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

BACKGROUND: 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. METHODS: 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). FINDINGS: 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). INTERPRETATION: 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. FUNDING: National Institute on Aging.