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[Personal View] The temporal order of genetic, environmental, and pathological risk factors in Parkinson's disease: paving the way to prevention

Genetics research in Parkinson's disease has identified over 100 risk loci, yet translating these findings into understanding of disease mechanisms, clinical and pathological heterogeneity, and disease progression remains a challenge. This task requires exploring how genetic risk factors operate over time, interact with environmental factors, and contribute to the diverse ways in which disease manifests. The development of α-synuclein seeding amplification assays (SAAs) offers the opportunity to understand Parkinson's disease pathogenesis and heterogeneity, and drive the development of new disease-modifying and prevention interventions.

[Series] Advances in screening and management of unruptured intracranial aneurysms

The clinical evaluation and decision making associated with the management of unruptured intracranial aneurysms are complex. In the past 5 years, studies have evaluated the benefits of screening in people at high-risk, such as those with a family history of aneurysmal subarachnoid haemorrhage or unruptured intracranial aneurysms, people with genetic or other disorders associated with intracranial aneurysms, and people who smoke and have hypertension. If an aneurysm is detected during screening or incidentally, prediction models now allow for estimating the risk of complications from preventive aneurysm occlusion.

[Series] Epidemiology, pathogenesis, and emerging concepts in unruptured intracranial aneurysms

About 3% of adults have an unruptured intracranial aneurysm and this prevalence can increase to 10% in high-risk groups. Aneurysms are not congenital, but develop throughout life. New evidence has established that genetic, anatomical, inflammatory, and modifiable risk factors interact in the formation, growth, and rupture of aneurysms. Genome-wide association studies have found an association with genetic risk variants in 17 loci. Furthermore, circle of Willis variations predispose to aneurysm formation and cluster within families.

[Articles] Intravenous alteplase versus oral aspirin for acute central retinal artery occlusion within 4·5 h of severe vision loss (THEIA): a multicentre, double-dummy, patient-blinded and assessor-blinded, randomised, controlled, phase 3 trial

Intravenous alteplase administered within 4·5 h of CRAO onset was not associated with a significant improvement in visual acuity compared with aspirin, despite a higher rate of improvement in the alteplase group. However, the study was likely underpowered to detect a statistical difference. Although no safety concerns related to alteplase were identified, the overall modest recovery rates underscore the need for individual patient-level data meta-analyses with forthcoming randomised controlled trials to clarify the potential benefit of thrombolysis or aspirin in patients with acute CRAO.

[In Context] Wrestling with the consequences of blood tests for Alzheimer's disease

“I’m quite happy to talk about it—I would prefer for people to know that I have Alzheimer's disease,” explained Gerry King, one of the founders of Striving Towards A New Day (STAND), a charity that supports people living with dementia in Fife, UK. King was diagnosed with young-onset Alzheimer's disease at the age of 55 years. “It gets me down when people say, I’m really sorry, I think that's terrible, it's awful. It's not awful, it's opened up a whole new world for me, meeting other people with young-onset dementia, meeting older people with dementia, and showing that people with dementia can actually do things.” King's comments were among the many stark statements that were digested by the audience at Alzheimer's: To Test or Not to Test?, a discussion held on April 9, 2025, at the National Museum of Scotland in Edinburgh, UK, as part of the Edinburgh Science Festival.

[In Context] The quality of life of patients with dementia and their caregivers: important and yet inadequately assessed

Dementia is one of the most pressing challenges for health and social care globally, with an estimated annual economic burden of £42 billion in the UK alone. The specific toll on individuals and their families is more difficult to quantify, yet often profound, with dementia now the most feared health condition among UK adults. The assessment of health-related quality of life in dementia has assumed increasing importance, particularly in evaluating whether the benefits of disease-modifying therapies for Alzheimer's disease newly approved in the UK justify their cost.

[In Context] Maximilian U Friedrich

Maximilian U Friedrich is a neurologist and incoming research group leader at the Department of Neurology, University Hospital Ulm, Germany. Previously, he worked as a postdoc with Michael D Fox at the Center for Brain Circuit Therapeutics, Harvard Medical School, Boston, USA. His research bridges clinical neurology, computer vision, and neuroimaging, with the goal of translating pixels and voxels into clinically meaningful outcomes, for both doctors and patients.

