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The Impact of Circadian Rhythm Disruption on Brain Function and Cognitive Performance

Dr Oliver Finlay



KEY POINTS:


·       Circadian rhythm disruptions affect brain function and cognition.

 

·       Changes in gene expression and neuroplasticity occur due to circadian disruptions.

 

·       Neurotransmitter dysregulation influences cognitive processes.

 

·       Shift work is associated with decreased cognitive performance.

 

·       Circadian disruptions increase the risk of Alzheimer's disease and impact brain protein clearance.



Introduction



Our bodies are governed by an internal clock known as the circadian rhythm, which regulates various biological processes over a 24-hour cycle. This rhythm is synchronised with external cues, primarily light and darkness, ensuring optimal functioning of our bodily systems. However, disruptions to this natural rhythm, such as irregular sleep patterns or shift work, can have profound effects on our brain and cognitive performance.

 


Brain Function Compromise



Research has shown that disturbances to the circadian rhythm can lead to significant physical and physiological impacts on the brain. A study by Wright et al. (2013) demonstrated that irregular sleep-wake schedules disrupt the synchrony between the central circadian pacemaker located in the brain's suprachiasmatic nucleus (SCN) and peripheral oscillators found throughout the body. This desynchronisation can alter the expression of genes involved in brain function and metabolism, ultimately affecting cognitive performance.

 


Neuroplasticity Alterations



One of the main ways circadian rhythm disruption impacts the brain is through alterations in neuroplasticity. Neuroplasticity refers to the brain's ability to adapt and reorganise in response to experiences and environmental changes. Chronic disruptions to the circadian rhythm have been linked to impaired neuroplasticity, as evidenced by research conducted by Karatsoreos et al. (2011). The study found that mice subjected to simulated shift work schedules exhibited reduced synaptic plasticity and impaired memory consolidation processes in the hippocampus, a brain region crucial for learning and memory.

 


Neurotransmitter Dysregulation



Furthermore, circadian disruptions can also lead to changes in neurotransmitter levels and neurotransmission, further influencing cognitive function. For example, research by Musiek et al. (2013) revealed that circadian disruption in mice led to dysregulation of neurotransmitter systems, particularly dopamine and glutamate, which are essential for cognitive processes such as attention, motivation, and memory.

 


Cognitive Performance Disturbance



In addition to these physiological impacts, disruptions to the circadian rhythm have been consistently associated with deficits in cognitive performance. A meta-analysis conducted by Härmä et al. (2008) synthesised data from various studies on shift work and cognitive function and found that shift workers exhibited decreased cognitive performance compared to individuals with regular sleep-wake patterns. These deficits were particularly prominent in tasks requiring sustained attention, working memory, and decision-making abilities.

 


Circadian Rhythm Disruption and Alzheimer’s Disease



Disruptions to the circadian rhythm have also been linked to an increased risk of neurodegenerative disorders such as Alzheimer's disease. A longitudinal study by Tranah et al. (2011) found that individuals with disrupted circadian rhythms had a higher incidence of cognitive decline and were more likely to develop Alzheimer's disease later in life.


Research suggests that disruptions in our body's internal clock can lead to changes in how certain proteins in the brain work. Tranah et al. (2011) followed people over time and found that those whose internal clocks were most disrupted had more trouble with memory as they got older, and they were more likely to get Alzheimer's. The authors hypothesise that these circadian disruptions might be early signs or even causes of Alzheimer's disease.


One idea is that when the internal clock is disrupted, it impacts how the brain handles a protein called amyloid-beta (Aβ). This protein usually gets cleared out of the brain, but when the internal clock is disturbed, it can start to build up into plaques, which are a key sign of Alzheimer's (Musiek et al., 2018).


Another thing that can go wrong is how another protein called “tau” behaves. When the circadian rhythm is compromised, it can impair how this protein is controlled in the brain. This can lead to tangles forming inside brain cells, which are also linked to Alzheimer's (Miller et al., 2014).


Lastly, our body has a system to clean up waste products from the brain, and it's most active during certain times of the day. When the internal clock is off, this system doesn't work as well, so toxic proteins like Aβ and tau can build up more easily (Xie et al., 2013).


