Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial.

BACKGROUND: This trial aimed to determine the efficacy of leucine and/or perindopril in improving physical function in older people with sarcopenia. METHODS: Placebo-controlled, parallel group, double-blind, randomized two-by-two factorial trial. We recruited adults aged ≥ 70 years with sarcopenia, defined as low gait speed (<0.8 m/s on 4 m walk) and/or low handgrip strength (women < 20 kg, men < 30 kg) plus low muscle mass (using sex and body mass index category-specific thresholds derived from normative UK BioBank data) from 14 UK centres. Eligible participants were randomized to perindopril 4 mg or placebo, and to oral leucine powder 2.5 g or placebo thrice daily. The primary outcome was the between-group difference in the short physical performance battery (SPPB) score over 12-month follow-up by repeated-measures mixed models. Results were combined with existing systematic reviews using random-effects meta-analysis to derive summary estimates of treatment efficacy. RESULTS: We screened 320 people and randomized 145 participants compared with an original target of 440 participants. For perindopril [n = 73, mean age 79 (SD 6), female sex 39 (53%), mean SPPB 7.1 (SD 2.3)] versus no perindopril [n = 72, mean age 79 (SD 6), female sex 39 (54%), mean SPPB 6.9 (SD 2.4)], median adherence to perindopril was lower (76% vs. 96%; P < 0.001). Perindopril did not improve the primary outcome [adjusted treatment effect -0.1 points (95%CI -1.2 to 1.0), P = 0.89]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect -0.4 kg (95%CI -1.1 to 0.3), P = 0.27]. More adverse events occurred in the perindopril group (218 vs. 165), but falls rates were similar. For leucine [n = 72, mean age 78 (SD 6), female sex 38 (53%), mean SPPB 7.0 (SD 2.1)] versus no leucine [n = 72, mean age 79 (SD 6), female sex 40 (55%), mean SPPB 7.0 (SD 2.5)], median adherence was the same in both groups (76% vs. 76%; P = 0.99). Leucine did not improve the primary outcome [adjusted treatment effect 0.1 point (95%CI -1.0 to 1.1), P = 0.90]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect -0.3 kg (95%CI -1.0 to 0.4), P = 0.47]. Meta-analysis of angiotensin converting enzyme inhibitor/angiotensin receptor blocker trials showed no clinically important treatment effect for the SPPB [between-group difference -0.1 points (95%CI -0.4 to 0.2)]. CONCLUSIONS: Neither perindopril nor leucine improved physical performance or muscle mass in this trial; meta-analysis did not find evidence of efficacy of either ACE inhibitors or leucine as treatments to improve physical performance.

Fracture Risk Assessment in Atypical Parkinsonian Syndromes.

BACKGROUND: Bone health and fracture risk reduction are increasingly recognized as important issues in Parkinson's disease (PD). However, the evidence for fracture risk management in atypical parkinsonism (AP) is less clear. Guidance on management of bone health in PD has recently been published. OBJECTIVES: To evaluate the outcome of fracture risk assessment in a cohort of patients with AP, compared to a population with idiopathic PD. METHODS: We did a cross-sectional study of patients with PD or AP who had fracture risk assessed at two tertiary movement disorder centres. Data on fracture risk as assessed using QFracture and FRAX were collected. To assess for the effect of age on fracture risk we compared the risks of PD and AP patients aged ≤70 and >70 years. RESULTS: We assessed 71 patients with AP and 267 with PD. Age, sex and body mass index were similar between groups; patients with AP were more likely to have fallen in the previous year. Major osteoporotic fracture risk was greater in patients with AP aged ≤70 compared to PD; no differences between groups were seen in those aged >70 years. 76% of those with AP, and 63% with PD, had an estimated fracture risk indicating bone-sparing treatment, but only 33% of patients with AP were receiving this where it was indicated. CONCLUSION: There is scope for considerable improvement in fracture risk assessment and treatment in atypical parkinsonism, taking into account the worse prognosis of this patient group.

Management of fracture risk in Parkinson's: A revised algorithm and focused review of treatments.

