What are the early signs of Parkinson's disease?

Early Signs of Parkinson's Disease

The early signs of Parkinson's disease include resting tremor, bradykinesia (slowness of movement), and rigidity, which are often preceded by prodromal non-motor symptoms such as rapid eye movement sleep behavior disorder, hyposmia (reduced sense of smell), and constipation. 1

Motor Symptoms

Parkinson's disease (PD) is primarily characterized by its cardinal motor symptoms that develop as dopaminergic neurons in the substantia nigra progressively degenerate. These include:

• Resting tremor: Often begins unilaterally, typically affecting the hands in a "pill-rolling" motion
• Bradykinesia: Slowness of movement and decreased amplitude of movements
• Rigidity: Stiffness in limbs and trunk that can be detected during passive movement
• Postural instability: Usually appears later in the disease progression

The onset of these motor symptoms typically occurs after approximately 40-50% of dopaminergic neurons in the substantia nigra have been lost, which explains why they are often not the earliest detectable signs of the disease 1, 2.

Prodromal Non-Motor Symptoms

Importantly, non-motor symptoms often precede the classic motor features by several years, representing a prodromal phase of Parkinson's disease:

• Olfactory dysfunction (hyposmia): Reduced sense of smell is one of the earliest signs, often appearing years before motor symptoms 3, 4
• REM sleep behavior disorder (RBD): Acting out dreams during REM sleep, which can precede motor symptoms by up to a decade 1, 4
• Constipation: Gastrointestinal dysfunction often appears early in the disease process 3
• Depression and anxiety: Mood disorders frequently develop before motor symptoms 3
• Subtle cognitive changes: Especially in executive function 2

Clinical Subtypes and Progression

PD is heterogeneous in its presentation and progression:

• Mild motor-predominant subtype (49-53% of patients): Characterized by mild symptoms, good response to dopaminergic medications, and slower disease progression 2
• Diffuse malignant subtype (9-16% of patients): Features prominent early motor and non-motor symptoms, poor medication response, and faster disease progression 2
• Intermediate subtype: Falls between the above categories in symptom severity and progression rate 2

Early Diagnostic Considerations

The diagnosis of early PD can be challenging due to the subtle and variable presentation of symptoms. Key points to consider:

• Motor symptoms often begin asymmetrically, typically affecting one side of the body before spreading to the other 1
• The estimated interval between initial loss of dopaminergic neurons and the appearance of motor symptoms is approximately 5 years 1
• Dopamine transporter single-photon emission computed tomography (DAT-SPECT) can improve diagnostic accuracy when the presence of parkinsonism is uncertain 2

Pitfalls in Early Diagnosis

• Misdiagnosis: Several conditions can mimic early PD, including essential tremor, drug-induced parkinsonism, and atypical parkinsonian syndromes 1
• Overlooking non-motor symptoms: The prodromal non-motor features are often attributed to aging or other conditions 3, 4
• Focusing solely on tremor: Not all PD patients present with tremor; some primarily show bradykinesia and rigidity 5
• Missing the prodromal phase: The opportunity for earlier intervention may be lost if prodromal symptoms are not recognized 3

Early recognition of these signs and symptoms is crucial for timely diagnosis and management, potentially allowing for interventions that might slow disease progression and improve quality of life.