The challenging quest of neuroimaging: From clinical to molecular-based subtyping of Parkinson disease and atypical parkinsonisms.

ABSTRACT

The current framework of Parkinson disease (PD) focuses on phenotypic classification despite its considerable heterogeneity. We argue that this method of classification has restricted therapeutic advances and therefore limited our ability to develop disease-modifying interventions in PD. Advances in neuroimaging have identified several molecular mechanisms relevant to PD, variation within and between clinical phenotypes, and potential compensatory mechanisms with disease progression. Magnetic resonance imaging (MRI) techniques can detect microstructural changes, disruptions in neural pathways, and metabolic and blood flow alterations. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging have informed the neurotransmitter, metabolic, and inflammatory dysfunctions that could potentially distinguish disease phenotypes and predict response to therapy and clinical outcomes. However, rapid advancements in imaging techniques make it challenging to assess the significance of newer studies in the context of new theoretical frameworks. As such, there needs to not only be a standardization of practice criteria in molecular imaging but also a rethinking of target approaches. In order to harness precision medicine, a coordinated shift is needed toward divergent rather than convergent diagnostic approaches that account for interindividual differences rather than similarities within an affected population, and focus on predictive patterns rather than already lost neural activity.