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Neurology 2022 Aug;99(7 Supplement 1):34-41

From the Department of Neurology, Massachusetts General Hospital, Boston.

Despite the sound epidemiologic and basic science rationales underpinning numerous "disease modification" trials in manifest Parkinson disease (PD), none has convincingly demonstrated that a treatment slows progression. Rapidly expanding knowledge of the genetic determinants and prodromal features of PD now allows realistic planning of prevention trials with initiation of putatively neuroprotective therapies earlier in the disease. In this article, we outline the principles of drug selection for PD prevention trials, focused on proof-of-concept opportunities that will help establish a methodological foundation for this fledgling field. Read More

Neurology 2022 Aug;99(7 Supplement 1):19-25

From the Department of Neurology, McGill University, Montreal, Quebec, Canada.

As neuroprotective therapies continue to be advanced against neurodegenerative synucleinopathies, such as Parkinson disease (PD), dementia with Lewy bodies (DLBs), and multiple system atrophy, increasing attention is turning to the prodromal stages of disease. Treatments at the prodromal stage have the compelling advantages of being applied early enough to make a meaningful difference and can be tested without confounding by symptomatic therapies used for clinical PD/DLB. As it currently stands, patients with idiopathic/isolated REM sleep behavior disorder (iRBD) represent the only large existing cohort of untreated prodromal PD/DLB that would be ready to start a clinical trial now. Read More

Neurology 2022 Aug;99(7 Supplement 1):10-18

From the Department of Neurology (K.N., R.S.-P.), Mount Sinai Beth Israel Medical Center; Department of Neurology (K.N., R.S.-P.), Icahn School of Medicine at Mount Sinai, New York; and Duke Center for Neurodegeneration Research (A.B.W.), Departments of Pharmacology and Cancer Biology, Neurology, and Neurobiology, Duke University, Durham, NC.

Therapies that prevent the occurrence of Parkinson disease (PD) (primary prevention) or mitigate the progression of symptoms in those with early disease (secondary prevention) are a critical unmet need in disease management. Despite great promise, PD prevention trials have not yet demonstrated success. Initiation of treatment too late in the disease course and the heterogeneity of disease are obstacles that may have contributed to the failure. Read More

Neurology 2022 Aug;99(7 Supplement 1):42-51

From the Department of Neurology (J.M.J.D., S.S., E.R., S.K.L.D., B.R.B.), Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior; Center of Expertise for Parkinson & Movement Disorders (J.M.J.D., S.S., S.K.L.D., B.R.B.); and Radboud University Medical Center Alzheimer Center (E.R.), the Netherlands.

The prevalence of Parkinson disease (PD) is growing fast, amplifying the quest for disease-modifying therapies in early disease phases where pathology is still limited. Lifestyle interventions offer a promising avenue for preventing progression from prodromal to manifest PD. We illustrate this primarily for 1 specific lifestyle intervention, namely aerobic exercise because the case for the other main lifestyle factor (dietary interventions) to modify the course of prodromal PD is currently less persuasive. Read More

BMJ 2022 Aug 15;378:o2021. Epub 2022 Aug 15.

The BMJ.