INTRODUCTION: Falls and fractures are a cause of substantial morbidity in Parkinson's. Despite an excess risk of both falls and osteoporosis, people with Parkinson's perceive that they are less likely to fracture than their peers, despite actually being at higher fracture risk. Recognising this increased risk, in 2014 we published an algorithm to guide management of fracture risk in this high-risk population. Recently, the National Osteoporosis Guideline Group (NOGG) published new guidance revising the 10 year fracture probability intervention thresholds for those over 70 years old to 20.3% for major osteoporotic fracture and 5.4% for hip fracture. METHODS: In light of the new guidance, we have reappraised the use of two fracture prediction tools, Qfracture and FRAX, and have updated the algorithm to guide the management of bone health and fracture risk in people with Parkinson's. RESULTS: We outline the treatment options available with particular consideration given to Parkinson specific factors that influence treatment choices. CONCLUSION: This guidance is relevant to all healthcare specialist managing Parkinson's including neurologists, geriatricians and primary care practitioners.

Comparison of Test Your Memory and Montreal Cognitive Assessment Measures in Parkinson's Disease.

Background. MoCA is widely used in Parkinson's disease (PD) to assess cognition. The Test Your Memory (TYM) test is a cognitive screening tool that is self-administered. Objectives. We sought to determine (a) the optimal value of TYM to discriminate between PD patients with and without cognitive deficits on MoCA testing, (b) equivalent MoCA and TYM scores, and (c) interrater reliability in TYM testing. Methods. We assessed the discriminant ability of TYM and the equivalence between TYM and MoCA scores and measured the interrater reliability between three raters. Results. Of the 135 subjects that completed both tests, 55% had cognitive impairment according to MoCA. A MoCA score of 25 was equivalent to a TYM score of 43-44. The area under the receiver operator characteristic (ROC) curve for TYM to differentiate between PD-normal and PD-cognitive impairment was 0.82 (95% CI 0.75 to 0.89). The optimal cutoff to distinguish PD-cognitive impairment from PD-normal was ≤45 (sensitivity 90.5%, specificity 59%) thereby correctly classifying 76.3% of patients with PD-cognitive impairment. Interrater agreement was high (0.97) and TYM was completed in under 7 minutes (interquartile range 5.33 to 8.52 minutes). Conclusions. The TYM test is a useful and less resource intensive screening test for cognitive deficits in PD.

Assessment and management of fracture risk in patients with Parkinson's disease.

Parkinson's disease (PD) is associated with substantially increased fracture risk, particularly hip fracture, which can occur relatively early in the course of PD. Despite this, current national clinical guidelines for PD fail to adequately address fracture risk assessment or the management of bone health. We appraise the evidence supporting bone health management in PD and propose a PD-specific algorithm for the fracture risk assessment and the management of bone health in patients with PD and related movement disorders. The algorithm considers (i) calcium and vitamin D replacement and maintenance, (ii) quantification of prior falls and fractures, (iii) calculation of 10-year major osteoporotic and hip fracture risks using Qfracture, (iv) application of fracture risk thresholds, which if fracture risk is high (v) prompts anti-resorptive treatment, with or without dual X-ray absorptiometry, and if low (vi) prompts re-assessment with FRAX and application of National Osteoporosis Guidelines Group (NOGG) guidance. A range of anti-resorptive agents are now available to treat osteoporosis; we review their use from the specific perspective of a clinician managing a patient population with PD. In conclusion, our current evidence base supports updating of guidelines globally concerning the management of PD, which presently fail to adequately address bone health.

Severe hypercalcaemia and lymphoma in an HTLV-1 positive Jamaican woman: a case report.

Human T cell lymphotrophic virus type-1 infection is endemic in the Afro-Caribbean community in Britain, with carriage rates of about 3%. Although there is a long latency, carriers have a 1-5% chance of developing adult T cell leukaemia/lymphoma, a condition frequently complicated by marked and refractory hypercalcaemia, and with a poor prognosis. We present the case of an elderly Jamaican woman with severe hypercalcaemia and a raised PTHrP who was found to have lymphoma and was positive for HTLV-1.