Association of circadian rhythms with brain disorder incidents: a prospective cohort study of 72242 participants

Abstract

Circadian rhythm disruption (CRD) is a shared characteristic of various brain disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and major depression disorder (MDD). Disruption of circadian rhythm might be a risk factor for brain disorder incidents. From 7-day accelerometry data of 72,242 participants in UK Biobank, we derived a circadian relative amplitude variable, which to some extent reflected the degree of circadian rhythm disruption. Records of brain disorder incidents were obtained from a wide range of health outcomes across self-report, primary care, hospital inpatient data, and death data. Using multivariate Cox proportional hazard ratio regression, we created two models adjusting for different covariates. Then, linear correlations between relative amplitude and several brain morphometric measures were examined in participants with brain MRI data. After a median follow-up of around 6.1 years, 72,242 participants were included in the current study (female 54.9%; mean age 62.1 years). Individuals with reduced relative amplitude had increasing risk of all-cause dementia (Hazard ratio 1.23 [95% CI 1.15 to 1.31]), PD (1.33 [1.25 to 1.41]), stroke (1.13 [1.06 to 1.22]), MDD (1.18 [1.13 to 1.23]), and anxiety disorder (1.14 [1.09 to 1.20]) in fully adjusted models. Additionally, significant correlations were found between several cortical regions and white matter tracts and relative amplitude that have been linked to dementia and psychiatric disorders. We confirm CRD to be a risk factor for various brain disorders. Interventions for regulating circadian rhythm may have clinical relevance to reducing the risk of various brain disorders.

Diurnal fluctuations in steroid hormones tied to variation in intrinsic functional connectivity in a densely sampled male

“…Fluctuations in hormone concentrations across shorter timescales, like diurnal rhythms, may also influence brain function. Existing neuroimaging studies of circadian rhythms focus on external influences that impact the human circadian clock, including sleep (Fang & Rao, 2017; Frank et al, 2013; Jiang et al, 2016; Mong et al, 2011), exposure to light sources (Schoonderwoerd et al, 2022), and psychopathology (Chen et al, 2022; Frank et al, 2013; McKenna et al, 2014), but the fundamental relationship between diurnal variation in sex steroid hormones and the large scale functional organization of the human brain is virtually unknown.…”

Systemic inflammation in relation to exceptional memory in the Long Life Family Study (LLFS)

“…However, in 43 Parkinson's Disease patients [31 males; mean (±SD) age: mean (±SD) age: 68.9 (±8.4) years], cognitive impairment was associated with increased circulating lymphocytes ( Magistrelli et al, 2020 ). A recent study with 161,968 participants [49% males; mean (±SD) age: 62.14 (4.07) years] from the UK Biobank found higher CRP and neutrophils, but not any other cell types, were associated with increased risk of incident dementia ( Zhong et al, 2023 ). In mouse models, extravasated neutrophils contributed to cognitive impairment and AD pathogenesis while depletion of neutrophils led to memory improvements ( Zenaro et al, 2015 ).…”

Antidepressant mechanism of traditional Chinese medicine: Involving regulation of circadian clock genes

“…Additional research has identified the restoration of rhythmical expression of circadian clock genes involved in regulating circadian rhythms. [8,9] This review was aimed to summarize recent relevant studies conducted abroad, explore the pathological relationship and regulatory mechanisms between the circadian clock system and depression, and assess the mechanism by which TCM interventions based on the regulation of circadian rhythm offer therapeutic benefits for depression, thereby providing valuable references for future basic research and clinical applications.…”