Combating Depression in Parkinson's Disease

Old information but good

By Matthew Menza, M.D.
Robert Wood Johnson Medical School,
New Brunswick, New Jersey

Updated version published in the Spring 2009 issue of PDF News & Review

Depression is one of the major, and most common, challenges for people living with Parkinson’s disease (PD).  Everyone feels sad from time to time and it is normal to experience sadness and stress when faced with a difficult disease such as Parkinson’s.  However, the sadness that is part of being human can become a significant problem if it crosses into the realm of clinical depression and is left untreated.  

Just four years ago, when this article was originally written, health professionals, researchers and people living with or affected by PD were just beginning to recognize the extent of the prevalence of depression in Parkinson’s and its impact on daily life.  Since that time, there has been a sharp and welcome increase in the awareness of depression as a common feature of the PD experience and of the importance of treating it.  Not only that, but new research has also advanced our understanding of how to treat PD-related depression and has increased the range of the treatment options we have available. 

What is the difference between sadness and depression?  While sadness is temporary, depression is persistent, and the people who experience it find that they cannot enjoy life as they used to.  A person who is depressed may have little energy and may struggle to get out of bed in the morning.  Other symptoms of depression can include poor appetite, sleep disturbances, fatigue, feelings of guilt, self-criticism and worthlessness, irritability and anxiety.  Some people may begin having persistent thoughts that they would be better off dead or may even begin planning on ending their life.  The presence of these symptoms on most days for two weeks suggests a diagnosis of depression and should be discussed with a physician. 

At least 40 percent of people with PD experience clinical depression at some time during the disease.  It may occur early or late in the course of  Parkinson’s, and may wax and wane in severity.  It causes personal suffering and also appears to intensify problems with mobility and memory.  A person with Parkinson’s, or his or her caregiver or physician, may at first dismiss the signs of depression because they assume that it is Parkinson’s that is causing the problem or because they assume it is normal to be depressed when faced with this illness.  This can lead to feelings of helplessness and confusion, which may further exacerbate the problem.

What causes depression in PD?  There is no clear answer but most specialists agree that it is probably a combination of living with the stress of a progressive chronic disease, along with changes in the neurochemistry of the brain that accompany Parkinson’s.  The experience of depression early in the disease may be a natural reaction to an anticipated loss of ability and quality of life, but research suggests that it may also be directly due to PD-related chemical changes in the brain.  Many of the areas of the brain that are affected in PD are also important in controlling mood.  Spe­cifically, Parkinson’s causes changes in areas of the brain that produce serotonin, norepinephrine and dopamine — chemicals that are involved in regulating mood, energy, motivation, appetite and sleep.  In addition, the frontal lobe of the brain, which is important in controlling mood, is known to be underactive in Parkinson’s.

It is very important to address depression because of the effects it can have on other symptoms and on quality of life.  If you are concerned that you or a loved one with Parkinson’s may be depressed, you should raise it with your doctor.  If you have been diagnosed with clinical depression, there is no simple formula for treating it, but there are several principles that are true for nearly everyone. 

First, it is extremely important that Parkinson’s disease itself be optimally treated.  People with Parkinson’s who experience uncontrolled “on-off” periods and freezing episodes are more prone to depression, so it is important to talk with a doctor about the best approach to controlling these symptoms.  The same is true of some other, nonmotor symptoms of PD — for example, poor sleep, constipation and fatigue — that need to be treated to decrease the burden of living with the disease.

Second, it is important to make the effort to exercise regularly, to eat well and to stay socially involved.  Exercise is an effective tool in helping the symptoms of both depression and PD.  The exercise does not need to be rigorous, but it does need to be regular.  Eating a healthy diet is another lifestyle approach that can help your overall wellness.  Staying involved in social and recreational activities is also very important.  Everyone needs something to look forward to, whether it be working on a hobby or socializing with friends and family. 