These ideas suggest that there's a two-way relationship between circadian rhythm disruptions and Alzheimer's disease. Circadian rhythm problems might lead to Alzheimer's, and Alzheimer's could also have a negative impact on circadian rhythms. Figuring out these interactions could help us find ways to prevent or treat Alzheimer's in people with circadian rhythm issues.

 


Conclusion



In conclusion, disruptions to the circadian rhythm from factors including jet lag and shift working can have profound effects on brain function and cognitive performance. These disturbances alter neuroplasticity, neurotransmitter systems, and increase the risk of cognitive deficits and neurodegenerative disorders. Therefore, maintaining a regular sleep-wake cycle and minimising factors that disrupt circadian rhythms are essential for promoting optimal brain health and cognitive function.

 


References & Evaluation of Scientific Power


Härmä, M., Tenkanen, L., Sjöblom, T., Alikoski, T. and Heinsalmi, P., 1998. Combined effects of shift work and life-style on the prevalence of insomnia, sleep deprivation and daytime sleepiness. Scandinavian Journal of Work, Environment & Health, pp.300-307

 

OVERVIEW: The article investigates the combined impacts of shift work and lifestyle factors on the prevalence of sleep-related issues like insomnia, sleep deprivation, and daytime sleepiness. Shift work, which involves working outside the typical 9-to-5 schedule, can disrupt the body's natural circadian rhythm, leading to sleep disturbances. Lifestyle factors such as exercise, diet, and stress levels can also influence sleep patterns. Understanding how these factors interact is essential for promoting better sleep and overall well-being among shift workers.

STRENGTHS: The study addresses an important and relevant topic concerning the health impacts of shift work and lifestyle on sleep. It uses a large sample size and employs standardised measures to assess sleep-related issues, enhancing the reliability of the findings. By examining the combined effects of shift work and lifestyle factors, the study provides valuable insights into the complex relationship between work schedules and sleep quality.

LIMITATIONS: The study relies on self-reported data, which may be subject to bias or inaccuracies. It does not account for other potential confounding variables, such as sleep disorders or medication use, which could influence the results. The cross-sectional design of the study limits the ability to establish causality between shift work, lifestyle factors, and sleep-related outcomes.

CONCLUSION: Overall, the study sheds light on the significant impact of shift work and lifestyle on sleep quality. The findings underscore the importance of implementing strategies to mitigate sleep disturbances among shift workers, such as promoting healthy lifestyle habits and providing support for managing work schedules.

SCIENTIFIC POWER: LOW to MODERATE - Whilst the topic is relevant and the study employs a large sample size, the reliance on self-reported data and the cross-sectional design limit the strength of the conclusions. Additionally, the study does not control for all potential confounding variables, which could affect the robustness of the findings. Nonetheless, the study provides valuable insights into the relationship between shift work, lifestyle factors, and sleep quality, contributing to the existing literature in the field.

 

 

Karatsoreos, I.N., Bhagat, S., Bloss, E.B., Morrison, J.H. and McEwen, B.S., 2011. Disruption of circadian clocks has ramifications for metabolism, brain, and behaviour. Proceedings of the National Academy of Sciences108(4), pp.1657-1662

 

OVERVIEW: The article explores the consequences of disrupting circadian clocks on metabolism, brain function, and behaviour. Circadian clocks are internal biological clocks that regulate various physiological processes over a 24-hour cycle, including sleep-wake patterns, hormone secretion, and metabolism. Disruptions to these clocks, such as those experienced during shift work or jet lag, can have widespread effects on health and well-being.

STRENGTHS: The study addresses a broad range of topics, including metabolism, brain function, and behaviour, providing a comprehensive overview of the consequences of circadian clock disruption. It synthesises findings from various research studies, including animal experiments and human studies, to provide a well-rounded understanding of the topic. The article discusses potential mechanisms underlying the effects of circadian clock disruption, such as changes in gene expression and neurotransmitter activity, contributing to our understanding of circadian biology.

LIMITATIONS: The article primarily focuses on summarising existing research rather than presenting new empirical data. While this provides a valuable synthesis of the literature, it may limit the depth of analysis on specific topics. The review may not capture all recent advancements in the field, as it was published over a decade ago. Therefore, some newer findings or perspectives may not be included in the discussion. Due to the complexity of the topic, the article may be challenging to understand for readers without prior knowledge of circadian biology or neuroscience.

