Gait variability as a marker of white matter integrity in individuals with Down syndrome

Elizabeth M. Leach; David K. Powell; Amanda C. Glueck; Elizabeth Head; Moaz W. Ibrahim; Amelia J. Anderson-Mooney; Kathryn L. Van Pelt; Jordan P. Harp; Frederick A. Schmitt; Ahmed A. Bahrani

doi:10.1002/alz.70407

Gait variability as a marker of white matter integrity in individuals with Down syndrome

Elizabeth M. Leach
, David K. Powell
, Amanda C. Glueck
, Elizabeth Head
, Moaz W. Ibrahim
, Amelia J. Anderson-Mooney
, Kathryn L. Van Pelt
, Jordan P. Harp
, Frederick A. Schmitt
, Ahmed A. Bahrani

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

INTRODUCTION: Individuals with Down syndrome (DS) face a significant risk of neurodegeneration, and gait variability may serve as a clinical biomarker of neurological health. This longitudinal parent substudy aimed to explore relationships between gait, white matter (WM) integrity, and cognitive function in DS. METHODS: The associations were investigated between magnetic resonance imaging diffusion tensor imaging (DTI), cognition, and self-paced gait data from 22 DS participants (mean age ± SD 37 ± 7.5 years). RESULTS: DTI measures, such as lower fractional anisotropy (FA) and higher mean diffusivity, were correlated with greater step time variability but not normalized velocities. Lower cognitive scores on the Vineland Adaptive Behavior Composite, Dementia Questionnaire for People with Learning Disabilities, and Motor Skill subscale were correlated with FA. DISCUSSION: Gait variability correlates with WM integrity and cognitive function in DS, suggesting that gait and DTI measures may serve as clinical markers of neurological decline. Highlights: Gait variability linked to white matter integrity in individuals with Down syndrome (DS). Lower fractional anisotropy and higher mean diffusivity are associated with increased step time variability in DS. Cognitive decline is tied to white matter changes in motor-related brain regions. Gait analysis alongside diffusion tensor imaging may aid in screening for cognitive impairment in DS.

Original language	English
Article number	e70407
Journal	Alzheimer's and Dementia
Volume	21
Issue number	7
DOIs	https://doi.org/10.1002/alz.70407
State	Published - Jul 2025

Bibliographical note

Publisher Copyright:
© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Funding

The authors are grateful to the study participants, their families, and all the research and support staff. This manuscript has been reviewed by all authors. The content is solely the responsibility of the authors. This work was supported by National Institutes of Health (NIH) grant R01‐HD064993, Aging and Dementia in Down Syndrome: Connectivity, Inflammation, and Cerebrovascular Contributions. The work was also supported by the Alzheimer's Biomarkers Consortium–Down Syndrome (ABC‐DS) and was funded by the National Institute on Aging and the National Institute for Child Health and Human Development (U19 AG068054).

Funders	Funder number
National Institute on Aging
Alzheimer's Biomarkers Consortium
National Institutes of Health (NIH)	R01‐HD064993
NIH National Institute of Child Health and Human Development National Center for Medical Rehabilitation Research	U19 AG068054

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

DTI
MRI
amyloid beta
dementia
gross motor skills
trisomy 21

ASJC Scopus subject areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

Access to Document

10.1002/alz.70407

Cite this

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title = "Gait variability as a marker of white matter integrity in individuals with Down syndrome",

abstract = "INTRODUCTION: Individuals with Down syndrome (DS) face a significant risk of neurodegeneration, and gait variability may serve as a clinical biomarker of neurological health. This longitudinal parent substudy aimed to explore relationships between gait, white matter (WM) integrity, and cognitive function in DS. METHODS: The associations were investigated between magnetic resonance imaging diffusion tensor imaging (DTI), cognition, and self-paced gait data from 22 DS participants (mean age ± SD 37 ± 7.5 years). RESULTS: DTI measures, such as lower fractional anisotropy (FA) and higher mean diffusivity, were correlated with greater step time variability but not normalized velocities. Lower cognitive scores on the Vineland Adaptive Behavior Composite, Dementia Questionnaire for People with Learning Disabilities, and Motor Skill subscale were correlated with FA. DISCUSSION: Gait variability correlates with WM integrity and cognitive function in DS, suggesting that gait and DTI measures may serve as clinical markers of neurological decline. Highlights: Gait variability linked to white matter integrity in individuals with Down syndrome (DS). Lower fractional anisotropy and higher mean diffusivity are associated with increased step time variability in DS. Cognitive decline is tied to white matter changes in motor-related brain regions. Gait analysis alongside diffusion tensor imaging may aid in screening for cognitive impairment in DS.",

