Parkinson's disease

What it's like

The movement symptoms everyone knows, the others most people don't, and what it isn't.

The three main symptoms

• Tremor: Shaking that usually begins in a hand or arm, often when it's resting.
• Slowness: Movements become much slower than normal: bradykinesia.
• Stiffness: Tight, tense muscles that make moving, and even the face's expressions, harder: rigidity.

The ones people don't expect

• Smell: Losing your sense of smell, sometimes several years before anything else.
• Sleep: Problems sleeping, and sleepiness in the day.
• Gut: Constipation.
• Mood: Depression and anxiety.
• Thinking: Slight memory problems and trouble planning.

A warning sign in sleep

REM sleep behaviour disorder — moving and acting out dreams, because the body's usual paralysis during dreaming fails — is one of the strongest early signs. Of 1,280 people who had it, 73.5% had developed Parkinson's or a related condition within 12 years.

• Myth: Parkinson's is a tremor. In fact: Tremor is one of three main symptoms, with slowness and stiffness, and loss of smell, sleep problems, constipation and low mood are part of it too.
• Myth: Only old people get it. In fact: Most people start to have symptoms over 50, but some first notice them under 40.
• Myth: It shortens your life a lot. In fact: Most people with Parkinson's now have a normal or near-normal life expectancy.
• Myth: Nothing can be done. In fact: There's no cure yet, but treatments can ease the main symptoms.

What's happening in the brain

A dopamine source running dry, a movement circuit starved of it, and a disease that starts somewhere else entirely. The model lights each one as you read.

The dopamine source

The substantia nigra's dopamine cells send their fibres to the putamen, feeding the circuits that control movement. In Parkinson's those cells die off gradually, and symptoms usually appear once around half their activity is gone. Its dark-pigmented cells, which give it its name, "black substance", are among the ones the disease attacks most.

The circuit, running dry

With its supply failing, the striatum runs short of dopamine, the putamen worst: in brains studied after death it had lost nearly all of it, while parts of the caudate kept up to about 40%. The damage starts at the far end: by the time symptoms appear, more of the fibres reaching the striatum have gone than the cells they come from.

Where it really starts

The disease doesn't begin in the substantia nigra. Its damage first appears low in the brainstem, in the nucleus of the vagus nerve, and in a nucleus of the smell system, then climbs the brainstem in a predictable order and only later reaches the cortex. It fits the early signs: loss of smell can come years before the shaking does.

The clumps

Inside the affected neurons, a protein called alpha-synuclein clumps together. Treatments that target those clumps are being tested, and one of the biggest goals is to spot the disease early enough to protect the cells before they're lost.

Why it happens

Mostly unknown: genes and environment together.

• 6.1 million people worldwide: In 2016, up from 2.5 million in 1990, mostly because populations are ageing.
• ~50% of the activity lost: When symptoms usually begin.
• 1.4× as common in men: Age-adjusted, worldwide.

No one knows exactly what sets it off. Genetic changes and environmental factors are thought to combine; it can run in families, but inheriting it directly is rare. Pesticides, herbicides and pollution have been suggested, but the evidence isn't conclusive.

Not every tremor is Parkinson's

Some medicines, other brain conditions and small strokes can cause similar symptoms, called parkinsonism.

What helps

Replacing the missing dopamine, and keeping the body moving.

• Levodopa (The medicine most people eventually need.): The brain turns it into dopamine, which usually improves the movement symptoms. Over years it can cause involuntary movements and on-off swings, and each dose can wear off sooner.
• Dopamine agonists (Drugs that stand in for dopamine.): Milder than levodopa. Side effects include sleepiness and hallucinations, and at high doses compulsive gambling, shopping or sex.
• MAO-B inhibitors (Selegiline, rasagiline: they stop dopamine being broken down.): An option early on, with smaller effects than levodopa.
• Deep brain stimulation (Fine wires in the brain, driven by a pacemaker-like device in the chest.): In advanced Parkinson's, stimulating the subthalamic nucleus improved movement and quality of life more than medication alone, though with more serious side effects (13% against 4%). It eases symptoms but isn't a cure.
• Exercise and physiotherapy (Movement as treatment.): Regular exercise relieves stiffness. In newly diagnosed people, six months of hard treadmill exercise held symptoms steady while a control group's worsened.
• Speech and language therapy (For speaking and swallowing.): Many people develop problems with speech and swallowing; exercises and aids help.

Watch for changes they may not notice

Dopamine agonists can bring on compulsive gambling, shopping or sex, and the person taking them may not realise it's happening. Family and carers are often the first to see it. Tell the doctor.

Living with it

Day to day, for the person and the people around them.

Day to day

• Keep exercising: it's one of the best things for stiffness, and walking or stretching still help as it progresses.
• Drivers must tell the licensing authority and their insurer, though that doesn't always mean stopping.
• Low mood is common, and part of the disease, not a weakness. A doctor, specialist nurse, counsellor or support group can help.
• Talk with family and the care team early about what you'd want later on.

• Instead of "Here, let me do it.", try "Take your time. I'm not in a rush.". Slowness of movement is a core symptom, and keeping moving is part of treatment.
• Instead of "You look fine — are you sure something's wrong?", try "How are you finding things — the bits people can't see, too?". Many symptoms don't show: low mood, anxiety, sleep problems, constipation, memory.

Put it into practice

Four real situations. Choose what you'd do, and see why.

• Your grandfather's right hand has started trembling when it rests in his lap, and he's slower getting up from chairs. What's the sensible next step? See a doctor: those are two of the main symptoms, and other conditions can cause similar ones. Resting tremor and slowness are main symptoms, and medicines, other conditions and small strokes can mimic it.
• A classmate asks why Parkinson's makes movement slow when the damage is in one tiny region. What's the best explanation? That region supplies dopamine to the basal ganglia circuit that controls movement; without it the whole circuit falters. The substantia nigra's fibres feed the putamen and the movement circuits, and the striatum runs short of dopamine.
• Your uncle started a dopamine agonist six months ago. Your aunt mentions he's been spending hours on betting apps. What should they do? Tell his doctor: compulsive gambling is a known side effect of these drugs. Dopamine agonists can cause compulsive gambling and shopping, which the person may not notice.
• Someone has started acting out their dreams in their sleep — punching, kicking, shouting. Why might a doctor take it seriously? It can be REM sleep behaviour disorder, which in most people is followed by Parkinson's or a related condition within years. 73.5% of 1,280 people with it had developed one within 12 years.