Changes in motor activity level in individuals with frontotemporal dementia.

Changes in motor activity are common in individuals with Frontotemporal dementia (FTD). Yet, it remains unclear why some individuals become motorically hyperactive, while others hypoactive even in early stages of the disease. This study aimed to examine the relationship between motor activity level and (1) FTD clinical subtype, and (2) cortical thickness and subcortical volumes. Eighty-two charts were retrospectively reviewed from patients meeting consensus criteria for one of the three main clinical subtypes of FTD: probable bvFTD, semantic variant Primary Progressive Aphasia (PPA), or non-fluent variant PPA. Participants were assigned to one of three groups: (1) hyperactive, (2) hypoactive, or (3) no record of change. Hyperactivity was prevalent among bvFTD (58.5%) and semantic PPA (68.8%) subtypes while hypoactivity was less common in both subtypes (29.3% and 18.8%, respectively). The majority of patients with non-fluent PPA showed no record of change in motor activity (66.7%). The analysis of cortical thickness and subcortical volumes did not identify significant associations with motor activity levels. In conclusion, increased motor activity is highly prevalent among individuals with FTD, especially bvFTD and svPPA subtypes. These findings may inform prognosis and prediction of changes in motor activity, and allow planning for appropriate environmental and behavioural interventions. Future studies with prospective, standardized longitudinal collection of information regarding the type and level of change in motor activity, including wearable measures of actigraphy, may help to further delineate the onset and progression of abnormal motor behaviours and determine neuroanatomic associations in FTD.

Ambroxol as a novel disease-modifying treatment for Parkinson's disease dementia: protocol for a single-centre, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Currently there are no disease-modifying treatments for Parkinson's disease dementia (PDD), a condition linked to aggregation of the protein α-synuclein in subcortical and cortical brain areas. One of the leading genetic risk factors for Parkinson's disease is being a carrier in the gene for ß-Glucocerebrosidase (GCase; gene name GBA1). Studies in cell culture and animal models have shown that raising the levels of GCase can decrease levels of α-synuclein. Ambroxol is a pharmacological chaperone for GCase and is able to raise the levels of GCase and could therefore be a disease-modifying treatment for PDD. The aims of this trial are to determine if Ambroxol is safe and well-tolerated by individuals with PDD and if Ambroxol affects cognitive, biochemical, and neuroimaging measures. METHODS: This is a phase II, single-centre, double-blind, randomized placebo-controlled trial involving 75 individuals with mild to moderate PDD. Participants will be randomized into Ambroxol high-dose (1050 mg/day), low-dose (525 mg/day), or placebo treatment arms. Assessments will be undertaken at baseline, 6-months, and 12-months follow up times. Primary outcome measures will be the Alzheimer's disease Assessment Scale-cognitive subscale (ADAS-Cog) and the ADCS Clinician's Global Impression of Change (CGIC). Secondary measures will include the Parkinson's disease Cognitive Rating Scale, Clinical Dementia Rating, Trail Making Test, Stroop Test, Unified Parkinson's disease Rating Scale, Purdue Pegboard, Timed Up and Go, and gait kinematics. Markers of neurodegeneration will include MRI and CSF measures. Pharmacokinetics and pharmacodynamics of Ambroxol will be examined through plasma levels during dose titration phase and evaluation of GCase activity in lymphocytes. DISCUSSION: If found effective and safe, Ambroxol will be one of the first disease-modifying treatments for PDD. TRIAL REGISTRATION: ClinicalTrials.gov NCT02914366, 26 Sep 2016/retrospectively registered.

Efficacy of a single intramuscular injection of porcine FSH in hyaluronan prior to ovum pick-up in Holstein cattle.

