Poor sleep health is associated with older brain age: the role of systemic inflammation

BACKGROUND: Poor-quality sleep has been linked to increased dementia risk. We investigated the relationship between healthy sleep pattern and older brain age, and the extent to which this is mediated by systemic inflammation. METHODS: The study included 27,500 adults from the UK Biobank (mean age 54.7 y, 54.0% female). The presence of five self-reported healthy sleep characteristics (early chronotype, 7-8 h daily sleep, no insomnia, no snoring, no excessive daytime sleepiness) were summed into a healthy sleep score (0-5 pts) and used to define three sleep patterns: healthy (≥4 pts), intermediate (2-3 pts), and poor (≤1 pt). Low-grade inflammation was estimated using the INFLA-score, a composite index of inflammatory biomarkers. After a mean follow-up of 8.9 y, brain age was estimated using a machine learning model based on 1079 brain MRI phenotypes and used to calculate brain age gap (BAG; i.e., brain age minus chronological age). Data were analysed using linear regression and generalised structural equation models. FINDINGS: At baseline, 898 (3.3%) participants had poor sleep, 15,283 (55.6%) had intermediate sleep, and 11,319 (41.2%) had healthy sleep. Compared to healthy sleep, intermediate (β = 0.25 [0.11, 0.40], P = 0.010) and poor (β = 0.46 [0.05, 0.87], P < 0.001) sleep were associated with significantly higher BAG. In mediation analysis, INFLA-score mediated 6.81% and 10.42% of the associations between intermediate and poor sleep and higher BAG. INTERPRETATION: Poor sleep health may accelerate brain ageing. This may be driven by higher levels of systemic inflammation. FUNDING: Alzheimerfonden; Demensfonden; Loo and Hans Osterman Foundation for Medical Research; the Knowledge Foundation; Swedish Research Council.