Third, people should consider taking advantage of psychological treatments such as stress management, relaxation and cognitive behavioral therapy, as well as the kind of peer support that can be found in support groups.  Receiving help from professionals and peers can help you learn to cope with stresses, improve social relationships and find solutions to practical day-to-day impairments.  For instance, your peers at a support group may have a lot of wisdom to share with you (and you with them) about the practical aspects of daily living with PD, such as handling finances or managing travel.

Lastly, people with Parkinson’s should be aware that many medications are available for depression in PD.  Recent studies have suggested that one class of antidepressants, called “dual reuptake inhibitors,” which affect both serotonin and norepinephrine, do improve depressive symptoms in people with PD.  These include medications such as Effexor® (venlafaxine), Cymbalta® (duloxetine), and Pamelor® (nortriptyline hydrochloride).  Another class of antidepressants, called selective “serotonin re-uptake inhibitors” (SSRIs), work by making serotonin available for use by the brain.  These are also sometimes useful.  Among the most common SSRIs are Paxil® (paroxetine), Prozac® (fluoxetine) and Zoloft® (sertraline). 

The pharmacological treatment of depression in Parkinson’s disease needs to be individualized and may involve a variety of strategies.  If you or your loved one is currently taking an antidepressant that does not appear to be helping, talk to your doctor to see if a switch to a different agent may better benefit your symptoms.

There remain many unanswered questions about the causes and the treatments of depression in people with PD and the problem is receiving increasing attention from the scientific community.  The National Institutes of Health, at the urging of clinicians and advocacy groups, has begun to fund studies on depression and some of these results are becoming available. (To learn more about clinical trials, visit www.PDtrials.org.)

One thing is certain: there is a clear consensus that awareness about depression in PD needs to be raised among people with PD, caregivers and health professionals.  More needs to be done to explore better ways to treat this illness in people living with Parkinson’s, and to better understand how the treatment of depression affects other aspects of life, including sleep, anxiety, memory and concentration.  In the meantime, if you or a loved one with PD experiences symptoms of depression, talk to your doctor and take advantage of the resources that are already available.

10 Signs of Depression in Parkinson's

   1. Excessive Worrying

   2. Persistent Sadness

   3. Crying

   4. Loss of interest in usual activities and hobbies

   5. Increased fatigue and lack of energy

   6. Feelings of guilt

   7. Loss of motivation

   8. Complaints of aches and pains

   9. Feelings of being a burden to loved ones

  10. Ruminations about disability, death, and dying

People with these symptoms should discuss them with a physician

http://www.pdf.org/en/combating_depression

In fight against Parkinson's, Muhammad Ali became the face of the debilitating disease

June 4, 2016

Muhammad Ali became the face of the struggle against Parkinson's disease in the later part of his life. Above, the heavyweight before a House committee on research for the illness.

(JOE MARQUETTE/AP)

Muhammad Ali fought bloody wars against a slew of boxing greats. But his toughest fight took place outside the ring against an opponent that couldn’t be knocked out.

For three decades, Ali waged a public battle against Parkinson’s disease — making brave appearances long after the degenerative disorder withered his body and stole his speech.

“Selflessness and bravery — those are the two things he epitomized,” said Leslie Chambers, president and CEO of the American Parkinson Disease Association.

In facing the cameras again and again, Ali played a crucial role in raising awareness of the incurable neurological disease.

Muhammad Ali was the greatest, even in later years of decline

“He brought the average American’s attention to this disease,” Chambers said. “We’re so grateful for him. In the long run, he’s helped our community in a tremendous way.”

Ali was just 42 years old when he was diagnosed with Parkinson’s in 1984, three years after the last fight of his legendary career. The disease ravages the body over time in a slow, savage march.People close to Ali noticed that his speech was already starting to slur and his body already starting to slow before his last bout in 1981.

