Sleep-wake behavior, perceived fatigability, and cognitive reserve in older adults

Alzheimers Dement. 2024 Jun;20(6):4020-4031. doi: 10.1002/alz.13802. Epub 2024 May 1.


Introduction: The effects of sleep-wake behavior on perceived fatigability and cognitive abilities when performing daily activities have not been investigated across levels of cognitive reserve (CR).

Methods: CR Index Questionnaire (CRIq) data were collected and subjected to moderated mediation analysis.

Results: In amnestic mild cognitive impairment (aMCI; n = 41), CR moderated sleep-related impairments (SRIs), and fatigability at low CR (CRIq < 105.8, p = 0.004) and mean CR (CRIq = 126.9, p = 0.03) but not high CR (CRIq > 145.9, p = 0.65) levels. SRI affected cognitive abilities mediated by fatigability at low CR (p < 0.001) and mean CR (p = 0.003) levels. In healthy controls (n = 13), SRI in fatigability did not alter cognitive abilities across CR levels; controls had higher leisure scores than patients with aMCI (p = 0.003, effect size = 0.93).

Discussion: SRI can amplify impaired cognitive abilities through exacerbation of fatigability in patients with aMCI with below-mean CR. Therefore, improving sleep-wake regulation and leisure activities may protect against fatigability and cognitive decline.

Highlights: Clinical fatigue and fatigability cannot be alleviated by rest. Clinical fatigability disrupts daily activities during preclinical Alzheimer's. High cognitive reserve mitigates sleep-wake disturbance effects. High cognitive reserve attenuates clinical fatigability effects on daily functioning. Untreated obstructive sleep apnea potentiates Alzheimer's pathology in the brain.

Keywords: Alzheimer's disease; cognitive ability; cognitive reserve; fatigue; leisure activities; older adults; sleep; sleep fragmentation; sleep–wake behavior; sleep–wake dysregulation; sleep–wake misalignment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Activities of Daily Living
  • Aged
  • Aged, 80 and over
  • Cognitive Dysfunction* / physiopathology
  • Cognitive Reserve* / physiology
  • Fatigue* / physiopathology
  • Female
  • Humans
  • Male
  • Neuropsychological Tests / statistics & numerical data
  • Sleep / physiology
  • Sleep Wake Disorders / physiopathology
  • Surveys and Questionnaires