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Glymphatic system, sleep, and shift work: a new paradigm in occupational and mental health?

Sistema glinfático, sono e trabalho por turnos: um novo paradigma em saúde ocupacional e mental?

Dear Editor,

October 21, 1879, was a pivotal date that changed the world. That day, Thomas Edison created a light bulb that shone for 48 h straight. After that, mankind extended the working day into the night. The economic and social gains were remarkable, with a substantial increase in the number of jobs, but causing sleep loss and circadian misalignment due to shift work. Sleep medicine, a relatively recent field of study, has made extraordinary discoveries regarding the impact of sleep on the general human health, notably on occupational and mental health.

Shift work is defined as a labor schedule that includes non-standard hours (especially evening and nighttime hours), performed constantly at a fixed schedule, at intermittent/rotating turns, or even according to less fixed time tables11 Wright KP Jr, Bogan RK, Wyatt JK. Shift work and the assessment and management of shift work disorder (SWD). Sleep Med Rev. 2013;17(1):41-54. https://doi.org/10.1016/j.smrv.2012.02.002
https://doi.org/10.1016/j.smrv.2012.02.0...
. Changes in the natural sleep/wake cycle, also known as circadian rhythm, can trigger sleep disorders over the lifetime. There are many studies showing that sleep disorders negatively influence workers’ health, leading to conditions as hypertension, stroke, cardiovascular disease, diabetes, obesity, decreased immunity, cancer, anxiety, and depression22 Jehan S, Zizi F, Pandi-Perumal SR, Myers KA, Auguste E, Jean-Louis G, et al. Shift work and sleep: medical implications and management. Sleep Med Disord. 2017;1(2):00008. PMID: 29517053.

A recent meta-analysis assembled the findings of 18 studies encompassing 18,802 workers exposed to shift working and compared to non-exposed controls. The results showed an unquestionable impairment in cognitive performance, by means of worsened working memory, processing speed, psychomotor vigilance, cognitive control, and visual attention33 Vlasak T, Dujlovic T, Barth A. Neurocognitive impairment in night and shift workers: a meta-analysis of observational studies. Occup Environ Med. 2022;79(6):365-72. https://doi.org/10.1136/oemed-2021-107847
https://doi.org/10.1136/oemed-2021-10784...
. The authors call attention to a deteriorated performance among shift workers, including work-related injuries as well as an increased risk of clinical and procedural prescribing errors by physicians.

However, these findings go beyond a one-off risk. A population-based study revealed inverted U-shaped associations between sleep duration and subsequent cognitive decline, as well with incidence of dementia44 Bokenberger K, Ström P, Dahl Aslan AK, Johansson AL, Gatz M, Pedersen NL, et al. Association between sleep characteristics and incident dementia accounting for baseline cognitive status: a prospective population-based study. J Gerontol A Biol Sci Med Sci. 2017;72(1):134-9. https://doi.org/10.1093/gerona/glw127
https://doi.org/10.1093/gerona/glw127...
. This remark was confirmed by a robust recent meta-analysis elucidating the influence of sleep disturbances on the incidence of dementia, highlighting the importance of regular sleep55 Shi L, Chen S-J, Ma M-Y, Bao Y-P, Han Y, Wang Y-M, et al. Sleep disturbances increase the risk of dementia: A systematic review and meta-analysis. Sleep Med Rev. 2018;40:4-16. https://doi.org/10.1016/j.smrv.2017.06.010
https://doi.org/10.1016/j.smrv.2017.06.0...
. Results of a prospective study of two cohorts indicate that mid-life shift work history, including nighttime work, was significantly associated with increased incidence of dementia in later life66 Bokenberger K, Sjölander A, Dahl Aslan AK, Karlsson IK, Åkerstedt T, Pedersen NL. Shift work and risk of incident dementia: a study of two population-based cohorts. Eur J Epidemiol. 2018;33(10):977-87. https://doi.org/10.1007/s10654-018-0430-8
https://doi.org/10.1007/s10654-018-0430-...
. Furthermore, higher dementia risk was associated with a long shift work history. In the past 10 years, new laboratory discoveries have shed light on the physiology of sleep, which may directly impact workers’ health.

