# Neural Mechanisms Underlying Cognitive Contributions to Walking as an Early Marker for Risk of Alzheimer’s Disease and Related Dementias

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $1,080,883

## Abstract

Project Summary/Abstract
Early detection of Alzheimer's Disease and Related Dementias (ADRD) is essential for implementing
interventions that can slow cognitive decline, benefiting individuals, caregivers, and society. Gait speed emerges
as a powerful predictor of ADRD, especially in the early stages of Mild Cognitive Impairment (MCI), often
preceding cognitive symptoms. However, the underlying mechanisms between gait speed and cognitive decline
remain unclear, limiting the specificity of gait as an ADRD predictor. This research project aims to investigate gait
deficits during tasks requiring cognitive input into walking control (Aim 1) and to unveil the neural processes
behind these cognitive contributions (Aim 2). The study focuses on two crucial gait markers: locomotor learning
and attentional need for gait control. Locomotor learning involves encoding and retrieving walking motor
memories. Attentional need for gait control indicates the requirement for explicit attentional resources, primarily
from the prefrontal cortex (PFC), during walking, often assessed through dual-tasking. Both markers are vital for
the mobility of older adults in the community, yet their neural mechanisms remain unclear. We will specifically
determine the contribution of basal ganglia dysfunction on these gait markers. Growing evidence suggests that
BG pathology, characterized by factors like iron deposition, white matter hyperintensities (WMH), and
compromised BG intra-connectivity, negatively affects mobility. Furthermore, we investigate the specific
contribution of BG's role in compensatory mechanisms for attentional control during mobility, particularly through
its connectivity with executive control networks (ECN), including the PFC. Our central hypothesis is that
individuals at high risk for ADRD (i.e., those with MCI) have diminished locomotor learning and higher attentional
need for gait control (Aim 1) due to BG pathology and weak BG-ECN inter-connectivity (Aim 2). Preliminary
results support this hypothesis, showing lower locomotor learning and higher attentional need for gait control in
MCI compared to age- and sex-matched controls. Interestingly, these gait markers prove to be more sensitive to
MCI than gait speed itself. Thus, we anticipate that BG pathology and BG-ECN inter-connectivity, which are
related to slow walking, will be strongly associated with the performance of locomotor learning and attentional
need for gait control. The expected findings from this research hold the potential to yield significant insights into
both behavioral and mechanistic deficits in cognitive contributions to gait in individuals with MCI. Such insights
can greatly enhance the specificity and validity of novel gait measures as preclinical indicators for risk of ADRD.

## Key facts

- **NIH application ID:** 10979831
- **Project number:** 1R01AG089175-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Gelsy Torres-Oviedo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,080,883
- **Award type:** 1
- **Project period:** 2024-09-17 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10979831

## Citation

> US National Institutes of Health, RePORTER application 10979831, Neural Mechanisms Underlying Cognitive Contributions to Walking as an Early Marker for Risk of Alzheimer’s Disease and Related Dementias (1R01AG089175-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10979831. Licensed CC0.

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