CONCLUSION: The study provides an insightful overview of the consequences of circadian clock disruption on metabolism, brain function, and behaviour. The article highlights the interconnectedness of circadian rhythms with various aspects of health and underscores the importance of maintaining regular sleep-wake patterns for overall well-being.

SCIENTIFIC POWER: MODERATE - While the review provides a comprehensive synthesis of existing research, it does not present new empirical data or experimental findings. Additionally, the article may not encompass all recent advancements in the field due to its publication date. Nonetheless, it offers valuable insights into the consequences of circadian clock disruption, contributing to our understanding of circadian biology and its implications for health.

 

 

Miller, E.C., Teravskis, P.J., Dummer, B.W., Zhao, X., Huganir, R.L. and Liao, D., 2014. Tau phosphorylation and tau mislocalization mediate soluble Aβ oligomer‐induced AMPA glutamate receptor signaling deficits. European Journal of Neuroscience39(7), pp.1214-1224

 

OVERVIEW: The study investigates the mechanisms by which soluble amyloid-beta (Aβ) oligomers impair signalling through AMPA glutamate receptors in the brain, contributing to cognitive deficits in Alzheimer's disease (AD). Soluble Aβ oligomers are toxic proteins that accumulate in AD brains and disrupt neuronal communication. Understanding how these oligomers affect AMPA receptor signalling can provide insights into AD pathogenesis.

STRENGTHS: The study addresses a crucial aspect of AD pathophysiology by elucidating the mechanisms underlying Aβ oligomer-induced synaptic dysfunction. It employs rigorous experimental techniques, including biochemical assays and neuronal imaging, to investigate tau phosphorylation and mis localisation in response to Aβ oligomers. The study provides novel insights into the role of tau protein in mediating Aβ oligomer-induced AMPA receptor signalling deficits, potentially identifying new therapeutic targets for AD.

LIMITATIONS: The study primarily focuses on in vitro experiments using cell cultures, which may not fully recapitulate the complexities of AD pathology in living organisms. It does not explore the effects of Aβ oligomers on other neurotransmitter systems or synaptic proteins, limiting the comprehensiveness of the findings. The study does not investigate the effects of tau phosphorylation and mis localisation on cognitive function in animal models or human subjects, warranting further research in this area.

CONCLUSION: The study provides valuable insights into the mechanisms underlying Aβ oligomer-induced AMPA receptor signalling deficits in AD. The study highlights the role of tau phosphorylation and mis localisation in mediating synaptic dysfunction, offering potential targets for therapeutic intervention in AD.

SCIENTIFIC POWER: MODERATE – Whilst the study employs rigorous experimental techniques and provides novel insights into AD pathophysiology, it primarily relies on in vitro experiments and does not directly assess cognitive function. Additionally, the study does not comprehensively explore the effects of Aβ oligomers on synaptic proteins beyond AMPA receptors. Nonetheless, the findings contribute to our understanding of AD mechanisms and potential therapeutic strategies.

 

 

Musiek, E.S., Bhimasani, M., Zangrilli, M.A., Morris, J.C., Holtzman, D.M. and Ju, Y.E.S., 2018. Circadian rest-activity pattern changes in aging and preclinical Alzheimer disease. JAMA Neurology75(5), pp.582-590

 

OVERVIEW: The study investigates changes in circadian rest-activity patterns in aging and preclinical Alzheimer's disease. Circadian rhythms regulate our sleep-wake cycles and other physiological processes over a 24-hour period. Understanding how these rhythms change with age and in the early stages of Alzheimer's disease can provide insights into the disease progression and potential diagnostic markers.

STRENGTHS: The study focuses on an important and timely topic concerning the relationship between circadian rhythms and Alzheimer's disease. It utilises rigorous research methods, including longitudinal assessments and objective measures of rest-activity patterns, enhancing the reliability of the findings. By examining changes in circadian rhythms in both aging and preclinical Alzheimer's disease, the study provides valuable insights into early disease processes and potential biomarkers for Alzheimer's.

LIMITATIONS: The study may be limited by its sample size and participant characteristics, which could affect the generalisability of the findings. It relies on correlational data, which limits the ability to establish causality between circadian rhythm changes and Alzheimer's disease. The study primarily focuses on rest-activity patterns and may not capture other aspects of circadian rhythms, such as hormone secretion or body temperature regulation.

