ArticleFrontiers in aging neuroscience2026
Dual decline in gait and cognition as a high-risk clinical phenotype: differential associations with cerebral amyloid-
Article in Frontiers in aging neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Gait slowing and cognitive impairment often coexist in older adults, yet their relationship with core Alzheimer's disease (AD) biomarkers remains incompletely understood. Objective: To investigate the associations of isolated and combined slow gait (SG) and cognitive impairment subtypes with cerebral amyloid- Methods: This cross-sectional study included 1,753 participants (mean age 65.9 years). Based on gait speed and cognitive status, participants were classified into six groups: normal, slow gait alone (SG-A), subjective cognitive decline alone (SCD-A), mild cognitive impairment alone (MCI-A), SCD with slow gait (SCD-SG), and MCI with slow gait (MCI-SG). 687 individuals underwent 18F-florbetapir positron emission tomography (PET) scans, 654 participants were examined for Apolipoprotein E (APOE) genotyping, and 618 participants had all relevant information recorded. Results: The MCI-SG group exhibited the most pronounced physical decline (slowest gait speed and weakest handgrip strength) and the highest burden of AD pathology, with a significantly higher prevalence of Aβ positivity (38%) and APOE ε4 carriage (32%) compared with other groups. While overall Aβ positivity rates across the six groups were not significantly different, logistic regression analyses revealed specific, strong associations. Aβ positivity was significantly associated with both SCD-SG (OR = 1.78, 95% CI: 1.03-3.08) and MCI-SG (OR = 1.85, 95% CI: 1.07-3.21) compared with the normal group. In contrast, APOE ε4 carriage was specifically and more strongly linked to MCI-SG (OR = 3.21, 95% CI: 1.41-7.31) compared with the SCD-A group. These combined gait-cognitive impairment phenotypes showed consistently stronger associations with AD biomarkers than isolated impairments across multiple reference groups. The risk was greatest for MCI-SG in individuals who were both Aβ positive and APOE ε4 carriers (OR = 2.27, 95% CI: 1.19-5.15). Conclusion: The co-occurrence of slow gait and mild cognitive impairment (MCI-SG) represents a distinct high-risk clinical phenotype strongly linked to AD pathology. Aβ and APOE ε4 show differential associations across the gait-cognitive spectrum. Integrated assessment of gait and cognition improves risk stratification in older adults and may guide early intervention strategies.
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