Ten years later, he appeared a shell of his former self in an interview with Bryant Gumbel on NBC’s “Today Show.”Gone was the mega-watt smile — Ali’s face appeared frozen.

Ali walks through the Phoenix Muhammad Ali Parkinson Center in 2012.  (DAVID KADLUBOWSKI/AP) 

Ali was responsible for one of the most indelible moments in sports history five years later.

One of the most closely guarded secrets leading up to the 1996 Summer Games in Atlanta was who would receive the honor of lighting the Olympic cauldron.

The world learned the answer when Ali appeared under the cauldron before American swimmer Janet Evans handed him the torch.

The stunned crowd roared as Ali, his left arm shaking and his entire body trembling, managed to light the wire that carried the flame to the cauldron.

Ali was responsible for one of the most indelible moments in sports history five years later.

One of the most closely guarded secrets leading up to the 1996 Summer Games in Atlanta was who would receive the honor of lighting the Olympic cauldron.

The world learned the answer when Ali appeared under the cauldron before American swimmer Janet Evans handed him the torch.

The stunned crowd roared as Ali, his left arm shaking and his entire body trembling, managed to light the wire that carried the flame to the cauldron.

Muhammad Ali watches as the flame climbs up to the Olympic torch during the opening ceremonies of the 1996 Summer Olympics.

 (DOUG MILLS/AP)

 “It was the rarest of Olympic moments, a moment of infinite sadness, yet supreme majesty,” wrote Baltimore Sun columnist Ken Rosenthal.

“You didn't know whether to cheer or to cry. All you could do was watch and root once more for Muhammad Ali.”

Chambers said she still has vivid memories of that moment.

“It was all about courage,” she said. “It was written all around his body that he was not going to let [it] do him in. He was still the greatest.”

n subsequent years, Ali grew more frail, his public appearances more infrequent.

But he surfaced again just two months ago at Celebrity Fight Night, the Phoenix-based gala that raises money for the treatment of Parkinson’s.

He wore sunglasses. His upper body was stooped over. He didn’t say a word.

But Ali, fittingly, received a standing ovation.

REST IN PEACE ALI !

://health.einnews.com/article/329355805/l9l0XGN6jDVWRIJf

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In Chinatown, Parkinson's Disease patients learn to cope

June 4, 2016

Xin Rong Xu touches her face during a group exercise session at a Parkinson's disease support group at the On Lok Senior Services Center in Philadelphia.

AS THE hushed sounds of a choir singing Chinese folk songs drifted in from an adjacent space, Yao Huang sat on a hard chair, lifting and stamping his feet at a senior center in Chinatown.

Julia Wood, an occupational therapist, sat facing her audience of about 12 elderly Asian Americans with Parkinson's disease.

"We're going to be using seated exercises taken from Tai Chi and yoga," Wood said. An interpreter, David Lee, translated her English words into Cantonese.

When prompted, Huang, 75, chanted "om" along with others in the Parkinson's support group that meets at the On Lok Senior Services Center, on 10th Street near Race.

Wood, from the Dan Aaron Parkinson's Rehabilitation Center at Pennsylvania Hospital, gave them vocal exercises because Parkinson's not only affects their movements, but can make it harder for them to speak loudly enough to be heard.

Parkinson's is a chronic and progressive movement disorder involving malfunction and death of the nerve cells in the brain called neurons.

Its symptoms, including tremors, impaired balance, and rigidity in the limbs, can worsen over time, said Yuliis Y. Bell, a social worker and outreach coordinator for the Parkinson's Disease and Movement Disorders Center at Pennsylvania Hospital.

Actor Michael J. Fox is among well-known figures with the disease.

The Chinatown Parkinson's group meets every other month at On Lok. It's a joint project of Pennsylvania Hospital and Thomas Jefferson University Hospital.

Bell said the hospitals formed the support group to help patients get information in a language and a culturally sensitive way that meets their needs, and to help others in their communities.