Plasma FSH profiles, in vitro embryo production (IVP) after ovum pickup (OPU), and establishment of pregnancy with IVP embryos were compared in untreated Holstein oocyte donors and those superstimulated with multiple injections or a single intramuscular (IM) injection of porcine FSH (pFSH) in hyaluronan (HA). Plasma FSH profiles were determined in 23 heifers randomly allocated to one of four groups. Controls received no treatment, whereas the F200 group received 200 mg of pFSH in four doses, 12 hours apart. The F200HA and F300HA groups received 200- or 300-mg pFSH in 5 mL or 7.5 mL, respectively of a 0.5% HA solution by a single IM injection. Plasma FSH levels were determined before the first pFSH treatment and every 6 hours over 96 hours. All data were analyzed by orthogonal contrasts. Circulating FSH area under curve (AUC) in pFSH-treated animals was greater than that in the control group (P = 0.02). Although the AUC did not differ among FSH-treated groups (P = 0.56), the total period with elevated plasma FSH was greater in the F200 group than in the HA groups (P < 0.0001). However, the F300HA group had a greater AUC than the F200HA group (P = 0.006), with a similar total period with elevated plasma FSH (P = 0.17). The IVP was performed in 90 nonlactating Holstein cows randomly allocated to one of the four treatment groups as in the first experiment. A greater proportion of medium-sized (6-10 mm) follicles was observed in cows receiving pFSH, regardless of the treatment group (P < 0.0001). Also, numbers of follicles (P = 0.01), cumulus-oocyte complexes (COCs) retrieved (P = 0.01) and matured (P = 0.02), cleavage rates (P = 0.002), and blastocysts produced per OPU session (P = 0.06) were greater in cows receiving pFSH, regardless of the treatment group. Cows in the F200HA group had a greater recovery rate (P = 0.009), number of COCs cultured (P = 0.04), and blastocysts produced per OPU session (P = 0.06) than cows in the F300HA group. Similar pregnancy rates were observed 50 to 60 days after transferring IVP embryos from donors in the different treatment groups (P > 0.05). In conclusion, a single IM injection of pFSH combined in 0.5% HA resulted in similar plasma FSH profiles as twice-daily pFSH treatments. Treatment of nonlactating donors with pFSH, with or without HA, resulted in increased IVP over untreated controls. A single dose of 200 mg of pFSH in 0.5% HA resulted in greater IVP than 300-mg pFSH in HA. Finally, pregnancy rates with IVP embryos were similar, regardless donor treatment.

Plasma anti-mullerian hormone: an endocrine marker for in vitro embryo production from Bos taurus and Bos indicus donors.

The aim of this study was to evaluate the association between plasma anti-mullerian hormone (AMH) concentration and in vitro embryo production (IVP) from Bos taurus (Holstein) and Bos indicus (Nelore) donors. A total of 59 Holstein (15 prepubertal heifers aged 8-10 mo, 15 cyclic heifers aged 12-14 mo, 14 lactating cows, and 15 nonlactating cows) and 34 Nelore (12 prepubertal heifers aged 10-11 mo, 10 prepubertal heifers aged 21-23 mo, and 12 cyclic heifers aged 24-26 mo) females were enrolled. All females underwent an ovum pick-up (OPU), without previous synchronization of the follicular wave, and IVP procedure. Immediately before the OPU procedure, blood samples were collected for subsequent AMH determination. A positive correlation was observed between the plasma AMH and number of in vitro embryos produced from Holstein (r = 0.36, P < 0.001) and Nelore (r = 0.50, P = 0.003) donors. For additional analyses, donors within each genotype were classified into 1 of 2 AMH categories (low or high) according to the average AMH concentration for each genotype. The results revealed that females classified as having high AMH presented a greater number of visible aspirated follicles (Holstein: 20.9 ± 1.5 vs 13.6 ± 0.9, P < 0.0001; Nelore: 54.3 ± 6.1 vs 18.6 ± 2.1, P < 0.0001) and a greater number of recovered cumulus-oocyte complexes (Holstein: 17.3 ± 1.5 vs 9.0 ± 0.9, P < 0.0001; Nelore: 45.3 ± 6.4 vs 13.4 ± 1.7, P < 0.0001). However, there was no difference in the blastocyst production rate (Holstein: 20.6% ± 4.0% vs 19.8% ± 4.2%, P = 0.60; Nelore: 33.7% ± 6.5% vs 27.4% ± 5.5%, P = 0.41, high and low AMH, respectively). Moreover, donors classified as having high AMH yielded a greater number of embryos produced per OPU (Holstein: 3.0 ± 0.7; Nelore: 7.0 ± 1.7) compared with those classified as having low AMH (Holstein: 1.2 ± 0.3, P = 0.04; Nelore: 2.2 ± 0.5, P = 0.007). In conclusion, although the plasma AMH concentration did not alter the ability of the cumulus-oocyte complex to reach the blastocyst stage, the AMH concentration in plasma can be an accurate endocrine marker for the in vitro embryo yield from either B. taurus (Holstein) or B. indicus (Nelore) donors. Therefore, AMH is a promising tool to enhance the overall efficiency of OPU-IVP programs in the field as a selective criterion for high embryo producing donors.

