Diurnal variation in neurovascular coupling and the impact of sleep quality: a UK Biobank study

Cerebrovascular events are more frequent in the morning, coinciding with disturbed circadian rhythms and poor sleep quality. Neurovascular coupling (NVC), a marker of neuronal activity and endothelium-dependent cerebrovascular function, may mediate the relationship between cerebrovascular dysfunction and chronic cerebrovascular disease. This study aims to determine whether NVC shows circadian variation and whether it is associated with sleep quality.

Functional MRI scans from the UK Biobank were adapted to assess NVC at different time points throughout the day. Analysis of Variance (ANOVA) with Tukey post hoc tests examined NVC differences between 3 and 2-h time blocks starting at 8 am Cosinor models assessed rhythmicity in NVC. General linear models evaluated the impact of sleep quality (a composite score and individual markers: snoring, insomnia, duration, chronotype, and daytime sleepiness) on NVC, adjusting for age, sex, and vascular risk factors.

Among 36 801 participants, NVC was significantly lower between 11 am and 2 pm, with a consistent pattern across ages in men but a midday decline in younger women (<60 years). While the composite measure of sleep quality risk was not associated with a change in NVC (p = .12), a diagnosis of insomnia (p = .04) or sleep apnea (p = .03) was associated with lower NVC.

The observed reduction in NVC in the late morning and its association with objective measures of impaired sleep quality suggest a potential role for endothelial dysfunction, potentially contributing to the associated increased cerebrovascular risk. Statement of Significance Cerebrovascular fluctuations with time-of-day and with sleep quality could offer insights into stroke mechanisms. This study provides the first large-scale evidence that neurovascular coupling (NVC), a functional marker of cerebrovascular health, follows a diurnal pattern characterized by a reproducible midday dip independent of age, sex, and vascular risks. This suggests a period of potential vulnerability in the cerebral blood supply. Furthermore, a history of stroke and sleep disorders such as sleep apnea are associated with impaired NVC, indicating a disruption of the brain's natural rhythms. These findings highlight translational opportunities to optimize sleep and align preventive strategies with diurnal physiology to reduce cerebrovascular risk. Remaining knowledge gaps include the need for 24-h assessments and longitudinal studies to clarify causal pathways.