"We fill a need, especially in minority communities, where we've found that information about Parkinson's is minimal," Bell said.

In addition to the Chinatown group, there are Parkinson's support groups for African Americans in West Philadelphia and for Latinos in Northeast Philadelphia.

At last month's session, Wood asked the group, "How many of you have had a fall in the last week?"

After several raised their hands, Wood told them it was important to exercise at home to remain as strong as possible.

Huang, who used to work in manufacturing, said he was diagnosed with Parkinson's eight years ago. He has been coming to the support group for a year.

"This is very important," Huang said, according to Lee, the interpreter. "My voice has gotten very soft, but because I was coming here, I knew to expect it and knew how to do exercises for it."

Also at On Lok were Xin Rong Xu, 80, a retired dentist, and her husband, Qinchun Wang, 85, a retired engineer. Xu was diagnosed with Parkinson's 10 years ago, her husband five years ago.

Wang said that in addition to coming to the support group, he takes Tai Chi classes.

Both husband and wife are patients of Tsao-Wei Liang, a neurologist at Jefferson.

He said that members of the group are "very highly educated" and that he has been pleased by the depth of their questions at the meetings.

"Persons with Parkinson's disease often live in fear and isolation, fear of what the future will bring, and isolation from their peer groups," Liang later wrote in an email.

"The Chinatown PD support group brings together a group of like-minded individuals linked by a condition, by ethnicity and language. The educational and nurturing environment provides comfort, hope, and enlightenment for local Chinese Americans living with PD."

russv@phillynews.com215-854-5987N>@ValerieRussDN

http://health.einnews.com/article/329358122/qIcQOHA4HSoUDYFg

Q&A: Parkinson's disease

June 4, 2016

FILE - In this Feb. 22, 2012, file photo, Muhammad Ali, center, with the support of sister in-law Marilyn Williams, left, and wife Lonnie, walks through the Muhammad Ali Parkinson Center at Barrow Neurological Institute at St. Joseph's in Phoenix. Mohammed Ali is in the hospital with respiratory problems, and while officials haven't given details about his condition, the boxing great’s health in general is complicated by advanced Parkinson’s _ a degenerative disease he’s lived with for three decades. (AP Photo/The Arizona Republic, David Kadlubowski) MARICOPA COUNTY OUT; MAGS OUT; NO SALES

Read more here: http://www.ledger-enquirer.com/news/article81783842.html#storylink=cpy

Before his death, Muhammad Ali was hospitalized with respiratory problems, his health complicated by advanced Parkinson's. The boxing great had lived with the degenerative disease for three decades. Here are some questions and answers about the disease:

Read more here: http://www.ledger-enquirer.com/news/article81783842.html#storylink=cpy

BY LAURAN NEERGAARDAP Medical Writer

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Before his death, Muhammad Ali was hospitalized with respiratory problems, his health complicated by advanced Parkinson's. The boxing great had lived with the degenerative disease for three decades. Here are some questions and answers about the disease:

Q: What is Parkinson's?

A: Parkinson's is a neurologic disease that robs people of control over their movements. It typically starts with tremors, and is characterized by slow movement, a shuffling gait, stiff limbs, balance problems and slurred speech.

Q: Who gets it?

A: About 1 million Americans are living with Parkinson's, and an estimated 4 million to 5 million people worldwide, according to the National Parkinson Foundation. It usually appears after age 60, although sometimes it can develop before age 40.

Q: What causes it?

A: The exact cause isn't known but Parkinson's develops when cells that produce one of the brain's chemical messengers, called dopamine, begin to deteriorate and die. Dopamine transports signals to parts of the brain that control movement. Parkinson's symptoms appear after enough dopamine-producing cells die that there's too little of this neurotransmitter in the brain.

Q: Is there a cure?

A: There is no cure but there are a range of treatments, from medications that affect dopamine levels to a surgically implanted tremor-blocking device. Patients also can benefit from physical and occupational therapy.

