Parkinson’s Disease (PD)
Parkinson’s disease (PD) is a progressive neurodegenerative condition resulting from the death of dopamine-containing cells of the substantia nigra in the brain.
Scope of this article:
This article focuses on idiopathic Parkinson’s disease (PD).
For a broader overview of parkinsonism, including secondary causes and Parkinson-plus / atypical parkinsonian syndromes, see: Parkinsonism and Parkinson-Plus Syndromes.
Terms and Definitions
Four commonly confused terms that are related but not interchangeable:
| Term | Definition |
|---|---|
| Parkinsonism (Parkinsonian syndrome) | An umbrella term, a clinical syndrome defined by the presence of bradykinesia plus at least one of the following: tremor, rigidity, postural instability |
| Parkinson’s disease | Idiopathic (primary) form of parkinsonism. Parkinson’s disease is the most common form of parkinsonism
Caused by dopaminergic neuron degeneration in the substantia nigra due to Lewy body deposition |
| Parkinson-plus syndromes (atypical parkinsonism) | A group of primary neurodegenerative disorders that mimic Parkinson’s disease with additional “plus” features and are often poorly responsive to levodopa
Key examples include Lewy body dementia, multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration |
| Secondary parkinsonism | Parkinsonism caused by an identifiable cause (i.e. non-idiopathic), such as drugs or toxins |
Pathophysiology
Hallmark: degeneration of dopaminergic neurons in the substantia nigra → ↓ dopamine signalling to the striatum → disruption in the basal ganglia motor circuits
Pathological hallmark: Lewy body deposition (rich in misfolded alpha-synuclein)
Epidemiology
- Advancing age
- Prevalence rates almost double every five-year interval between 50–69 years for both men and women
- Males
Risk Factors
Key risk factors: [Ref]
- Genetic susceptibility
- Most common genetic risk factor: GBA gene variants
- Examples of monogenic causes: LRRK2, SNCA, PARKIN, and PINK1
- Occupational / environmental exposure to specific pesticides (e.g. paraquat, rotenone, maneb, benomyl, 2,4-D, and organochlorines)
- Industrial solvents and pollutants
- Chlorinated solvents
- Heavy metals
- Welding fumes
- Air pollution
- History of head trauma / TBI (dose-response relationship)
Protective factors (reduces risk of developing PD): [Ref]
- Cigarette smoking and other tobacco use
- Caffeine
- Physical activity
- Diets high in vegetables, fruits, and grains
Diagnosis
Clinical Features
Prodromal / non-motor features often precede the onset of classic motor symptoms. Clinical features of PD have a gradual onset and course, often >10 years
Prodromal Features
- Constipation – one of the most common prodromal features [Ref]
- Anosmia (reduced sense of smell)
- Sleep disturbances (esp. REM sleep behaviour disorder)
- Cognitive impairment
- Mood disorders (e.g. depression, anxiety)
- Fatigue
Motor Symptoms
Motor symptoms can be categorised according to the core clinical features used to define parkinsonism.
| Category | Description / symptoms |
|---|---|
| Bradykinesia | Bradykinesia: slowness in initiating and performing voluntary movement + progressive reduction in speed and amplitude of sustained repetitive actions
May present as:
Bradykinesia can be assessed clinically by asking the patient to perform repetitive movements like finger tapping, hand opening and closing, and foot tapping Look for slowness, reduced amplitude, and progressive decrement. |
| Rigidity | Asymmetrical, predominantly affecting the side of onset
|
| Tremor |
A tremor can be absent in up to 20% of patients with PD |
| Postural instability | Postural instability is suggested by the ‘pull test’ – a tendency to fall backwards after a sharp forward pull from the examiner |
Non-Motor Symptoms
Non-motor features in established PD:
| Category | Features |
|---|---|
| Neuropsychiatric / cognitive |
|
| Sleep-related |
|
| Autonomic |
|
| Other |
|
Investigation and Diagnosis
If PD is suspected:
- Refer to specialist
- PD is a clinical diagnosis using the UK Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria (see below)
Imaging is NOT routinely required for diagnosis:
- DaT scan (123I‑FP‑CIT SPECT) – if essential tremor cannot be clinically differentiated from parkinsonism
- Reduced dopamine transporter activity in Parkinsonism (NB it does not reliably differentiate Parkinson’s disease from other causes of parkinsonism)
- Normal in essential tremor
- MRI – only if Parkinson-plus syndromes are suspected
- In PD: often normal, esp. in early stages
- Parkinson-plus syndromes have distinct MRI findings
There is no single definitive test that reliably distinguishes PD from all other causes of parkinsonism. Investigations are mainly used where the diagnosis is uncertain or to exclude alternative causes.
UK Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria
This is a simplified, high-yield version for PD:
| Steps | Description | Criteria |
|---|---|---|
| Step 1 | Diagnosis of Parkinsonian syndrome |
|
| Step 2 | Exclusion criteria |
|
| Step 3 | Supportive prospective criteria | 3 or more of the following are required:
|
To see the full diagnostic criteria, view this link.
