Signs, Symptoms, and Diagnosis
Dopamine is a neurotransmitter that, among other functions, allows messages to be sent to regions of the brain responsible for coordinating movement. When dopamine levels decline, due to the death of dopaminergic cells, these messages no longer reach their destination, and so the regions of the brain that control movement no longer function properly. This results in loss of conscious control of movement, and, in advanced Parkinson's disease, loss of control over several other bodily functions.
The onset and course of Parkinson's disease may be different for each patient. For example, while tremor is evident in most patients, some may not experience movement complications until the disease has advanced considerably.
Initial symptoms of primary Parkinson's disease typically develop slowly and randomly as the supply of dopamine dwindles over time. In some cases, symptoms do not appear until approximately 70% of the dopaminergic cells in the substantia nigra are already destroyed.2
The onset of a slight tremor, usually in the hand, which increases in intensity over time, is often the initial sign of Parkinson's. However, roughly 30% of patients do not develop a tremor. Parkinson's patients often experience muscle rigidity or cramping that can be painful—movements as simple as turning over in bed or buttoning a shirt can become arduous, and as the disease advances, nearly impossible. Progression of Parkinson's disease leads to slowness of movements, which can cause a great deal of frustration for patients who cannot move as quickly as they would like.
"Freezing" is a frequently reported motor symptom in advancing Parkinson's. This involves the sudden onset of the inability to move at all; patients sometimes describe freezing as feeling as if their feet are stuck to the floor. Freezing is temporary and usually lasts from a few seconds to a few minutes.
Dopamine is involved in a number of functions beyond control of movement, so loss of dopaminergic neurons (and other neurons in late-stage Parkinson's) can cause several non-motor symptoms as well. However, non-motor symptoms usually develop at later stages of disease progression; nonetheless, they can be equally as debilitating as motor symptoms for many patients.
Patients with advanced Parkinson's disease may experience a variety of non-motor symptoms. These can include incontinence, constipation, difficulty swallowing, inability to control saliva, dizziness, which can lead to falls, excessive daytime sleepiness, intense frightening dreams, depression and/or anxiety, and hallucinations.2 In addition, Parkinson's disease can cause perceptible pain throughout the body, which is sometimes severe.
Dementia and related cognitive decline is a major concern among those with advanced Parkinson's disease; up to 75‒80% of those with Parkinson's develop dementia near the end of their life.27,28 In addition to loss of dopaminergic neurons, cholinergic neurons are also at risk. Cholinergic neurons produce a neurotransmitter called acetylcholine, which is important for cognitive function. The accumulation of protein aggregates (clumps of dysfunctional proteins) known as Lewy bodies within cholinergic neurons is a common characteristic of Parkinson's disease.
As Lewy bodies accumulate inside neurons, the cells can no longer function, and eventually die. Loss of acetylcholine leads to diminished attention span, blunted sensory perceptions, loss of arousal and structural changes in the synaptic junctions (the connections between neurons through which they communicate using chemical and electrical signals). Loss of acetylcholinergic signaling is thought to be associated with memory deficits in Alzheimer's disease as well, though the exact mechanisms are complex.29
Two subsets of dementia exist in the context of Parkinson's disease, Parkinson's disease dementia (PDD) and Dementia with Lewy bodies (DLB). The distinction of the two is quite subjective and largely based upon the time of dementia diagnosis in relation to onset of motor symptoms. Whether or not the two dementias are truly separate entities, or simply manifestations of different points along the "Lewy body spectrum," is a hotly debated topic.30
Clinicians must rely on clinical experience, interpretation of symptoms, and evaluation of medical history in order to tentatively diagnose a patient as having Parkinson's disease. This is because there are no lab tests available that definitively diagnose Parkinson's disease. Parkinson's disease is a diagnosis of exclusion; in other words, the physician will first rule out other possible diagnoses before assuming Parkinson's.
If Parkinson's is suspected because the patient is exhibiting signs such as a tremor on one side of their body, or rigidity with loss of postural reflexes, oftentimes L-DOPA, a drug used to treat Parkinson's symptoms, is administered. If L-DOPA causes the symptoms to subside, the diagnosis of Parkinson's disease can be made more confidently, yet still not definitively.
Due to the elusive nature of a definitive Parkinson's disease diagnosis, patients should be reevaluated regularly to make sure that their symptoms are not due to another neurological disorder that causes similar symptoms.