Early Signs of Parkinson's Disease

When you think of Parkinson's disease, issues such as constipation, depression, and trouble smelling aren't likely the first things that come to mind. While it's true that motor symptoms such as resting tremor and rigidity are classic signs of Parkinson's and aid doctors in diagnosing it, pre-motor symptoms (those unrelated to movement) predate these—often by years.

While not everyone with Parkinson's disease experiences these pre-motor symptoms, most do. Awareness of the early signs and symptoms of Parkinson's is important, as their presence may prompt closer monitoring for the eventual development of the disease. Moreover, an earlier diagnosis of Parkinson's disease can lead to earlier treatment, which means better outcomes for the patient. 

The following pre-motor symptoms are strongly linked to Parkinson's disease. While not indicative of Parkinson's on their own, they can be early indicators.

Normally, nerve cells within a region of the brain called the substantia nigra make a chemical called dopamine, which helps control movement. In patients with Parkinson's disease, however, these dopamine-producing nerve cells slowly degenerate and/or die. As a result, dopamine is not produced in sufficient amounts in the brain, which leads to symptoms like slowness of movement (bradykinesia).

Constipation can be an early sign of this cascade of events.

Alpha-synuclein, a protein normally found normally in the human brain, plays an important role in the regulation of dopamine release. In those with Parkinson's, alpha-synuclein is abnormally folded and accumulates in large amounts in the brain to form something called a Lewey body. Lewey bodies are toxic and cause the destruction of nerve cells in the brain that produce dopamine.

Interestingly, because of the finding of high levels of alpha-synuclein clumps (Lewey bodies) in the guts of patients with Parkinson's disease, some experts suspect that the gut may be where Parkinson's disease begins—and that the pathological alpha-synuclein spreads to the brain via the vagus nerve. More investigation is needed.

Approximately 90% of patients with Parkinson's disease have a reduced sensitivity to odor (hyposomia). This pre-motor symptom typically occurs five or more years before the onset of movement symptoms.

As opposed to the aforementioned gut theory, because this occurs, some experts suspect that Parkinson's disease may actually start out in the olfactory system (what allows you to smell).

They postulate that a disease-causing substance (for example, a heavy metal such as zinc) is introduced into the nose and then into the olfactory bulb (located in the front of your brain). Once in there, the heavy metal may trigger the accumulation of alpha-synuclein clumps.

The olfactory bulb is not protected from the outside environment by the blood-brain barrier, so once in the olfactory bulb, the aggregated alpha-synuclein can theoretically spread more easily to other parts of the brain. 

Of course, this theory (like the gut theory) is still being investigated, but it supports the idea of hyposmia as an early biomarker for Parkinson's disease.

REM sleep behavior disorder causes a person to play out their dreams—yelling, flailing arms and legs, or punching, for example—while still asleep. This sleep disorder can be dangerous, as it may result in injury to the patient and/or their bed partner.

The tie between RBD and Parkinson's disease is pretty strong. In fact, research has found that up to 80% of patients diagnosed with idiopathic RBD (i.e., that of unknown cause) eventually develop a neurodegenerative disorder like Parkinson's disease.

RBD is also strongly tied to rigidity, the classic Parkinson's symptom defined by muscles that won't relax and are stiff. Specifically, patients with Parkinson's disease and a history of RBD tend to have more rigidity compared to patients with Parkinson's disease and no RBD.

Research shows that approximately 30% to 50% of patients with Parkinson's disease suffer from depression and that this symptom predates motor symptoms by about five to 10 years.

Common symptoms of depression in patients with PD include a pervasive sadness, lack of interest in activities, and a reduced ability to feel pleasure (anhedonia).

Other depression-related symptoms, such as suicidality, self-blame, and a pessimistic self-attitude, may be less common in Parkinson's disease-related depression.

Similar to other pre-motor symptoms, the pathogenesis (the "why" behind depression in Parkinson's disease) is tied to abnormal alpha-synuclein aggregates—in this case, in the brain ,rather than the gut or nose.

In the end, by learning more about the pre-motor symptoms of Parkinson's disease, experts hope to ultimately find a treatment that can halt the disease in its tracks—before motor symptoms develop.

If you are experiencing any early signs or symptoms of Parkinson's disease, please talk with your doctor. Keep in mind, though, that these pre-motor symptoms—especially constipation and depression—are common and nonspecific. They are certainly not a slam-dunk indication of a future Parkinson's disease diagnosis, but they are worth evaluation.