Q: What's the prognosis?

A: Symptoms worsen over time, usually slowly. The severity of symptoms, and how quickly they progress, varies widely between patients. In advanced cases, people may be unable to walk or care for themselves. They also can suffer non-motor symptoms, including depression and memory and other cognitive dysfunction.

While Parkinson's itself isn't considered fatal, people can die from complications of the disease.

Q: What complications are of most concern?

A: Lung problems are a risk as muscle weakness impedes the ability to cough and to swallow. While any kind of pneumonia can occur, what's called aspiration pneumonia — when bits of food or liquid land in the lungs instead of being swallowed properly — is the leading cause of death among Parkinson's patients, said National Parkinson Foundation medical director Dr. Michael S. Okun.

http://health.einnews.com/article/329379430/d3Vn1jBeuGyfYYQS

Read more here: http://www.ledger-enquirer.com/news/article81783842.html#storylink=cpy

Muhammad Ali remembered by Michael J. Fox, fellow face of Parkinson’s, as ‘a warrior for the cure’

June 4, 2016

Muhammad Ali and Michael J. Fox pretend to duke it out before a Senate subcommittee hearing on May 22, 2002.

 (KENNETH LAMBERT/AP)

In the hours after Muhammad Ali died, another famous face of Parkinson’s disease threw his tribute into the ring.

“Ali, the G-O-A-T. A giant, an inspiration, a man of peace, a warrior for the cure. Thank you,” Michael J. Fox tweeted Saturday morning.

The “Back to the Future” alum included one of many photos of himself faux-sparring with Ali, who died late Friday of complications from the degenerative disease.

The heavyweight champ, who was diagnosed with Parkinson’s in 1984, three years after his retirement, teamed up with Fox to raise awareness after the actor revealed in 1998 that he, too, suffered from the yet-incurable neurological condition.

Over the years, the two appeared together in Parkinson’s PSAs, at fund-raising benefits and even a May 2002 Senate subcommittee hearing to make a case for funding research for a cure.

Fox further memorialized the boxing great Saturday in a blog post on his Parkinson’s research foundation website.

“Muhammad was a true legend — a champion in the boxing ring, and a champion for millions of Parkinson’s families,” he said in a statement. “We looked up to him as an example of grace and courage in the face of great challenges. He will be missed.”

Fox described Ali, born Cassius Marcellus Clay Jr., as one of his role models in a 2009 Guardian profile. He recalled once phoning the former athlete’s wife, Lonnie Ali, to ask how Ali viewed his legacy in the face of declining health.

“I was thinking, ‘What does he think when he sees himself on television as he was as Cassius Clay? Ducking and weaving and joking and spouting poetry. Does he feel sadness? A sense of loss?’ Lonnie said, ‘He loves it. He loves to see himself. He can’t get enough of it.’”

“And I got that,” Fox told the Guardian. “Because it’s still him. Parkinson’s doesn’t take away anything of his identity.”

Ali died Friday at Scottsdale Osborn Medical Center in Arizona. Funeral arrangements, slated to be in his native Louisville, Ky., had yet to be announced Saturday morning.

http://health.einnews.com/article/329388938/K-zjTeDQ46MhT9gN

Dietary supplement may slow progress of Alzheimer’s: Study

By: PTI | Toronto |  Published: June 4, 2016

A dietary supplement containing a blend of 30 vitamins and minerals may be 

able to "dramatically" slow the progress of catastrophic neurological...

A dietary supplement containing a blend of 30 vitamins and minerals may be able to “dramatically” slow the progress of catastrophic neurological diseases such as Alzheimer’s and Parkinson’s, a new study has claimed.

The supplement contains all natural ingredients widely available in health food stores and has shown remarkable anti-ageing properties that can prevent and even reverse massive brain cell loss, researchers said.

