Project Y: The search for clues explaining phenotype variability in MS

Abstract

Background: To study phenotypic variability in MS patients, well-defined unbiased cohort studies are necessary. The most common and probably most important confounding factor when studying disease phenotype in MS is age.Objective: To describe study design and subject characteristics of a unique birth cohort (Project Y). The overall aim of Project Y is to identify determinants associated with phenotypic variability in MS, eliminating the possibility of confounding by age. Methods: Project Y is a population-based cross-sectional study of all people with MS born in the Netherlands in 1966. Patients and healthy controls were subjected to comprehensive examinations: functional and static imaging, physical and cognitive measurements, and lifestyle factors early and later in life. In addition body fluids were collected and stored for future biomarker research. Results: 452 eligible MS patients were identified. Between December 2017 and January 2021, 367 MS patients and 125 healthy controls participated. The total number of identified cases results in a current prevalence of at least 189/100.000 for people born in the year 1966 in The Netherlands. Conclusion: Project Y is a unique cohort designed to identify factors associated with phenotypic variability in MS patients without the confounding effects of age. This first description of the Project Y cohort indicates that the prevalence of MS in the Netherlands might be higher than previously presumed. Various studies using Project Y data are ongoing and results will be published in upcoming years.

The prevalence of internuclear ophthalmoparesis in a population-based cohort of individuals with multiple sclerosis

“…For this cross-sectional study individuals with MS and healthy controls (HCs) were included from project Y, an observational cohort study of individuals with MS and HCs of the same birth year conducted at the Amsterdam University Medical Center (Amsterdam UMC), which is previously described (Loonstra et al, 2021). Project Y received approval from the medical ethical committee of the Amsterdam UMC, location VUMC and written informed consent was obtained from all participants.…”

Subtypes of relapsing-remitting multiple sclerosis identified by network analysis

“…Similarly, Dahlke et al ( 70 ) examined the clinical course in 34,987 MS patients who had entered into clinical trials (31,863 with relapsing-remitting MS, 1873 with secondarily progressive MS, and 986 with primary progressive MS) but did not characterize MS subjects further as to clinical phenotype. Other ongoing longitudinal studies have been undertaken to characterize MS clinical phenotypes ( 16 , 71 ) but they have not yet yielded new subtypes.…”

Adipokines in multiple sclerosis patients are related to clinical and radiological measures

“…This study, therefore, aimed to investigate the association between adipokines and disease severity in the different MS phenotypes. To remove potential bias effects of age, this was assessed in a cohort of PwMS and healthy controls (HC) of the same age (Project Y) [ 21 ]. We explored (1) differences in adiponectin, leptin and resistin levels in MS and how these relate to clinical, disability, and MRI measures, adjusted and unadjusted for BMI and (2) how BMI relates to clinical, disability and MRI measures.…”