Parkinson’s disease (PD) can be difficult to diagnose by clinicians, especially in early stages of the disease. This means that some people with PD may get diagnoses only late in the disease when the symptoms are more obvious. Others may never get a formal diagnosis at all. 

Jacob Simmering, PhD, recipient of a Parkinson’s Foundation Stanley Fahn Junior Faculty Award, is digging through healthcare data to find clues that could lead to earlier and more accurate diagnoses of PD. Using statistical analysis, he hopes to identify diagnostic patterns that commonly precede PD and that could be used as future medical signposts, guiding doctors toward earlier detection of the disease. 

“This award is crucial to my career development as a researcher in Parkinson’s disease,” said Dr. Simmering. “Parkinson’s disease is a common neurodegenerative disease without any disease-modifying, neuroprotective therapies. One issue with degenerative diseases is that the damage is irreversible. By the time clinical symptoms become apparent, the disease is often very advanced in terms of neuronal death. Earlier intervention may allow for treatments that preserve neurons — slowing, if not preventing, progression.” 

From his lab at the University of Iowa, a Parkinson’s Foundation Center of Excellence, Dr. Simmering is utilizing health insurance databases to collect healthcare data on nearly 250,000 deidentified people recently diagnosed with PD. From this information, he hopes to identify a “diagnostic window” for PD—a stretch of time with repeated doctor’s visits for PD-like symptoms signaling the presence of the disease. 

Dr. Simmering will then use this diagnostic window as a frame, looking at people with recent diagnoses and figuring out what prevented physicians from diagnosing PD sooner. His hypothesis is that the three biggest factors that play into delayed diagnoses are: 

• Unique symptom patterns of PD 

• Living in more rural areas 

• Not being seen by a neurologist 

Sorting through this data will provide evidence for other repeated symptoms that could clue doctors into a PD diagnosis earlier. While tremor and involuntary movements are most commonly used to lead to a PD diagnosis, other symptoms like urinary problems and anxiety could be just as valuable. Altogether, Dr. Simmering will use this detailed analysis to generate a forward-looking “risk score” to identify people who are most at risk of developing PD.  

“These results will allow us to screen for people who have symptoms and characteristics similar to people who will go on to be diagnosed with Parkinson's disease, potentially allowing for earlier detection of disease,” said Dr. Simmering.  

Earlier detection means providing symptom relief sooner to those with the disease, improving their quality of life with early treatment. 

Meet more Parkinson’s researchers! Explore our My PD Stories featuring PD researchers. 

Medication plays a key role in managing Parkinson’s disease (PD), but it’s only one part of a broader care plan.  

The following article is based on a Parkinson’s Foundation  Expert Briefing  exploring how medications fit into integrated, holistic Parkinson’s care, hosted by Danny Bega, MD, MSCI, associate professor of neurology, medical director and director of the Parkinson's Disease & Movement Disorders Center neurology residency program at Northwestern University Feinberg School of Medicine, a Parkinson's Foundation Center of Excellence. Dr. Bega is also the director of the Huntington's and Wilson’s diseases programs at Northwestern. 

Understanding the Dopamine-Parkinson’s Connection 

Parkinson’s is a progressive disorder linked to declining levels of dopamine, a brain chemical that influences movement, memory and many other vital body processes. Other brain chemicals, including norepinephrine and serotonin, can also be impacted in Parkinson's disease and influence symptoms.  

As Parkinson’s advances, the number of brain cells making dopamine continues to decrease, and remaining cells struggle to store and release it. This leads to slowness of movement, tremor, rigidity and other motor symptoms. It can also cause various non-motor symptoms, such as constipation, loss of smell and thinking changes. 

Managing Parkinson’s 

Parkinson’s is a complex disease. There is no standard treatment. However, medications — along with exercise, comprehensive care, a nutritious diet and mindfulness practices — can manage Parkinson’s symptoms and help you live well.  

Establishing a regular exercise routine soon after diagnosis may help slow disease progression and can improve movement, strength, balance and mood. It can also help you sleep better. Staying social and engaged can reduce feelings of loneliness.  