“The findings are dramatic. Our hope is that this supplement could offset some very serious illnesses and ultimately improve quality of life,” said Jennifer Lemon from McMaster University in Canada.

The formula, which contains common ingredients such as vitamins B, C and D, folic acid, green tea extract, cod liver oil and other nutraceuticals, was first designed by scientists in McMaster in 2000.

A series of studies published over the 15 years have shown its benefits in mice, in both normal mice and those specifically bred for such research because they age rapidly, experiencing dramatic declines in cognitive and motor function in a matter of months, researchers said.

The mice used in this study had widespread loss of more than half of their brain cells, severely impacting multiple regions of the brain by one year of age, the human equivalent of severe Alzheimer’s disease, they said.

The mice were fed the supplement on small pieces of bagel each day over the course of several months.

Over time, researchers found that it completely eliminated the severe brain cell loss and abolished cognitive decline.

It is a mixture scientists believe could someday slow the progress of catastrophic neurological diseases such as Alzheimer’s, Amyotrophic lateral sclerosis (ALS) and Parkinson’s.

“The research suggests that there is tremendous potential with this supplement to help people who are suffering from some catastrophic neurological diseases,” said Lemon.

“We know this because mice experience the same basic cell mechanisms that contribute to neurodegeneration that humans do. All species, in fact. There is a commonality among us al,” she said.

In addition to looking at the major markers of ageing, researchers also discovered that the mice on the supplements experienced enhancement in vision and most remarkably in the sense of smell – the loss of which is often associated with neurological disease – improved balance and motor activity.

The findings were published in the journal Environmental and Molecular Mutagenesis.

http://www.financialexpress.com/article/lifestyle/health/dietary-supplement-may-slow-progress-of-alzheimers-study/273819/?

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Muhammad Ali, 'The Greatest of All Time', Dead at 74

June 4, 20116

Speaking at a press conference in Chicago on Sept. 25, 1970, deposed world heavyweight champion Muhammad Ali "Cassius Clay" said he might fight Jerry Quarry in New York if Georgia Gov. Lester Maddox succeeds in halting the scheduled Atlanta bout. Charles Kolenovsky / AP, file

Muhammad Ali, the silver-tongued boxer and civil rights champion who famously proclaimed himself "The Greatest" and then spent a lifetime living up to the billing, is dead. 

Ali died Friday at a Phoenix-area hospital, where he had spent the past few days being treated for respiratory complications, a family spokesman confirmed to NBC News. He was 74.

After a 32-year battle with Parkinson's disease, Muhammad Ali has passed away at the age of 74. The three-time World Heavyweight Champion boxer died this evening," Bob Gunnell, a family spokesman, told NBC News. 

Ali had suffered for three decades from Parkinson's, a progressive neurological condition that slowly robbed him of both his legendary verbal grace and his physical dexterity. A funeral service is planned in his hometown of Louisville, Kentucky. 

His daughter Rasheda said early Saturday that the legend was "no longer suffering," describing him as "daddy, my best friend and hero" as well as "the greatest man that ever lived." 

Even as his health declined, Ali did not shy from politics or controversy, releasing a statement in December criticizing Republican presidential candidate Donald Trump's proposal to ban Muslims from entering the United States. "We as Muslims have to stand up to those who use Islam to advance their own personal agenda," he said. 

The remark bookended the life of a man who burst into the national consciousness in the early 1960s, when as a young heavyweight champion he converted to Islam and refused to serve in the Vietnam War, and became an emblem of strength, eloquence, conscience and courage. Ali was an anti-establishment showman who transcended borders and barriers, race and religion. His fights against other men became spectacles, but he embodied much greater battles.

Born Cassius Marcellus Clay on Jan. 17, 1942 in Louisville, Kentucky, to middle-class parents, Ali started boxing when he was 12, winning Golden Gloves titles before heading to the 1960 Olympics in Rome, where he won a gold medal as a light heavyweight. 