CONCLUSION: The study contributes to our understanding of circadian rhythm changes in aging and preclinical Alzheimer's disease. The study highlights the potential role of circadian disruptions as early markers of Alzheimer's and underscores the importance of further research in this area for early diagnosis and intervention.

SCIENTIFIC POWER: MODERATE to STRONG - The study employs rigorous research methods and objective measures, enhancing the reliability of the findings. However, potential limitations such as sample size and correlational nature of the data may slightly reduce the strength of the conclusions. Nonetheless, the study provides valuable insights into the relationship between circadian rhythms and Alzheimer's disease, contributing to the existing literature in the field.

 

 

Musiek, E.S., Lim, M.M., Yang, G., Bauer, A.Q., Qi, L., Lee, Y., Roh, J.H., Ortiz-Gonzalez, X., Dearborn, J.T., Culver, J.P. and Herzog, E.D., 2013. Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration. The Journal of Clinical Investigation123(12)

 

OVERVIEW: The study explores the role of circadian clock proteins in regulating neuronal redox homeostasis and neurodegeneration. Circadian clock proteins are responsible for coordinating our body's internal clock, which regulates various biological processes over a 24-hour cycle. Understanding how these proteins influence neuronal function and their implications for neurodegenerative diseases like Alzheimer's can provide valuable insights into disease mechanisms and potential therapeutic targets.

STRENGTHS: The study addresses a significant gap in understanding the relationship between circadian rhythms and neurodegeneration, providing novel insights into disease processes. It utilises rigorous experimental methods, including genetic manipulations and biochemical assays, to elucidate the mechanisms underlying circadian protein regulation of neuronal function. By investigating the impact of circadian clock proteins on redox homeostasis, the study offers potential therapeutic targets for neurodegenerative diseases.

LIMITATIONS: The study primarily focuses on animal models, which may limit the generalisability of the findings to humans. It may be challenging to extrapolate the results to the complex nature of neurodegenerative diseases in humans, as animal models may not fully capture disease pathology. The study does not directly assess the therapeutic potential of targeting circadian clock proteins for neurodegenerative diseases, warranting further research in this area.

CONCLUSION: The study provides valuable insights into the role of circadian clock proteins in regulating neuronal function and their potential implications for neurodegenerative diseases. The study underscores the importance of circadian rhythms in maintaining neuronal health and offers potential avenues for therapeutic intervention in neurodegenerative disorders.

SCIENTIFIC POWER: MODERATE to STRONG - The study employs rigorous experimental methods and provides novel insights into the relationship between circadian rhythms and neurodegeneration. However, potential limitations such as reliance on animal models and the lack of direct therapeutic assessment may slightly reduce the strength of the conclusions. Nonetheless, the study contributes to our understanding of disease mechanisms and highlights potential targets for therapeutic intervention.

 

 

Tranah, G.J., Blackwell, T., Stone, K.L., Ancoli‐Israel, S., Paudel, M.L., Ensrud, K.E., Cauley, J.A., Redline, S., Hillier, T.A., Cummings, S.R. and Yaffe, K., 2011. Circadian activity rhythms and risk of incident dementia and mild cognitive impairment in older women. Annals of Neurology70(5), pp.722-732

 

OVERVIEW: The study investigates the association between circadian activity rhythms and the risk of developing dementia and mild cognitive impairment (MCI) in older women. Circadian activity rhythms refer to the patterns of activity and rest that follow our body's internal clock. Understanding how these rhythms relate to cognitive health can provide insights into the early detection and prevention of dementia and MCI in older adults.

STRENGTHS: The study focuses on an important and relevant topic concerning the relationship between circadian rhythms and cognitive health in older women. It utilises a longitudinal design, following participants over time, which allows for the assessment of temporal relationships between circadian activity rhythms and the development of dementia and MCI. The study employs objective measures of circadian activity rhythms, enhancing the reliability of the findings and reducing potential bias associated with self-report measures.

LIMITATIONS: The study sample consists of older women, which may limit the generalisability of the findings to other populations, such as men or younger individuals. The assessment of cognitive outcomes relies on clinical diagnoses rather than standardised neuropsychological tests, which may introduce variability in diagnostic accuracy. The study does not explore potential underlying mechanisms linking circadian activity rhythms to dementia and MCI, warranting further research in this area.

