When does Parkinson's disease begin?

Area of Science:

• Neurology
• Neuroscience
• Pathology

Background:

• Parkinson's disease (PD) exhibits a premotor period where dopaminergic neuron degeneration occurs before motor symptoms.
• This subclinical phase is estimated to last 3-6 years, but recent evidence suggests a longer duration and extranigral onset.
• Non-motor symptoms like hyposmia and constipation often precede classical motor signs by years.

Purpose of the Study:

• To review clinical, pathological, and neuroimaging data on the onset of Parkinson's disease.
• To propose that PD's pathological process begins non-motorly, potentially 10-20 years before motor symptom manifestation.
• To highlight the uncertainty surrounding the exact timing and location of PD's neuropathological initiation.

Main Methods:

• Review of clinical findings in Parkinson's disease.
• Analysis of pathological studies, including nigral cell counts and striatal dopamine levels.
• Examination of in vivo neuroimaging data assessing the nigrostriatal pathway.

Main Results:

• The neuropathological process of PD may initiate outside the substantia nigra, possibly in the lower brainstem, olfactory bulb, or peripheral autonomic nervous system.
• Non-motor symptoms could emerge 10-20 years prior to the onset of motor symptoms in Parkinson's disease.
• The progression of premotor Parkinson's disease is highly variable and may differ based on the etiology of the syndrome.

Conclusions:

• The onset of Parkinson's disease is likely non-motor and precedes motor symptom development by a significant margin.
• The precise initiation point and timeline of the neuropathological process in Parkinson's disease remain uncertain.
• Understanding the early, non-motor phases of PD is crucial for potential earlier diagnosis and intervention.