by Raphael Wurm, Simone Salemme, & Charlotte Dumas
Each month the eanNews editorial team reviews the scientific press for recently published papers of outstanding interest to neurologists. Below we present our selection for October 2026.
For our Paper of the Month, go here: Research Paper of the Month: Prevalence of Chronic Traumatic Encephalopathy at Death in National Football League Players – eanNews
Cognitive resilience and pathological burden jointly determine risk of cognitive symptoms in Alzheimer’s disease
This large prospective cohort study evaluated whether biologically confirmed pathology and cognitive resilience operate as independent and/or synergistic determinants of cognitive symptoms in Alzheimer’s disease (AD). Analysing 3,119 older adults from the China Cognition and Aging Study over a median follow-up of 13.7 years, the authors derived two longitudinal indices: a pathology score (p-tau181/Aβ42 ratio) and a cognitive resilience score derived statistically from the rate of cognitive decline after adjustment for pathology, age, and sex. Both indices independently predicted incident major neurocognitive dysfunction, with higher pathology conferring increased risk (HR 2.50 per SD, 95% CI 2.30–2.72) and higher resilience conferring almost equal protection (HR 0.51 per SD, 95% CI 0.48–0.55).
The two metrics contributed comparable, complementary shares of the ten-year AD risk, explaining the risk significantly better than either did alone. The lowest incident AD risk was observed in individuals with high resilience and low pathology, whereas the highest risk occurred among those with high pathology and low resilience. These findings were replicated in an independent cohort and confirmed in reverse-causation sensitivity analyses. While researchers had proposed such a model of pathology x resilience to explain why some people never develop cognitive symptoms despite significant burden, this study adds much needed statistical confirmation. The fact that both determinants are roughly equally important further supports the implementation of preventive strategies to strengthen the population’s cognitive reserve and resilience.
Read the paper here: Joint impact of pathological burden and cognitive resilience on Alzheimer’s disease risk | Nature Medicine
Oveporexton for Narcolepsy Type 1 — Results from Two Phase 3 Trials
These two phase-3, randomised, placebo-controlled trials evaluated the efficacy and safety of oveporexton, an oral orexin receptor 2-selective agonist, in patients with narcolepsy type 1. Participants were randomly assigned in a 3:3:2 ratio to twice-daily oveporexton (1 mg or 2 mg) or placebo in the First Light trial, and in a 2:1 ratio twice-daily oveporexton (2 mg) or placebo in the Radiant Light trial. The primary endpoint was the change from baseline to week 12 in mean sleep latency on the maintenance of wakefulness test (MWT).
A total of 168 participants were enrolled in the First Light trial and 105 patients in the Radiant Light trial. Mean sleep latency on the MWT significantly improved with oveporexton, with changes ranging from 14.3 to 19.8 minutes, compared with -0.4 to -0.8 minutes with placebo (adjusted p<0.001 for all comparisons vs placebo). Secondary endpoints also showed significant improvements. Mean changes in the Epworth Sleepiness Scale ranged from -9.7 to -11.8 with oveporexton, compared with -1.5 to -1.7 with placebo (adjusted p<0.001 for all comparisons vs placebo). Median percent reductions in weekly cataplexy rate ranged from 79% to 88.8%, compared with 27.7 to 39.1% with placebo (adjusted p<0.001 for all comparisons with placebo). Adverse events occurred in 86-89% of participants receiving oveporexton, compared with 43-54% receiving placebo. The most common adverse events were increased urinary frequency and transient insomnia, which occurred in a majority of participants receiving oveporexton.
Overall, these results show that oveporexton significantly improved measures of wakefulness, daytime sleepiness and cataplexy in patients with narcolepsy type 1 over a period of 12 weeks.
Read the paper here: Oveporexton for Narcolepsy Type 1 — Results from Two Phase 3 Trials | New England Journal of Medicine
Higher Exhaled Carbon Monoxide Is Associated with Lower Parkinson’s Disease Risk, Including in Never-Smokers
This nationwide Chinese prospective cohort study evaluated the association between self-reported smoking status and measured exhaled CO and Parkinson’s disease (PD), using data from the China Kadoorie Biobank, which covers ten urban and rural regions of China.
It included 512,701 adults (mean age 52 years, 58.9% female), recruited between 2004 and 2008 and followed for a mean of twelve years. Participants self-reported their smoking status, and exhaled carbon monoxide (CO) was measured at baseline in parts per million (ppm). Incident Parkinson’s disease (PD; 1,131 cases) and other neurodegenerative diseases (2,949 cases) were identified through death, disease and health insurance registries. Cox models were adjusted for sociodemographic factors, lifestyle factors and other confounders (i.e., solid fuel use and passive exposure to smoke).
Regular smoking was associated with higher risks of lung cancer, ischaemic heart disease, stroke and all-cause mortality, but with a lower risk of PD (adjusted HR 0.70, 95% CI 0.62–0.79). Among the 675 never-smokers who developed PD, higher exhaled CO was associated with a dose-dependent risk reduction (reference: <2.0 ppm, P for trend <0.001). The association was most pronounced in female never-smokers. It was absent for other neurodegenerative diseases and for smoking-related vascular diseases.
The authors interpret these results as supporting a protective role of CO in PD aetiology and state that ongoing clinical trials of CO in the treatment of PD will be helpful in establishing its role in this disease.
Read the paper here: Smoking, Exhaled Carbon Monoxide, and Risk of Parkinson Disease | JAMA Neurology | JAMA Network
