Reviews & Analysis

Twenty years after UK Biobank was established, the incidence of dementia among participants is set to rise rapidly. In this Perspective, Matthews et al. highlight how UK Biobank has advanced dementia research in its first 20 years and consider how future developments will leverage increasing incidence to further advance understanding of dementias.

Delirium presents a major challenge in intensive care and postoperative settings; however, the pathophysiology is poorly understood. In this Perspective, Nedergaard and colleagues examine the evidence for impaired glymphatic flow as a central mechanism in the development of delirium and discuss potential strategies to mitigate delirium risk.

Spreading depression is a slowly propagating wave of mass depolarization that successively engulfs contiguous brain regions, causing transient neuronal hyperexcitability at its leading edge, followed by complete but reversible neuronal silence lasting minutes. Here, the authors present an evidence-based view of spreading depression as a probable cause of characteristic neurological signs and symptoms in numerous neurological conditions.

Low-income and middle-income countries and other under-represented populations remain largely excluded from Parkinson disease research despite the growing disease burden. Here the authors detail diversity gaps across Parkinson disease research and outline priority actions to address them.

Multiple sclerosis is among the most common causes of disability in the young and its prevention is a feasible, albeit ambitious, goal. In this Perspective, Dobson et al. discuss the challenges in developing and testing preventive interventions in MS and propose strategies and solutions.

Advances in biomarkers, blood tests and disease-modifying therapies have created a credible path to clinical prevention of Alzheimer disease (AD). In this Perspective, the authors discuss promising approaches to the prevention of AD and highlight strategic gaps.

This Perspective centres on alterations in the fatty acid-ome as the critical feature of lipid aberration in α-synucleinopathies, specifically Parkinson disease. Here, the authors explain the biological and genetic basis for their hypothesis, with an emphasis on the transient binding of α-synuclein to fatty acids of various lipids.

Deep brain stimulation (DBS) is a highly effective treatment option for movement disorders and is also being explored for other brain disorders. This Perspective proposes a unified framework, termed adaptive circuit targeting, which combines adaptive and connectomic DBS to enable decoding of symptom severity from brain signals and activation of relevant symptom-response circuits.

Earlier this year, the Nav1.8 channel inhibitor suzetrigine became the first new pain therapeutic to be approved in 20 years. Here, Waxman et al. discuss the challenges of improving Nav1.8-targeted relief for acute pain and the translation to chronic pain.

This Perspective article explores the efficacy of multimodal lifestyle interventions to tackle the rising incidence of dementia in low- and middle-income countries. The authors discuss a contextual adaptation of the Finnish FINGER trial, Africa-FINGERS, which is pioneering a culturally relevant, multidomain approach to dementia risk reduction for African settings.

Racial and ethnic disparities in MS susceptibility and outcomes are often attributed to immutable factors such as genetic ancestry. In this Perspective, however, the authors argue that structural racism can lead to biological changes by shaping environmental exposures and lived experiences — a phenomenon termed ‘embodiment’.

Genetic studies in Africa can provide a unique window into hereditary neurological diseases (HNDs). This Review highlights the benefits and challenges of conducting genetic research in Africa and summarizes the insights into HNDs gained from previous studies on the continent.

The development of α-synuclein biomarkers has raised debate as to whether Parkinson disease dementia and dementia with Lewy bodies should fall under a single biological diagnosis. Here the authors discuss the similarities and differences in symptoms, neuropathology and biomarkers of the two dementias, highlighting potential important divergent biological mechanisms.

In this Perspective, the authors provide a detailed description of rare autoimmune encephalitic conditions that present with recurrent seizures that are resistant to immunotherapy, grouped under the term autoimmune encephalitis-associated epilepsy. The article considers the clinical characteristics and pathophysiological mechanisms of these conditions, alongside current knowledge of treatment and outcomes.

Autoimmunity in multiple sclerosis (MS) is generally considered to be directed against components of myelin or oligodendrocytes. However, this Perspective argues that an immune attack on the ion and water homeostasis machinery in astrocytic endfeet is the primary event in MS and that myelin damage results from astrocyte dysfunction.

Evidence suggests that anthropogenic climate change is accelerating, with serious consequences for human health. This Perspective explores how the effects of climate change, such as extreme temperatures, altered weather patterns and increased air pollution, interact with the brain, and discusses how neurologists can respond constructively to the climate crisis.

The importance of active involvement of people living with diseases in various aspects of medicine, including disease management and follow-up, regulatory issues, health advocacy and clinical research, is increasingly recognized. This Perspective reviews the current status of patient involvement in neurological and other medical research, highlighting the role of patient experts.

Evidence for the effects of sex hormones on inflammation, myelination and neurodegeneration has implications for both cisgender and gender-diverse individuals with multiple sclerosis. Here, the authors summarize what is known about the effects of endogenous and exogenous sex hormones, and they highlight the need for future research inclusive of gender-diverse individuals.

In this Perspective, the authors present the Digitized Memory Clinic, a new framework for the diagnostic pathway of neurodegenerative dementias that incorporates digital health technologies with currently available assessment tools, such as fluid and imaging biomarkers, in an interplay with the physician.

In this Perspective, the authors discuss how our understanding of coeliac disease could provide insights into the mechanisms of multiple sclerosis, the involvement of Epstein–Barr virus and the possibility of antiviral treatment against the virus as a therapy for multiple sclerosis.