Superstimulation prior to the ovum pick-up to improve in vitro embryo production in lactating and non-lactating Holstein cows.

The present study evaluated the efficacy of superstimulation with p-FSH (Folltropin) before the ovum pick-up (OPU) on IVP in lactating and nonlactating Holstein donors. A total of 30 Holstein cows (15 lactating and 15 nonlactating) were blocked by lactation status to one of two groups (control or p-FSH), in a cross-over design. On a random day of the estrous cycle, all cows received an intravaginal progesterone device and 2.0 mg IM of estradiol benzoate (Day 0). Cows in the control group received no further treatment, whereas cows in the p-FSH group received a total dosage of 200 mg of p-FSH on Days 4 and 5 in four decreasing doses 12 hours apart (57, 57, 43, and 43 mg). On Day 7, the progesterone device was removed, and OPU was conducted in both groups (40 hours after the last p-FSH injection in the p-FSH-treated group). There was no difference between groups (P = 0.92) in the numbers of follicles that were aspirated per OPU session (17.2 ± 1.3 vs. 17.1 ± 1.1 in control and p-FSH-treated cows, respectively); however, p-FSH-treated cows had a higher (P < 0.001) percentage of medium-sized follicles (6-10 mm) at the time of the OPU (55.1%; 285/517) than control cows (20.8%; 107/514). Although recovery rate was lower (60.0%, 310/517 vs. 69.8%, 359/514; P = 0.002), p-FSH-treated cows had a higher blastocyst production rate (34.5%, 89/258 vs. 19.8%, 55/278; P < 0.001) and more transferable embryos per OPU session were produced in the p-FSH group (3.0 ± 0.5 vs. 1.8 ± 0.4; P = 0.02). Regardless of treatment, non-lactating cows had a higher blastocyst rate (41.9%, 106/253 vs. 13.4%, 38/283; P = 0.001) and produced more transferable embryos per OPU session (3.5 ± 0.5 vs. 1.3 ± 0.3; P = 0.003) than lactating cows. Thus, superstimulation of Holstein donors with p-FSH before OPU increased the efficiency of IVP. In addition, non-lactating donors had higher percentage of in vitro blastocyst development and produced more embryos per OPU session than lactating cows.

Evaluating the acute contributions of dopaminergic replacement to gait with obstacles in Parkinson's disease.

The influence of dopaminergic replacement (DR) on gait in people with Parkinson's disease (PD) is well documented. However, little is known about the acute effects of dopamine on more complex locomotor tasks that require visual guidance to avoid obstacles during gait. The authors investigated the influence of DR on locomotor behavior in a task where movement planning and control might be challenged by the height of the obstacle. The PD group included patients diagnosed with idiopathic PD (n = 12), as well as healthy controls (n = 12). Patients walked and stepped over obstacles of different heights before (OFF) and after (ON) levodopa intake. Spatial adjustments were not modulated by DR, but the step time to perform these anticipatory gait adjustments was longer only in PD-OFF (compared with healthy controls) when approaching the highest obstacle, but not PD-ON. During the crossing phase, trail limb toe clearance of PD patients was shorter than healthy controls only during the OFF state. ON-OFF comparisons were significantly different only for the time to reach the lead foot clearance over the highest obstacle. In summary, DR partially improved movement slowness but did not directly affect movement amplitude of lower limb regulation in this gait task.

