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Gait tests like the Timed Up and Go (TUG) can help identify Alzheimer's disease (AD) risk by correlating with plasma biomarkers. Subtle mobility changes in cognitively unimpaired individuals may signal early AD pathology.

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Area of Science:

  • Neurology
  • Gerontology
  • Biomarker Research

Background:

  • Gait impairments are common in Alzheimer's disease (AD) and related dementias, increasing fall risk and mortality.
  • The Timed Up and Go (TUG) test assesses mobility and dual-task performance, with its dual-task version (TUG-DT) evaluating dual-task cost (DTC).
  • Plasma biomarkers such as pTau217, pTau181, and neurofilament light chain (NfL) aid in assessing AD risk in cognitively unimpaired (CU) and mild cognitive impairment (MCI) individuals.

Purpose of the Study:

  • To investigate the relationship between TUG performance and plasma biomarkers in CU and MCI patients.
  • To determine if gait parameters from TUG and TUG-DT can predict AD risk.
  • To explore the utility of plasma biomarkers in conjunction with gait analysis for early AD detection.

Main Methods:

  • Participants included CU low-risk (n=75), CU high-risk (n=87), and CI (n=32) older adults (55-80 years).
  • Cognitive status was assessed using the Clinical Dementia Rating Scale and Montreal Cognitive Assessment.
  • Plasma pTau217, pTau181, NfL levels were measured, and participants underwent TUG and TUG-DT tests. Statistical analyses included ANOVAs, ANCOVAs, logistic regression, and generalized additive models (GAMs).

Main Results:

  • CU high-risk and MCI groups showed similar TUG step counts, both significantly higher than the CU low-risk group.
  • Plasma pTau181 and NfL levels interacted to predict gait performance specifically in the CU high-risk group.
  • The TUG test demonstrated high specificity in predicting plasma pTau217 levels, differentiating non-at-risk CU individuals.

Conclusions:

  • The TUG test can predict plasma pTau217 levels, helping to identify CU individuals not at risk for AD.
  • Interactions between pTau181 and NfL predict TUG/TUG-DT performance in CU high-risk individuals, suggesting gait changes may indicate early AD pathology.
  • Reduced step count in CU low-risk individuals may signify preclinical AD with subtle mobility deficits, supporting TUG's role in AD risk assessment.