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. 2025 Apr;21(4):e70211.
doi: 10.1002/alz.70211.

Longitudinal investigation of gait and Alzheimer's disease in adults with Down syndrome

Ashlyn Barry  1 , Jamie C Peven  2 , Benjamin L Handen  3 , Daniel Bolt  1 , Sharon J Krinsky-McHale  4 , Christy L Hom  5 , Isabel C H Clare  6 , Amanda Glueck  7 , Jordan Harp  7 , Frederick Schmitt  7 , Matthew Zammit  1 , Davneet Minhas  8 , Weiquan Luo  9 , Charles Laymon  8 , Julie Price  10 , Joseph H Lee  11 , Ira Lott  12 , Annie Cohen  2 , Beau M Ances  13 , Margaret Pulsifer  10 , H Diana Rosa  10 , Florencia Lai  13 , Shahid H Zaman  6 , Elizabeth Head  14 , Mark Mapstone  15 , Bradley T Christian  1 , Sigan L Hartley  1   16 ; Alzheimer Biomarker Consortium ‐ Down syndrome
Affiliations

Longitudinal investigation of gait and Alzheimer's disease in adults with Down syndrome

Ashlyn Barry et al. Alzheimers Dement. 2025 Apr.

Abstract

Introduction: Gait abnormalities are associated with Alzheimer's disease (AD) in the general population, but it is unclear if the same is true for individuals with Down syndrome (DS). This study examined gait across 32 months in relation to neuroimaging biomarkers (amyloid beta [Aβ], neurofibrillary tangles [NFTs], and hippocampal volume), cognitive decline, and clinical AD status in adults with DS.

Methods: Participants were 218 adults with DS who underwent Aβ and NFT positron emission tomography (PET) and magnetic resonance imaging (MRI) scans, cognitive testing, and gait assessments at baseline and 32 months. Residual change regression models were conducted.

Results: Higher baseline Aβ PET and NFT PET and lower MRI hippocampal volume were associated with gait declines across 32 months. Cognitive declines were associated with gait declines. Participants with clinical dementia at 32 months had greater gait decline than those who were cognitively stable.

Discussion: Gait impairments are a key feature of DS-associated AD (DSAD). Gait assessments could offer a quick, cost-effective, non-invasive screen for DSAD.

Highlights: Those with clinical status of dementia had lower gait performance than those who were cognitively stable. Higher baseline amyloid beta and neurofibrillary tangle volume was associated with more gait impairments. Lower baseline hippocampal volume was associated with more gait impairments. Greater decline in gait performance was associated with cognitive decline. Greater decline in gait performance was associated with more dementia symptoms.

Keywords: amyloid beta; cognitive decline; dementia; gross motor skills; hippocampal volume; neurofibrillary tangles of tau; trisomy 21.

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Conflict of interest statement

M.M. received royalties from the University of Rochester and consulting fees from NovoGlia, Inc. and Ireno Health, PBC. S.Z. received royalties from Pavilion Publishing for CAMDEX‐DS‐II, paid to the Horizon‐21 Research Consortium. S.H. received consulting fees from Ionis Pharmaceuticals. M.Z. received consulting fees from LuMind IDSC. E.H. received consulting fees from Cyclo Therapeutics, Alzheon, and Elsevier.

Figures

FIGURE 1
FIGURE 1
Example population model.
FIGURE 2
FIGURE 2
Baseline Tinetti Gait score by intellectual disability level (A), presence of seizures (B), presence of cataracts (C), and presence of orthopedic condition (D)
FIGURE 3
FIGURE 3
Change in cognitive functioning in relation to change in Tinetti score from baseline to 32‐month follow‐up. A, Modified Cued Recall Test (mCRT). B, Down Syndrome Mental Status Examination (DSMSE); C, National Task Group—Early Dementia Screener (NTG). Each line represents a participant. Circles denote scores at baseline and arrows denote scores at the 32‐month follow‐up. The solid black line represents the locally estimated scatterplot smoothing data trend, and the gray band represents the 95% confidence interval
FIGURE 4
FIGURE 4
Change in Tinetti score from baseline to the 32‐month follow‐up. Each line represents a participant based on (A) amyloid burden in Centiloids, (B) low versus high hippocampal volume, (C) high versus low neurofibrillary tangles (NFTs) in Braak V and VI regions. Circles denote scores at baseline and arrows denote scores at 32‐month follow‐up
FIGURE 5
FIGURE 5
Change in Tinetti scores from baseline to the 32‐month follow‐up by clinical Alzheimer's disease (AD) status at the 32‐month follow‐up. The y axis represents the change in Tinetti scores from baseline to the 32‐month follow‐up. Negative numbers represent a decrease Tinetti scores and positive numbers represent an increase in Tinetti scores
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