Preditores espaço-temporais do andar para testes de capacidade funcional em pacientes com doença de Parkinson / Gait spatial and temporal predictors for functional capacity tests in Parkinson's disease patients

OBJETIVOS: Determinar quais parâmetros espaço-temporais são preditores do andar de indivíduos com doença de Parkinson idiopática para os testes de resistência aeróbia e agilidade, propostos pela bateria de testes da American Alliance for Health, Physical Education, Recreation and Dance (AAHPERD). MATERIAIS E MÉTODOS: Foram selecionados seis homens e seis mulheres com comprometimento e estágio da doença em níveis leve e moderado, que realizaram os testes de agilidade e resistência aeróbia, conforme o protocolo da AAHPERD, e andaram 8m sobre uma passarela. Uma câmera digital registrou uma passada central. Marcadores foram fixados no quinto metatarso e na face lateral do calcâneo do membro inferior direito e no primeiro metatarso e na face medial do calcâneo do membro inferior esquerdo. As variáveis dependentes selecionadas foram: tempo nos testes de agilidade e resistência e as variáveis cinemáticas (comprimento da passada - CP, cadência - CAD, duração da passada - DP, duração da fase de duplo suporte - DDS, duração do suporte simples - SS, duração da fase de balanço - DB e velocidade da passada - VP). RESULTADOS: Para agilidade, o teste de Pearson apontou correlação estatisticamente significativa entre as variáveis CP (r=-0,70; p<0,05), CAD (r=-0,72; p<0,01), VP (r=-0,83; p<0,01), DP (r=0,71; p<0,01) e DDS (r=0,90; p<0,01). Para resistência, houve correlação com as variáveis CP (r=-0,67; p<0,05), CAD (r=-0,72; p<0,01), VP (r=-0,82; p<0,01), DP (r=0,71; p<0,01) e DDS (r=0,90; p<0,01). A análise de regressão múltipla revelou que a DDS foi a única variável preditora dos testes de agilidade (R²=0,82; p<0,01) e resistência (R²=0,81; p<0,01). CONCLUSÕES: Observou-se o uso potencial da DDS como parâmetro espaço-temporal do andar preditor do desempenho dos testes de resistência aeróbia e agilidade em pacientes com doença de Parkinson idiopática.

OBJECTIVE: To determine which spatial and temporal parameters are predictors of the gait pattern of individuals with idiopathic Parkinson's disease, for the aerobic endurance and agility tests included in the battery of tests of the AAHPERD protocol. METHODS: Six men and six women with mild and moderate impairment and disease stage were selected. They performed agility and aerobic endurance test in accordance with the AAHPERD protocol, and walked 8 m on a walkway. A digital video camera recorded one central stride. Markers were attached to the fifth metatarsal and lateral face of the calcaneus of the right leg and to the first metatarsal and medial face of the calcaneus of the left leg. The dependent variables selected were the time taken in the agility and endurance tests and the kinematic variables: stride length (SL), cadence (CAD), stride time (ST), double support time (DS), single support time (SS), swing time (SW) and stride velocity (SV). RESULTS: For agility, Pearson's test showed statistically significant correlations with SL (r=-0.70; p<0.05), CAD (r=-0.72; p<0.01), SV (r=-0.83; p<0.01), ST (r=0.71; p<0.01) and DS (r=0.90; p<0.01). For endurance, there were correlations with SL (r=-0.67; p<0.05), CAD (r=-0.72; p<0.01), SV (r=-0.82; p<0.01), ST (r=0.71; p<0.01), and DS (r=0.90; p<0.01). Multiple regression analysis revealed that DS was the only variable that predicted performance in both the agility (R²=0.82; p<0.01) and the endurance (R²=0.81; p<0.01) tests. CONCLUSIONS: It was observed that DS measure has a potential use as a kinematic parameter of gait that predicts the performance in agility and aerobic endurance tests in patients with idiopathic Parkinson's disease.