Excessive daytime sleepiness and fatigue may indicate accelerated brain aging in cognitively normal late middle-aged and older adults

Abstract

Excessive daytime sleepiness (EDS) and fatigue increases with age. The aim of this study was to investigate the association between EDS and fatigue with cortical thickness and hippocampal volume in cognitively normal, late middle-aged and older adults. We performed a cross-sectional observational study of 1374 cognitively-normal subjects aged 50 years and older who had a structural MRI. Regional cortical thickness and hippocampal volume were measured. Multiple linear regression models were fit to explore associations between EDS and fatigue and structural MRI measures in different brain regions, adjusting for multiple covariates. EDS was defined as Epworth Sleepiness Scale ≥10. Fatigue severity was assessed with the Beck Depression Inventory-2. 208 participants had EDS, 27 had significant fatigue, and 11 had both. Participants with EDS or fatigue had significantly lower cognitive scores, more disturbed sleep, and medical comorbidities. The presence of EDS was associated with both global and regional atrophy, whereas fatigue was more associated with frontal and temporal changes. Cortical thinning predicted by EDS and fatigue was maximal in the temporal region with average reduction of 34.2 µm (95% CI, −54.1, −14.3; P=.001) and 90.2 µm (95% CI, −142.1, −38.2; P=.001), respectively. Fatigue was also associated with hippocampal volume reduction of −374.2 mm3 (95%CI, −670.8, −77.7; P=.013). Temporal cortical thinning predicted by presence of EDS and fatigue was equivalent to more than 3.5 and nine additional years of aging, respectively. EDS and fatigue were associated with cortical thickness reduction primarily in regions with increased age-susceptibility, which may indicate accelerated brain aging.

Psychomotor Vigilance Test and Its Association With Daytime Sleepiness and Inflammation in Sleep Apnea: Clinical Implications

“…19,38,39 It is also possible sleepiness as measured by objective and subjective assessments and fatigue reflect different central nervous system processes with possibly different underlying neuroanatomic and neurophysiologic pathways. 40 For example, in late middleaged and older adults, subjective EDS is associated with reduction of global cortical thickness whereas fatigue is associated with reduction of frontal and temporal cortical thickness and hippocampal volume. 40 In this study, neither mBDI-II scores nor original scores of BDI-II were significantly associated with PVT performance.…”

“…40 For example, in late middleaged and older adults, subjective EDS is associated with reduction of global cortical thickness whereas fatigue is associated with reduction of frontal and temporal cortical thickness and hippocampal volume. 40 In this study, neither mBDI-II scores nor original scores of BDI-II were significantly associated with PVT performance. The lack of association between depression and PVT performance may be explained by the narrow range of depression scores in our samples.…”

The Epidemiology of Patient‐Reported Hypersomnia in Persons With Advanced Age

“…Scores range from 0 to 24 (higher scores indicate more severe sleepiness) . In the current study, patient‐reported hypersomnia was established epidemiologically with a threshold of 10 or greater, previously validated in older populations and associated with adverse health outcomes . As a supplemental analysis, we also examined associations of patient characteristics with an ESS threshold of 11 or greater, which is more commonly used in younger age groups .…”

Do Older Adults Need Sleep? A Review of Neuroimaging, Sleep, and Aging Studies

“…An early study that used the ESS in middle-aged adults found that greater sleepiness was associated with lower ventromedial prefrontal cortex volume [44], a region that is implicated in emotional regulation and decision making (see Figure 1)[45]. In a recent, large study of older adults (N=1,374), Carvalho et al [46] found that higher ESS scores not only related to lower cortical thickness in the frontal lobe, but also lower thickness in the parietal, temporal, and occipital lobes. An important question though is whether the daytime sleepiness (ESS) data reflected the presence of sleep apnea, general deficits in sleep quality, or the influence of non-sleep fatiguing factors.…”

“…Dusak et al [97] and Akhan et al [98] both observed that hippocampal volume was lower in sleep apnea participants than in healthy control participants. The hippocampal reductions related to a greater apnea-hypopnea index [98] and greater subjective sleepiness [46, 97, 99]. …”