From the nose to the gut: Understanding the non-motor symptoms of Parkinson’s disease

When it comes to understanding and treating Parkinson’s disease, there’s more to it than movement.

To mark Parkinson’s Awareness Month, we’re highlighting some of the disease’s lesser known yet common symptoms. Collectively known as non-motor symptoms, this diverse group of problems play a major role in quality of life for people with Parkinson’s and provide important clues for better understanding a condition that affects seven to 10 million worldwide.

Non-motor symptoms refer to any symptom that is not directly related to movement.
These symptoms include loss of sense of smell, constipation, depression, pain, cognitive impairment, trouble sleeping, fatigue and autonomic problems. Some of these symptoms can even precede the traditional motor symptoms of the Parkinson’s by years or even decades. They also pose significant quality of life issues for people with the disease (thankfully, many of them are treatable).

Understanding non-motor symptoms help us better study and treat Parkinson’s.
Non-motor symptoms give us a window into an incredibly complex disease that can differ greatly from person to person.

At the end of the day, it’s improbable that one single thing causes Parkinson’s. Rather, it is likely the result of a combination of factors, including genetic and epigenetic predisposition and exposure to environmental influences (although it is worth noting that a small subset of cases — fewer than 10 percent — are directly caused by a handful of genetic mutations).

The more we know about all the components of Parkinson’s, the more equipped we are to develop ways to slow, stop or even possibly prevent the disease. Loss of sense of smell and constipation are two good examples of symptoms that are changing the way we think about, diagnose and treat Parkinson’s (more details on why below).

Loss of sense of smell is often one of the earliest symptoms of the disease.
Up to 90 percent of people who are eventually diagnosed with Parkinson’s report a reduction in their sense of smell years or even decades before the disease’s traditional motor symptoms start (some even lose the ability to smell altogether).

The likely reasons can be summed up in two words — proximity and exposure.

The nose acts as a gateway to the outside world, and comes into direct contact with a host of influences, including environmental toxins. This exposure can cause inflammation, which scientists believe may then lead to critical changes in the nose that may trigger neurodegeneration if left unchecked (read more about what scientists think is going on behind the scenes here).

It’s important to remember the loss of sense of smell on its own doesn’t necessary point to Parkinson’s. There are many other reasons that this can happen, including head injuries and even bad cases of rhinitis (a fancy name for a stuffy nose).

However, when there are no other reasons for the deficit and other early indicators are present, loss of sense of smell can be a useful way to help assess risk and, one day, may even aid in early diagnosis.

Like the nose, the gut also likely plays an important role in Parkinson’s and is home to another one of the disease’s earliest symptoms.
Many people with Parkinson’s also experience gastrointestinal issues such as constipation, both before and after their diagnosis.

Like the nose, evidence suggests the gut harbors a reserve of normal alpha-synuclein, a protein whose abnormal, toxic form is closely linked to Parkinson’s. And again, much like the nose, mounting evidence suggests that inflammatory changes in the gut may prompt alpha-synuclein to transform into a problematic version of itself.

That brings us back to exposure and proximity. Not only is the gut exposed to outside influences through food consumption, but it also has a direct route to the brain via the vagus nerve, a biological “superhighway” of sorts. These two factors, coupled with constipation as a common symptom of Parkinson’s, put the gut smack in the center of researchers’ radar (read more about ongoing research into the gut and Parkinson’s here).

Other symptoms, such as pain, sleep problems, fatigue and depression also are commonly reported in Parkinson’s disease.
Here again it’s important to note that many of these symptoms can be treated, making close consultation with a physician critical. Parkinson’s disease is as unique as the people who have it, meaning no two cases and no two treatment plans will be exactly alike.

  • Pain: Pain in Parkinson’s can be attributed to several factors, including stiffness, rigidity and dystonia (involuntary muscle contractions that are common in Parkinson’s). For more on the types of pain often associated with Parkinson’s, please read this post from The Michael J. Fox Foundation.
  • Sleep problems and fatigue: One of the most common sleep problems in Parkinson’s is waking up after only a few hours and being unable to return to sleep. Other issues, such as restless leg syndrome and vivid dreams or nightmares can also occur, contributing to fatigue. Often, these problems are linked to the medications used to treat Parkinson’s or the disease’s other symptoms, including pain and tremor, which wake a person up. For more, check out this info from University of California, San Francisco.
  • Depression: Increasing evidence suggests that depression may be related to elevated levels of inflammatory chemicals, part of the body’s defense mechanisms that go awry. Research is underway to investigate inflammation’s role as potential contributor to Parkinson’s onset as well as depression in people with the disease, which has implications for understanding and better treating both conditions.

Other symptoms may include cognitive changes, issues with low blood pressure and anxiety. Discussing these symptoms with a physician is an important part of developing a comprehensive treatment plan aimed at improving quality of life.

To mark World Parkinson’s Day, VARI will host a Facebook Live panel discussion about the latest advances in research and treatment at 11:30 a.m. EST on April 11 on the Institute’s Facebook page: www.facebook.com/VanAndelInstitute.

Looking to learn more about non-motor symptoms in Parkinson’s? They’re the theme of this year’s Grand Challenges in Parkinson’s Disease symposium and parallel Rallying to the Challenge patient and advocate meeting, which will be held Sept. 26–27, 2018 at the Institute in Grand Rapids. Learn more by visiting www.grandchallengesinpd.org.


Alpha-synuclein: Alpha-synuclein is a protein whose role in healthy brain cells isn’t entirely clear, although it has been linked to communication between cells. Clumps of abnormal alpha-synuclein called Lewy bodies are a key feature of Parkinson’s disease. Normal alpha-synuclein is found in the nose and the gut, two areas of particular interest to Parkinson’s researchers.

Inflammation: Inflammation is the body’s response to an injury, infection or other insults. During this process, inflammatory chemicals are released to help the body either heal and fight off invading pathogens. However, when the mechanisms that keep inflammatory responses in check go awry, these chemicals can be overproduced and have harmful side-effects.

Neurodegeneration: The progressive loss of brain function.