Many people think of a tremor as the quintessential warning sign of Parkinson’s disease. But other symptoms — many of them not involving changes in movement — can appear much earlier than what’s known as a resting tremor.
In fact, a resting tremor, which is a rhythmic shaking of a body part such as a hand when at rest, isn’t even required for diagnosis. Up to 20% of people with Parkinson’s disease don’t have one.
“Parkinson’s is what we call a movement disorder because it affects our movement, but there’s a whole side of Parkinson’s that is non-motor,” said Rachel Dolhun, a neurologist and principal medical adviser at the Michael J. Fox Foundation for Parkinson’s Research. “We long thought it was just a movement disease, but now we see that it affects the whole body in different ways.”
Certain symptoms show up years before motor changes
Parkinson’s disease is one of the most common neurological disorders in the world, with cases expected to reach 25.2 million by 2050. While inherited genetic mutations are associated with 10 to 15% of cases, the rest have no known cause. Symptoms can be managed with available treatments, but there is no cure — although exercise is thought to reduce the risk of developing the condition. And there are several other things you can do to reduce your risk of Parkinson’s disease, as well.
To make a Parkinson’s diagnosis, neurologists look for characteristic movement symptoms, including slowness, stiffness, and resting tremor. However, common non-motor symptoms of Parkinson’s, such as constipation and loss of sense of smell, often precede such changes in movement by more than a decade. This early stage of Parkinson’s, known as the prodromal phase, marks the beginning of a gradual onset of disease.
“It’s a slow disease, and we’re realizing just how slow it can be,” said Ronald Postuma, a professor of neurology and neurosurgery at McGill University in Montreal. “It’s progressing in the brain, year by year, until it crosses a threshold at which doctors can make the diagnosis.”
Parkinson’s disease damages neurons that produce dopamine, a chemical that transmits signals between cells and plays a crucial role in controlling movement and coordination in the brain. By the time motor symptoms show up, 50 to 70% of these neurons in the substantia nigra, a small but vital structure for voluntary movement located in the brain stem, have already died.
In the last two decades, researchers have made major advances in understanding markers of prodromal Parkinson’s that they hope could, one day, be used for earlier diagnosis.
“It’s important to stress that not everyone who has these symptoms goes on to develop Parkinson’s,” Dolhun said. “But we know that in some people, these can be some of the earliest signs.”
Here are four early symptoms that often appear in people who are later diagnosed with Parkinson’s disease:
Loss of sense of smell
The inability to detect odors, known as anosmia, can be a temporary side effect from a cold or sinus infection, or even a more permanent issue after COVID. But more than 90% of people with Parkinson’s disease lose their sense of smell gradually over a long period of time. It can begin years or even decades before motor symptoms.
“We’ve estimated that the loss of the sense of smell is occurring 20 years before the disease is diagnosed,” Postuma said.
“We know that people who lose their sense of smell have about a fivefold increased risk of developing Parkinson’s in the future,” he said. “People lose their ability to detect and identify odors, and they are often not very aware because it happens so gradually.”
Researchers are still trying to understand what causes anosmia in Parkinson’s disease and why it is one of the earliest symptoms. One hypothesis states that the disease could actually begin in the olfactory bulb, the part of the brain that controls sense of smell, where abnormal proteins wreak havoc and damage neurons.
Adults ages 40 and older in the United States or Canada who have not been diagnosed with Parkinson’s disease can request a free scratch-and-sniff smell test from the Michael J. Fox Foundation for Parkinson’s Research. The test is part of a brain health study that uses loss of sense of smell as a way of identifying people who haven’t yet developed Parkinson’s but might in the future.
Acting out dreams
Normally, the body enters a state of almost total paralysis during rapid eye movement (REM) sleep, which is the sleep stage with the most vivid dreams. REM sleep behavior disorder is a chronic condition characterized by a loss of this paralysis that leads people to physically act out their dreams. They will sit up in bed, have one-sided conversations, and even punch or kick their partner.
Studies have shown that between 50 and 70% of people with REM sleep behavior disorder will develop Parkinson’s disease or a related condition such as Lewy body dementia within an average of five to 10 years. People ages 50 and older with REM sleep behavior disorder have a 130 times greater likelihood of developing Parkinson’s compared with someone without the sleep condition.
If you think you’re acting out your dreams, talk to your doctor and request a sleep study for confirmation. People who receive a diagnosis can sign up for a registry established by the North American Prodromal Synucleinopathy (NAPS) Consortium, which aims to develop treatments to delay or prevent Parkinson’s and related diseases.
Constipation
Constipation is one of the most common gastrointestinal complaints in the United States and usually not serious. However, chronic constipation that persists for several weeks or longer affects two-thirds of all people with Parkinson’s. Parkinson’s can affect the nerves that line the digestive tract, and studies have found clumps of abnormal protein in neurons lining the intestines of people with Parkinson’s.
A meta-analysis of nine studies found that people with constipation — either assessed by a questionnaire or diagnosed by a healthcare professional — were twice as likely to develop Parkinson’s compared with those without constipation. Another study followed 6,790 men ages 51 to 75 over a 24-year period, and those who had a bowel movement less often than once a day had a greater risk of Parkinson’s.
“Even people who are constipated in their 20s or 30s seem to have an increased chance of getting Parkinson’s 30, 40 years later,” Postuma said. “So, now we’re starting to wonder: Is the disease affecting the nerves that control the gut, or is being constipated a risk factor for Parkinson’s, as well?”
Dizziness when standing up
Postural low blood pressure, known as orthostatic hypotension, is a drop in blood pressure that occurs when a person goes from sitting or lying down to standing. It can lead to dizziness, lightheadedness, and even fainting. Orthostatic hypotension can be triggered by mild dehydration, low blood sugar, or overheating. But chronic, persistent orthostatic hypotension can be more serious.
“When it’s neurological in origin — in other words, not dehydration, medication, or a heart problem — about half of these patients develop Parkinson’s or a related condition,” Postuma said. “So it’s a very high risk factor. Most people, though, don’t have a neurologic cause.”
Researchers have identified orthostatic hypotension as a possible feature of prodromal Parkinson’s disease, although the evidence is not as strong as for other markers. For example, one study found that otherwise unexplained orthostatic hypotension was associated with an eventual diagnosis of Parkinson’s or a related condition in 18 of 79 (23%) patients after a 10-year follow-up.
What prodromal markers mean
At this point, these prodromal markers aren’t specific enough to definitively signal Parkinson’s on their own, and there’s a good chance they may be because of a different cause or medical condition. But if you have several markers at once or a family history of the disease, you may want to speak to your doctor.
“If you start to combine some of these symptoms, then it really increases your risk for developing Parkinson’s disease in the future,” said Kelly Mills, director of the Parkinson’s disease and Movement Disorders Center at Johns Hopkins Medicine. “If someone has constipation, loss of smell sensation, and they’re acting out their dreams, you’re adding the risk of those different factors. But don’t necessarily jump to any conclusions without getting an evaluation.”
