Loading ...

Patients with Parkinson’s disease rarely present to the clinic with the textbook signs — forward stooped posture, slow and rigid movements, or shuffling gait. Instead, the earliest indicators are often vague and nonspecific, though they can later be recognized as early warning signs in retrospect.

By the time the first clear symptoms appear, nearly 50% of dopaminergic neurons are irreversibly lost. The resulting dopamine deficiency disrupts the motor system, leading to hallmark symptoms such as tremor, rigidity, akinesia, and postural instability (TRAP). Diagnosis is clinical, supported by characteristic signs, and often confirmed with imaging (eg, dopamine transporter scan [DaT SCAN]). Onset is usually gradual and progressive, and symptoms may present asymmetrically.

Although Parkinson’s disease remains incurable, identifying these early signs before the onset of classic motor symptoms can enable timely monitoring and potential early intervention. The earlier the disease is detected, the better its progression may be slowed. Some symptoms may manifest years in advance.

Below is an overview of early and prodromal Parkinson’s symptoms. While most clinicians routinely ask about sleep or gastrointestinal function, the following list may help prompt more targeted follow-up when suspicion arises.

Rapid Eye Movement (REM) Sleep Behavior Disorder (RBD)

Sleep disturbances are often mentioned as early Parkinson’s symptoms, but the specific disorder — REM sleep behavior disorder — is frequently overlooked. Unlike insomnia or sleep maintenance issues, RBD involves vivid dreaming accompanied by physical movements, such as shouting, punching, or kicking during sleep, often affecting the sleep partner.

RBD occurs in about 0.5%-1% of the population, rising to 5% in those older than 60 years. Importantly, it is considered a prodromal condition for Parkinson’s: 80% of those affected may go on to develop the disease within 15 years. Patients reporting these symptoms should be monitored regularly for neurologic changes.

In clinical history-taking, ask specifically about vivid dreams, violent movements during sleep, or vocalizations. Though often dismissed as quirky or anecdotal, recurring incidents should raise red flags.

Constipation

Parkinson’s doesn’t begin with tremors or slowed movement. Nonmotor symptoms, especially gastrointestinal issues, often appear first. The disease affects the autonomic nervous system, including the enteric nervous system that regulates bowel motility.

There is evidence that pathological changes — such as alpha-synuclein accumulation — begin in the gut and olfactory bulb before affecting the brain, aligning with the Braak hypothesis. These protein aggregates can cause constipation or olfactory dysfunction long before motor symptoms emerge.

Studies suggest chronic constipation can precede a Parkinson’s diagnosis by 10-20 years. Up to 75% of patients with Parkinson’s experience it. While constipation alone is nonspecific, it gains significance when combined with other prodromal signs.

Constipation should raise concern in these contexts:

• Persistent, unexplained symptoms.
• Co-occurrence with other early signs such as:
  • Loss of smell (hyposmia).
  • REM sleep behavior disorder.
  • Depressed mood.
  • Fatigue or lack of motivation.
  • Family history of Parkinson’s.

Olfactory Dysfunction

Loss of smell, either partial (hyposmia) or total (anosmia), is another early and often unnoticed sign. Patients may have difficulty detecting even strong odors like coffee, bananas, or pickles.

In Parkinson’s, misfolded alpha-synuclein protein aggregates disrupt brain regions, including those responsible for olfaction. These changes may impair neuron function and contribute to early sensory loss.

Animal studies suggest alpha-synuclein may behave like a prion — spreading through neural pathways. Trials are ongoing to determine whether monoclonal antibodies such as prasinezumab could help degrade these protein aggregates.

Micrographia

As Parkinson’s disrupts dopamine pathways, it impairs fine motor control. Writing — a highly complex motor task — often becomes affected. Reduced movement amplitude can lead to smaller, cramped handwriting known as micrographia.

Micrographia is a typical, though not universal, early motor sign and may precede other motor symptoms. It often appears alongside other signs like a softer, monotone voice or reduced arm swing while walking — both early signs of extrapyramidal dysfunction.

Classic Motor Signs: TRAP

Parkinson’s is commonly associated with:

• Tremor: A resting tremor, typically 4-8 Hz, which diminishes with movement (unlike intention tremor).
• Rigidity: Muscle stiffness is often described as “cogwheel rigidity” due to a ratcheting resistance during passive limb extension.
• Akinesia/bradykinesia: Slowness or poverty of movement, including “freezing” episodes that require verbal cues to initiate or stop movement.
• Postural instability: Impaired balance and increased risk of falls, not due to cerebellar, visual, or vestibular dysfunction.

Postural instability is now recognized as a cardinal sign in the TRAP framework. Damage to extrapyramidal reflexes means patients may be unable to catch themselves when off balance.

Additional Early Signs

• Depression and anxiety: Often overlooked or misdiagnosed as primary psychiatric conditions.
• Reduced facial expression (hypomimia): “Masked” appearance due to reduced facial muscle movement.
• Diffuse pain: Especially in the shoulders, back, or arms, sometimes preceding motor signs.
• Fatigue: Persistent lack of energy not relieved by rest.
• Reduced arm swing: Subtle early sign of movement asymmetry. 

When to Refer for Neurological Evaluation

None of these symptoms alone confirm Parkinson’s disease, as many are nonspecific or seen in other conditions. However, the presence of multiple early signs — especially the combination of REM sleep behavior disorder, olfactory loss, constipation, or family history — should prompt further evaluation.

Referral should ideally be made to a neurologist specializing in movement disorders. A thorough neurologic exam, smell testing, sleep studies (polysomnography), and imaging (eg, DaT SCAN) may be warranted.

Summary Table. Common Early and Prodromal Parkinson’s Symptoms

Identifying these signs early and recognizing meaningful combinations — not isolated symptoms — can help clinicians initiate earlier referral and intervention, potentially altering the disease trajectory.

This story was translated from Medscape’s German edition.