Diagnosing premotor Parkinson's disease using a two-step approach combining olfactory testing and DAT SPECT imaging

Area of Science:

• Neurology
• Neuroscience
• Medical Imaging

Background:

• Parkinson's disease (PD) may involve neuropathological changes outside the substantia nigra, preceding nigrostriatal dopaminergic neuron degeneration.
• Non-motor symptoms, such as olfactory dysfunction, are potential early indicators of premotor PD.
• Impaired sense of smell (hyposmia) is prevalent in PD patients and their relatives.

Purpose of the Study:

• To evaluate a two-step approach combining olfactory testing and dopamine transporter (DAT) SPECT imaging for detecting premotor PD in asymptomatic first-degree relatives.
• To assess the risk of developing PD associated with unexplained hyposmia.

Main Methods:

• A prospective study involving 361 asymptomatic first-degree relatives of PD patients.
• Olfactory testing and DAT SPECT imaging were used as a two-step diagnostic approach.
• Cox regression analysis was employed to determine risk factors for PD development.

Main Results:

• Unexplained hyposmia alone indicated a 12.5% risk of developing PD within five years.
• Olfactory discrimination performance was the strongest predictor of future PD.
• All individuals who later developed PD exhibited both hyposmia and reduced striatal DAT binding at baseline.

Conclusions:

• A combined olfactory testing and DAT SPECT imaging approach shows promise for diagnosing PD in its premotor phase.
• The low positive predictive value of hyposmia necessitates further research to identify additional markers for broader screening.
• Larger studies are needed to refine early PD diagnosis and identify susceptibility markers.