Abstract

BackgroundGait deficits are associated with brain atrophy and white matter hyperintensities (WMH) – both markers of underlying cerebral small vessel disease (SVD). Given reduced subcortical cerebral blood flow (CBF) is prevalent in SVD, we tested the hypothesis that regional CBF is positively associated with gait performance among older adults.MethodsThirty-two older adults (55–80 years) with at least one vascular risk factor were recruited. We assessed gait during 2 consecutive walking sequences using a GAITRite system: (1) at a self-selected pace, and (2) while performing a serial subtraction dual-task challenge. We quantified CBF using pseudo-continuous arterial spin labeling MRI within 4 regions of interest: putamen, pallidum, thalamus, and hippocampus. We investigated associations between gait characteristics and overall CBF adjusting for age, sex, and height in an omnibus approach using multivariate analysis of variance, followed by regression analysis with each individual region. We also conducted further regression analyses to investigate associations between gait characteristics and frontal lobe CBF. Sensitivity analyses examined how the observed associations were modified by WMH, executive function, and depressive symptoms. A change of 10% in the model’s adjusted r2 and effect size was considered as a threshold for confounding.ResultsOverall subcortical CBF was not associated with self-paced gait. When examining individual ROI, gait velocity was directly related to thalamic CBF (p = 0.026), and across all gait variables the largest effect sizes were observed in relation to thalamic CBF. In the dual-task condition, gait variables were not related to CBF in either the omnibus approach or individual multiple regressions. Furthermore, no significant associations were observed between frontal CBF and gait variables in either the self-paced or dual-task condition. Sensitivity analyses which were restricted to examine the association of velocity and thalamic CBF identified a cofounding effect of depressive symptoms which increased the effect size of the CBF-gait association by 12%.ConclusionSubcortical hypoperfusion, particularly in regions that comprise central input/output tracts to the cortical tissue, may underlie the association between gait deficits and brain aging.

Highlights

  • Slowing of gait, cognitive decline, and mood disorders are aging-related conditions that predict frailty and functional dependence

  • When examining individual regions of interest (ROI), gait velocity was directly related to thalamic cerebral blood flow (CBF) (p = 0.026), and across all gait variables the largest effect sizes were observed in relation to thalamic CBF

  • Sensitivity analyses which were restricted to examine the association of velocity and thalamic CBF identified a cofounding effect of depressive symptoms which increased the effect size of the CBF-gait association by 12%

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Summary

Introduction

Cognitive decline, and mood disorders are aging-related conditions that predict frailty and functional dependence. Cerebral small vessel disease (SVD) may be a driver of these behavioral changes by disrupting the interaction between frontal-subcortical circuits, the basal ganglia, and the thalamus which regulates motor and cognitive functions (Schmahmann and Pandya, 2008). Speaking, aging and cardiovascular risk factors lead to vascular remodeling, which alters cerebral hemodynamics and can impact brain metabolism or the autoregulatory processes that protect the brain (Pugh and Lipsitz, 2002; Pantoni, 2010). There is a 30% risk of a fall per annum among adults over 65 years of age (Bergen et al, 2016). Gait deficits are associated with brain atrophy and white matter hyperintensities (WMH) – both markers of underlying cerebral small vessel disease (SVD). Given reduced subcortical cerebral blood flow (CBF) is prevalent in SVD, we tested the hypothesis that regional CBF is positively associated with gait performance among older adults

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