BackgroundCurrently 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 β-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.MethodsThis 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.DiscussionIf found effective and safe, Ambroxol will be one of the first disease-modifying treatments for PDD.Trial registrationClinicalTrials.gov NCT02914366, 26 Sep 2016/retrospectively registered.

This study provides Class I evidence that for patients with FTD, intranasal oxytocin is not significantly associated with adverse events or significant changes in the overall neuropsychiatric inventory.

How best to operationalize the mindfulness construct requires further research. In two related studies, we examined undergraduates' self-reported ability to maintain their attention toward the process of their breathing during 10-and 15-min practices of mindful breath meditation, referred to as "Meditation Breath Attention Scores" (MBAS). MBAS were positively correlated with self-reported interest in and awareness of the breath during both 10-and 15-min meditations and negatively correlated with self-reported difficulties maintaining attention toward breathing (i.e., mind wandering) during the 15-min meditation. MBAS were not positively correlated with the Toronto Mindfulness Scale (TMS) measures of mindful "decentering" and "curiosity." In study 2 but not study 1, MBAS were positively correlated with the five-factor mindfulness trait "Acting with Awareness." Secondary analyses replicated an association between measures of trait mindfulness and trait difficulty letting go of depressive thoughts, although MBAS and the TMS measures were unrelated with trait difficulty letting go of depressive thoughts. Future research directions are discussed.