Amyloid-ß42/Neurogranin Ratio as a Potential Index for Cognitive Impairment in Parkinson's Disease.

BACKGROUND: Synaptopathy is critical in pathophysiology of Parkinson's disease (PD). Cerebrospinal fluid (CSF) levels of neurogranin (NG) and amyloid-ß42 (Aß42) are considered markers of synaptic dysfunction in neurodegenerative diseases. OBJECTIVE: To evaluate the CSF synaptopathy-related biomarkers, especially the novel Aß42/NG ratio, in PD, establishing possible associations with cognitive level and other clinical parameters. METHODS: Levels of NG, Aß42, amyloid-ß40, total and phosphorylated tau, and Aß42/NG ratio were measured in 30 PD patients and 30 controls and correlated with cognitive and motor parameters. The accuracy in distinguishing the cognitive status was determined. RESULTS: NG and Aß42 were significantly reduced in PD, with higher NG levels in patients with worse cognition. The Aß42/NG ratio showed a direct correlation with Mini-Mental State Examination, independently from age and sex, and differentiated cognitively impaired patients with 92% sensitivity and 71.4% specificity, accuracy higher than NG alone. No correlations resulted with motor disturbances or therapy. CONCLUSIONS: The novel Aß42/NG ratio couples either presynaptic or postsynaptic markers of synaptic dysfunction, representing a potential global index of synaptopathy, useful to track cognitive functions in PD.

Proposed Tandem Effect of Physical Activity and Sirtuin 1 and 3 Activation in Regulating Glucose Homeostasis.

Sirtuins (SIRTs) are seven nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases enzymes (SIRT1-7) that play an important role in maintaining cellular homeostasis. Among those, the most studied are SIRT1 and SIRT3, a nuclear SIRT and a mitochondrial SIRT, respectively, which significantly impact with an increase in mammals' lifespan by modulating metabolic cellular processes. Particularly, when activated, both SIRT1 and 3 enhance pancreatic ß-cells' insulin release and reduce inflammation and oxidative stress pancreatic damage, maintaining then glucose homeostasis. Therefore, SIRT1 and 3 activators have been proposed to prevent and counteract metabolic age-related diseases, such as type 2 diabetes mellitus (T2DM). Physical activity (PA) has a well-established beneficial effect on phenotypes of aging like ß-cell dysfunction and diabetes mellitus. Recent experimental and clinical evidence reports that PA increases the expression levels of both SIRT1 and 3, suggesting that PA may exert its healthy contribute even by activating SIRTs. Therefore, in the present article, we discuss the role of SIRT1, SIRT3, and PA on ß-cell function and on diabetes. We also discuss the possible interaction between PA and activation of SIRTs as a possible therapeutic strategy to maintain glucose hemostasis and to prevent T2DM and its complications, especially in the elderly population.

The effect of postural deformities on back function and pain in patients with Parkinson's disease.

BACKGROUND: Postural deformities, such as Pisa syndrome (PS), and camptocormia and antecollis (C&A) are common in patient with Parkinson's disease (PwPD). These deformities can lead to back disability and pain with different mechanisms, including abnormal loading or stress on soft tissues as muscles, lumbar discs and ligaments. OBJECTIVES: To evaluate the effect of different postural deformities including PS and C&A on back function and pain in PwPD. METHODS: The function, disability and pain were assessed by Oswestry disability index (ODI) and brief pain inventory (BPI). All participants completed clinical assessments by the Unified Parkinson's Disease Rating Scale (UPDRS), Modified Hoenh & Yahr (mH&Y) staging and the Levodopa Equivalent Daily Dose (LEDD). RESULTS: PS and C&A groups significantly showed worse disability ODI and pain BPI, and higher LEDD and mH&Y stage compared with PD groups. However, no differences were found in PD duration and UPDRS in the same groups. Moreover, no differences were observed between PS and C&A groups in the mentioned scales. CONCLUSION: These results demonstrated that PS and C&A are associated with severe impairment of back functions and pain. Rehabilitation programs for PwPD and PS, and C&A should include spine alignment and postural training.

Dietary Vitamin E as a Protective Factor for Parkinson's Disease: Clinical and Experimental Evidence.

