Parkinson’s disease or PD, is the second commonest neurodegenerative disorder after Alzheimer disease. The estimated prevalence of PD is 0.3% in the general population, affecting 1 in 100 persons over age 60, and 3% of those age 80 or more. New cases of PD occur in up to 18 per 100,000 persons in the general population. The median age of onset is 60 years for both sexes, with a mean duration of disease of 15 years. The disease affects men more often than women, with an incidence and prevalence 1.5 to 2 times higher.
Clinical Subtypes and Progression
Subtypes of PD have emerged enabling patients to be classified according to distinctive clinical features such as tremor, posture or gait instability. Patients with prominent tremor at onset have a slower progression of disease than those with unstable posture or gait who may also manifest a faster rate of cognitive decline and a higher incidence of dementia. Those with predominant tremor often show signs of dementia much later when gait and postural problems occur.
There are non-motor symptoms that contribute to disturbances in the quality of life. Autonomic involvement leads constipation, bladder over-activity and sexual disturbances. Unstable blood pressure and pulse particularly are due to brain-mediated orthostatic intolerance. Sleep disturbances are common with restless legs, insomnia, and daytime sleepiness. Depression, anxiety, and apathy are common in PD. A feared complication is dementia that may be insidious in onset. The prevalence of dementia is >75% in individuals who survive 10 years; mild cognitive impairment affects upon to a third of patients in the early stages of the disorder.
Genome wide association studies (GWAS) have identified at least 18 PD-related gene loci and 7 disease causing genes. A history of pesticide exposure, certain occupations, and traumatic brain injury may appear to contribute to the disease onset in a given individual. There are also protective factors such as caffeine, cigarette smoking, alcohol consumption, non-steroidal anti-inflammatory, statin, calcium channel medication drug use, exercise and estrogens in women. Enteric pathogens have been implicated in the onset of some patients, as well as prion pathogens as triggers of the initial neurodegenerative process that starts in striatal dopaminergic neurons in the brain where the disease process begins suggesting a role for post-infectious dysimmunity or autoimmunity in some cases. .
Symptomatic treatment is considered when symptoms become bothersome or cause disability. Available symptomatic medications include anticholinergic and dopaminergic agents, and amantadine. Anticholinergic medications are used to treat tremor especially in younger patients who tolerate the medication better than do the elderly. Potent symptomatic treatment requires treatment with levodopa or dopamine agonist. Levodopa is always combined with carbidopa or benserazide to prevent peripheral conversion to dopamine by dopa-decarboxylase to reduce side effects. Commencement of levodopa is often delayed in early-onset disease because of the occurrence of motor fluctuation which begins as the effects of levodopa wear off, causing bradykinesia and tremor, which over time, can fluctuate between “on” periods of increased mobility, and “off” periods of relative immobility. Levodopa-induced dyskinesia is a major motor complication of therapy that occurs at the time of peak dose effect or in the beginning or end of a dose cycle. Surgical treatment of PD employing deep brain stimulation is another option for patients with persistent disabling motor fluctuations and intact cognition. Deep brain stimulation alleviates motor complications, tremor and reduces the need for medication so that side effects can be minimized.