Management
Motor Symptoms
Non-Pharmacological Management
At early stages, consider referring the patient to:
- Physiotherapy (e.g. PD-specific physiotherapy, Alexander technique for those with balance or motor function problems)
- Occupational therapy (e.g. PD-specific occupational therapy for those with difficulties with their activities of daily living)
- Speech and language therapy
- Strategies to improve speech and communication, e.g. attention to effort therapies
- Strategies to improve the safety and efficiency of swallowing to minimise aspiration risks, e.g. expiratory muscle strength training
- Dietitian (e.g. protein redistribution diet – where most of the daily protein is consumed in the final main meal of the day for those who take levodopa and experience motor fluctuations)
Patients should have regular access to a PD nurse specialist.
Pharmacological Therapy
| Treatment stage | Recommended management |
|---|---|
| 1st line therapy | The choice depends on the severity of motor symptoms:
In practice, levodopa is routinely combined with a DOPA decarboxylase inhibitor to enhance efficacy and reduce side effects. Examples include: co-careldopa (levodopa and carbidopa), co-beneldopa (levodopa and benserazide). |
| Adjuvant therapy | If the patient develops dyskinesia or motor fluctuations, manage with the following step-wise approach:
|
| Advanced PD |
|
When offering a dopamine agonist:
- Avoid ergot-derived dopamine agonists (e.g. cabergoline, bromocriptine) due to the risk of fibrosis affecting the heart valve, lungs and retroperitoneum
- Only consider ergot-derived dopamine agonists if symptoms are not adequately controlled with non-ergot dopamine agonists
DO NOT withdraw abruptly due to risk of neuroleptic malignant syndrome and acute akinesia
- If the patient is unable to take oral medicine (e.g. vomiting, fasting for surgery) → use rescue rotigotine transdermal patches
Do not offer ‘drug holidays’ to reduce motor complications (due to risk of neuroleptic malignant syndrome)
Non-Motor Symptoms
| Non-motor symptom | Management |
|---|---|
| Drooling of saliva (sialorrhoea) | First consider non-pharmacological management (e.g. speech and language therapy)
Consider:
Only consider anticholinergic medicines other than glycopyrronium bromide to manage drooling of saliva in PD if the risk of cognitive adverse effects is thought to be minimal. Use topical preparations if possible (e.g. topical atropine) to reduce the risk of adverse events. |
| PD dementia |
|
| Psychotic symptoms (hallucinations and delusions) | Only treat if symptoms are NOT well tolerated
Management
Note that other antipsychotic medications (esp. 1st generation) can worsen motor features of PD. NICE explicitly recommends NOT to offer olanzapine. |
| Daytime sleepiness | Adjust existing medicines to reduce occurrence (esp. dopamine agonists) + exclude reversible physical or pharmacological causes
Consider modafinil |
| Orthostatic hypotension |
|
| REM sleep behaviour disorder | Conduct a medicines review to address possible pharmacological causes
Consider clonazepam or melatonin |
PD Pharmacology
Overview of PD Medications
Shared drug adverse effects (across all classes):
| Category | Adverse effects |
|---|---|
| Neuropsychiatric | Confusion, somnolence, psychosis (including hallucinations, delusions) |
| Impulse control / compulsive disorders | Gambling, hypersexuality, compulsive eating / shopping |
| Autonomic | Orthostatic hypotension |
| Gastrointestinal | Nausea and vomiting |
| Other | Peripheral oedema
Sleep attacks (dopamine agonists and levodopa) |
Class-specific adverse effects:
| Class | Examples | MoA | Unique / distinctive adverse effects |
|---|---|---|---|
| Levodopa* | Levodopa | Dopamine precursor that is converted into dopamine | Motor complications (esp. with long-term use & higher doses)
|
| Dopamine decarboxylase inhibitors* | Benserazide, Carbidopa | Inhibit peripheral conversion of levodopa to dopamine (increases delivery to the CNS) | Reduce peripheral side effects of levodopa (e.g. nausea, vomiting, hypotension) by limiting peripheral dopamine conversion |
| Dopamine agonists | Ropinirole, Pramipexole, Rotigotine, Apomorphine | Dopamine receptor agonist (mainly D2) | Highest risk of:
Ergot-derived dopamine agonists
|
| MAO-B inhibitors | Selegiline, Rasagiline, Safinamide | Inhibit MAO-B → ↓ dopamine breakdown in CNS | Serotonin syndrome (rare)
NB – at standard doses there is not a clinically significant increased risk of tyramine reaction with selective MAO-B inhibitors (risk present with non-selective MAO inhibitors) [Ref] |
| COMT inhibitors | Entacapone, Opicapone, Tolcapone | Inhibit COMT → ↓ Levodopa breakdown, prolonging its CNS action |
|
| NMDA receptor antagonist | Amantadine |
|
|
*Levodopa is always combined with a dopamine decarboxylase inhibitor to maximise delivery to the CNS and minimise peripheral side effects.