Perspectives

Here, the authors offer their perspective on the roles of cell states in sustaining health and counteracting disease, and examine how cellular ageing might set the stage for pathological fate loss and neurodegeneration.

In this Perspective, Owolabi et al. propose strategies to improve brain health and address the growing global burden of neurological disorders. They present a new framework — the neurological quadrangle — which aims to provide equitable and effective surveillance, prevention, acute care and rehabilitation of neurological disorders globally.

In this Perspective, Edwards and colleagues present their opinion that functional neurological disorder is categorically different from feigning and malingering. They discuss clinical, epidemiological and experimental evidence in support of this view.

In this Perspective article, Lipkin et al. consider the contribution of cohort studies to our understanding of autism spectrum disorders (ASDs) and debate the promise and potential challenges of such studies for dissecting the causes of ASDs and developing interventional strategies.

Despite substantial research advances, treatment of neuropathic pain remains inadequate and responses to treatment are highly variable. In this Perspective, the authors argue that rational stratification of patients with neuropathic pain will aid identification of subgroups of patients who will benefit most from a given treatment.

In this Perspective, the authors discuss the importance of performing well-designed observational studies on Alzheimer disease. They highlight novel approaches to enhance causal inference and discuss ways in which observational data can provide a bridge between preclinical findings and clinical trials.

Following successful clinical trials of a gene therapy for Leber hereditary optic neuropathy, Pitceathly and colleagues discuss progress towards genetic therapies for other primary mitochondrial diseases. They highlight advances in DNA editing technologies and offer their view on obstacles to clinical application.

In this Perspective article, the authors outline how studying multiple sclerosis (MS) genetics in ancestrally diverse populations is likely to yield insights that could benefit individuals with MS from all ancestral groups.

In this Perspective, Fiorio et al. discuss the relationship between functional neurological disorder and placebo and nocebo effects, with the aim of providing insights into the pathogenesis of the disorder and identifying potential therapeutic targets.

Numerous studies have attempted to identify pathogenic autoantibodies in people with multiple sclerosis (MS), but their results are conflicting. In this Perspective, the authors explore the available evidence and provide their own opinions on a possible role for autoantibodies in MS.

In this Perspective, the authors present their vision for a closed-loop system for automatic symptom monitoring and levodopa administration in individuals with Parkinson disease. The system would capitalize on the ongoing advances in wearable sensor technology, drug delivery systems and machine learning.

Many episodes of status epilepticus do not respond to first-line treatment with benzodiazepines. In this Perspective, Richard Burman and colleagues discuss seizure-induced alterations to the sensitivity of the GABA receptor to benzodiazepines, presenting these changes as a possible mechanism of treatment resistance.

In this Perspectives article, David Fischer and colleagues present a stepwise conceptual framework for neuroprognostication after severe brain injury, with the aim of providing structure and guidance to supplement clinical judgement and direct future investigation.

This Perspective highlights the importance of integrating cultural factors into dementia research and care. Focusing on minoritized groups in the USA, the authors explore the effects of culture on clinical evaluation, dementia risk, research and study recruitment, and caregiving practices.

Traditionally, CNS diseases have been classified into early-onset neurodevelopmental disorders and late-onset neurodegenerative disorders. However, as this article highlights, we now recognize that developmental and neurodegenerative disorders can involve shared mechanisms, with some classic neurodegenerative diseases also having a neurodevelopmental component.

In this Perspective, Barnes introduces three key obstacles to progress in our understanding of racial differences in Alzheimer disease and highlights evidence-informed strategies that can move the field forward.

Here, the authors summarize the evidence concerning the neurological health of individuals affected by the 11 September 2001 terrorist attacks and present the outcome of a meeting convened by the US National Institute for Occupational Safety and Health that aimed to generate recommendations for future research in this population.

To date, all phase III trials of β-site amyloid precursor protein (APP)-cleaving enzyme (BACE) inhibitors for Alzheimer disease were either discontinued or produced negative results. Here the authors present their opinion that BACE inhibitors still hold promise as a preventative therapy for Alzheimer disease and outline a series of experiments to inform future trials.

The FDA recently granted accelerated approval to aducanumab for the treatment of Alzheimer disease. Here, the authors reflect on the events that led to this controversial approval and consider whether any lessons can be learned for the field.

The AT(N) system is a classification scheme based on biomarkers that reflect the core pathophysiological features of Alzheimer disease. This Perspective outlines the conceptual framework and clinical importance of the AT(N) system and considers its potential expansion to incorporate biomarkers for additional pathophysiological mechanisms.