Objectives: Amyloid-lowering immunotherapies can cause amyloid-related imaging abnormalities (ARIA), requiring brain MRI for detection and monitoring. The European Society of Neuroradiology (ESNR)/European Academy of Neurology (EAN) ARIA Working Group conducted a survey to assess European clinicians’ readiness for this logistical challenge and need for further education on ARIA. Materials and methods: An online questionnaire with 32 items (multiple choice, single best choice, and free text) was distributed to ESNR and EAN members. Between June and July 2024, we collected 422 responses from 41 European countries, including 47% neurologists and 51% (neuro)radiologists; 15% were residents, and 58% worked in academic hospitals. Results: Of respondents, 69% were familiar with the concept of ARIA, and 60% reportedly understood its risk factors. Confidence in evaluating ARIA-E (edema/effusion) and ARIA-H (hemorrhage) subtypes was reported by 60% and 69%, respectively, with (neuro)radiologists more confident than neurologists. However, 34% of respondents felt poorly equipped to meet logistical demands, and 82% lacked a dedicated ARIA imaging protocol. Key barriers included limited organizational adaptability and radiology expertise. Notably, 72% saw potential in having support by artificial intelligence approaches, and 93% expressed the wish for further training on how to monitor ARIA. Conclusions: Despite the current unavailability of amyloid-lowering therapies, European neurologists and (neuro)radiologists report reasonable ARIA awareness. There is a clear need for additional practical preparation and training in ARIA assessment, which can inform future ESNR/EAN educational initiatives. Key Points: Question Are neurologists and neuroradiologists ready for ARIA monitoring? Findings Neurologists and neuroradiologists were moderately familiar with the concept of ARIA, its risk factors, and its identification on MRI, but felt poorly equipped to meet the logistical demands. Clinical relevance With the potential introduction of amyloid-lowering therapies in European countries, identifying key barriers, such as limited organizational adaptability and radiology expertise, highlights the need for further practical preparation by clinical departments and additional training in ARIA assessment. ... Read more

Introduction
Unraveling how Alzheimer's disease (AD) genetic risk is related to neuropathological heterogeneity, and whether this occurs through specific biological pathways, is a key step toward precision medicine.

Methods
We computed pathway-specific genetic risk scores (GRSs) in non-demented individuals and investigated how AD risk variants predict cerebrospinal fluid (CSF) and imaging biomarkers reflecting AD pathology, cardiovascular, white matter integrity, and brain connectivity.

Results
CSF amyloidbeta and phosphorylated tau were related to most GRSs. Inflammatory pathways were associated with cerebrovascular disease, whereas quantitative measures of white matter lesion and microstructure integrity were predicted by clearance and migration pathways. Functional connectivity alterations were related to genetic variants involved in signal transduction and synaptic communication.

Discussion
This study reveals distinct genetic risk profiles in association with specific pathophysiological aspects in predementia stages of AD, unraveling the biological substrates of the heterogeneity of AD-associated endophenotypes and promoting a step forward in disease understanding and development of personalized therapies.

Highlights
- Polygenic risk for Alzheimer's disease encompasses six biological pathways that can be quantified with pathway-specific genetic risk scores, and differentially relate to cerebrospinal fluid and imaging biomarkers.
- Inflammatory pathways are mostly related to cerebrovascular burden.
- White matter health is associated with pathways of clearance and membrane integrity, whereas functional connectivity measures are related to signal transduction and synaptic communication pathways. ... Read more