Neurology — Weekly Evidence Brief

Recent advancements highlight the growing potential of advanced neuroimaging and novel biomarkers to enhance early detection and risk stratification across a spectrum of neurological conditions. For instance, blood transcriptomic data now allows for molecular stratification of mild cognitive impairment (MCI) patients, improving the precision of early dementia diagnosis 1. Similarly, brain-predicted age difference (brain-PAD) from routine T1-weighted MRI serves as a sensitive biomarker for preclinical Alzheimer's disease risk and cognitive aging trajectories 2. In Parkinson's disease, salivary biomarkers, including alpha-synuclein and TNFalpha, have shown promise in predicting both motor and non-motor symptom progression 3. Furthermore, specific thalamic nuclei volume changes are being linked to the cognitive and motor manifestations of Parkinson's disease, deepening our understanding of its neuroanatomical basis 4.

Understanding the heterogeneity and underlying mechanisms of neurological disorders is also rapidly evolving. In Multiple Sclerosis (MS), multimodal MRI patterns, integrating structural and functional brain changes, now explain physical and cognitive disability more effectively than traditional MRI, offering a path to more sensitive biomarkers 5. Complementary cerebrospinal fluid (CSF) molecular tests have been externally validated to distinguish MS subtypes and predict future disability progression, laying the groundwork for personalized MS care 6. Research also indicates that older adults with depressive symptoms exhibit altered structural-functional connectivity in specific brain networks, with metabolic diseases and sleep disorders influencing these distinct neural mechanisms 7. Moreover, cell-weighted polygenic risk scores reveal unique cell-type specific genetic contributions to β-amyloid and tau pathology in Alzheimer's disease, providing crucial mechanistic insights 8.

Identification of robust prognostic markers is crucial for optimizing management in both acute and chronic neurological conditions. In acute ischemic stroke (AIS), microembolic signals (MES) detected in the acute phase are predictive of worse cognitive outcomes 12 months post-stroke, serving as an early risk indicator 9. Concurrently, markers of brain frailty, such as white matter changes and cortical atrophy observed on NCCT and MRI, correlate with poorer functional outcomes after thrombolysis in AIS patients, which can inform treatment expectations 10. For Amyotrophic Lateral Sclerosis (ALS), 18F-FDG PET-CT identifies distinct metabolic phenotypes that correlate with survival and function, offering a basis for personalized prognostication and therapy 11. Even in asymptomatic carriers of C9orf72 and SOD1 variants for ALS, magnetoencephalography (MEG) can detect divergent brain network dynamics, accurately distinguishing at-risk groups and suggesting potential biomarkers for preventative interventions 12.

Novel interventions and a broader perspective on health risks are also shaping future clinical practice. Repetitive transcranial magnetic stimulation (rTMS) shows promising results in early Alzheimer's disease, improving cognition, reducing neuropsychiatric symptoms, and inducing beneficial neuroplastic and biomarker changes 13. For Parkinson's disease patients with mild cognitive impairment (PD-MCI), a therapist-guided, home-based virtual reality cognitive stimulation program has proven effective in improving global cognition, offering a scalable alternative to traditional therapies 14. Furthermore, monitoring cardiovascular risk trajectories over a decade reveals that an accelerated increase in risk is independently associated with a higher incidence of stroke and vascular dementia, emphasizing the need for dynamic preventive strategies beyond baseline risk assessment 15. Studies also reveal shared gray matter atrophy patterns in cerebellar and subcortical networks linked to gait impairment in both healthy aging and multiple sclerosis, suggesting common neurobiological underpinnings that could guide targeted rehabilitation 16.