Your care team is equally important. Look for healthcare professionals with expertise in Parkinson’s, including a neurologist, speech-language pathologist, physical and occupational therapist, social worker and other healthcare professionals, to help manage your PD symptoms. Be sure to attend regular checkups. 

The Role of Medication 

Most Parkinson’s medications work to improve symptoms by either increasing dopamine in the brain or acting like dopamine. Levodopa is the most effective drug for managing Parkinson’s symptoms. During the course of Parkinson’s, most people will take levodopa at some point.  

Anxiety and depression can also be common in Parkinson’s and can impact well-being even more than motor symptoms. Treating these symptoms using a combination of medication, such as an SSRI, SNRI or mirtazapine — a tricyclic antidepressant drug — along with therapy, stress management and staying active, can significantly decrease disability.  

People newly diagnosed with Parkinson’s often wonder when to begin prescription medication. Studies show there is no benefit in holding off. Most doctors agree you should start medication when symptoms begin to bother you.  

Because no two people experience PD in exactly the same way, treatments vary from person to person, as does the rate of progression. However, knowing the typical stages of Parkinson’s can help you anticipate changes: 

• In the first five years following diagnosis, you may find symptoms don’t significantly impact your daily life. Your doctor might recommend a clinical trial. Participation in Parkinson’s research can potentially give you early access to new treatments, improve care and lay the foundation for a cure.  

• Within one to 10 years, as symptoms begin to interfere with activities, most people with Parkinson’s can expect a long-lasting, steady response to medication.  

• Between five and 20 years after diagnosis, it becomes increasingly harder for the brain to store dopamine. Your body’s response to levodopa can become shorter and less efficient. This can lead to motor fluctuations — "on" periods, when medication works well, and "off" periods, when medication wears off and symptoms return. It is important to work closely with your doctor to adjust your treatment and find what works best for you. 

• After 10 or more years of living with Parkinson’s, a person can experience more significant issues. Some people can develop significant memory and thinking problems. Trouble with balance, falls and freezing, a temporary inability to move, can also become an issue. Your doctor can discuss medication adjustments or drug therapies or provide a referral to the right healthcare professional for your needs, which might include a neuropsychologist, psychiatrist, or a speech or occupational therapist. 

Types of Medications Used in Parkinson’s 

It can be common for people with Parkinson’s to take a variety of medications, at different doses and different times of day, to manage symptoms. This can include: 

Dopamine agonists: Early on, drugs that stimulate dopamine in the brain, such as pramipexole, ropinirole and rotigotine, can usually treat Parkinson’s movement symptoms. Dopamine agonists pose less risk for dyskinesia — involuntary erratic movements that usually begin after a few years of levodopa treatment.  

Side effects can include nausea, dizziness, sleepiness, confusion and impulse control disorders, such as uncontrolled shopping, gambling, eating and sexual urges. Studies show 28% of people with Parkinson’s stop taking dopamine agonists due to side effects, while 40% need to add another medication within two years. 

Levodopa: Levodopa, the most effective drug for Parkinson’s movement symptoms, replaces dopamine in the brain. It is usually given in combination with the drug carbidopa to reduce nausea, a common side effect. Taking levodopa with meals can also reduce nausea, but protein may interfere with the drug’s effectiveness. About 2% of people taking levodopa stop due to side effects, while 15% need to add another medication within two years.  

Dyskinesia, also linked to levodopa, can often be managed by a dose adjustment or through direct treatment, using a medication called amantadine. It works by blocking NMDA, a chemical that causes extra movement. Immediate-release amantadine is also sometimes used alone for Parkinson’s movement symptoms. There is an increased risk of confusion and hallucinations with amantadine use in people over 75. It can also be associated with leg swelling, skin changes and other side effects.  

Anticholinergics: The medications trihexyphenidyl and benztropine are sometimes used to improve tremor or dystonia — painful, sustained cramping . They work by blocking acetylcholine, a brain chemical tied to movement. However, their use should be avoided in people 70 and older due to the risk of confusion and hallucinations. Anticholinergics can also be associated with blurred vision, dry mouth, constipation and urinary retention. 

