Unraveling the Intertwined Threads of Insomnia and Sarcopenia in Cognitive and Functional Decline in Octogenarians

Introduction: Although insomnia and sarcopenia may seem unrelated in the context of older adult health, recent evidence has revealed shared underlying pathophysiological pathways. However, the extent to which these two factors jointly impact crucial clinical outcomes still needs to be determined. This study aimed to elucidate the associations of insomnia and sarcopenia with cognitive impairment and functional decline, shedding light on potential mechanistic connections. Methods: In this observational study, we scrutinized data collected from 493 individuals aged ≥80 years between 2016 and 2018. Sarcopenia was assessed using the EWGSOP2 criteria, insomnia was assessed using the Insomnia Severity Index, functional status was assessed using the Instrumental Activity of Daily Living Scale, and cognition was assessed using the Mini Mental Condition Examination. The baseline assessments included blood lipid, IFN-γ, IL-2, IL-4, IL-6, IL-10, and CRP levels and DNA methylation. Results: Insomnia alone was not associated with cognitive impairment or functional dependence. However, sarcopenia alone increased the odds of cognitive impairment by a factor of 2.6 (95% confidence interval [CI] 1.2 - 5.6, p = 0.011), although it did not impact functional decline. When examined together, insomnia and sarcopenia were associated with 4.8-fold increased odds of cognitive impairment (95% CI 2.1 - 10.9, p <0.001) and 7.1-fold increased odds of functional decline (95% CI 1.7 - 29.0, p = 0.007) compared to those with neither condition. Lipid profiles and inflammatory marker levelsdid not differ, but sarcopenic individuals had significantly greater DNA methylation (p <0.001). Conclusions: Insomnia and sarcopenia synergistically increase the risk of cognitive impairment and functional decline among long-lived older adults. Sarcopenia alone impacted cognition in individuals, whichcould be related to the increase in inflammation-independent DNA methylation observed among individuals with sarcopenia.