White Matter Structure in Older Adults Moderates the Benefit of Sleep Spindles on Motor Memory Consolidation

Abstract

Sleep spindles promote the consolidation of motor skill memory in young adults. Older adults, however, exhibit impoverished sleep-dependent motor memory consolidation. The underlying pathophysiological mechanism(s) explaining why motor memory consolidation in older adults fails to benefit from sleep remains unclear. Here, we demonstrate that male and female older adults show impoverished overnight motor skill memory consolidation relative to young adults, with the extent of impairment being associated with the degree of reduced frontal fast sleep spindle density. The magnitude of the loss of frontal fast sleep spindles in older adults was predicted by the degree of reduced white matter integrity throughout multiple white matter tracts known to connect subcortical and cortical brain regions. We further demonstrate that the structural integrity of selective white matter fiber tracts, specifically within right posterior corona radiata, right tapetum, and bilateral corpus callosum, statistically moderates whether sleep spindles promoted overnight consolidation of motor skill memory. Therefore, white matter integrity within tracts known to connect cortical sensorimotor control regions dictates the functional influence of sleep spindles on motor skill memory consolidation in the elderly. The deterioration of white matter fiber tracts associated with human brain aging thus appears to be one pathophysiological mechanism influencing subcortical-cortical propagation of sleep spindles and their related memory benefits. Numerous studies have shown that sleep spindle expression is reduced and sleep-dependent motor memory is impaired in older adults. However, the mechanisms underlying these alterations have remained unknown. The present study reveals that age-related degeneration of white matter within select fiber tracts is associated with reduced sleep spindles in older adults. We further demonstrate that, within these same fiber tracts, the degree of degeneration determines whether sleep spindles can promote motor memory consolidation. Therefore, white matter integrity in the human brain, more than age per se, determines the magnitude of decline in sleep spindles in later life and, with it, the success (or lack thereof) of sleep-dependent motor memory consolidation in older adults.

Sleep and Human Aging

“…In young adult humans and rodents, white matter integrity in fiber tracts that form cortico-thalamic loops is associated with the quantitative and qualitative expression of sleep spindles (Piantoni et al, 2013; Steriade et al, 1987). In agreement with these findings, preliminary human data indicate that age-related deterioration in white matter integrity within the body and splenium of the corpus callosum predicts the severity of impaired sleep spindle expression in older adults (Mander et al, 2016b). These effects remain significant when controlling for age, reemphasizing the notion that processes associated with aging, but not an individual’s age, per se, are the more significant determinant of these links between brain deterioration and sleep deterioration.…”

“…For example, stage 2 NREM sleep duration does not change appreciably with age, yet sleep spindle expression within stage 2 NREM sleep deteriorates significantly in older adults (De Gennaro and Ferrara, 2003; Fogel et al, 2016; Mander et al, 2014, 2016b; Martin et al, 2013). Furthermore, the characteristic reduction in total NREM sleep in older individuals is related to the selective loss of NREM stages 3 and 4, or slow wave sleep, wherein slow waves are principally expressed (Feinberg and Carlson, 1968).…”

“…In contrast, age-related reductions in spindle duration are maximal over posterior EEG derivations (Martin et al, 2013). All three of these age-related disruptions in sleep spindles are most prominent during the last sleep cycles of the night (De Gennaro and Ferrara, 2003; Mander et al, 2016b; Martin et al, 2013). …”

“…For both slow waves and sleep spindles, older adults demonstrate the largest regional oscillation impairments over frontal EEG derivations. The data are adapted from previous reports (Mander et al, 2013, 2014, 2015, 2016b). …”

“…Impairments in NREM sleep spindle duration and density (bottom right bar graph) reductions in older (orange) relative to younger (green) adults are associated with the magnitude of decreased hippocampal gray matter volume and white matter integrity within the body and splenium of the corpus callosum (middle; red regions; adapted from Fogel et al, 2016; Mander et al, 2016b) (lower image).…”