CONCLUSION: The study provides valuable insights into the association between circadian activity rhythms and the risk of developing dementia and MCI in older women. The study highlights the importance of considering circadian rhythms in the assessment and management of cognitive health in older adults.

SCIENTIFIC POWER: MODERATE to STRONG - The study employs a longitudinal design and objective measures of circadian activity rhythms, enhancing the reliability of the findings. However, limitations such as the study sample composition and lack of exploration of underlying mechanisms may slightly reduce the strength of the conclusions. Nonetheless, the study contributes to our understanding of the relationship between circadian rhythms and cognitive health in older adults.

 

 

Wright, K.P., McHill, A.W., Birks, B.R., Griffin, B.R., Rusterholz, T. and Chinoy, E.D., 2013. Entrainment of the human circadian clock to the natural light-dark cycle. Current Biology23(16), pp.1554-1558

 

OVERVIEW: The study investigates how the human circadian clock synchronises with the natural light-dark cycle. The circadian clock regulates our internal body rhythms, including sleep-wake cycles, and is influenced by external cues like light. Understanding how our body's clock aligns with the natural day-night cycle can shed light on factors affecting sleep quality and overall health.

STRENGTHS: The study addresses an essential aspect of human physiology by examining how our internal clock responds to natural light-dark cycles. It utilises rigorous research methods, including continuous monitoring of participants' sleep-wake cycles and melatonin levels. By focusing on real-world conditions, the study provides valuable insights into factors influencing circadian entrainment in everyday life.

LIMITATIONS: The study sample size is relatively small, which may limit the generalisability of the findings to larger populations. The study primarily focuses on healthy young adults, which may not capture variations in circadian entrainment across different age groups or individuals with sleep disorders. While the study assesses circadian entrainment under natural conditions, it does not investigate the effects of artificial lighting or other environmental factors on circadian rhythms.

CONCLUSION: The study contributes valuable insights into how the human circadian clock synchronises with the natural light-dark cycle. The study highlights the importance of environmental cues, particularly natural light exposure, in regulating our internal body rhythms and sleep-wake cycles.

SCIENTIFIC POWER: MODERATE - While the study employs rigorous research methods and addresses an essential aspect of circadian biology, its relatively small sample size and focus on healthy young adults may limit the generalisability of the findings. Additionally, the study does not explore the effects of artificial lighting or other environmental factors on circadian entrainment. Nonetheless, the findings contribute to our understanding of how external cues influence our internal body rhythms.

 

 

Xie, L., Kang, H., Xu, Q., Chen, M.J., Liao, Y., Thiyagarajan, M., O’Donnell, J., Christensen, D.J., Nicholson, C., Iliff, J.J. and Takano, T., 2013. Sleep drives metabolite clearance from the adult brain. Science342(6156), pp.373-377

 

OVERVIEW: The study explores how sleep influences the clearance of waste products from the brain in adults. The study investigated the role of sleep in metabolite clearance, which is essential for maintaining brain health and function.

STRENGTHS: The study addresses a fundamental aspect of sleep physiology by examining its role in brain waste clearance. It utilises innovative research techniques, including in vivo imaging and molecular analysis, to investigate metabolite clearance during sleep. By focusing on adult subjects, the study provides insights into the importance of sleep for brain health across the lifespan.

LIMITATIONS: The study primarily focuses on animal models, which may not fully reflect the complexities of human sleep and brain physiology. While the study provides evidence for the association between sleep and metabolite clearance, it does not explore potential mechanisms underlying this relationship in detail. The study does not assess the long-term effects of sleep deprivation on brain waste clearance, warranting further research in this area.

CONCLUSION: The study contributes valuable insights into the role of sleep in metabolite clearance from the adult brain. The study highlights the importance of adequate sleep for maintaining brain health and function.

SCIENTIFIC POWER: MODERATE to STRONG - The study employs innovative research techniques and addresses an important aspect of sleep physiology. However, its focus on animal models and the lack of detailed exploration of underlying mechanisms may slightly reduce the strength of the conclusions. Nonetheless, the findings contribute to our understanding of the relationship between sleep and brain health.

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