We argue that willpower as well as its depletion may, in some circumstances, adversely impact on clinical decision‐making and patient care. This psychological phenomenon has been dubbed ego depletion in social psychology. Willpower and its depletion which is known as ‘ego depletion’ are well‐established and validated theoretical constructs in social psychology and have been studied across a range of experimental contexts. Willpower is closely related to the concept of self‐control, which refers to the ability to regulate one's own behaviour and actions in order to pursue and achieve either a short‐ or long‐term goal. We outline the clinical relevance of willpower and its depletion in relation to clinical case examples drawn from three of the authors' clinical experience with the view of developing a clinical‐research agenda for future research studies. We examine willpower and its depletion in the context of three clinical case examples, which include (i) doctor–patient interactions, (ii) willpower and its depletion in relation to challenging interpersonal interactions with clinical and non‐clinical work colleagues and (iii) willpower and its depletion in response to working within a challenging and unpredictable clinical environment. In contrast to the more widely recognised external resources (including space, staff allocations and night shifts), a greater understanding of how this important but under‐recognised internal resource can be depleted in response to a range of different factors within clinical settings has the potential to inform and improve patient care through a renewed focus on the developing interdisciplinary clinical studies which draw upon contemporary findings from social psychology. Future work aimed at developing evidence‐based interventions to help mitigate the negative impact of impaired self‐control and decision fatigue within healthcare systems may in turn lead to improved patient care as well as more effective healthcare service and delivery.

Sirtuins (SIRTs), nicotine adenine dinucleotide (+)-dependent histone deacetylases, have emerged as critical regulators in many signalling pathways involved in a wide range of biological processes. Currently, seven mammalian SIRTs have been characterized and are found across a number of cellular compartments. There has been considerable interest in the role of SIRTs in the brain due to their role in a plethora of metabolic- and age-related diseases, including their involvement in learning and memory function in physiological and pathophysiological conditions. Although cognitive function declines over the course of healthy ageing, neurological disorders including Alzheimer’s disease (AD) can be associated with progressive cognitive impairments. This review aimed to report and integrate recent advances in the understanding of the role of SIRTs in cognitive function and dysfunction in the context of AD. We have also reviewed the use of selective and/or natural SIRT activators as potential therapeutic agents and/or adjuvants for AD.

Epilepsy is a neurological disorder affecting approximately 50 million people globally and is characterised by recurrent, unprovoked seizures resulting from abnormal, excessive synchronised firing of neurons. Developing new therapeutic targets and biomarkers is key to improving the diagnosis, treatment, and management. This scoping review examines the current literature on the preclinical and clinical applications of dietary interventions that target the neurolipidome in epilepsy. Specifically, it investigates the role of lipids in the underlying pathogenesis of epilepsy. A comprehensive search of databases was conducted to identify peer-reviewed articles published in the past ten years. Original research articles focusing on both adult and paediatric epilepsy and disrupted lipid metabolism were included, resulting in a total of 101 papers. Our review identified several key lipids implicated in the pathogenesis of epilepsy, including sphingolipids, free fatty acids, endocannabinoids, cholesterol, triglycerides, and phospholipids, and also explores the complex interactions between these lipids and their roles in the disease process. Furthermore, our study highlighted that the Ketogenic Diet (KD) and Modified Atkins Diet (MAD) have proven effective adjunctive or alternative treatments in paediatric and adult populations, improving patient quality of life and reducing seizure frequency. Additionally, treatment with lipid-based supplements, such as eicosapentaenoic acid, docosahexaenoic acid, fish oil, and cannabidiol, has been associated with a reduction in seizure rates in patients with drug-resistant epilepsy. In summary, findings from this study indicate that KD and MAD lipid-based supplements are effective for managing epilepsy in paediatrics, adults, and animal models. However, further research is necessary to elucidate the pathophysiological mechanisms underlying the role of lipids in the development and progression of epilepsy.