Medications your doctor might consider to improve the effects of levodopa include: 

MAO-B inhibitors: Monoamine oxidase-B inhibitors rasagiline, selegiline and safinamide make more dopamine available to the brain. These medications can be used alone or in combination with levodopa to extend effectiveness. MAO-B inhibitors are generally well tolerated, but 70% of people taking them alone for Parkinson’s will need to add another medication within two years. 

COMT inhibitors: Medications such as entacapone and opicapone increase available levodopa in the brain by blocking the catechol-O-methyl transferase enzyme.  

A2A receptor antagonist: Istradefylline, an adenosine A2A antagonist, blocks adenosine at A2A receptors in the brain to reduce levodopa “off “time. 

Inhaled levodopa is often used with levodopa, as needed, for sudden “off” time. Injectable apomorphine can also be used on demand, for “off” time relief. Both medications can increase the risk of dyskinesia. 

It is important to work with your doctor to find the right balance for you. Your doctor might increase or decrease your levodopa based on your symptoms. For example, tremor, stiffness or mobility issues might benefit from an increase in levodopa. However, hallucinations, confusion and low blood pressure might improve with a decrease in levodopa. 

There are also strategies and medications to manage drooling, runny nose, sleep issues, gut issues, thinking changes and other Parkinson’s challenges. 

What if levodopa doesn’t seem to be working? 

If you are taking levodopa but aren’t seeing benefits, talk to your doctor. Here are some questions to ask: 

• Is the symptom troubling you one that doesn’t respond well to levodopa? Could it be related to another health issue?  
• Would you benefit from a referral to a rehabilitation therapist or another health professional? 
• Could something be interfering with how your body is absorbing medication? Some people experience less benefit when taking levodopa with a high-protein meal. 
• Do you have a condition that mimics Parkinson’s? 

It is also important to discuss whether your dose needs to be adjusted. For example, the effects of Sinemet, a form of levodopa, only last a short time — after 90 minutes half of it is gone. Your doctor might adjust the timing and dose of levodopa, use a longer-acting formulation or recommend taking your medications 30 minutes before or 60 minutes after eating a meal. 

Advanced Therapies 

If it becomes difficult to control motor fluctuations by adjusting oral medications, there are other options to improve medication absorption and reduce “off” time:  

• Duopa therapy delivers carbidopa-levodopa gel directly to your intestine through a surgically placed tube.  

• Foscarbidopa and foslevodopa (Vyalev) therapy uses a pump to steadily deliver a form of levodopa under the skin through a small tube called a cannula. A needle is used to place the cannula. 

• Continuous apomorphine therapy (Onapgo) uses a pump to deliver continuous apomorphine through a fine needle placed under the skin.  

These medications require lifestyle adjustments, training to use and a commitment to good skin care to reduce the risk of irritation and infections. 

Options Beyond Medication 

More advanced Parkinson’s symptoms can sometimes benefit from other treatment strategies, such as deep brain stimulation (DBS) — which involves surgically implanting an electrical pulse generator connected to electrodes placed in the brain to address Parkindeep-brainson’s movement symptoms and some non-movement symptoms.  

DBS might be considered for someone who:  

• lives with classic Parkinson’s disease  

• has symptoms that respond to levodopa  

• experiences frequent motor fluctuations and tremor, despite consistent medication dosing 

• has bothersome dyskinesia 

Following DBS, many people can reduce their medications and still experience a reduction of their PD symptoms. The reduction in dose of medication can lead to decreased dyskinesia. 

Focused ultrasound, a non-invasive therapy, does not require a surgical incision. During the procedure, high-frequency sound waves are aimed at a specific area of the brain connected to tremor to relieve Parkinson’s tremor. Unlike DBS therapy, which is adjustable and reversible, focused ultrasound changes are permanent. 

If you have questions about PD treatment options, contact our Helpline at 1-800-4PD-INFO (473-4636) or Helpline@Parkinson.org. 

