by Raphael Wurm and Agne Straukiene
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 2025.
For our Paper of the Month, go here: Research Paper of the Month: AI-driven reclassification of multiple sclerosis progression – eanNews
Smartwatch- and smartphone-based remote assessment of brain health and detection of mild cognitive impairment | Nat Med
The ubiquity of smartphones and smartwatches presents a novel opportunity for real-world monitoring of cognitive health. The ‘Intuition’ study was a remote observational study enrolling 23,004 adults across the US. For 24 months, data from smartwatches and smartphones were collected, including routine device usage patterns, self-reported health information, and performance on interactive cognitive assessments. The goal was to develop and validate tools for detecting mild cognitive impairment (MCI) and tracking cognitive trajectories in a more diverse population than what is typically enrolled in clinical research.
Partnering up with a major manufacturer of such devices, the researchers present their initial conceptual results of the interactive cognitive assessments, showing that they were able to construct a model to classify MCI. While specific performance metrics are yet to be detailed, it demonstrates the feasibility of using consumer devices in this setting. The preliminary results indicate that this approach could identify patients at risk and map their cognitive trajectory over time, opening up many opportunities for future research.
Read the full paper: Smartwatch- and smartphone-based remote assessment of brain health and detection of mild cognitive impairment | Nature Medicine
Potentiation of mitochondrial function by mitoDREADD-Gs reverses pharmacological and neurodegenerative cognitive impairment in mice | Nat Neurosci
Mitochondrial dysfunction is implicated in many neurodegenerative diseases, but its precise function is hard to study owing to a lack of experimental methods to activate it. To address this, researchers developed a chemogenetic tool. Using DREADD technology, they were able to insert a G-protein-coupled receptor into cerebral mitochondria that could then be activated by drugs with little to no systemic effects. Through this, they could study the effects of selective mitochondrial activation in various settings and disease models.
To test the therapeutic potential of this approach, the researchers expressed mitoDREADD-Gs in the hippocampus of two different mouse models of neurodegeneration: P301S mice, which model frontotemporal dementia (FTD), and APP/PS1 mice, which model Alzheimer’s disease. At 6 months of age, both models exhibit significant memory impairments. Exogenous activation of hippocampal mitochondria rescued the memory deficits in both models. These findings provide strong evidence for a direct causal link between reduced mitochondrial activity and cognitive symptoms in these diseases and introduce a promising new strategy for therapeutic intervention.
Read the full paper: Potentiation of mitochondrial function by mitoDREADD-Gs reverses pharmacological and neurodegenerative cognitive impairment in mice | Nature Neuroscience
Ambient Air Pollution and the Severity of Alzheimer’s Disease Neuropathology | JAMA Neurol
Mounting evidence suggests that exposure to air pollution increases dementia risk, but the underlying neuropathological drivers are unclear. In this study, researchers examined brains from a cohort of patients with dementia, movement disorders, and older controls. They combined pathological data with detailed cognitive evaluations ante-mortem. They correlated the individuals’ residential exposure to fine particulate matter (PM2.5) in the year before death with their final clinical dementia severity scores and detailed neuropathological assessments.
Including 602 patients, they found that higher PM2.5 exposure was significantly associated with more severe Alzheimer’s disease neuropathologic change (ADNC), with an odds ratio of 1.19 (95% CI, 1.11-1.28) for a higher ADNC stage. This increased brain pathology translated to worse clinical outcomes: higher PM2.5 levels were also associated with greater cognitive and functional impairment (β = 0.48; 95% CI, 0.22-0.74). A mediation analysis revealed that 63% of the total effect of PM2.5 exposure on clinical dementia severity was explained by the increase in ADNC. These results suggest that air pollution may directly trigger or exacerbate AD pathology, leading to accelerated cognitive decline.
Read the full paper: Ambient Air Pollution and the Severity of Alzheimer Disease Neuropathology | JAMA Neurology | JAMA Network
2024 Revisions of the McDonald Criteria for the Diagnosis of Multiple Sclerosis | Lancet Neurol
The 2024 update of the McDonald criteria provides clearer, evidence-based guidance for diagnosing multiple sclerosis (MS). The revision expands the diagnostic framework to include five anatomical regions periventricular, juxtacortical/cortical, infratentorial, spinal cord, and optic nerve and introduces new MRI and laboratory markers that enhance accuracy and allow for earlier diagnosis.
MRI remains central, with T2/FLAIR and gadolinium-enhanced T1 sequences as core measures. The addition of central vein sign (CVS) and paramagnetic rim lesions (PRL) supports distinction from MS mimics. Cerebrospinal fluid analysis now includes both oligoclonal bands (OCBs) and the kappa free light chain (kFLC) index, which increases sensitivity for detecting intrathecal inflammation. Optic nerve involvement can now be demonstrated by MRI, optical coherence tomography (OCT), or visual evoked potentials (VEP).
The revised criteria also refine definitions for clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS), allowing selected RIS cases with supportive biomarkers to be diagnosed as MS. For progressive presentations, fewer MRI regions are required if CSF or imaging evidence supports dissemination in space and time.
These updates strengthen diagnostic precision and support earlier recognition of disease, particularly in atypical or radiologically isolated cases. However, they depend on access to advanced MRI protocols and validated CSF testing, which may limit use in some settings. Interpretation of new imaging markers also requires appropriate training.
The 2024 McDonald revisions represent an evolution rather than a redesign, balancing innovation with caution and aligning diagnostic practice with current scientific understanding of MS.
Read the full paper: Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria – The Lancet Neurology
