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

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

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.

PMID:40289844 | DOI:10.1002/alz.70211