Cognitive behavioural therapy for insomnia and epigenetic ageing: secondary analysis from a randomised controlled trial.

Abstract

Insomnia in later life has been associated with accelerated biological ageing; however, little is known about the effects of insomnia treatment on it. In this study, we evaluated the effects of cognitive behavioural therapy for insomnia (CBT-I), compared with sleep education therapy (SET), an active comparator condition, on epigenetic indicators of biological ageing in older adults with insomnia. This secondary analysis was conducted within a larger single-site, investigator-initiated randomised controlled trial (ClinicalTrials.govNCT01641263) of adults aged 60 years or older meeting DSM-IV criteria for insomnia disorder recruited from the Los Angeles, CA, USA. Participants in the parent study were randomly assigned to CBI-T or SET according to a computer-generated random number sequence with block sizes ranging from 5-10. Analyses included participants with complete paired epigenetic data. Peripheral blood mononuclear cells were collected before treatment initiation (baseline) and at a follow-up visit occurring at 20-39 months after baseline. Follow-up times exceeding 30 months were winsorised to 30 months. Biological age was measured by use of DNA methylation-derived epigenetic clocks; Dunedin pace of ageing (DunedinPACE), GrimAge, and the principal component version of PhenoAge (PCPhenoAge). Recruitment for the parent trial was conducted between July 1, 2012, and April 30, 2015. Participants from the CBT-I (n=47; mean age=69·5 [SD 7·0] years) and SET (n=45; mean age=69·4 [5·1] years) groups were randomly selected based on sample availability. Participants receiving CBT-I in the current analysis were more likely to have full remission following treatment than those receiving SET (34% [16 of 47] vs 13% [six of 45]). Compared with those receiving SET, older adults receiving CBT-I showed a significantly slower pace of biological ageing, as estimated by DunedinPACE (-0·02, 95% CI -0·04 to -0·01, false discovery rate [FDR]-adjusted p=0·03). No statistically significant differences were observed for GrimAge (-0·33, -0·68 to 0·03, FDR-adjusted p=0·11) and PCPhenoAge (-0·49, -1·34 to 0·36, FDR-adjusted p=0·26). These findings indicate that a cognitive behavioural intervention for insomnia might slow the pace of biological ageing, as estimated using DunedinPACE. Treatment of insomnia in older adults could therefore represent a strategy for slowing biological ageing in this clinically vulnerable population. National Institute on Aging.