Parkinson’s disease is caused by the death and dysfunction of dopamine-producing nerve cells in the brain. There is no single test to diagnose Parkinson’s; a diagnosis is made based on the presence of disease symptoms and signs. Notably, many symptoms of Parkinson’s also are found in other conditions, which can further complicate a diagnosis.
A clinician, usually a neurologist, will conduct examinations to assess for these cardinal symptoms: looking for signs of tremor, and seeing whether tremor changes under different circumstances — for example, Parkinson’s tremors tend to get worse when a person is distracted with mental tasks.
To look for bradyinesia and tremor, the clinician will have the patient perform certain motions, or try to passively move the patient’s limbs to check for tightness.
To test for balance issues, a pull test, also known as a retropulsion test, may be carried out. In this test, the clinician stands behind the patient and pulls him or her back slightly to see the reaction. A patient with Parkinson’s will often fall backward with many shuffling footsteps, called retropulsion.
Several other diagnostic tests may be useful in reaching the diagnosis of Parkinson’s.
Levodopa and its derivatives are a class of medications widely considered the gold standard for Parkinson’s treatment. They work by essentially giving the brain more raw material with which to make dopamine, thereby increasing dopamine levels in the brain.
In a levodopa test, levodopa or a similar medication will be administered at a high enough dose that would show benefit in someone with Parkinson’s (low doses for a day or two aren’t reliable). Then, the patient and clinicians assess whether the treatment eases symptoms — if it does, it’s likely that the person has Parkinson’s.
Loss of smell, also called olfactory dysfunction or hyposmia, is one of the most common non-motor symptoms of Parkinson’s disease. People with Parkinson’s may have a notable loss of smell for years or even decades before other symptoms become apparent.
Testing for a loss of smell may be a useful way to look for early signs of Parkinson’s, and it may be helpful in distinguishing between Parkinson’s and other conditions. However, the smell test is not very specific: many people will experience a loss of taste and smell as they age, and not everyone who does will go on to develop Parkinson’s.
The smell test usually has a person sniff and describe several pre-defined odors. For example, the widely used University of Pennsylvania smell identification test is a “scratch and sniff” test made up of 40 microencapsulated odorants (smells), where the person being tested is required to choose among four descriptors for each odorant.
Dopamine transporter scan
A dopamine transporter scan, or DaTscan, is a form of single-photon emission computerized tomography (SPECT) scan used to visualize dopamine transporters in the brain. Put more simply, it’s a way to image the dopamine-producing cells in the brain that are impacted in Parkinson’s.
During a DaTscan, a radioactive agent is injected into the patient’s bloodstream and is tracked using SPECT — a noninvasive scanner that uses radiation detectors to image the cells that take up the agent and emit radioactivity. DaTscan specifically marks the brain cells that carry a protein used to transport dopamine in and out of cells, which show up as brighter areas in the scan. In people with Parkinson’s disease, there are reduced levels of these cells in certain parts of the brain, especially the basal ganglia, which is a brain region important in controlling movement.
DaTscan is approved by the U.S. Food and Drug Administration for adults with Parkinson’s, and it may be helpful in differentiating between this disease and other conditions with similar symptoms. However, in most cases, a DaTscan is not needed to reach a diagnosis; a review of symptoms is sufficient.
Of note, DaTscan cannot distinguish between Parkinson’s disease and other diseases that cause abnormal dopamine trafficking in the brain, such as progressive supranuclear palsy, corticobasal ganglionic degeneration, and multiple system atrophy.
Outside of DaTscan, other imaging tests — such as magnetic resonance imaging (MRI), functional MRI (fMRI), ultrasound of the brain, and positron emission tomography (PET) scans — may be conducted during a diagnostic workup. These techniques generally aren’t very helpful for diagnosing Parkinson’s, but they may be useful for ruling out other conditions.
Testing for alpha-synuclein aggregates
Parkinson’s disease is marked by certain molecular anomalies in the brain. In particular, the protein alpha-synuclein forms aggregates (clumps) in brain cells of people with Parkinson’s, which is thought to drive disease progression. Alpha-synuclein aggregates also are a hallmark of other neurodegenerative diseases including dementia with Lewy bodies, and multiple system atrophy.
Real-time quaking-induced conversion (RT-QuIC), also called protein misfolding cyclic amplification (PMCA), is a technique that uses a fluorescent probe to detect misfolded protein aggregates. The test is usually done on a sample of cerebrospinal fluid (CSF), the fluid that surrounds the brain and spinal cord.
Although RT-QuIC can help in the early diagnosis of Parkinson’s, the technique has certain limitations. For example, RT-QuIC cannot currently be used to distinguish Parkinson’s from other forms of neurodegenerative disorders such as dementia with Lewy bodies or multiple system atrophy that also involve alpha-synuclein, and specific modifications to the test might be needed to increase specificity for Parkinson’s.
Last updated: Sept. 24, 2021
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