Diagnostic Evidence Profiles

Every diagnostic criterion or biomarker is evaluated along a validation chain. Strength at one link does not substitute for another.

DP001 | Boston criteria v2.0

Context: Etiologic classification of sporadic CAA in defined age/presentation contexts

Technical: Depends on high-quality hemorrhagic and nonhemorrhagic MRI marker rating

Biological: Markers are associated with CAA but are not individually pathognomonic

Diagnostic: Strongest in symptomatic tissue-selected cohorts; lower in community and nonhemorrhagic validations

Prognostic: Criteria category is not itself a complete outcome-risk model

Incremental value: Adds nonhemorrhagic markers over earlier versions; context-dependent

Transportability: Limited outside populations resembling validation cohorts

Clinical utility: Useful diagnostic framework when applied within intended context

Failure mode: Spectrum effects, mixed pathology, inadequate MRI, and using criteria as universal screening

Next validation: Prospective presentation-specific external validation with full reference standard

DP002 | ARTS

Context: Research prediction of pathology-linked arteriolosclerosis risk

Technical: Promising repeatability evidence, including conference-level validation

Biological: Development linked MRI/demographic features to autopsy pathology

Diagnostic: Development AUC reported; independent external pathology accuracy not established

Prognostic: Associations with cognition and vascular outcomes reported

Incremental value: Not yet demonstrated against strong conventional baselines across independent cohorts

Transportability: Uncertain beyond ROSMAP/ADNI-related research settings

Clinical utility: Not established

Failure mode: Conflating reproducibility or outcome association with diagnostic validation

Next validation: Locked independent MRI-autopsy validation with calibration and decision analysis

DP003 | CVR MRI

Context: Physiological measurement of vascular reserve in SVD/VCID

Technical: Multisite protocol evidence exists; acquisition and gas delivery remain demanding

Biological: Measures vascular responsiveness and predicts some structural progression

Diagnostic: No pathology-specific CAA or arteriolosclerosis threshold

Prognostic: Associated with cognition and one-year WMH/PVS progression; not all clinical outcomes

Incremental value: Needs comparison with conventional MRI and vascular risks

Transportability: Promising across research sites; routine-care feasibility limited

Clinical utility: Research only

Failure mode: Treating a general vascular-function signal as an etiologic diagnosis

Next validation: Pathology-linked and intervention-responsive multisite qualification

DP004 | Regional amyloid PET

Context: Research differentiation of CAA, AD, and controls

Technical: Tracer and pipeline dependent

Biological: Detects fibrillar amyloid but vascular/parenchymal compartment assignment is indirect

Diagnostic: Group-level regional differences; no validated universal patient threshold

Prognostic: Insufficient for routine CAA prognosis

Incremental value: Unclear beyond MRI and AD biomarkers

Transportability: Limited by tracer, stage, and reference-standard heterogeneity

Clinical utility: Not standalone CAA diagnosis

Failure mode: Calling amyloid positivity vascular CAA in an older person with AD

Next validation: Multi-tracer PET-to-autopsy study with mixed-pathology modeling

DP005 | CAA-ri clinicoradiologic criteria

Context: Recognition of inflammatory CAA syndrome

Technical: Requires appropriate FLAIR, susceptibility, diffusion, and often contrast imaging

Biological: Phenotype reflects inflammatory/permeability injury around amyloid-laden vessels

Diagnostic: Validated in selected cohorts; mimic-rich external performance remains uncertain

Prognostic: Not a complete treatment-response or relapse model

Incremental value: Can reduce unnecessary biopsy when syndrome and imaging align

Transportability: Best in specialist contexts with alternative-diagnosis assessment

Clinical utility: Clinically useful with expert evaluation

Failure mode: Missing infection, neoplasm, PRES, vasculitis, or therapy-associated ARIA

Next validation: Prospective blinded accuracy study including realistic mimics

DP006 | Total SVD score

Context: Compact summary of MRI burden

Technical: Simple and reproducible when component ratings are reliable

Biological: Combines downstream injury markers from potentially different etiologies

Diagnostic: Not intended to diagnose a vessel pathology

Prognostic: Associated with clinical and network outcomes in several cohorts

Incremental value: May summarize burden efficiently but can discard spatial and continuous information

Transportability: Reasonable for burden comparisons with harmonized definitions

Clinical utility: Descriptive/prognostic research adjunct

Failure mode: Interpreting a burden score as CAA or arteriolosclerosis

Next validation: Outcome-specific comparison with continuous and spatial measures

DP007 | ARIA monitoring framework

Context: Safety monitoring during anti-amyloid therapy

Technical: Standardized serial MRI and communication are central

Biological: ARIA-E and ARIA-H reflect therapy-associated permeability/inflammatory and hemorrhagic injury

Diagnostic: Designed for treatment context, not spontaneous CAA diagnosis

Prognostic: Baseline markers inform risk; severe-event prediction remains limited

Incremental value: Provides operational safety value beyond unsystematic MRI review

Transportability: Therapy-, protocol-, and healthcare-system dependent

Clinical utility: High within current treatment pathways using drug-specific guidance

Failure mode: Confusing ARIA with infarct, PRES, spontaneous CAA-ri, or other mimics

Next validation: Large real-world registry with standardized MRI and adjudicated severe outcomes