Progression of motor symptoms in Parkinson’s disease

Abstract

Parkinson's disease (PD) is a chronic progressive neurodegenerative disease that is clinically manifested by a triad of cardinal motor symptoms - rigidity, bradykinesia and tremor - due to loss of dopaminergic neurons. The motor symptoms of PD become progressively worse as the disease advances. PD is also a heterogeneous disease since rigidity and bradykinesia are the major complaints in some patients whereas tremor is predominant in others. In recent years, many studies have investigated the progression of the hallmark symptoms over time, and the cardinal motor symptoms have different rates of progression, with the disease usually progressing faster in patients with rigidity and bradykinesia than in those with predominant tremor. The current treatment regime of dopamine-replacement therapy improves motor symptoms and alleviates disability. Increasing the dosage of dopaminergic medication is commonly used to combat the worsening symptoms. However, the drug-induced involuntary body movements and motor complications can significantly contribute to overall disability. Further, none of the currently-available therapies can slow or halt the disease progression. Significant research efforts have been directed towards developing neuroprotective or disease-modifying agents that are intended to slow the progression. In this article, the most recent clinical studies investigating disease progression and current progress on the development of disease-modifying drug trials are reviewed.

Long‐term effects of rasagiline and the natural history of treated Parkinson's disease

“…Although most of the odds ratios for factors that predict a slower rate of progression were statistically significant, they were small and of questionable clinical relevance on the basis of this study. A slower rate of disease progression has been reported for females, younger patients, and patients with the tremor‐dominant form of PD . Interestingly, in contrast to the findings of ADAGIO, which showed that higher baseline severity (higher UPDRS scores) predicted a faster rate of progression in early disease, the results of the AFU analysis indicated that, at this moderate stage of the disease, higher baseline UPDRS scores predicted a somewhat slower rate of progression.…”

The SH-SY5Y cell line in Parkinson’s disease research: a systematic review

“…PD has a high socioeconomic burden since it is slowly progressive and disease-modifying treatments are not available. PD presents with motor and non-motor symptoms [3, 4] that worsen with advancing age, leading to a need for assistance with all daily activities. Disease manifestation is characterized by the presence of Lewy bodies (abnormal protein aggregates containing α-synuclein), death of dopaminergic (DAergic) neurons in the substantia nigra (SN) projecting to the striatum, and microgliosis (accumulation of activated microglial cells) [5].…”

Progressive loss of striatal dopamine terminals in MPTP-induced acute parkinsonism in cynomolgus monkeys using vesicular monoamine transporter type 2 PET imaging ([18F]AV-133)

“…The cardinal clinical symptoms are bradykinesia, tremor, rigidity, and postural instability with the pathological characteristic of evolutional nigrostriatal dopaminergic neurodegeneration [2,3] . 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that induces parkinsonism in both humans [4] and non-human primates [5] with the cognitive, biochemical, histological and classical behavioral changes that occur in PD [6] .…”