Walking energetics and white matter hyperintensities: findings from the Baltimore Longitudinal Study of Aging (BLSA)

Abstract

AbstractBackgroundWhite matter hyperintensities (WMH) increase with advancing age and may contribute to the development of Alzheimer’s Disease. Energy utilization, as defined by walking efficiency, worsens with advancing age and is a prognostic marker of physical and cognitive function in older adults. While both WMH and energy utilization have been associated with cognition and Alzheimer’s‐related pathology, the links between WMH and walking energy utilization are unexplored. The purpose of this study was to examine the cross‐sectional association between walking energy utilization and WMH in cognitively normal middle‐to‐late aged men and women.MethodThe study included 708 BLSA participants who completed standardized slow‐ and peak‐pace walking assessments with indirect calorimetry (VO2 ml/kg/min) and underwent brain magnetic resonance imaging. Energy utilization was defined as the ratio of slow‐to‐peak walking energy capacity (the cost‐ratio), which describes the percentage of peak walking capacity required for the standardized slow walking task; a higher percentage indicates worse energy utilization. T2‐weighted scans and FLAIR images based on a validated support vector machine classifier approach were used to quantify total WMH volumes, which were log‐transformed to normalize the distribution. Sample characteristics were summarized using means and standard deviations. Linear regression was used to examine the association between WMH and the cost‐ratio adjusted for total white matter volume, age, sex, race, lean mass, fat mass, education, height, and comorbid conditions.ResultIn this sample of cognitively normal adults (56% women, mean age 66.7±15.3 years) the average cost‐ratio was 71.6±12.2% (range 34.3‐98.7) and mean log10(WHH) was 3.01±0.80 (range 0.08‐4.68). After covariate adjustment, a higher cost‐ratio was associated with greater total WMH (B = 0.008; SE = 0.002; p<.001; Table 1). Aside from age and total white matter volume, which track closely with WMH, the cost‐ratio was most strongly associated with WMH in our model (Table 1).ConclusionIn a large sample of community‐dwelling middle‐to‐late aged adults, walking energy utilization was associated with WMH volumes, suggesting that a combination of higher energy cost of walking and lower peak walking energy capacity is associated with adverse brain health in mid‐to‐late life. Longitudinal research is needed to elucidate the directionality and temporality of the observed association.