Neurovascular coupling is impaired in slow walkers: The MOBILIZE Boston Study

Abstract

Objective-Neurovascular coupling may be involved in compensatory mechanisms responsible for preservation of gait speed in elderly people with cerebrovascular disease. Our study examines the association between neurovascular coupling in the middle cerebral artery and gait speed in elderly individuals with impaired cerebral vasoreactivity.Methods-Twenty-two fast and 20 slow walkers in the lowest quartile of cerebral vasoreactivity were recruited from the MOBILIZE Boston Study. Neurovascular coupling was assessed in bilateral middle cerebral arteries by measuring cerebral blood flow during the N-Back Task. Cerebral white matter hyperintensities were measured for each group using magnetic resonance imaging.Results-Neurovascular coupling was attenuated in slow compared to fast walkers (2.8% [CI 95%: −0.9-6.6] vs. 8.2% [CI 95%: 4.7-11.8]; p=0.02). The odds of being a slow walker were 6.4 (CI 95%: 1.7-24.9, p=0.007) if there was a high burden of white matter hyperintensity, however, this risk increased to 14.5 (CI 95%: 2.3-91.1, p=0.004) if neurovascular coupling was also attenuated.Interpretation-Our results suggest that intact neurovascular coupling may help preserve mobility in elderly people with cerebral microvascular disease.

Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence

“…Experimental studies support this concept, demonstrating that pharmacologically induced selective neurovascular uncoupling in mice mimics important aspects of both age-related and WBI-induced cognitive impairment (Tarantini et al 2015). There are also studies extant linking impaired neurovascular coupling to gait dysfunction in the elderly (Sorond et al 2011). Thus, we speculate that WBIinduced neurovascular coupling may also contribute to the gait/motor coordination abnormalities observed in our present study as well as in previous reports (Brown et al 2016;Hatcher-Martin and Factor 2016).…”

Pharmacologically induced impairment of neurovascular coupling responses alters gait coordination in mice

“…In the present study, short-term experimentally induced isolated neurovascular uncoupling resulted in significant change in duty cycle, phase dispersion, and gait pattern, whereas no significant changes in gait speed, cadence, base of support, stride length, and stride time. These findings provide direct evidence that a cause-and-effect relationship likely exists between impairment of neurovascular coupling responses and alteration in gait coordination, supporting the conclusions of earlier clinical studies (Sorond et al 2011). Our results also warrant further studies on different modalities of gait (e.g., indices reflecting gait coordination) in the context of neurovascular uncoupling in humans.…”

“…Clinical studies suggest that neurovascular coupling may be involved in preservation of gait function in elderly people (Sorond et al 2011). In the present study, we did not observe differences between control mice and mice treated with MSPPOH+ NAME+INDO in the following parameters indicative of gait: speed (Fig.…”

“…Clinically diagnosed gait abnormalities in older adults involve multiple contributing factors, including neurological diseases (e.g., strokes, Parkinson's disease) (Hajjar et al 2009). Clinical studies, including the MOBILIZE Boston study (Sorond et al 2011), link neurovascular uncoupling to subtle gait dysfunction (e.g., slowing of gait) in humans. Recent studies extend these findings, demonstrating that neurovascular coupling, assessed using transcranial Doppler, is related to activation of brain regions within the executive network, which predicts gait alterations in older adults (Jor'dan et al 2017).…”

“…Human studies suggested that age-related neurovascular uncoupling also associates with gait abnormalities (Sorond et al 2011). The significance of this observation is threefold.…”