He turned professional shortly afterward, supported at first by Louisville business owners who guaranteed him an unprecedented 50-50 split in earnings. His knack for talking up his own talents — often in verse — earned him the dismissive nickname "the Louisville Lip," but he backed up his talk with action, relocating to Miami to train with the legendary trainer Angelo Dundee and build a case for getting a shot at the heavyweight title.

As his profile rose, Ali acted out against American racism. After he was refused services at a soda fountain counter, he said, he threw his Olympic gold medal into a river. 

Recoiling from the sport's tightly knit community of agents and promoters, Ali found guidance instead from the Nation of Islam, an American Muslim sect that advocated racial separation and rejected the pacifism of most civil rights activism. Inspired by Malcolm X, one of the group's leaders, he converted in 1963. But he kept his new faith a secret until the crown was safely in hand.

That came the following year, when heavyweight champion Sonny Liston agreed to fight Ali. The challenger geared up for the bout with a litany of insults and rhymes, including the line, "float like a butterfly, sting like a bee." He beat the fearsome Liston in a sixth-round technical knockout before a stunned Miami Beach crowd. In the ring, Ali proclaimed, "I am the greatest! I am the greatest! I'm the king of the world."

A Controversial Champion 

The new champion soon renounced Cassius Clay as his "slave name" and said he would be known from then on as Muhammad Ali — bestowed by Nation of Islam founder Elijah Muhammad. He was 22 years old. 

The move split sports fans and the broader American public: an American sports champion rejecting his birth name and adopting one that sounded subversive.

Ali successfully defended his title six times, including a rematch with Liston. Then, in 1967, at the height of the Vietnam War, Ali was drafted to serve in the U.S. Army. 

He'd said previously that the war did not comport with his faith, and that he had "no quarrel" with America's enemy, the Vietcong. He refused to serve. 

"My conscience won't let me go shoot my brother, or some darker people, some poor, hungry people in the mud, for big powerful America, and shoot them for what?" Ali said in an interview. "They never called me nigger. They never lynched me. They didn't put no dogs on me." 

His stand culminated with an April appearance at an Army recruiting station, where he refused to step forward when his name was called. The reaction was swift and harsh. He was stripped of his boxing title, convicted of draft evasion and sentenced to five years in prison. 

Released on appeal but unable to fight or leave the country, Ali turned to the lecture circuit, speaking on college campuses, where he engaged in heated debates, pointing out the hypocrisy of denying rights to blacks even as they were ordered to fight the country's battles abroad. 

"My enemy is the white people, not Vietcongs or Chinese or Japanese," Ali told one white student who challenged his draft avoidance. "You my opposer when I want freedom. You my opposer when I want justice. You my opposer when I want equality. You won't even stand up for me in America for my religious beliefs and you want me to go somewhere and fight but you won't even stand up for me here at home."

Muhammad Ali is held back by referee Joe Walcott, left, after Ali knocked out challenger Sonny Liston in the first round of their title fight in Lewiston, Maine on May 25, 1965. AP, file

Ali's fiery commentary was praised by antiwar activists and black nationalists and vilified by conservatives, including many other athletes and sportswriters. 

His appeal took four years to reach the U.S. Supreme Court, which in June 1971 reversed the conviction in a unanimous decision that found the Department of Justice had improperly told the draft board that Ali's stance wasn't motivated by religious belief. 

Return to the Ring 

Toward the end of his legal saga, Georgia agreed to issue Ali a boxing license, which allowed him to fight Jerry Quarry, whom he beat. Six months later, at a sold-out Madison Square Garden, he lost to Joe Frazier in a 15-round duel touted as "the fight of the century." It was Ali's first defeat as a pro. 

That fight began one of boxing's and sport's greatest rivalries. Ali and Frazier fought again in 1974, after Frazier had lost his crown. This time, Ali won in a unanimous decision, making him the lead challenger for the heavyweight title. 

