title: 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 = 0.001) and 90.2 μm (95% CI, -142.1, -38.2; P = 0.001), respectively. Fatigue was also associated with hippocampal volume reduction of -374.2 mm3(95% CI, -670.8, -77.7; P = 0.013). Temporal cortical thinning predicted by presence of EDS and fatigue was equivalent to more than 3.5 and 9 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.
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Diego Z
authors.initials: DZ
authors.lastname: Carvalho
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Erik K
authors.initials: EK
authors.lastname: St Louis
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Bradley F
authors.initials: BF
authors.lastname: Boeve
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, USA; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Mielke
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Przybelski
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.affiliation: Department of Psychology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Machulda
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, USA; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Rosebud O
authors.initials: RO
authors.lastname: Roberts
authors.affiliation: Department of Psychology, Mayo Clinic, Rochester, MN, USA; Department of Psychiatry, Mayo Clinic, Scottsdale, AZ, USA; Department of Neurology, Mayo Clinic, Scottsdale, AZ, USA.
authors.forename: Yonas E
authors.initials: YE
authors.lastname: Geda
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA. Electronic address: vemuri.prashanthi@mayo.edu.
authors.forename: Prashanthi
authors.initials: P
authors.lastname: Vemuri
mesh_terms: D000368:Aged; D000375:Aging / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D003430:Cross-Sectional Studies; D006970:Disorders of Excessive Somnolence / Q000150:complications* / Q000473:pathology; D005221:Fatigue / Q000150:complications* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
keywords: Aging; Cortical thickness; Fatigue; Hippocampal volume; Sleepiness; Structural MRI