# Brain predictors of mobility and falls in older adults with multiple sclerosis

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2022 · $684,921

## Abstract

Mobility impairments are often the most visible symptom of Multiple Sclerosis (MS) and the
clinical hallmark of the disease. Falls are also very common in MS. The loss of mobility and the
frequent falls that are observed in patients with MS are associated with a multitude of adverse
outcomes including disability and death. Recent epidemiological evidence suggests a shift in
the peak prevalence of MS into older age groups, and this will likely coincide with co-occurring
aging and MS-related declines in mobility and cognition. Research concerning brain systems of
mobility and falls in MS, notably among older adults with MS, is scarce. This proposal offers a
novel theoretical and empirical approach specifically designed to address existing limitations in
mobility and falls research in older adults with MS.
Our overarching hypothesis is that the prefrontal cortex (PFC) and related functional circuits –
including the basal ganglia and thalamus – and white matter integrity are critical for cognitive
control of mobility. We aim to identify brain systems of walking under single and dual-task
conditions and of falls in 120 older (age≥60) adults with a definite diagnosis of MS and 120
controls (age≥60). We propose that according to “neural inefficiency,” patients with MS will
demonstrate higher HbO2 levels during locomotion to support similar or worse walking
performance compared to controls. We further postulate that higher (i.e., inefficient) HbO2 levels
during dual-task walking will predict increased risk of incident falls among MS patients. Finally,
white matter integrity is proposed as mechanism underlying inefficient brain activation during
locomotion.
In aim 1 we will determine PFC HbO2 patterns associated with Single-Task-Walk (STW) and
Dual-Task-Walk (DTW) in 120 MS patients and 120 controls. Using DTI, we will examine the
moderating effect of white matter integrity on PFC HbO2 patterns assessed during active
walking. In aim 2 we will use multi-modal neuroimaging methods to establish brain systems
controlling STW and DTW in 120 MS patients and 120 healthy controls. In aim 3 we will use
PFC HbO2 levels, assessed with fNIRS during DTW, to predict incident falls among 120 MS
patients over a longitudinal follow-up (years 1-5).
Identifying novel and potentially modifiable biomarkers of falls and mobility impairments in older
adults with MS is of paramount epidemiological and clinical significance. Elucidating the
mechanistic underpinnings of brain systems controlling mobility in older adults with MS will have
a major impact on knowledge and important implications for treatment of mobility impairments
and falls.

## Key facts

- **NIH application ID:** 10338168
- **Project number:** 5R01NS109023-04
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Roee Holtzer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $684,921
- **Award type:** 5
- **Project period:** 2019-05-15 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10338168

## Citation

> US National Institutes of Health, RePORTER application 10338168, Brain predictors of mobility and falls in older adults with multiple sclerosis (5R01NS109023-04). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10338168. Licensed CC0.

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