Alzheimer's Imaging Consortium

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.