Effective disease-modifying treatments are an urgent need for Parkinson's disease (PD). A putative successful strategy is to counteract oxidative stress, not only with synthetic compounds, but also with natural agents or dietary choices. Vitamin E, in particular, is a powerful antioxidant, commonly found in vegetables and other components of the diet. In this work, we performed a questionnaire based case-control study on 100 PD patients and 100 healthy controls. The analysis showed that a higher dietary intake of Vitamin E was inversely associated with PD occurrence independently from age and gender (OR = 1.022; 95% CI = 0.999-1.045; p < 0.05), though unrelated to clinical severity. Then, in order to provide a mechanistic explanation for such observation, we tested the effects of Vitamin E and other alimentary antioxidants in vitro, by utilizing the homozygous PTEN-induced kinase 1 knockout (PINK1 -/-) mouse model of PD. PINK1 -/- mice exhibit peculiar alterations of synaptic plasticity at corticostriatal synapses, consisting in the loss of both long-term potentiation (LTP) and long-term depression (LTD), in the absence of overt neurodegeneration. Chronic administration of Vitamin E (alpha-tocopherol and the water-soluble analog trolox) fully restored corticostriatal synaptic plasticity in PINK1 -/- mice, suggestive of a specific protective action. Vitamin E might indeed compensate PINK1 haploinsufficiency and mitochondrial impairment, reverting some central steps of the pathogenic process. Altogether, both clinical and experimental findings suggest that Vitamin E could be a potential, useful agent for PD patients. These data, although preliminary, may encourage future confirmatory trials.

The influence of postural deformities on neck function and pain in patients with Parkinson's disease.

BACKGROUND: Trunk alignment is thought to contribute to neck function. However, this common assumption is not clear in patients with Parkinson's disease (PwPD) suffering from different postural deformities such as: Pisa syndrome (PS), Camptocormia & Antecollis (C&A). OBJECTIVES: to investigate the effect of different postural deformities including PS and C&A on neck function and pain in patient (PwPD). METHODS: Forty-five participants belonging to three groups: 15 PD patients without postural disorders (PD), 15 with PS, and 15 with C&A. The function, disability and pain were assessed by Neck Disability Index (NDI), and Brief Pain Inventory (BPI) which used to assess the pain severity (BPI-PS) and Pain Interference (BPI-PI). All groups completed clinical assessments by the Unified Parkinson's Disease Rating Scale (UPDRS), Modified Hoenh & Yahr (mH&Y) staging and the Levodopa Equivalent Daily Dose (LEDD). RESULTS: PD group compared with PS and C&A groups showed differences in NDI, BPI-PS, BPI-PI, LEDD and mH&Y staging (P < 0.001), but no differences found in PD duration, UPDRS-II and III in the same groups. Moreover, no differences were observed between PS and C&A groups in the mentioned scales. DISCUSSION AND CONCLUSION: These results demonstrated that PS and C&A are associated with severe impairment of neck functions, and pain in PwPD.

Association between physical activity and dementia's risk factors in patients with Parkinson's disease.

Evidence suggests that physical activity (PA) exerts beneficial effects on neurodegenerative processes, either as symptomatic relief or disease-modifying strategy. Actually, it may represent a viable neuroprotective intervention in Parkinson's disease dementia (PDD), a severe, frequent, and untreatable complication of Parkinson's disease (PD). According to such hypothesis, this cross-sectional study tested, in PD patients, the association between levels of PA and well-known risk factors for PDD, such as mood disorders and amyloid-ß42 CSF content. Amount of PA was measured by the International Physical Activity Questionnaires-Short Form (IPAQ-SF) in 128 cognitively intact PD patients and correlated with the Hamilton-Depression (HAM-D) and the Hamilton-Anxiety (HAM-A) scores; in a homogenous subgroup of 40 patients, it was further correlated with a panel of CSF biomarkers, including amyloid-ß42, total α-synuclein, total, and phosphorylated tau. The statistical model was corrected for the main potential confounding factors (motor impairment, dopaminergic treatment, disease duration, age, and sex). Both the HAM-A and HAM-D scores, as well as the Aß42 CSF content, improved in parallel with the increase of the total week amount of PA. Although with several limitations, we preliminarily demonstrated that a high level of PA is associated with a more favourable profile of PDD risk factors, in terms of both mood disturbances and CSF markers of neurodegeneration. However, confirmative studies are necessary to validate the efficacy of PA as protective intervention for PDD.

Influence of FTO rs9939609 and Mediterranean diet on body composition and weight loss: a randomized clinical trial.

