Sleep, beautiful sleep

Photo by S L on Unsplash

Human biology is systems biology; perturb one aspect of human biology and it will have downstream effects, which can be noted throughout the body. As you know sleep is critical for brain health; if you have poor sleep hygiene you are putting yourself at greater risk of developing dementia when you get older. Why? 

In this study of cognitively normal older Chinese adults, spinal fluid soluble TREM2 (sTREM2) was associated with self-reported poor sleep hygiene using the Pittsburgh Sleep Quality Index. sTREM2 is shed from activated microglia or macrophages and is thought to be a marker of microglial activation. The implications are that this association may be causal, i.e. poor sleep is pro-inflammatory, both in the periphery and central nervous system and the latter contributes to driving neurodegeneration.

Could improved sleep hygiene be anti-inflammatory? Or is the microglial activation simply a response to poorer clearance of CNS debris, which occurs when we are asleep? Whatever the reasons this study provides some evidence that the role poor sleep plays in driving neurodegeneration may be more complex than we realise.

I don’t think we can ignore poor sleep hygiene in our push to improve brain health. The question is how do we get the population to improve their sleep? What interventions work? How do we drive the necessary behavioural changes to get the whole country to improve their sleep quality?

I would be interested to know if we could use CSF sTREM levels as a response marker in trials designed to improve brain health.

Hu et al. Associations of Sleep Characteristics with Cerebrospinal Fluid sTREM2 in Cognitively Normal Older Adults: the CABLE Study. Neurotox Res . 2021 Jun 7. doi: 10.1007/s12640-021-00383-5. Online ahead of print.

As brain insults, sleep disorders could enhance microglial activation and aggravate neuroinflammation. Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) serves as a readout for TREM2-associated microglial responses. We aimed to study the association of sleep characteristics with CSF sTREM2 in cognitively normal (CN) older adults. Linear and non-linear regression analyses were conducted in 830 participants with measurements of sleep characteristics and CSF sTREM2, after adjusting for age, sex, education, the Chinese-Modified Mini-Mental State Examination (CM-MMSE) scores, and APOE4 status. These analyses were also performed in amyloid-negative (A -) and amyloid-positive (A +) individuals. Linear relationships between sleep characteristics and CSF sTREM2 were found. In all the participants, sleep efficiency score in Pittsburgh Sleep Quality Index (PSQI) (p = 0.037) showed a positive linear association with CSF sTREM2. In A + individuals, the grade of PSQI total score (p = 0.011) as well as subjective sleep quality score (p = 0.048) and sleep efficiency score (p < 0.001) in PSQI were positively associated with CSF sTREM2. Besides, several U-shaped relationships were revealed of sleep-time measures, such as insufficient or excessive nocturnal sleep duration, with CSF sTREM2 in A + individuals (the optimal model: bedtime 22:21 p.m., time to fall asleep 22:52 p.m., nocturnal sleep duration 7.36 h). In A - individuals, the above relationships were not found. Poor self-reported sleep characteristics and sleep indicators were associated with higher CSF sTREM2, suggesting that sleep might play an important role in the regulation of TREM2-associated microglial activity.

Conflicts of Interest

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General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice.