In the past 25 years, it has become clear that some symptoms
of Parkinson’s disease (PD) occur decades before the development of motor
symptoms and clinical diagnosis, and that monitoring these emerging symptoms
may provide important insights into the origin and development of the disease.

Understanding this “prodromal” phase, along with
the development of new treatments, may enable earlier treatment to prevent the
disease from developing, according to experts writing in a supplement to
the Journal of Parkinson’s Disease.

“Brilliant work of many in different scientific fields has
paved the way for the concept of prodromal PD; that is, a phase of years to
decades in which non-motor and subtle motor symptoms may indicate spreading PD
pathology, but do not meet the threshold for diagnosis according to the classic
motor-based clinical criteria,” explained authors Daniela Berg, MD, of the
Department of Neurology, Christian-Albrechts-University of Kiel, Kiel, Germany,
and Ronald B. Postuma, MD, MSc, of the Department of Neurology, Montreal
General Hospital, Montreal, Canada.

The authors define the main anchors of the concept of the
prodromal phase as:

• The broadly accepted fact that the neurodegenerative
process in PD spreads slowly, possibly starting in the gut or olfactory system
and finally encompassing much of the nervous system

• Increasing knowledge of risk factors and clinical
symptoms that precede the typical motor manifestations by years to decades and
can be correlated to imaging and histopathological findings

• Longitudinal studies that observed conversion to PD
in groups of patients with different combinations of risk and prodromal markers

The authors and colleagues have constructed a mathematical
model that makes it possible to calculate an individual’s personal risk of
being in the prodromal phase of PD. As they point out, there are several
limitations to this model, such as the time taken to conversion to PD, age and
sex factors, and subtypes with undetectable prodromal stages. “The prodromal PD
criteria are meant to be research criteria and constitute a first step in what
should be a continually-updated process,” noted the authors.

Biomarkers and wearable technology such as mobile phones are
expected to play a role in greater accuracy of diagnosis in the prodromal
phase. The goal of biomarker research, as well as quantitative motor
assessment, is to use new data arising from objective measurements to enable
earlier detection of the neurodegenerative process and possibly motor symptoms.
It would also facilitate the development of neuroprotective trials in early

Key questions that the authors hope to see resolved are:
When is the starting point of PD? What will define the disease; will it still
be motor symptoms (possibly typical subtle ones), or will it be biomarker
evidence of nigrostriatal system neurodegeneration without motor symptoms? Will
it be a certain combination of non-motor signs? Or will it be based upon
non-clinical biomarkers, similar to changes in Alzheimer’s disease?

By 2040, the authors hope that prodromal criteria will be
incorporated into active neuroprotective treatment programmes, allowing a
program of population-based screening followed by early treatment and
ultimately the prevention of clinical PD from ever becoming manifest.

“Our review highlights the importance of making an earlier
diagnosis of neurodegenerative diseases, and in particular PD, for now
primarily to understand the disease better,” said Dr Berg and Dr Postuma.
“However, in the future, once we have preventive therapy, it will become
critical to find patients in the earliest stages of disease, so that we can prevent
the disease from developing and affecting quality of life.”


Reference: Berg D, et al. From Prodromal to Overt
Parkinson’s Disease: Towards a New Definition in the Year 2040.  Journal
of Parkinson’s Disease
, vol. 8, no. s1, pp. S19-S23, 2018. Published 18
December 2018.