Neurology — Weekly Evidence Brief

New research is enhancing the understanding and prediction of Alzheimer's disease (AD) progression. Multi-modal integration of imaging, omics, and clinical data can identify two distinct mild cognitive impairment (MCI) subgroups, notably a 'Vulnerable Neurodegenerative' group prone to rapid conversion to AD, which holds significant importance for personalized prognostication and targeted interventions 1. In individuals with discordant cerebrospinal fluid (CSF) profiles (A-T+), distinct brain functional connectivity patterns, particularly in the temporo-occipital axis, differentiate them from A+T+ individuals, offering insights for precise diagnostic tools 2. Furthermore, a meta-analysis underscores the critical need for standardized cognitive assessments to accurately identify MCI patients at risk of AD conversion, given reported hippocampal atrophy and amyloid-β/tau deposition in converters 3. White matter free water and peak width of skeletonized mean diffusivity are also emerging as imaging biomarkers for cerebral amyloid angiopathy severity, correlating with cognitive decline in executive function and memory 4.

Advancements are also improving the early detection and understanding of Parkinsonian disorders and related alpha-synucleinopathies. A longitudinal study identifies lower baseline executive function and reduced N2 slow oscillation density as potential early neurophysiological markers and significant predictors of phenoconversion in isolated Rapid Eye Movement Behavior Disorder (iRBD) 5. While diagnostic accuracy for Parkinsonian disorders remains suboptimal (e.g., 82.1% for dementia with Lewy bodies), new probabilistic models leveraging clinical observations and likelihood ratios can help refine and improve diagnostic precision 6. Moreover, directed brain connectivity analysis using fMRI shows promise in distinguishing prodromal Parkinson's disease from manifest disease, highlighting changes like somatomotor network isolation 7. In mild cognitive impairment with Lewy bodies (MCI-LB), impaired sentence comprehension is linked to decreased subcortical-cortical and dorsal language network connectivity, providing a potential indicator for language-related cognitive impairment 8.

Insights into the mechanisms and prognostication of stroke and cerebral small vessel disease (cSVD) are progressing. In acute ischemic stroke, sarcopenia, indicated by low temporal muscle thickness, is independently associated with dysphagia, early neurological deterioration, and poorer post-discharge recovery, particularly in patients with motor deficits, thereby mediating functional outcomes 9. For post-stroke cognitive impairment (PSCI), peak alpha frequency, especially T4PAF, has been identified as a robust electrophysiological biomarker with excellent discriminatory power for detection 10. In subarachnoid hemorrhage (SAH), the presence of barrier-dysfunctional tissue on contrast-enhanced MRI is a powerful independent predictor of both early mortality and long-term epilepsy or death, offering significant potential for enhanced risk stratification 11. Additionally, white matter hyperintensities in cSVD are found to drive propagating grey matter atrophy originating in the right insula, a critical hub mediating cognitive decline in executive function and processing speed, suggesting a novel intervention target 12.

Prognostic indicators are also being refined for other complex neurodegenerative and neurological conditions. The presence of a C9orf72 expansion significantly increases the risk and accelerates the onset of subsequent motor or cognitive-behavioral features in patients across the amyotrophic lateral sclerosis-frontotemporal degeneration (ALS-FTD) spectrum, providing crucial prognostic information and advocating for proactive monitoring 13. For traumatic encephalopathy syndrome (TES), higher fractional anisotropy at the gray matter/white matter boundary is associated with greater certainty for CTE pathology and correlates with CSF p-tau levels, suggesting a potential dMRI biomarker for tau pathology-associated neurodegeneration 14. Furthermore, in progressive multiple sclerosis (PMS), frailty is positively associated with increased disability, and is linked to underlying inflammatory and metabolic vulnerabilities 15. Early multiple sclerosis patients with non-optic neuritis onset may also benefit from serum neurofilament light chain (sNFL) as a predictor of future disease activity, although this prognostic value appears dependent on the initial manifestation 16.