Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to the classic motor features known as the TRAP tetrad: Tremor, Rigidity, Akinesia/Bradykinesia, and Postural instability. It is the second most common neurodegenerative disease after Alzheimer's, affecting approximately 1% of people over 60 years. The disease also causes significant non-motor symptoms including anosmia, depression, constipation, and REM sleep behavior disorder. While there is no cure, levodopa remains the most effective treatment, though long-term use leads to motor complications including dyskinesias and motor fluctuations.

Clinical Pearls:

• Second most common neurodegenerative disease (after Alzheimer's)
• Asymmetric onset is characteristic (distinguishes from atypical parkinsonism)
• Resting tremor (4-6 Hz) is the most recognizable feature but not always present
• Non-motor symptoms often precede motor symptoms by years
• Levodopa is most effective treatment but causes dyskinesias after 5-10 years

Red Flags (Suggesting Atypical Parkinsonism):

• Falls early in disease: Suggests progressive supranuclear palsy (PSP)
• Poor levodopa response: Suggests multiple system atrophy (MSA) or PSP
• Symmetrical onset: Atypical for PD
• Rapid progression: Suggests atypical parkinsonism
• Early cognitive decline: Suggests dementia with Lewy bodies
• Early autonomic failure: Suggests MSA

Non-Modifiable Risk Factors:

• Age: Strongest risk factor, risk increases exponentially after age 60
• Gender: Male sex (1.5:1 ratio)
• Genetics: 10-15% have family history, multiple genes identified (SNCA, LRRK2, GBA, PARKIN)
• Ethnicity: Slight variations, but affects all populations

Modifiable Risk Factors:

• Pesticide exposure: Increased risk with organochlorine pesticides
• Head trauma: Controversial, some studies suggest increased risk
• Rural living: Slightly increased risk, possibly due to pesticide exposure
• Well water: Possible association

Genetic Factors:

• SNCA (alpha-synuclein): First gene identified, rare but highly penetrant
• LRRK2: Most common genetic cause, 1-2% of sporadic PD
• GBA: Glucocerebrosidase mutations, 5-10% of PD
• PARKIN, PINK1, DJ-1: Early-onset PD, autosomal recessive
• >20 genes identified: Most are rare

Protective Factors:

• Caffeine: Moderate coffee consumption reduces risk
• Smoking: Inverse association (not recommended due to other risks)
• Exercise: Regular physical activity may reduce risk
• NSAIDs: Some studies suggest protective effect

"What is Parkinson's disease?" Parkinson's disease is a condition where certain nerve cells in your brain gradually stop working. These cells produce a chemical called dopamine that helps control movement. When dopamine levels drop, it causes problems with movement like shaking, stiffness, and slowness. It's a progressive condition, meaning it gets worse over time, but treatments can help manage symptoms for many years.

"What causes it?" We don't know exactly what causes Parkinson's in most people. It's likely a combination of genetic and environmental factors. In about 10-15% of cases, it runs in families. Most cases happen by chance. It's not caused by anything you did or didn't do.

"What symptoms will I notice?" The main symptoms are:

• Tremor: Shaking, usually in your hands, that's worse when you're resting
• Stiffness: Your muscles feel tight and rigid
• Slowness: Movements become slow and smaller
• Balance problems: Trouble with balance and falls (usually later in the disease)

You might also notice:

• Loss of smell (often years before other symptoms)
• Constipation
• Depression or anxiety
• Sleep problems
• Small handwriting

"How is it diagnosed?" Your doctor will examine you and look for the characteristic signs. There's no specific test - the diagnosis is based on your symptoms and examination. Your doctor might do some scans or tests to rule out other conditions. Sometimes a trial of medication (levodopa) helps confirm the diagnosis if your symptoms improve.

"Is there a cure?" Unfortunately, there's no cure yet. However, there are very effective treatments that can:

• Control your symptoms for many years
• Help you stay active and independent
• Improve your quality of life

Research is ongoing, and new treatments are being developed.

"How is it treated?" The main treatment is a medication called levodopa, which your brain converts to dopamine. It's very effective for movement problems. Other medications include:

• Dopamine agonists (mimic dopamine)
• MAO-B inhibitors (help dopamine last longer)
• Medications to help with specific symptoms

Your doctor will work with you to find the best combination. As the disease progresses, you might need:

• Adjustments to your medications
• Physical therapy
• Occupational therapy
• Speech therapy
• Sometimes surgery (deep brain stimulation)

"Will I become disabled?" Most people with Parkinson's stay active and independent for many years - often 10-15 years or more. The disease progresses slowly, and treatments help manage symptoms. Some people do eventually need more help, but many continue to work, drive, and enjoy life for a long time.

"What about the shaking?" Not everyone with Parkinson's has a tremor, and if you do, medications usually help control it. The tremor is often worse when you're resting and may improve when you're using your hands. It's usually not painful, but it can be bothersome. Treatments can significantly reduce it.

"Will I get dementia?" Some people with Parkinson's develop thinking and memory problems, but not everyone. It's more common in advanced disease, usually after many years. If it does happen, there are treatments that can help. Your doctor will monitor your thinking and memory over time.

"What can I do to help myself?"

• Take your medications as prescribed
• Stay active: Exercise is very important and can help with symptoms
• Eat well: A balanced diet helps
• Stay socially active: Don't isolate yourself
• Learn about the condition: Knowledge helps you manage better
• Join a support group: Connecting with others helps
• Work with your healthcare team: Regular follow-ups are important

"What about work and driving?" Many people continue working for years after diagnosis. You may need accommodations, but many people manage well. For driving, you'll need to be honest with yourself and your doctor about your abilities. Your doctor can help assess if it's safe for you to drive.

"Is there hope?" Absolutely. While there's no cure, treatments have come a long way, and research continues. Many people with Parkinson's live full, active lives for many years. The key is working closely with your healthcare team, staying active, and taking your medications as prescribed. New treatments are being developed, and there's reason to be optimistic about the future.