A recent method for exploring and quantifying the extracellular space of the living brain (in rats) showed that deep sleep (natural or induced) increases cerebral interstitial fluid by 60%, resulting in a remarkable rise in the convective exchange between cerebrospinal fluid and interstitial fluid, which substantially increases the rate of β-amyloid protein clearance during sleep77 Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, et al. Sleep drives metabolite clearance from the adult brain. Science. 2013;342(6156):10.1126/science.1241224. https://doi.org/10.1126/science.1241224
https://doi.org/10.1126/science.1241224...
. This protein is linked to Alzheimer's disease pathology. This perivascular system (named glymphatic system) clears the brain of protein waste products, being active mainly during the deepest (stage 3) phase of the non-rapid eye movement (NREM) sleep, characterized by slow-wave electroencephalogram activity88 Rasmussen MK, Mestre H, Nedergaard M. The glymphatic pathway in neurological disorders. Lancet Neurol. 2018;17(11):1016-24. https://doi.org/10.1016/S1474-4422(18)30318-1
https://doi.org/10.1016/S1474-4422(18)30...
. Since this level of sleep tends to occur in the first half of the night, shift workers are at a higher risk for glymphatic disturbance.

Is it possible to reorganize the shift work? In modern society, more people work during “non-standard” working hours, including shift and night work. We can learn from experiences abroad. Following a growing body of evidence that children/teens have different sleep needs, hundreds of schools in developed countries have moved school start times to later hours. Now, results of a 4-year observational study carried out in a state-funded high school in England showed that changing to a 10:00 a.m. start time can significantly reduce illness and improve academic performance99 Kelley P, Lockley SW, Kelley J, Evans MD. Is 8:30 a.m. still too early to start school? A 10:00 a.m. school start time improves health and performance of students aged 13–16. Front Hum Neurosci. 2017;11:588. https://doi.org/10.3389/fnhum.2017.00588
https://doi.org/10.3389/fnhum.2017.00588...
.

Interventions to improve the health status and the working performance of healthcare professionals who undertake night shifts are of uttermost importance. Switching strict night shifts to rotating shifts may improve sleep disturbances1010 Thun E, Bjorvatn B, Åkerstedt T, Moen BE, Waage S, Molde H, et al. Trajectories of sleepiness and insomnia symptoms in Norwegian nurses with and without night work and rotational work. Chronobiol Int. 2016;33(5):480-9. https://doi.org/10.3109/07420528.2016.1148045
https://doi.org/10.3109/07420528.2016.11...
. Some integrated interventions focusing on changing individual lifestyle and working conditions have been tested1111 van Elk F, Robroek SJ, Smits-de Boer S, Kouwenhoven-Pasmooij TA, Burdorf A, Oude Hengel KM. Study design of PerfectFit@Night, a workplace health promotion program to improve sleep, fatigue, and recovery of night shift workers in the healthcare sector. BMC Public Health. 2022;22(1):779. https://doi.org/10.1186/s12889-022-13206-9
https://doi.org/10.1186/s12889-022-13206...
, but we need to go further. It is time to discuss how shift work suits in occupational medicine.

We need to understand the impact on the sleep quality from adjustments in work schedules, possibly by adding physiological data and cognitive/physical functioning tests into more comprehensive protocols of assessment. Would it be effective to introduce shorter night shifts of 4–6 h per night? Would it be favorable to reduce the workload performed at night? How about shorting the number of consecutive night shifts? How much recovery from a night shift would allow the glymphatic system to clean the brain?

Many questions remain unanswered, and researchers in mental and occupational health are invited to address these issues over the following years.

  • This study was conducted by the Geriatrics Center, Hospital Universitário de Brasília, Universidade de Brasília, Brasília, DF, Brazil.
  • Funding: Fundação de Apoio à Pesquisa do Distrito Federal, project 00193-00002602/2022-69, grant # 623/2022.

