ֱ

Neil Diamond Opens Up About Parkinson's

— Singer details his condition and makes rare appearance

MedpageToday
A photo of Neil Diamond performing on stage

Singer/songwriter Neil Diamond gave a surprise performance on the stage at MGM Grand Garden Arena in Las Vegas last week. Diamond had retired from touring two years ago after being diagnosed with Parkinson's disease (PD).

Diamond performed at the 24th annual benefit, where he was being honored. The Gala celebrates life and raises funds for the Cleveland Clinic's . Diamond performed some of his greatest hits, such as "Hello Again," "Forever in Blue Jeans," "Cracklin' Rosie," "I Am ... I Said," and, of course, "Sweet Caroline," which he sang alongside Billy Ray Cyrus, Sammy Hagar, Chris Isaak, Katlyn Nichol, and Kenny "Babyface" Edmonds.

Diamond was diagnosed with PD in January 2018, during his 50 Year Anniversary World Tour. Although he feels no longer able to tour, he has continued to work on his health in the hope he would be able to get back on stage. He told the :

"Well, I'm doing pretty well. I'm active. I take my meds. I do my workouts. I'm in pretty good shape. I'm feeling good. I want to stay productive ... I just can't do the traveling that I once did, but I have my wife there supporting me (and) friends."

"It does have its challenges, but I'm feeling good and I feel very positive about it. I'm feeling better every day. [I'm] just dealing with it as best I can, and just keep the music coming."

Diamond is hoping that at some point he could do a residency: "Well, I feel I can do it. I want to do it," he said. "It's just a matter of resting up, finding the time, preparing, and then just doing the show."

Parkinson's Disease

PD belongs to a group of conditions called motor system disorders, which cause unintended or uncontrollable movements of the body. PD's effects on the central nervous system are both chronic and progressive. As nerve cells (neurons) in parts of the brain become impaired or die, people may notice problems with movement, tremor, stiffness in the limbs or trunk of the body, or impaired balance. As these symptoms become more pronounced, people may have difficulty walking, talking, or completing other simple tasks.

PD is the second-most common neurodegenerative disorder in the U.S., after Alzheimer's disease. Most people diagnosed with PD are age 60 years or older, although some 5%-10% of people with PD are diagnosed before the age of 50. Approximately 500,000 Americans are diagnosed with PD, but given that many individuals go undiagnosed or are misdiagnosed the actual number is likely much higher. Some experts estimate that as many as 1 million Americans have PD.

What Causes the Disease?

Although many brain areas are affected, the most common symptoms result from the loss of neurons in the substantia nigra. Normally, the neurons in this area produce dopamine, which carries signals to the next "relay station" of the brain, the corpus striatum, producing smooth, purposeful movement. Loss of dopamine results in abnormal nerve firing patterns. Studies have shown that most people with Parkinson's have lost 60%-80% or more of the dopamine-producing cells in the substantia nigra by the time symptoms appear. People with PD also have loss of the nerve endings that produce the neurotransmitter norepinephrine. Norepinephrine is the main chemical messenger of the sympathetic nervous system, the part of the nervous system that controls many autonomic functions such as pulse and blood pressure. The loss of norepinephrine might explain several of the non-motor features seen in PD, including fatigue and abnormalities of blood pressure regulation.

The affected brain cells of people with PD contain Lewy bodies -- deposits of the protein alpha-synuclein. Researchers do not yet know why Lewy bodies form or what role they play in the disease. Some research suggests that the cell's protein disposal system may fail in people with PD, causing proteins to build up to harmful levels and trigger cell death. Some researchers speculate that the protein buildup in Lewy bodies is part of an unsuccessful attempt to protect the cell from the toxicity of smaller aggregates, or collections, of synuclein.

Genetics

Scientists have identified several genetic mutations associated with PD, including the alpha-synuclein gene, and many more genes have been tentatively linked to the disorder. The same genes and proteins that are altered in inherited cases may also be altered in sporadic cases by environmental toxins or other factors. Researchers also hope that discovering genes will help identify new ways of treating PD.

Environment

Exposure to certain toxins has caused parkinsonian symptoms in rare circumstances (such as exposure to MPTP, an illicit drug, or in miners exposed to the metal manganese). Other still-unidentified environmental factors may also cause PD in genetically susceptible individuals.

Mitochondria

Several lines of research suggest that mitochondria may play a role in the development of PD. Abnormalities in the mitochondria are major sources of free radicals -- molecules that damage membranes, proteins, DNA, and other parts of the cell, often referred to as oxidative stress. Oxidative stress-related changes, including free radical damage to DNA, proteins, and fats, have been detected in the brains of individuals with PD. Some mutations that affect mitochondrial function have been identified as causes of PD.

Symptoms of PD

PD's effects on the central nervous system are both chronic and progressive. By the time a diagnosis is made, PD has typically already progressed to a point where people have difficulty controlling the movement of their bodies due to tremors, bradykinesia (slowness of movement and reflexes), stiffness in their limbs or the trunk of their body, and impaired balance. As these symptoms progress, walking, talking, swallowing, and completing other simple tasks can become challenging.

In addition to motor-related symptoms, non-motor symptoms such as cognitive impairment, mood and behavioral problems, sleep disorders, and constipation can significantly impair quality of life and require careful symptom-based treatment. Some non-motor symptoms such as hyposmia (reduced ability to detect odors), REM sleep-behavior disorder (acting out vivid dreams), and constipation typically precede the motor symptoms by several years. Other non-motor symptoms such as cognitive impairment commonly appear after the onset of motor symptoms.

Many people with PD eventually develop dementia, but the time from the onset of movement symptoms to the onset of dementia symptoms varies greatly from person to person. Dementia is a leading reason for people with PD to transition from independent living at home to long-term care facilities.

Treatments

Medications for PD fall into several categories. The first category includes drugs that increase the level of dopamine in the brain. The most common drugs for PD are dopamine precursors -- substances such as levodopa that cross the blood-brain barrier and are then changed into dopamine. Other drugs mimic dopamine or prevent or slow its breakdown.

Another category of PD drugs affects other neurotransmitters in the body in order to ease some of the symptoms of the disease. For example, anticholinergic drugs interfere with production or uptake of the neurotransmitter acetylcholine. These can be effective in reducing tremors.

The third category of drugs prescribed for PD includes medications that help control the non-motor symptoms of the disease, that is, the symptoms that don't affect movement. For example, people with PD-related depression may be prescribed antidepressants.

These treatments can be summarized in the following chart:

Clinical trials for PD can be found at .

Sources: , ,

Michele R. Berman, MD, and Mark S. Boguski, MD, PhD, are a wife and husband team of physicians who have trained and taught at some of the top medical schools in the country, including Harvard, Johns Hopkins, and Washington University in St. Louis. Their mission is both a journalistic and educational one: to report on common diseases affecting uncommon people and summarize the evidence-based medicine behind the headlines.