Gait Disturbances are Associated with Increased Cognitive Impairment and Cerebrospinal Fluid Tau Levels in a Memory Clinic Cohort

J Alzheimers Dis. 2020;76(3):1061-1070. doi: 10.3233/JAD-200225.

Abstract

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's disease pathology.

Objective: In this study, we tested if calculated features of gait 1) differ between cognitively normal subjects (CN), mild cognitive impairment (MCI) patients, and dementia patients, 2) are correlated with cerebrospinal fluid (CSF) biomarkers related to Alzheimer's disease, and 3) predict cognitive decline.

Methods: Gait was measured using tri-axial accelerometers attached to the fifth lumbar vertebra (L5) in 58 CN, 58 MCI, and 26 dementia participants, while performing a walk and dual task. Ten gait features were calculated from the vertical L5 accelerations, following principal component analysis clustered in four domains, namely pace, rhythm, time variability, and length variability. Cognitive decline over time was measured using MMSE, and CSF biomarkers were available in a sub-group.

Results: Linear mixed models showed that dementia patients had lower pace scores than MCI patients and CN subjects (p < 0.05). In addition, we found associations between the rhythm domain and CSF-tau, especially in the dual task. Gait was not associated with CSF Aβ42 levels and cognitive decline over time as measured with the MMSE.

Conclusion: These findings suggest that gait - particularly measures related to pace and rhythm - are altered in dementia and have a direct link with measures of neurodegeneration.

Keywords: Alzheimer’s disease; cognitive dysfunction; dementia; gait analysis; tau proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / complications
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Biomarkers / cerebrospinal fluid
  • Cognition / physiology*
  • Cognitive Dysfunction / cerebrospinal fluid
  • Cognitive Dysfunction / complications
  • Cognitive Dysfunction / diagnosis
  • Cognitive Dysfunction / physiopathology*
  • Cohort Studies
  • Disease Progression
  • Female
  • Gait / physiology*
  • Gait Disorders, Neurologic / etiology*
  • Humans
  • Male
  • Memory / physiology
  • Middle Aged
  • Neuropsychological Tests
  • Peptide Fragments / cerebrospinal fluid
  • tau Proteins / cerebrospinal fluid*

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • tau Proteins