Learn More 

Explore our resources about medications to treat symptoms of Parkinson’s:  

• Download our book Medications: A Treatment Guide to Parkinson’s Disease 

• Watch Understanding Deep Brain Stimulation (DBS) 

• Read The Latest in Parkinson’s Medications: Taking a Personalized Approach 

Levodopa, which helps with the movement symptoms of Parkinson’s, tends to work less well over time, especially for women. 

Parkinson's disease (PD) is a condition that gets worse over time, impacting the nervous system. It's caused by the gradual death of brain cells that produce dopamine, a crucial chemical messenger for controlling movement. When these cells are lost and dopamine levels drop, people with Parkinson's begin to experience noticeable symptoms like shaking or tremors, muscle stiffness, a general slowness of movement and problems with balance. 

A primary treatment for these movement symptoms is the drug levodopa. The body converts this medication into dopamine, helping to replenish the brain's supply. By doing so, levodopa can significantly reduce the physical challenges of the disease and improve a person's daily life. 

However, for many individuals with Parkinson's, the effectiveness of levodopa can begin to diminish between doses. In other words, it starts "wearing off." Patients may notice their movement symptoms, such as tremors and stiffness, gradually returning before their next scheduled dose. 

Parkinson’s also impacts men and women differently. Men are estimated to be 1.5 times more likely to develop Parkinson’s. Women with Parkinson's are often diagnosed at a later age and may have slightly different symptoms. These differences between men and women with Parkinson’s could be due to a variety of factors, including hormonal differences and genetics. 

To better understand how these gender differences impact experience with levodopa, a recent study tracked 216 individuals with Parkinson's over a two-year period. The goal was to investigate whether men and women experience levodopa wearing off at different rates and to examine the symptoms that occur while on this medication. 

Study Results 

Participants included 139 men and 77 women with Parkinson’s who began taking levodopa for the first time at the start of the study. After two years in the study, almost 65% of women experienced symptom fluctuations, or times when the medication's effects seem to "wear off" before the next dose is due. This was compared to about 53% of men. This suggests that for many women, the medication was less effective in managing symptoms and did not feel as consistent over time. 

In addition, more women in the study developed dyskinesia, a side effect of levodopa that leads to involuntary, uncontrolled movements. About 14% of women developed dyskinesia compared to only 5% of men. Taken together, these results suggest that there may be differences in how levodopa is processed in the body between men and women. 

The study concluded that being female was the strongest predictor for both the wearing-off effect and dyskinesia after taking levodopa for two years. This indicates that gender is an important factor when considering how a person might respond to this medication. 

Highlights 

• The study followed 139 men and 77 women with Parkinson’s for two years after they started taking levodopa for the first time.  

• During the two-year study period, 65% of women experienced times when the medication's effects seemed to "wear off" before the next dose. This was compared to about 53% of men. 

• During the study, about 14% of women developed dyskinesia, compared to only 5% of men.  

• The study concluded that female gender predicted the development of motor fluctuations and dyskinesia more than any other factor.  

What does this mean? 

Women’s experiences have been historically underrepresented in PD research. This study adds to increasing evidence that men and women often experience various aspects of PD differently, including in their response to the PD medication levodopa. Specifically, these results indicate that women may be more likely to have worse responses to levodopa treatment over time compared to men. However, the reasons for these differences between men and women are still unknown. Additionally, it is common for both men and women to have breakthrough symptoms on levodopa over time.  

What do these findings mean to people with PD right now? 

Knowing that men and women may react differently to prolonged levodopa treatment can help healthcare providers develop more effective treatment plans for patients. While more research needs to be done, the findings from this study suggest that more tailored, “gender-oriented” treatment recommendations may be needed. If you are struggling with symptoms related to levodopa treatment, talk to your doctor to discuss your treatment plan.  

Learn More 

The Parkinson’s Foundation believes in empowering the Parkinson’s community through education. Learn more about PD and the topics in this article through our below resources, or by calling our free Helpline at 1-800-4PD-INFO (1-800-473-4636) for answers to your Parkinson’s questions. 

• Levodopa 
• PD and Medication: Advancing Treatment 
• Episode 6: New Levodopa Delivery Methods for Parkinson’s