P arkinson disease is the second most common neurodegenerative disorder after Alzheimer disease. 1 Parkinson disease typically develops between the ages of 55 and 65 years and occurs in 1%-2% of people over the age of 60 years, rising to 3.5% at age 85-89 years. 2-4 About 0.3% of the general population is affected, and the prevalence is higher among men than women, with a ratio of 1.5 to 1.0. 5 Parkinson disease may be more common among white people than those of Asian or African descent; however, the data are conflicting. 4,6 In 2011, the estimated number of people living with Parkinson disease in Canada had reached 85 200. 7 By 2031, the projected number of people with this disease will double. 1,7 Management remains complicated over the course of the disease and should be individualized based on the patient's quality of life at each stage of disease. There have been many advancements in the management of Parkinson disease and ongoing research. Many options are now available. This review presents current treatment strategies and recommendations in managing motor and nonmotor symptoms in the various stages of Parkinson disease. Methods for developing this review are outlined in Box 1.

The simple definition of tone as the resistance to passive stretch is physiologically a complex interlaced network encompassing neural circuits in the brain, spinal cord, and muscle spindle. Disorders of muscle tone can arise from dysfunction in these pathways and manifest as hypertonia or hypotonia. The loss of supraspinal control mechanisms gives rise to hypertonia, resulting in spasticity or rigidity. On the other hand, dystonia and paratonia also manifest as abnormalities of muscle tone, but arise more due to the network dysfunction between the basal ganglia and the thalamo-cerebello-cortical connections. In this review, we have discussed the normal homeostatic mechanisms maintaining tone and the pathophysiology of spasticity and rigidity with its anatomical correlates. Thereafter, we have also highlighted the phenomenon of network dysfunction, cortical disinhibition, and neuroplastic alterations giving rise to dystonia and paratonia.

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 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. 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. If found effective and safe, Ambroxol will be one of the first disease-modifying treatments for PDD. ClinicalTrials.gov NCT02914366, 26 Sep 2016/retrospectively registered.