BACKGROUND: The Mediterranean diet (MeD) plays a key role in the prevention of obesity. Among the genes involved in obesity, the Fat mass and obesity-associated gene (FTO) is one of the most known, but its interaction with MeD remained uncertain so far. METHODS: We carried out a study on a sample of 188 Italian subjects, analyzing their FTO rs9939609 alleles, and the difference in body composition between the baseline and a 4-weeks nutritional intervention. The sample was divided into two groups: the control group of 49 subjects, and the MeD group of 139 subjects. RESULTS: We found significant relations between MeD and both variation of total body fat (ΔTBFat) (p = 0.00) and gynoid body fat (p = 0.04). ∆TBFat (kg) demonstrated to have a significant relation with the interaction diet-gene (p = 0.04), whereas FTO was associated with the variation of total body water (p = 0.02). CONCLUSIONS: MeD demonstrated to be a good nutritional treatment to reduce the body fat mass, whereas data about FTO remain uncertain. Confirming or rejecting the hypothesis of FTO and its influence on body tissues during nutritional treatments is fundamental to decide whether its effect has to be taken into consideration during both development of dietetic plans and patients monitoring. Trial Registration ClinicalTrials.gov Id: NCT01890070. Registered 01 July 2013, https://clinicaltrials.gov/ct2/show/NCT01890070.

Effectiveness of robot-assisted gait training on motor impairments in people with Parkinson's disease: a systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to evaluate the effectiveness of robot-assisted gait training (RAGT) on motor impairments in people with Parkinson's disease (PD). A computer-based systematic literature search was performed in six databases according to PRISMA guidelines. Randomized controlled trials (RCTs) that assessed the effects of RAGT on motor impairments in people with PD were included. GRADE approach and PEDro scale were used to determine the studies' quality of evidence. Meta-analyses were performed by calculating the weighted mean difference (WMD) at 95% confidence interval. Seven RCTs (PEDro: 5-8) met the inclusion criteria for systematic review and meta-analyses. The meta-analysis showed significant improvement on Unified Parkinson Disease Rating Scale Part III after intervention [WMD=3.292; 95% confidence interval (CI)=1.378-5.207; P=0.000], and after 1-month follow-up (WMD=5.512; 95% CI=2.396-8.629; P=0.001). Stride length (WMD=9.283; 95% CI=7.153-11.414; P=0.00) and gait speed (WMD=0.166; 95% CI=-0.090 to 0.243; P=0.000) showed significant improvements after RAGT. Balance as measured by Berg Balance Scale was improved significantly after intervention (WMD=3.87; 95% CI=0.374-6.735; P=0.029) and at 1-month follow-up (WMD=3.87; 95% CI=1.324-6.413; P=0.002). The pooled analysis did not detect any significant changes regarding stride time, cadence and functional balance scales. GRADE level of evidence ranged between high and low. The RAGT showed better outcomes than conventional interventions on some motor aspects in PD. However, RAGT did not seem superior to control interventions. Further RCTs that examine the effect of RAGT on more specific outcomes and at different medication statuses are required.

Alcoholic Beverage and Meal Choices for the Prevention of Noncommunicable Diseases: A Randomized Nutrigenomic Trial.

BACKGROUND: Noncommunicable diseases (NCDs) are the first cause of death worldwide. Mediterranean diet may play a crucial role in the prevention of NCDs, and the presence of wine in this diet could play a positive role on health. METHODS: 54 healthy volunteers consumed one of the following beverages: red (RW) or white wine (WW), vodka (VDK), and/or Mediterranean meal (MeDM) and high-fat meal (HFM). RESULTS: OxLDL-C changed significantly between baseline versus HFM, MeDM versus HFM, and HFM versus HFM + RW (p < 0.05). Significant upregulation of catalase (CAT) was observed only after RW. Conversely, WW, VDK, RW + MeDM, HF + WW, and HF + VDK determined a significant downregulation of CAT gene. Superoxide dismutase 2 (SOD2) gene expression was upregulated in WW, MeDM + VDK, and RW. Contrariwise, HFM + VDK determined a downregulation of its expression. RW, RW + MeDM, and RW + HFM caused the upregulation of glutathione peroxidase-1 (GPX1). CONCLUSIONS: Our results suggest that the association of low/moderate intake of alcohol beverages, with nutraceutical-proven effectiveness, and ethanol, in association with a Mediterranean diet, could determine a reduction of atherosclerosis risk onset through a positive modulation of antioxidant gene expression helping in the prevention of inflammatory and oxidative damages.