Emerging Research on Early Diagnosis

Reviewed by: HU Medical Review Board | Last reviewed: March 2017 | Last updated: March 2018

One of the areas of focus for research in Parkinson’s disease (PD) is early diagnosis. As a chronic, progressive disease, the ability to intervene and slow the progression is in the earliest stages of PD. Scientists are searching for markers that are evident in the early stages of PD to be able to diagnose and find ways to treat the disease before the progression to symptoms that are disabling and disruptive to the person’s quality of life.

PD has traditionally been classified as a movement disorder and is diagnosed based on the presence of motor symptoms of bradykinesia (slowed movement), tremor, postural instability (balance impairment), and rigidity. However, doctors now know that by the time these motor symptoms appear, the disease has been affecting the nervous system for several years to decades. Early signs of PD are seen in the presence of non-motor symptoms, including constipation, sleep disorders, and loss of the sense of smell.

Researchers define three stages in the early disease course of Parkinson’s:

  • Preclinical stage – the disease has begun degeneration of the neurons (nerve cells) but there are not yet any detectable signs or markers
  • Prodromal stage – clinical symptoms of PD begin to appear (non-motor symptoms), but the patient does not yet meet the diagnostic criteria (motor symptoms are not evident)
  • Clinical stage – the classic motor symptoms of PD are present (bradykinesia, plus either resting tremor, rigidity, or both)

Biomarkers for Parkinson’s disease

Biomarkers are biological signs of a disease. In research to identify biomarkers for PD, scientists evaluate the specificity and predictive qualities of markers. For example, the loss of the sense of smell is a proven marker in the prodromal stage of PD, but it also occurs in about 25% of the general population as they age.1 Another factor in identifying biomarkers is to understand the lead time of the marker, or the length of time between the marker becoming detectable and the development of the clinical signs of PD (the motor symptoms). Longer lead times are preferable, as they provide a greater opportunity to prevent the disease progression. Finally, the practicalities and difficulties involved in screening for biomarkers are assessed, including the financial costs and feasibility of testing people for the markers.

Some of the biomarkers that researchers have identified as being predictive of PD include:

  • REM sleep behavior disorder – abnormal behavior during rapid eye movement (REM) sleep that causes the person to act out their dreams
  • Subtle motor dysfunction, such as decreased expression in the face or voice, or slowing of hand motor speed
  • Loss of the sense of smell, or olfactory loss
  • Autonomic dysfunction, which includes constipation, urinary dysfunction, orthostatic hypotension (a falling of blood pressure that occurs when standing), sexual dysfunction, sleepiness, depression, and anxiety

Other potential markers that are still being evaluated in research include:

  • Restless legs syndrome (RLS) – an unpleasant, restless feeling that is only relieved by moving the legs and usually occurs as one is trying to fall asleep
  • Color vision loss – the inability to distinguish colors, particularly in the blue-yellow spectrum
  • Mild cognitive impairment – reduced attention and executive function (the ability to plan, organize, initiate and regulate behavior to meet goals)


In addition to identifying markers of the disease, researchers are studying which imaging technologies are best for identifying PD in its earliest stages. Some of the imaging techniques being evaluated include:

  • Dopaminergic imaging – Dopamine is the neurotransmitter (chemical messenger) that is significantly reduced by the disease process of PD, and the depletion of dopamine causes the motor symptoms of PD. Dopaminergic imaging looks at the damage to the dopamine-producing neurons and can be conducted with dopaminergic PET (positron emission tomography) or single-photon emission computed tomography (SPECT)
  • Substantia nigra ultrasound – The substantia nigra is part of the brain that is damaged by PD. The neurons in the substantia nigra produce dopamine, and damage to the neurons causes the loss of dopamine and produces the motor symptoms of PD. In people with PD, the substantia nigra has abnormally high echogenicity (appears as a lighter color) on ultrasound imaging, leading researchers to study this as a potential marker and potential screening for PD.
  • Electrocardiography – Electrocardiography measures the electrical activity in the heart. PD causes changes to the heartbeat variability, and some studies have suggested that the heartbeat variability can be a marker for PD, however, other studies have not found this to be a reliable marker.

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