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Dear Colleagues,

Parkinson’s disease (PD) is a chronic, complex, and progressive neurodegenerative disease defined by the loss of dopaminergic neurons in the substantia nigra pars compacta, situated in the midbrain and associated with Lewy bodies, which are cytoplasmic inclusions of alpha-synuclein aggregates. Clinical diagnosis of PD is based primarily on motor symptoms, such as a slowly progressive asymmetric resting tremor, rigidity, and bradykinesia. Although non-motor symptoms, which include olfactory deficits, constipation, autonomic dysfunction, depression, and REM sleep behavior disorder, usually precede the presence of motor deficits.

Different factors may influence PD risk such as mitochondrial dysfunction, impaired autophagy, oxidative stress, protein aggregation, neuroinflammation, environmental and genetic status.

The aim of this Special Issue is to better characterize PD, covering aspects related to the motor and non-motor symptoms that negatively impact health-related quality of life. With this purpose in mind, we invite colleagues to share their recent research on this topic; original research articles, review articles, short communications, and case reports are all welcome.

Dr. Carla Masala
Dr. Paolo Solla
Dr. Francesco Loy
Dr. Tommaso Ercoli
Guest Editors

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Keywords

Parkinson’s disease
neurodegenerative disorders
nonmotor symptoms
quality of life
cognition
olfactory deficits

Published Papers (1 paper)

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12 pages, 778 KiB

Open AccessViewpoint

How Lifetime Evolution of Parkinson’s Disease Could Shape Clinical Trial Design: A Shared Patient–Clinician Viewpoint

by Jules M. Janssen Daalen, Aranka Gerritsen, Gijs Gerritse, Jan Gouman, Hannie Meijerink, Leny E. Rietdijk and Sirwan K. L. Darweesh

Brain Sci. 2024, 14(4), 358; https://doi.org/10.3390/brainsci14040358 - 03 Apr 2024

Viewed by 777

Abstract

Parkinson’s disease (PD) has a long, heterogeneous, pre-diagnostic phase, during which pathology insidiously accumulates. Increasing evidence suggests that environmental and lifestyle factors in early life contribute to disease risk and progression. Thanks to the extensive study of this pre-diagnostic phase, the first prevention trials of PD are being designed. However, the highly heterogenous evolution of the disease across the life course is not yet sufficiently taken into account. This could hamper clinical trial success in the advent of biological disease definitions. In an interdisciplinary patient–clinician study group, we discussed how an approach that incorporates the lifetime evolution of PD may benefit the design of disease-modifying trials by impacting population, target and outcome selection. We argue that the timepoint of exposure to risk and protective factors plays a critical role in PD subtypes, influencing population selection. In addition, recent developments in differential disease mechanisms, aided by biological disease definitions, could impact optimal treatment targets. Finally, multimodal biomarker panels using this lifetime approach will likely be most sensitive as progression markers for more personalized trials. We believe that the lifetime evolution of PD should be considered in the design of clinical trials, and that such initiatives could benefit from more patient–clinician partnerships. Full article

(This article belongs to the Special Issue New Approaches in the Exploration of Parkinson’s Disease)

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