Gait disturbances are associated with increased CSF tau levels in a memory clinic cohort: Neuropsychiatry and behavioral neurology/Mild cognitive impairment/Early symptomatic disease

Background
Gait analysis with accelerometers is a relatively inexpensive and easy to use method to potentially support clinical diagnoses of Alzheimer’s Disease and other dementias. It is not clear however, which gait features are most informative and how these measures relate to Alzheimer pathology. In this study, we used in-depth evaluation of gait in cognitively normal (CN) subjects, Mild Cognitive Impairment (MCI) patients, and dementia patients. We evaluated the associations between dynamics of gait, level of cognitive impairment and CSF biomarkers of Alzheimer’s pathology.

Method
We included CN participants (n=58), MCI patients (n=58) and participants with different types of dementia (n=26) of the multicenter PredictND cohort. Participants performed gait tests in two conditions: a normal walk task and a cognitively complex dual task. Gait was measured using tri-axial accelerometers attached to the fifth lumbar vertebra (L5). Following principal component analysis, calculated gait features were clustered into four domains: pace, rhythm, time variability and length variability. Associations between gait domains, clinical diagnosis and CSF biomarkers (Aβ42, total tau, pTau) were examined using linear mixed models, included an interaction term with condition (normal and dual walk task) and were corrected for age, sex and center.

Result
Dementia patients showed gait disturbances in the pace domain (p<0.05), meaning that dementia patients walk slower and with a smaller step length compared to CN and MCI participants. Rhythm disturbances were associated with increased levels of CSF (p)tau in the dual task. No associations were found with CSF Aβ42 levels in any gait domain.

Conclusion
These findings suggest that gait disturbances increase with level of syndrome diagnosis. Moreover, rhythm disturbances increase with higher levels of CSF total tau and pTau, providing evidence for a direct link with neurodegeneration. These results demonstrate that in-depth gait analysis with accelerometers might be a potential helpful tool to support clinical diagnosis or can be used as clinical outcome tool in clinical trials.