He took it from George Foreman later that year in a fight in Zaire dubbed "The Rumble in the Jungle," a spectacularly hyped bout for which Ali moved to Africa for the summer, followed by crowds of chanting locals wherever he went. A three-day music festival featuring James Brown and B.B. King preceded the fight. Finally, Ali delivered a historic performance in the ring, employing a new strategy dubbed the "rope-a-dope," goading the favored Foreman into attacking him, then leaning back into the ropes in a defensive stance and waiting for Foreman to tire. Ali then went on the attack, knocking out Foreman in the eighth round. The maneuver has been copied by many other champions since. 

The third fight in the Ali-Frazier trilogy followed in 1975, the "Thrilla in Manila" that is now regarded as one of the best boxing matches of all time. Ali won in a technical knockout in the 15th round. 

Ali successfully defended his title until 1978, when he was beaten by a young Leon Spinks, and then quickly took it back. He retired in 1979, when he was 37, but, seeking to replenish his dwindling personal fortune, returned in 1980 for a title match against Larry Holmes, which he lost. Ali lost again, to Trevor Berbick, the following year. Finally, Ali retired for good.

'He's Human, Like Us' 

The following year, Ali was diagnosed with Parkinson's Disease. 

"I'm in no pain," he told The New York Times. "A slight slurring of my speech, a little tremor. Nothing critical. If I was in perfect health — if I had won my last two fights — if I had no problem, people would be afraid of me. Now they feel sorry for me. They thought I was Superman. Now they can go, 'He's human, like us. He has problems.' '' 

Even as his health gradually declined, Ali — who switched to more mainstream branches of Islam — threw himself into humanitarian causes, traveling to Lebanon in 1985 and Iraq in 1990 to seek the release of American hostages. In 1996, he lit the Olympic flame in Atlanta, lifting the torch with shaking arms. With each public appearance he seemed more feeble, a stark contrast to his outsized aura. He continued to be one of the most recognizable people in the world.

Muhammad Ali attends the Sports For Peace Fundraising Ball at The V&A on July 25, 2012 in London. Ian Gavan / Getty Images, file

He traveled incessantly for many years, crisscrossing the globe in appearances in which he made money but also pushed philanthropic causes. He met with presidents, royalty, heads of state, the Pope. He told "People" magazine that his largest regret was not playing a more intimate role in the raising of his children. But he said he did not regret boxing. "If I wasn't a boxer, I wouldn't be famous," he said. "If I wasn't famous, I wouldn't be able to do what I'm doing now." 

In 2005, President George W. Bush honored Ali with the Presidential Medal of Freedom, and his hometown of Louisville opened the Muhammad Ali Center, chronicling his life but also as a forum for promoting tolerance and respect. 

Divorced three times and the father of nine children — one of whom, Laila, become a boxer — Ali married his last wife, Yolanda "Lonnie" Williams, in 1986; they lived for a long time in Berrien Springs, Michigan, then moved to Arizona. 

In recent years, Ali's health began to suffer dramatically. There was a death scare in 2013, and last year he was rushed to the hospital after being found unresponsive. He recovered and returned to his new home in Arizona. 

In his final years, Ali was barely able to speak. Asked to share his personal philosophy with NPR in 2009, Ali let his wife read his essay: 

"I never thought of the possibility of failing, only of the fame and glory I was going to get when I won," Ali wrote. "I could see it. I could almost feel it. When I proclaimed that I was the greatest of all time, I believed in myself, and I still do." 

Family time: Ali poses with some of his seven daughters and two sons (above) at his most recent birthday party in January of this year

As Mrs. Lonnie Ali looks on, President George W. Bush embraces Muhammad Ali after presenting him with the Presidential Medal of Freedom on November 9, 2005, ...

Lonnie & Ali

http://www.nbcnews.com/news/sports/muhammad-ali-greatest-all-time-dead-74-n584776