[In Context] William Harvey, neurologist?

History can be put to any number of uses. One of the more common of these is the construction of a story that links present day developments to events in the past, seeking legitimacy for the present by enrolling historical figures in an ancestral lineage that inexorably, and inevitably, leads to the present. This storytelling is often achieved by picking out statements from past writings that seem, in some way, to be ahead of their time or otherwise prescient.

[In Context] Stéphanie Debette: a neurologist with a passion for the arts

Stéphanie Debette, a French neurologist and epidemiologist, had one condition before she would accept her appointment as Executive Director of the Paris Brain Institute in January 2025: she wanted to continue the research she had been pursuing, most recently as founding director of the Vascular Brain Health Institute in Bordeaux. She told the hiring committee: “I have always insisted on keeping my research activity, especially as it is embedded in a number of international consortia”. Her appointment followed her being awarded the Inserm Grand Prix, the most prestigious annual award for biomedical research in France, and her induction into the French Academy of Sciences, both in 2024.

[Corrections] Correction to Lancet Neurol 2025; 24: 880–92

Saidha S, Green AJ, Leocani L, et al. The use of optical coherence tomography and visual evoked potentials in the 2024 McDonald diagnostic criteria for multiple sclerosis. Lancet Neurol 2025; 24: 880–92—For this Personal View, the International Multiple Sclerosis Visual System consortium should have been included in the authorship line, and a list of consortium members are included in the appendix. These corrections have been made to the online version as of Sept 18, 2025.

[Corrections] Correction to Lancet Neurol 2025; 24: 850–65

Montalban X, Lebrun-Frénay C, Oh J, et al. Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria Lancet Neurol 2025; 24: 850–65—In this Position Paper, figures 2 and 3 have been swapped so that figure 2 is now: “Diagnostic algorithm for radiologically isolated syndrome and other non-specific presentations” and figure 3 is now: “Diagnostic algorithm for relapsing and progressive presentations of multiple sclerosis”. These corrections have been made to the online version as of Sept 23, 2025.

[Comment] Multidomain lifestyle interventions for cognitive function

The burden of cognitive decline is growing, affecting many people worldwide and placing a substantial strain on health-care systems.1 As such, effective interventions to slow down, prevent, or reverse cognitive decline are of utmost importance. Cognitive decline is affected by various lifestyle factors, and consequently, multidomain interventions (eg, encouraging physical activity, healthy diet, social engagement, and physical health monitoring) likely lead to the best outcomes.2

[Comment] Promises, hopes, and dreams in Parkinson's disease research

Since James Parkinson first described his eponymous disease, our knowledge of its pathophysiology has grown enormously. However, in clinical settings, many of the original concepts remain in use, and diagnosis is still focused on the motor features arising due to the loss of dopaminergic neurons in the substantia nigra. Although these concepts have been useful for the field, enabling the development of a panoply of highly efficacious symptomatic therapies, they might have also hindered the development of disease modifying therapies, which require a deep understanding of the underlying biology.

[Comment] Probing our understanding of intracranial aneurysms

Intracranial aneurysms are detected in about 3% of adults who undergo brain vascular imaging.1,2 About 7 million people in the US alone have an intracranial aneurysm, which are being detected more frequently due to the increasing use and sensitivity of brain vascular imaging. The most important manifestation of an intracranial aneurysm is subarachnoid haemorrhage, but its incidence is only 6 per 100 000 population per year.3 This discrepancy between the prevalence of intracranial aneurysms and the incidence of subarachnoid haemorrhage means that most intracranial aneurysms never rupture.

[Comment] Neuropathology of Alzheimer's disease after anti-amyloid β antibody treatment

Treatment with anti-amyloid β antibodies is becoming standard therapy for early Alzheimer's disease, as lecanemab and donanemab received full approval in the USA, Japan, and other countries between 2023 and 2024. However, only about ten autopsy cases involving passive immunisation with these treatments have been reported so far. These reports include three cases involving aducanumab treatment;1,2 two cases after lecanemab treatment that experienced severe amyloid-related imaging abnormalities (ARIA),3,4 an adverse event specific to this therapy; one case of lecanemab treatment without ARIA;5 and four cases of gantenerumab or solanezumab treatment from the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU; table).