKGROUND: The rates of cognitive decline in patients with Parkinson's disease (PD) are higher than in the general population. Age and disease duration have been associated with increasing rates of dementia in PD. However, the role of other factors including gender has been poorly investigated. We investigated the relationship between dementia and gender along with other established risk factors, such as age and disease duration. METHODS: We conducted a cross-sectional retrospective study including all consecutive patients diagnosed with idiopathic PD attending a single out-patient tertiary clinic over an 18-year period (1995-2013). Dementia was diagnosed according to DSM-IV criteria. RESULTS: Prevalence of dementia was 11.5% (95%CI, 10.8-12.3) and 13.5% (95%CI, 12.7-14.5) in the whole population (N = 6599) and in those aged ≥60 years (N = 5373), respectively. Age and disease duration were independently associated with dementia, and the latter was associated with dementia up to 84 years of age. Male gender was an independent risk factor. In addition, while the rate of dementia increased in males over all age strata, we found that in females prevalence began to increase steadily after the age of 65 years, reaching male estimates only after 80 years of age. Higher rates in male gender were observed between 60 and 80 years of age. CONCLUSION: Age and PD duration are confirmed risk factors for dementia. However, disease duration appeared to be a less important factor in cognitive decline in patients aged ≥85 years. As opposed to gender-specific estimates in the general population, male gender is likely associated with higher rates of dementia in PD patients.