Background: Ultra-processed foods (UPFs) account for approximately 38% of the adult diet, corresponding with a global increase in the prevalence of mental illnesses. Understanding the relationship between UPF consumption and mental health is crucial for public health and clinical practice. Objectives: To uncover the association between consumption of ultra-processed food (UPF), dysregulated lipid metabolism, and increased risk of mental illnesses, including depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), eating disorders (ED), and food addiction (FA). In addition, this review explores the potential biological and behavioral mechanisms that may underlie these associations for each disorder. Methods: Following the PRISMA extension for scoping reviews guideline, a comprehensive search was conducted across PubMed, Web of Science, and EMBASE databases. The retrieved records, screened using Covidence, included English-language studies published between 2020 and 2025 that involved participants without significant comorbidities. Relevant data on associations and proposed mechanisms were extracted and synthesized using a narrative approach. Results: UPF consumption was associated with dysregulated lipid metabolism and increased risk of Anxiety, Depression, ADHD, Autism, ED, and FA. Dose-dependent increases in risk were identified in all mental illnesses except for autism. Proposed mechanisms for all these increased risks included systemic low-grade inflammation, alterations in neuronal signaling, particularly dopamine and serotonin signaling pathways, and the influence of UPF additives on neurochemical regulation. Conclusion: There is a strong association between UPF consumption, disrupted lipid metabolism and increased risk of mental disorder in populations without significant comorbidities. Diets rich in minimally processed foods appear protective. The findings support the potential of public health initiatives aimed at reducing UPF consumption to mitigate the mental health burden. Future studies should focus on mechanistic pathways, UPF and minimally processed food consumption patterns to provide evidence for targeted dietary and policy interventions that improve health outcomes.

Delirium is a complex medical condition marked by acute episodes of cognitive dysfunction and behavioral disturbances, with a multifaceted etiology and challenging management across various clinical settings. Older adults, particularly in postoperative contexts, are at increased risk of developing delirium. Despite extensive research, a single underlying pathophysiological mechanism for delirium remains elusive. However, emerging evidence suggests a correlation between lipid dysregulation and delirium development in elderly patients, especially in postoperative settings. This connection has led to proposed treatments targeting dyslipidemia and associated neuroinflammatory effects in acute-phase delirium. This review aims to synthesize current literature on the relationship between lipid dysregulation and delirium in older adults, highlighting the need for further research into specific neurolipidome constituents and age-related lipid profile changes, potentially uncovering novel therapeutic strategies for delirium.

Multiple Sclerosis (MS) is a heterogeneous neuroinflammatory disease with complex aetiology and diverse clinical presentations, often accompanied by neurodegenerative pathology. While current therapies primarily focus on immunomodulation, emerging evidence underscores a critical bidirectional interplay between mitochondrial dysfunction and lipid dysregulation in driving MS progression. Understanding this metabolic-mitochondrial axis may reveal novel therapeutic opportunities beyond immune modulation. This scoping review systematically maps recent literature (2015-2025) to delineate the mechanistic connections between mitochondrial dysfunction and lipid dysregulation in MS, identify current knowledge gaps, and highlight translational opportunities for targeted intervention. A systematic search of PubMed, Embase, and Scopus was conducted in 2025 following PRISMA-ScR guidelines. Thirty-six eligible studies examining mitochondrial-lipid interactions in human MS and preclinical models were included and synthesised thematically. Evidence converges on a self-reinforcing pathological cycle in MS, where dysregulated lipid metabolism impairs mitochondrial integrity, amplifying reactive oxygen species generation, energy failure, and further lipid disruption. This cascade contributes to oligodendrocyte injury, demyelination, ferroptosis, and axonal degeneration. Importantly, therapeutic strategies that restore lipid-mitochondrial homeostasis, such as mitochondrial antioxidants, lipid modulators, and metabolically active immunotherapies, demonstrate promising neuroprotective effects in preclinical studies. The evidence supports a model in which the bidirectional feedback loop between mitochondrial dysfunction and lipid dysregulation represents a significant mechanism contributing to neurodegeneration in MS. Clinically, these insights highlight opportunities for earlier diagnosis and more personalised disease management through the integration of lipid-based biomarkers into patient monitoring and treatment selection. Targeting this metabolic axis holds significant promise for developing next-generation disease-modifying therapies to slow disease progression, enhance neuroprotection, and improve functional recovery across different MS subtypes.