Clinical interventions in aging · 2026
The Relationship Between Gait Task Performance and Plasma Biomarkers for Alzheimer's Disease in Cognitively Unimpaired Older Adults and Patients with Mild Cognitive Impairment.
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Sergio Jordan, Price Ashley, Snyder Peter J, Doster Savannah A, Durkin Maeve, Strenger Jennifer R, Thompson Louisa I, Stradtman Megan, Sinoff Stuart, Alber Jessica
Аннотация
PURPOSE: The Timed Up and Go (TUG) is a 20-foot gait assessment, with TUG-dual task (DT) serial subtractions to determine dual-task cost. Alzheimer's disease (AD) risk is established using plasma biomarkers and APOE genotyping.
METHODS: We investigated: 1) TUG/TUG-DT differences between AD low-risk cognitively unimpaired (CU) older adults (N = 74), AD high-risk CU older adults (N = 87), and mild cognitively impaired (MCI) older adults (N = 33) and 2) the relationship between TUG/TUG-DT performance and plasma biomarkers. One hundred and ninety-four older adults ages 55-80 completed TUG/TUG-DT, a fasting blood draw, and APOE genotyping. Scores on the Clinical Dementia Rating Scale (CU = 0; CI = ≥0.5) and Montreal Cognitive Assessment (CU ≥ 24; CI = ≤23) determined whether participants were placed into the CU low-risk, CU high-risk, or MCI groups. Risk level for CU participants were assessed by APOE genotyping. Those participants who carried at least one copy of the APOE ε4 allele were designated to the high-risk group (n = 87). Participants with no APOE ε4 allele were assigned to the low-risk group (n = 75).
RESULTS: MCI participants took longer to perform the TUG than CU participants (p < 0.001). CU high-risk and MCI group performed similarly on step counts, while the CU low-risk took significantly fewer steps (p<0.001). Speed predicted whether someone was below an AD-risk threshold for pTau217 in CU participants (n = 150). Exploratory generalized additive models showed plasma biomarkers predicted gait metrics in CU groups.
CONCLUSION: Step count may be more sensitive, compared to speed alone, in identifying those in preclinical AD stages. Gait metrics (speed and efficiency) played a key role as a clinical manifestation of early AD pathophysiology determined by blood-based biomarker concentration. Combining these assessments offers a multidimensional, cost-effective approach for preclinical-AD screening and potential early intervention.
METHODS: We investigated: 1) TUG/TUG-DT differences between AD low-risk cognitively unimpaired (CU) older adults (N = 74), AD high-risk CU older adults (N = 87), and mild cognitively impaired (MCI) older adults (N = 33) and 2) the relationship between TUG/TUG-DT performance and plasma biomarkers. One hundred and ninety-four older adults ages 55-80 completed TUG/TUG-DT, a fasting blood draw, and APOE genotyping. Scores on the Clinical Dementia Rating Scale (CU = 0; CI = ≥0.5) and Montreal Cognitive Assessment (CU ≥ 24; CI = ≤23) determined whether participants were placed into the CU low-risk, CU high-risk, or MCI groups. Risk level for CU participants were assessed by APOE genotyping. Those participants who carried at least one copy of the APOE ε4 allele were designated to the high-risk group (n = 87). Participants with no APOE ε4 allele were assigned to the low-risk group (n = 75).
RESULTS: MCI participants took longer to perform the TUG than CU participants (p < 0.001). CU high-risk and MCI group performed similarly on step counts, while the CU low-risk took significantly fewer steps (p<0.001). Speed predicted whether someone was below an AD-risk threshold for pTau217 in CU participants (n = 150). Exploratory generalized additive models showed plasma biomarkers predicted gait metrics in CU groups.
CONCLUSION: Step count may be more sensitive, compared to speed alone, in identifying those in preclinical AD stages. Gait metrics (speed and efficiency) played a key role as a clinical manifestation of early AD pathophysiology determined by blood-based biomarker concentration. Combining these assessments offers a multidimensional, cost-effective approach for preclinical-AD screening and potential early intervention.