REFERENCES

  • 1
    Wright KP Jr, Bogan RK, Wyatt JK. Shift work and the assessment and management of shift work disorder (SWD). Sleep Med Rev. 2013;17(1):41-54. https://doi.org/10.1016/j.smrv.2012.02.002
    » https://doi.org/10.1016/j.smrv.2012.02.002
  • 2
    Jehan S, Zizi F, Pandi-Perumal SR, Myers KA, Auguste E, Jean-Louis G, et al. Shift work and sleep: medical implications and management. Sleep Med Disord. 2017;1(2):00008. PMID: 29517053
  • 3
    Vlasak T, Dujlovic T, Barth A. Neurocognitive impairment in night and shift workers: a meta-analysis of observational studies. Occup Environ Med. 2022;79(6):365-72. https://doi.org/10.1136/oemed-2021-107847
    » https://doi.org/10.1136/oemed-2021-107847
  • 4
    Bokenberger K, Ström P, Dahl Aslan AK, Johansson AL, Gatz M, Pedersen NL, et al. Association between sleep characteristics and incident dementia accounting for baseline cognitive status: a prospective population-based study. J Gerontol A Biol Sci Med Sci. 2017;72(1):134-9. https://doi.org/10.1093/gerona/glw127
    » https://doi.org/10.1093/gerona/glw127
  • 5
    Shi L, Chen S-J, Ma M-Y, Bao Y-P, Han Y, Wang Y-M, et al. Sleep disturbances increase the risk of dementia: A systematic review and meta-analysis. Sleep Med Rev. 2018;40:4-16. https://doi.org/10.1016/j.smrv.2017.06.010
    » https://doi.org/10.1016/j.smrv.2017.06.010
  • 6
    Bokenberger K, Sjölander A, Dahl Aslan AK, Karlsson IK, Åkerstedt T, Pedersen NL. Shift work and risk of incident dementia: a study of two population-based cohorts. Eur J Epidemiol. 2018;33(10):977-87. https://doi.org/10.1007/s10654-018-0430-8
    » https://doi.org/10.1007/s10654-018-0430-8
  • 7
    Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, et al. Sleep drives metabolite clearance from the adult brain. Science. 2013;342(6156):10.1126/science.1241224. https://doi.org/10.1126/science.1241224
    » https://doi.org/10.1126/science.1241224
  • 8
    Rasmussen MK, Mestre H, Nedergaard M. The glymphatic pathway in neurological disorders. Lancet Neurol. 2018;17(11):1016-24. https://doi.org/10.1016/S1474-4422(18)30318-1
    » https://doi.org/10.1016/S1474-4422(18)30318-1
  • 9
    Kelley P, Lockley SW, Kelley J, Evans MD. Is 8:30 a.m. still too early to start school? A 10:00 a.m. school start time improves health and performance of students aged 13–16. Front Hum Neurosci. 2017;11:588. https://doi.org/10.3389/fnhum.2017.00588
    » https://doi.org/10.3389/fnhum.2017.00588
  • 10
    Thun E, Bjorvatn B, Åkerstedt T, Moen BE, Waage S, Molde H, et al. Trajectories of sleepiness and insomnia symptoms in Norwegian nurses with and without night work and rotational work. Chronobiol Int. 2016;33(5):480-9. https://doi.org/10.3109/07420528.2016.1148045
    » https://doi.org/10.3109/07420528.2016.1148045
  • 11
    van Elk F, Robroek SJ, Smits-de Boer S, Kouwenhoven-Pasmooij TA, Burdorf A, Oude Hengel KM. Study design of PerfectFit@Night, a workplace health promotion program to improve sleep, fatigue, and recovery of night shift workers in the healthcare sector. BMC Public Health. 2022;22(1):779. https://doi.org/10.1186/s12889-022-13206-9
    » https://doi.org/10.1186/s12889-022-13206-9

Publication Dates

  • Publication in this collection
    05 May 2023
  • Date of issue
    2023

History

  • Received
    09 Sept 2022
  • Reviewed
    31 Oct 2022
  • Accepted
    03 Nov 2022
Academia Brasileira de Neurologia, Departamento de Neurologia Cognitiva e Envelhecimento R. Vergueiro, 1353 sl.1404 - Ed. Top Towers Offices, Torre Norte, São Paulo, SP, Brazil, CEP 04101-000, Tel.: +55 11 5084-9463 | +55 11 5083-3876 - São Paulo - SP - Brazil
E-mail: revistadementia@abneuro.org.br | demneuropsy@uol.com.br