# Reserve against Disability in Early Multiple Sclerosis (RADIEMS) Longitudinal Cohort Study

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $712,098

## Abstract

Multiple sclerosis (MS) is a prevalent chronic neurologic disease diagnosed during early adulthood that often
leads to cognitive and sensorimotor decline. Inflammatory demyelinating lesions are key neuropathological
features of MS, but neurodegeneration leading to gray matter loss is prominent, begins early, and is the main
driver of functional decline. Lack of neuroregenerative therapies or functionally restorative treatments highlights
a need to identify modifiable risk and protective factors that preserve gray matter and function. This R01
renewal of the Reserve against Disability in Early MS (RADIEMS) cohort extends our prior work on “reserve”
against disability to establish a much-needed framework for investigating functional decline in MS. We propose
a dynamic model of reserve in which candidate modifiable risk and protective factors contribute to functional
outcomes through (a) maintenance of gray matter (Aim 1), or (b) by modulating one’s ability to maintain
function despite loss of gray matter (compensation; Aim 2). RADIEMS enrolled 185 MS patients diagnosed
≤5.0 years (median=2.0) receiving high resolution MRIs and comprehensive cognitive and sensorimotor
evaluations at baseline (Y0) and Y3; this renewal adds Y6 and Y8 follow-ups. Retention is excellent (95.0%).
Aim 1a investigates whether MIND diet consumption (e.g., leafy greens, fish, nuts, berries) and body mass
index (BMI) independently predict maintenance of (a) cerebral gray matter and (b) cognitive and sensorimotor
functional outcomes over Y0-Y3-Y6-Y8. We will also evaluate percent body fat measured via bioelectrical
impedance as a key culprit in obesity-related morbidity. Aim 1b assesses whether links between MIND diet and
BMI with functional outcomes are mediated through gray matter change. Aim 1c analyzes blood and stool
samples banked at Y3 for metabolomics & microbiome sequencing to identify nutrient and gut microbiotic
mediators of dietary effects on outcomes. Aim 2a: preliminary data link depressed mood to poor cognitive and
gait speed / endurance, which fluctuate with mood changes over time. We will assess whether cognitive and
sensorimotor functions fluctuate with mood across Y0-Y3-Y6-Y8, and if mood moderates links between gray
matter loss and outcomes. We will also investigate independent contributions of positively-valanced aspects of
psychological function. Aim 2b assessed whether memory fluctuates with subjective (Y0-Y3-Y6-Y8) and
objective (Y6-Y8) sleep disturbance. Little is known about sleep quality and functional outcomes in MS. A large
subsample of patients will undergo actigraphy and ambulatory polysomnography at Y6 & Y8; we expect sleep
efficiency (especially sleep fragmentation) to explain memory. RADIEMS is a large deeply-phenotyped cohort
study of functional outcomes in early MS: a unique and valuable resource for the field. This R01 renewal
extends our work on reserve to establish a critical framework for investigating functional decline. This dynamic
mo...

## Key facts

- **NIH application ID:** 10909196
- **Project number:** 5R01HD082176-09
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** James Francis Sumowski
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $712,098
- **Award type:** 5
- **Project period:** 2016-07-11 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909196

## Citation

> US National Institutes of Health, RePORTER application 10909196, Reserve against Disability in Early Multiple Sclerosis (RADIEMS) Longitudinal Cohort Study (5R01HD082176-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10909196. Licensed CC0.

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