This article originally appeared in the June 2006 Harvard Women’s Health Watch and is provided courtesy of Harvard Health Publications.

After the diagnosis: Living with Parkinson’s

There’s no cure for Parkinson’s disease, but new treatments can ease the symptoms and prolong independence.

“You’ll be fine for years. Go out and do your job.”

That’s how Janet Reno, diagnosed with Parkinson’s disease (PD) at age 57, recalls her neurologist’s advice. She took it to heart, not only returning to her demanding job as U.S. Attorney General but also taking up kayaking.

Reno and about a million others in the United States and Canada are living with PD, a progressive disorder caused by a loss of brain cells that produce the chemical messenger dopamine, most noticeably in an area of the brain that controls movement. For now, there’s no cure, but advances in treatment have made it easier for Reno and others to remain active for many years. Physicians are also increasingly recognizing that dopamine-producing nerve cells can be disturbed in brain areas other than those involved in motor control — and even outside the brain — which helps explain a host of mysterious symptoms that can accompany the disorder (see “More than a movement disorder”).

More than a movement disorder
Although movement problems are the most noticeable PD symptom, many patients will tell you they’re not the most distressing. In one survey, 88% reported troubling nonmotor symptoms, and these tend to become more prominent as the disease progresses. If they’re not recognized as part of PD and treated accordingly, they can severely impair your quality of life. Tell your neurologist if you or a loved one experiences any of the following symptoms:

   Depression. Depression affects more than half of people with PD. It’s increasingly recognized as a symptom of the disease itself (sometimes even appearing before tremor) and not a secondary reaction to chronic illness. Depression and PD share certain symptoms, such as decreased energy and weight loss, so a clinician may not recognize your depression unless she or he asks you about feelings of sadness, anxiety, and hopelessness, or thoughts of death or suicide.

According to the American Academy of Neurology, the most effective drug treatment for depression in PD is the tricyclic antidepressant amitryptiline — although it’s not necessarily a first choice because of side effects that include drowsiness, a drop in blood pressure, and dry mouth. Deep brain stimulation may be effective for depression and other symptoms.

   Cognitive problems. Although the cause isn’t clear, dementia occurs in an estimated 40% of people with PD, a rate six times that in the general population. If you have trouble staying alert, solving problems, or switching your thoughts from topic to topic, it may be a sign of PD-associated dementia. To find out, your doctor may ask questions that test your memory, problem-solving ability, attention span, and language skills. Two medications, rivastigmine and donepezil, are sometimes used to treat PD-associated dementia, but the benefits seem to be small, and rivastigmine can worsen tremors.

   Hallucinations and delusions. At least 20% of people with PD develop hallucinations (seeing things that aren’t there, often terrifying images of people or animals) or delusions (persistent beliefs not based in reality). Hallucinations and delusions may be a side effect of medications or result from the loss of certain brain cells. A common delusion is the belief that a spouse is having an affair. The neurologist must rely on the patient or caregiver to report these symptoms, which can be treated by adjusting medications or adding an antipsychotic drug, such as clozapine or quetiapine.

   Sexual problems. Women with PD sometimes report decreased libido, vaginal tightness, and loss of the ability to achieve orgasm. Treatment with dopamine-boosting agents may overcorrect this deficiency, leading to out-of-control sexual behavior that can seriously damage relationships, especially if it is not recognized as a side effect of the treatment. Whether the problem is diminished or excessive libido, your neurologist may be able to help by changing your medication.

   Other compulsive behaviors. In a survey of people with Parkinson’s disease presented at the April 2006 meeting of the American Academy of Neurology, researchers from NINDS found that 10 patients developed problem gambling after they started treatment, losing an average of $150,000 each. Seven others developed hypersexuality, and two began compulsive shopping. Almost all were being treated with both levodopa and a dopamine-boosting drug. Don’t conceal uncharacteristic behavior from your neurologist: It may be important to change your medication to prevent irreversible damage to your finances or relationships.

   Loss of smell. A loss of dopamine-producing cells in one part of the brain can alter your senses of smell and taste, often long before motor symptoms emerge. Smell can’t be revived, but foods with strong flavors and a pleasing appearance can help spur your appetite.

   Constipation. This is a common symptom of Parkinson’s disease. Autopsies have shown that Lewy bodies, a characteristic of Parkinson-affected cells, can develop in nerves controlling the colon. Physicians recommend standard treatments, such as increased fiber, fluid, and exercise, with added laxatives if necessary.

   Blood pressure instability. PD interferes with the nervous system’s control of heart function, making it difficult for the body to adjust blood pressure. A drop in blood pressure on standing up may result in fainting or a fall. It may help to change medications, increase fluids and salt in the diet, or add a drug that counters sudden drops in blood pressure.

What goes wrong
Normally, smooth and controlled movements are regulated in a mid-brain area called the substantia nigra. Classic PD symptoms — tremor, slow movement, rigidity or stiffness, and poor balance and posture — occur when 80% of the dopamine-producing cells in this area are lost. What causes the loss of cells isn’t clear.

In some cases, PD is simply inherited; several of the mutations involved have been identified. Heredity alone accounts for only a handful of cases, but studying these cases suggests what may go wrong in all PD. For example, some mutations interfere with the functioning of mitochondria (the energy-producing components of cells). Toxins that interfere with mitochondrial function, such as the chemical MPTP, can also cause PD.

