A large population-based study of nearly 90,000 adults found that irregular circadian rhythms—specifically inconsistent sleep-wake timing and low daytime activity—were associated with brain volume loss, cognitive decline, and increased dementia risk.
The investigators measured two indicators of circadian disruption: composite phase deviation (CPD)—which reflects variability in daily activity timing—and relative amplitude (RA), which indicates the strength of contrast between day and night activity. Both metrics were derived from 7-day wrist-worn accelerometer data in UK Biobank participants.
“Circadian disruption was associated with widespread brain structural alterations in cerebrum and cerebellum,” wrote Siwen Luo, of the Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, and colleagues.
Specifically, they found that participants with more irregular activity patterns (higher CPD) had smaller volumes in key brain regions, including the hippocampus and thalamus. Those with weaker rhythms (lower RA) showed significantly reduced cerebellar volume. In mediation analyses, reduced thalamic volume accounted for 8.6% of the association between CPD and non-Alzheimer’s, nonvascular dementia. Hippocampal volume accounted for 8.2% of the effect.
Participants in the highest CPD quartile had a 1.37-fold greater risk of developing dementia than those in the lowest quartile. For RA, those in the lowest quartile had a 1.78-fold higher risk than those with the most stable rhythms.
Participants with higher CPD also performed worse on six cognitive tasks that assessed memory, attention, and processing speed, including reaction time, symbol-digit substitution, and two pairs-matching tasks. Lower RA was significantly associated with slower reaction time but not with other cognitive measures.
Reaction time performance itself explained approximately 1.2% of the CPD-related dementia risk.
Over a median follow-up of nearly eight years, 714 participants developed dementia: 303 with Alzheimer’s disease, 130 with vascular dementia, and 474 with other types.
Although brain volume reductions were modest, they were considered clinically relevant. Higher CPD was associated with a 1.11% decrease in hippocampal volume and a 1.03% decrease in thalamic volume. By comparison, annual hippocampal shrinkage in aging adults typically ranges from 0.18% to 0.3%. The hippocampal decrease "suggested that circadian disruption was associated with a 3.7 to 6.2 year increase in aging of the hippocampus," the authors noted.
Sensitivity analyses supported the findings, even after excluding participants diagnosed with dementia within 1 year of accelerometry. Results were consistent across chronotypes (morning, evening, and intermediate).
The investigators concluded that disrupted circadian rhythms were consistently associated with early brain structural changes and lower cognitive performance, and that these alterations may partially mediate the increased risk of dementia. "For individuals with specific circadian disruption such as shift workers," they wrote, "the volume of key brain regions such as the hippocampus and thalamus can serve as a potential marker for occupational health screenings, enabling early prediction and treatment of cognitive impairment and dementia."
The researchers acknowledged limitations, including a temporal overlap between the recording of MRI data (2014 and later) and accelerometric measurements (2013 to 2015), as well as a lack of control over factors that influence cognitive assessment results, such as education level. They suggested further studies are warranted to consider as many confounders as possible, and to explore the protective effects of daytime activity on dementia risk.
The authors reported no conflicts of interest.
Source: BMJ Mental Health
