Nature Reviews Neurology最新文献

Diet is a modifiable lifestyle factor with a proven role in cardiovascular disease risk reduction that might also play an important part in cognitive health. Evidence from observational studies has linked certain healthy dietary patterns to cognitive benefits. However, clinical trials of diet interventions have demonstrated either null or, at best, small effects on cognitive outcomes. In this Review, we summarize the currently available evidence from observational epidemiology and clinical trials regarding the potential role of diet in the prevention of cognitive decline and dementia. We further discuss possible methodological limitations that might have hindered the ability of previous diet intervention trials to capture potential neuroprotective effects. Considering the overwhelming and continuously expanding societal, economic and health-care burden of Alzheimer disease and other dementias, future nutritional research must address past methodological challenges to accurately and reliably inform clinical practice guidelines and public health policies. Within this scope, we provide a roadmap for future diet intervention trials for dementia prevention. We discuss study designs involving both intensive personalized interventions — to evaluate pharmacokinetic and pharmacodynamic properties, establish neuroprotective thresholds, and test hypothesized biological mechanisms and effects on brain health and cognition through sensitive and precise biomarker measures — and large-scale, pragmatic public health interventions to study population-level benefits.

Intracerebral haemorrhage (ICH) is a devastating condition associated with high mortality and substantial residual disability among survivors. Effective treatments for the acute stages of ICH are limited. However, promising findings from randomized trials of therapeutic strategies, including acute care bundles that target anticoagulation therapies, blood pressure control and other physiological parameters, and trials of minimally invasive neurosurgical procedures have led to renewed optimism that patient outcomes can be improved. Currently ongoing areas of research for acute treatment include anti-inflammatory and haemostatic treatments. The implementation of effective secondary prevention strategies requires an understanding of the aetiology of ICH, which involves vascular and brain parenchymal imaging; the use of neuroimaging markers of cerebral small vessel disease improves classification with prognostic relevance. Other data underline the importance of preventing not only recurrent ICH but also ischaemic stroke and cardiovascular events in survivors of ICH. Ongoing and planned randomized controlled trials will assess the efficacy of prevention strategies, including antiplatelet agents, oral anticoagulants or left atrial appendage occlusion (in patients with concomitant atrial fibrillation), and optimal management of long-term blood pressure and statin use. Together, these advances herald a new era of improved understanding and effective interventions to reduce the burden of ICH.

A recent analysis of dementia risk scores across diverse populations found that the validity of scores can differ between ethnic groups. The widely investigated Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) risk score, which estimates 20-year dementia risk at midlife on the basis of age, sex, education, systolic blood pressure, body mass index, cholesterol level and physical activity, was compared with a modified version (mCAIDE) that includes self-reported information on sociodemographic characteristics, personal and family medical history and mood. Higher CAIDE scores were associated with increased risk of dementia in non-Latinx White, Latinx, and Asian Americans, but not Black Americans, whereas mCAIDE scores were associated with risk in all groups. The findings highlight the need to evaluate and revise risk score methods to suit the specific racial and ethnic make-up of the studied population.

Transplantation of genetically modified oligodendrocyte progenitor cells (OPCs) into a mouse model of MS improves remyelination, new research has demonstrated. The researchers used CRISPR in human embryonic stem cell-derived OPCs to delete neuropilin 1, a receptor for SEMA3A that is highly expressed in demyelinated lesions in people with MS and is chemorepulsive to OPCs. Transplantation of the modified OPCs enhanced remyelination in the mice, providing proof of concept for OPC transplantation as a potential therapeutic strategy for MS.

A new study of a Taiwanese cohort found a high prevalence of resolved hepatitis B virus (HBV) infection in people with neuromyelitis optica spectrum disorder (NMOSD). Resolved HBV was found in 63.4% of people with NMOSD, compared with 16.4% in healthy controls, equating to a 5.7-fold increased risk of NMOSD following HBV infection. Furthermore, resolved HBV was associated with later onset of NMOSD and higher disability scores compared with individuals without HBV infection when adjusted for age and sex, suggesting that the immune response to HBV could contribute to NMOSD pathogenesis.

Risk of clinical milestones in Parkinson disease (PD) is associated with reduced glymphatic drainage, according to new research. The study of 175 people with PD showed that lower glymphatic function, measured by diffusion tensor imaging analysis of the perivascular space, was associated with increased risk of recurrent falls, wheelchair dependence and dementia. The study adds to growing evidence for a role of the glymphatic system in PD pathology that warrants further investigation.

Parkinson disease (PD) is the fastest growing neurological disorder globally and poses substantial management challenges owing to progressive disability, emergence of levodopa-resistant symptoms, and treatment-related complications. In this Review, we examine the current state of research into PD therapies and outline future priorities for advancing our understanding and treatment of the disease. We identify two main research priorities for the coming years: first, slowing the progression of the disease through the integration of sensitive biomarkers and targeted biological therapies, and second, enhancing existing symptomatic treatments, encompassing surgical and infusion therapies, with the goal of postponing complications and improving long-term patient management. The path towards disease modification is impeded by the multifaceted pathophysiology and diverse mechanisms underlying PD. Ongoing studies are directed at α-synuclein aggregation, complemented by efforts to address specific pathways associated with the less common genetic forms of the disease. The success of these efforts relies on establishing robust end points, incorporating technology, and identifying reliable biomarkers for early diagnosis and continuous monitoring of disease progression. In the context of symptomatic treatment, the focus should shift towards refining existing approaches and fostering the development of novel therapeutic strategies that target levodopa-resistant symptoms and clinical manifestations that substantially impair quality of life.

Several major challenges, including an ageing population and declining workforce and the implementation of recent breakthrough therapies for Alzheimer disease, are prompting a necessary rethink of how people with neurodegenerative dementias are diagnosed and medically managed. Digital health technologies could play a pivotal part in this transformation, with new advances enabling the collection of millions of data points from a single individual. Possible applications include unobtrusive monitoring that aids early detection of disease and artificial intelligence-based health advice. To translate these advances to meaningful benefits for people living with a disease, technologies must be implemented within a system that retains the physician expert as a central figure in decision-making. This Perspective presents a new framework, termed the Digitized Memory Clinic, 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. The Digitized Memory Clinic will manage people across the entire disease spectrum, from the detection of risk factors for cognitive decline and the earliest symptoms to dementia, and will replace the present paradigm of a pure ‘brick-and-mortar’ memory clinic. Important ethical, legal and societal barriers associated with the implementation of digital health technologies in memory clinics need to be addressed. The envisioned Digitized Memory Clinic aims to improve diagnostics and enable precise disease-tracking prognostication for individuals with memory disorders and to open new possibilities, such as precision medicine for prevention and treatment.