Other PD genes disrupt the processes that clear away the protein alpha synuclein, which forms naturally inside body cells. Its function isn’t fully known. But excess amounts of it appear to play a role in the death of cells in the substantia nigra.

Some theories link PD to chronic inflammation, premature aging, or an overabundance of free radicals — molecules that are produced during normal metabolism but may damage cells if not disarmed by protective antioxidants. Discovering the combination of factors that causes PD will point the way to better strategies for preventing and treating it.

Starting treatment
PD usually isn’t the first diagnosis considered, especially if there’s another obvious explanation for the symptoms, such as exposure to toxic heavy metals. The diagnosis is best made by a neurologist familiar with movement disorders. She or he will look for the classic movement symptoms along with other telltale signs, such as tiny handwriting, soft speech, an uneven or shuffling gait, or an expressionless face.

No lab test or scan clinches the diagnosis, but tests may be used to rule out other explanations, such as a stroke or other neurological disease with similar symptoms. If your symptoms improve when you take a single dose of a PD medication, it’s likely that you have the disorder. But all PD medications have side effects, so your clinician may wait a while before starting drug treatment.

“It’s okay to have some of the symptoms as long as they’re not interfering with your professional or other important activities,” says Dr. Anne B. Young, head of the neurology department at Boston’s Massachusetts General Hospital. “When you’re not able to work, be active socially, or travel, it’s time for treatment.”

Several nondrug approaches — including exercise and physical therapy to improve strength, balance, stamina, and flexibility — can help maximize your ability to function. Other types of therapy can help ease swallowing and speech difficulties and teach you new ways to carry out movements and tasks made difficult by PD.

Supplements that may help delay the progression of PD symptoms are under investigation. The National Institute of Neurological Disorders and Stroke (NINDS) is evaluating coenzyme Q10, a compound important for energy production in the mitochondria; some physicians already recommend it on the basis of safety and encouraging preliminary findings. On the other hand, vitamin E does not delay the development of Parkinson’s symptoms and is not recommended.

Once symptoms warrant treatment, patients may receive a dopamine-boosting agent or other drugs such as selegiline and amantadine. Sinemet, an older but effective medication, is also commonly used. Sinemet contains levodopa, an amino acid that is converted into dopamine, combined with an enzyme inhibitor (carbidopa) that helps prevent the conversion of levodopa before it reaches the brain. More than 90% of patients respond to Sinemet, with motor symptoms and the ability to carry out normal activities improving by about 50%. Possible side effects include nausea and abnormal involuntary muscle movements called dyskinesias.

For more information about medications used to treat Parkinson’s, see www.health.harvard.edu/womenextra.

After the honeymoon
Unfortunately, levodopa and other medications often provide reliable relief only for a brief “honeymoon” period. After that, medications may become less effective or totally ineffective — or effective only on and off (called the on-off phenomenon). You may need higher doses that can cause troubling side effects, including dyskinesias.

In April 2006, the American Academy of Neurology announced new guidelines for the management of on-off phenomenon and dyskinesia. After evaluating research results on a number of medications, they found evidence that two drugs can reduce the amount of “off” time. Entacapone is an enzyme inhibitor that increases the amount of levodopa that reaches the brain. (A medication called Stalevo combines entacapone with levodopa and carbidopa.) Rasagiline — available in many countries since 2005 but still awaiting final FDA approval — slows dopamine breakdown. Other drugs have less evidence behind them but may help with your particular symptoms.

The Academy also reported that deep brain stimulation (DBS) can reduce motor symptoms and the need for medication. In this procedure, the surgeon inserts an electric probe into the subthalamus region of the brain and attaches it to a pacemaker-like device that regulates brain activity with bursts of electricity. DBS doesn’t help with speech or balance, but it can reduce tremor and dyskinesias in the 10%–20% of patients for whom levodopa loses its effectiveness. Because it’s reversible and adjustable, DBS is generally preferred over surgical techniques that destroy portions of brain tissue. About 30,000 patients now have a DBS device implanted, and use of the technique is becoming more widespread.

As the disease advances
Medications and surgery may ease symptoms, but they don’t stop or reverse the underlying disease process. Odds are that if you have Parkinson’s disease, your symptoms will eventually become worse, you will require more medications, and you will need to adapt in new ways.

Whatever your condition, physical, occupational, and speech therapy can help improve your functioning. Therapeutic exercise can help prevent falls and improve your ability to breathe, speak, and swallow. Take advantage of the excellent practical materials and support offered to people with PD and their caregivers by organizations like the National Parkinson Foundation, Inc. (see “Selected resources”).

On the horizon
The search continues for ways to slow or halt the progression of PD and make the disease more manageable.

In February 2006, at the first World Parkinson Congress in Washington, D.C., NINDS announced that two compounds — the antibiotic minocycline and the amino acid creatine — showed enough promise to warrant large clinical trials of their ability to protect healthy nerve cells and delay the need for drug treatment in early PD. Investigators are also considering new ways to deliver standard dopamine-influencing drugs (such as keeping dopamine levels steady by the use of a skin patch or direct infusion into the intestine), medications that act on other neurotransmitters involved in movement control, and a protein that promotes the growth of brain cells.

If you aren’t yet in need of drug treatment, ask your neurologist about participating in a trial of neuroprotective therapies. You can learn about government-funded studies at www.clinicaltrials.gov. To have your experience with PD included in a developing database intended to guide new research, go to the Web site for the Muhammad Ali Parkinson Center, www.maprc.com.