Evidence Completeness Map

The atlas is organized around answerable questions. A topic is not considered complete merely because it has a review paragraph.

Status vocabulary

Bounded: a defensible answer exists within a clearly limited population or context.
Emerging: coherent evidence exists, but important validation or causal tests remain.
Critical gap: the question is central and current evidence cannot support a stable answer.

Q037 [critical gap]: Which baseline and dynamic markers predict symptomatic or severe ARIA?

Q005 [bounded]: How accurately does Boston v2.0 identify CAA in symptomatic referral populations?
Q006 [critical gap]: How accurately does Boston v2.0 perform in nonhemorrhagic cognitive presentations?
Q007 [critical gap]: Can Boston v2.0 be used for community screening?
Q008 [emerging]: Does cortical versus juxtacortical microbleed localization improve CAA specificity?
Q010 [emerging]: Does severe centrum semiovale PVS add independent diagnostic information for CAA?
Q011 [emerging]: Is the multispot WMH pattern independently informative for CAA?
Q012 [bounded]: When do CT morphology and APOE genotype add value after lobar ICH?

Q009 [bounded]: How should cortical superficial siderosis extent and progression be used for prognosis?

Q017 [critical gap]: Does ARTS externally predict pathology-confirmed arteriolosclerosis?
Q018 [critical gap]: Does ARTS add clinically meaningful information beyond conventional measures?

Q013 [critical gap]: What ante-mortem MRI phenotype best predicts pathology-confirmed brain arteriolosclerosis?
Q014 [critical gap]: How specific are deep microbleeds for nonamyloid arteriolosclerosis?
Q015 [critical gap]: Which lacune locations and morphologies are most informative for arteriolosclerosis?
Q016 [critical gap]: Can WMH spatial patterns distinguish arteriolosclerosis from CAA, AD, and mixed disease?

Q033 [critical gap]: How much cognitive decline is mediated by infarcts, white-matter injury, network disruption, and neurodegeneration?

Q025 [critical gap]: Can CSF or plasma distinguish CAA from AD and mixed amyloid disease?

Q034 [emerging]: Which findings from hereditary CAA transport to sporadic CAA?
Q035 [bounded]: How does APOE modify CAA burden, hemorrhage, inflammation, and ARIA risk?

Q036 [bounded]: How accurately do clinicoradiologic criteria identify CAA-ri among realistic mimics?

Q003 [bounded]: What minimum MRI protocol is required to phenotype hemorrhagic and nonhemorrhagic cSVD reproducibly?
Q004 [emerging]: Which cSVD measures are repeatable enough for longitudinal or treatment-response use?

Q020 [emerging]: Is impaired perivascular clearance an initiating cause, amplifier, or consequence of CAA?
Q021 [emerging]: Does vascular physiological dysfunction precede irreversible tissue injury?
Q022 [emerging]: Is BBB leakage an early driver of CAA and arteriolosclerosis or a downstream marker?
Q023 [emerging]: Which inflammatory pathways are causal, protective, or secondary in CAA?
Q024 [critical gap]: How do pulsatility, stiffness, autoregulation, and smooth-muscle loss interact in deep perforator injury?

Q030 [emerging]: How do vascular amyloid and AD neuropathologic change interact to produce cognition?
Q031 [critical gap]: How do arteriolosclerosis and CAA jointly shape MRI phenotypes and outcomes?
Q032 [emerging]: What links arteriolosclerosis to hippocampal sclerosis and LATE-related pathology?

Q026 [emerging]: Can regional amyloid PET distinguish vascular from parenchymal amyloid at the patient level?

Q029 [critical gap]: Does multimodal integration improve etiologic inference beyond MRI alone?

Q001 [critical gap]: What vessel-wall features constitute brain arteriolosclerosis, and which should remain separate constructs?
Q002 [critical gap]: How should regional arteriolosclerosis measurements be aggregated into a person-level burden?
Q019 [critical gap]: How reproducible are visual and quantitative arteriolosclerosis ratings across regions and laboratories?

Q039 [critical gap]: Which combination best predicts hemorrhage, cognitive decline, disability, and death?

Q038 [critical gap]: What is the temporal sequence from vascular dysfunction to nonhemorrhagic and hemorrhagic injury?

Q027 [emerging]: Which diffusion metric best captures clinically meaningful SVD microstructural injury?
Q028 [emerging]: Are PSMD and free-water measures responsive and interpretable enough for trials?

Q040 [critical gap]: Which biomarkers are sufficiently reliable, causal, and responsive to serve as trial endpoints?