keywords = "DTI, MRI, amyloid beta, dementia, gross motor skills, trisomy 21",

author = "Leach, \{Elizabeth M.\} and Powell, \{David K.\} and Glueck, \{Amanda C.\} and Elizabeth Head and Ibrahim, \{Moaz W.\} and Anderson-Mooney, \{Amelia J.\} and \{Van Pelt\}, \{Kathryn L.\} and Harp, \{Jordan P.\} and Schmitt, \{Frederick A.\} and Bahrani, \{Ahmed A.\}",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). Alzheimer's \& Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2025",

month = jul,

doi = "10.1002/alz.70407",

language = "English",

volume = "21",

number = "7",

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AU - Glueck, Amanda C.

AU - Head, Elizabeth

AU - Ibrahim, Moaz W.

AU - Anderson-Mooney, Amelia J.

AU - Van Pelt, Kathryn L.

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AU - Schmitt, Frederick A.

AU - Bahrani, Ahmed A.

PY - 2025/7

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N2 - INTRODUCTION: Individuals with Down syndrome (DS) face a significant risk of neurodegeneration, and gait variability may serve as a clinical biomarker of neurological health. This longitudinal parent substudy aimed to explore relationships between gait, white matter (WM) integrity, and cognitive function in DS. METHODS: The associations were investigated between magnetic resonance imaging diffusion tensor imaging (DTI), cognition, and self-paced gait data from 22 DS participants (mean age ± SD 37 ± 7.5 years). RESULTS: DTI measures, such as lower fractional anisotropy (FA) and higher mean diffusivity, were correlated with greater step time variability but not normalized velocities. Lower cognitive scores on the Vineland Adaptive Behavior Composite, Dementia Questionnaire for People with Learning Disabilities, and Motor Skill subscale were correlated with FA. DISCUSSION: Gait variability correlates with WM integrity and cognitive function in DS, suggesting that gait and DTI measures may serve as clinical markers of neurological decline. Highlights: Gait variability linked to white matter integrity in individuals with Down syndrome (DS). Lower fractional anisotropy and higher mean diffusivity are associated with increased step time variability in DS. Cognitive decline is tied to white matter changes in motor-related brain regions. Gait analysis alongside diffusion tensor imaging may aid in screening for cognitive impairment in DS.

AB - INTRODUCTION: Individuals with Down syndrome (DS) face a significant risk of neurodegeneration, and gait variability may serve as a clinical biomarker of neurological health. This longitudinal parent substudy aimed to explore relationships between gait, white matter (WM) integrity, and cognitive function in DS. METHODS: The associations were investigated between magnetic resonance imaging diffusion tensor imaging (DTI), cognition, and self-paced gait data from 22 DS participants (mean age ± SD 37 ± 7.5 years). RESULTS: DTI measures, such as lower fractional anisotropy (FA) and higher mean diffusivity, were correlated with greater step time variability but not normalized velocities. Lower cognitive scores on the Vineland Adaptive Behavior Composite, Dementia Questionnaire for People with Learning Disabilities, and Motor Skill subscale were correlated with FA. DISCUSSION: Gait variability correlates with WM integrity and cognitive function in DS, suggesting that gait and DTI measures may serve as clinical markers of neurological decline. Highlights: Gait variability linked to white matter integrity in individuals with Down syndrome (DS). Lower fractional anisotropy and higher mean diffusivity are associated with increased step time variability in DS. Cognitive decline is tied to white matter changes in motor-related brain regions. Gait analysis alongside diffusion tensor imaging may aid in screening for cognitive impairment in DS.

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Gait variability as a marker of white matter integrity in individuals with Down syndrome

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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