Parkinson's disease (PD)

Course of disease

The progression of disease varies among the Parkinson’s disease (PD) patients. The diagnosis of PD occurs with the onset of motor symptoms, but the disease can be preceded by a premotor or prodromal phase of more than 20 years (Figure 1).¹ In early in the course of the disease, the symptoms are associated with reduced health-related quality of life.¹ In this period, non-motor features include olfactory dysfunction, constipation, depression, excessive daytime sleepiness, and rapid eye movement sleep behavior disorder (RBD), autonomic dysfunction, pain, and fatigue may appear.¹ These symptoms are usually mild and the response to treatment is often excellent with no variability in motor function over the day (Figure 2).² It has been shown to nearly twice the risk of subsequently developing PD if people experience mood disorders and constipation. The prodromal period could be prolonged; the average latency between onset of RBD and occurrence of parkinsonian motor symptoms is 12–14 years. This premotor phase provides a potential temporal window during which disease-modifying therapy, treatments could be administered to prevent or delay the development and progression of disease.¹

After the motor features worsen with the progression, drug treatment response becomes less reliable and the anti-parkinsonian drugs induce potentially disabling dyskinesias; as the disease advances, the emergence of complications related to long-term symptomatic treatment, including motor and non-motor fluctuations, dyskinesia, and psychosis.¹

In addition, a range of neuropsychiatric symptoms also occur in the majority of patients including fatigue, insomnia, daytime sleepiness, behavioural disorders, mood changes, anxiety, apathy, anhedonia, depression, cognitive dysfunction, and hallucinations. Psychosis appears to be a marker for PD progression and is often induced by dopamine replacement therapy, while dementia is common but is not an inevitable result of progression over 15 - 20 years.²

During late stage of PD, both motor and non-motor features showed treatment-resistant situation, patients suffer from axial motor symptoms such as postural instability, freezing of gait, falls, dysphagia, and speech dysfunction. Up to 80% of PD patients have freezing of gait and falls, and up to 50% of patients report choking after 17 years of PD onset.¹ 83% of patients with PD who have had 20 years disease duration occurred dementia. In late-stage of PD, these levodopa-resistant symptoms contribute to disability and may need for admission to an institution and mortality.¹

The nature of PD is progressive, and it gets worse over time. The followings are five stages of PD explained by the Parkinson’s Foundation.³

Stage 1

Mild symptoms mostly do not affect daily activities. Tremor and other movement symptoms occur on one side of the body only. Some patients have changes in posture, walking and facial expressions.

Stage 2

Symptoms start getting worse. Tremor, rigidity and other movement symptoms affect both sides of the body, and walking problems and poor posture may be apparent. The patients are still able to live alone, but daily tasks are more difficult and lengthier.

Stage 3

In the mid-stage, loss of balance and slowness of movements are hallmarks. The patients are more often to fall. While the patient is still fully independent, these symptoms significantly impair activities such as dressing and eating.

Stage 4

Symptoms are severe and limiting. Individuals may stand without assistance, but movement may require a walker. The patients need help with activities of daily living and are unable to live alone.

Stage 5

This is the most advanced and debilitating stage. Stiffness in the legs may make it impossible to stand or walk. The patients require wheelchair or are bedridden. Nursing care is needed for all activities. The patients may experience hallucinations and delusions.