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Cerebral amyloid angiopathy

TL;DR — Cerebral amyloid angiopathy (CAA) is amyloid-β deposition in cortical and leptomeningeal vessel walls, producing lobar haemorrhage, microbleeds, superficial siderosis, microinfarction, white-matter injury, and cognitive decline (Charidimou 2022, PMID 35841910; Greenberg 2020, PMID 31827267). Boston criteria v2.0 combine strictly lobar haemorrhagic lesions with selected white-matter markers; autopsy-standard sensitivity was 74.5% and specificity 95.0% in the validation study (Charidimou 2022, PMID 35841910). In non-haemorrhagic cognitive presentations, v2.0 probable-CAA sensitivity was only 28.6% (95% CI 13.2–48.7) and specificity 65.3% (44.3–82.8) (Switzer 2024, PMID 38710005). CAA is simultaneously vascular and amyloid disease and is the vessel substrate of amyloid-related imaging abnormalities (ARIA) during anti-amyloid therapy: ARIA-E occurred in 12.6% on lecanemab and 24.0% on donanemab in phase 3 Alzheimer trials (van Dyck 2023, PMID 36449413; Sims 2023, PMID 37459141).

Biological position

CAA deposits amyloid in vessel walls rather than primarily in plaques. One peptide (Aβ) therefore feeds two pathways—parenchymal plaques and vascular CAA—with overlapping but non-identical clinical consequences (Greenberg 2020, PMID 31827267). Vessel fragility causes haemorrhagic lesions; altered reactivity, occlusion, and impaired clearance can contribute to ischaemic and white-matter injury. The overlap with Alzheimer disease is substantial but incomplete, so parenchymal and vascular amyloid should not be treated as synonyms (Jellinger 2007, PMID 17324442).

Clinical presentations

Presentation Typical evidence Major differential
Lobar ICH cortical/subcortical haemorrhage age ≥50 tumour, AVM, anticoagulant-associated bleed
Transient focal neurological episode spreading sensory/motor spells with siderosis TIA, seizure, migraine (Smith 2021, PMID 34016709)
Cognitive impairment executive/processing and multidomain decline Alzheimer disease, hypertensive SVD
Inflammatory CAA subacute decline, seizures, headache, asymmetric edema infection, neoplasm, vasculitis
Incidental MRI phenotype lobar microbleeds/siderosis trauma and other haemorrhagic causes

TFNEs are brief motor, somatosensory, visual, or language disturbances that can be mistaken for TIA; they herald a high rate of subsequent lobar ICH, so antithrombotics given for presumed TIA can be harmful (Smith 2021, PMID 34016709).

Boston criteria v2.0

Probable CAA in the validation study required either at least two strictly lobar haemorrhagic lesions or one strictly lobar haemorrhagic lesion plus a qualifying white-matter feature (severe centrum-semiovale perivascular spaces or multispot WMH pattern) in an appropriate clinical setting (Charidimou 2022, PMID 35841910).

Cohort Sensitivity (95% CI) Specificity (95% CI)
Derivation 74.8% (65.4–82.7) 84.6% (71.9–93.1)
Temporal validation 92.5% (79.6–98.4) 89.5% (66.9–98.7)
Geographic validation 80.2% (70.8–87.6) 81.5% (61.9–93.7)
Autopsy-standard cases 74.5% (65.4–82.4) 95.0% (83.1–99.4)

These values derive from hospital-based patients selected for potential CAA presentations and available pathology; v2.0 was more sensitive than modified Boston criteria at the autopsy standard (64.5% vs 74.5%) without losing specificity (Charidimou 2022, PMID 35841910).

In 54 MRI–pathology cases without haemorrhagic presentation (median age 75; 28/54 with moderate-to-severe CAA), v2.0 probable CAA had sensitivity 28.6% (13.2–48.7) and specificity 65.3% (44.3–82.8); any (possible+probable) CAA had sensitivity 75.0% and specificity 38.5% and was not superior to v1.5 (Switzer 2024, PMID 38710005).

MRI markers

Marker CAA-supporting pattern Interpretation limit
Microbleeds strictly lobar detection depends on susceptibility sequence
ICH lobar hypertension can also cause lobar ICH
Superficial siderosis cortical, especially disseminated other prior subarachnoid bleeding exists
Convexity SAH cortical sulci requires acute differential diagnosis
Perivascular spaces severe centrum semiovale supportive, not independently diagnostic
WMH multispot pattern nonspecific alone
Cortical microinfarcts pathology/high-resolution imaging usually invisible clinically

Cognition

Cognition may decline without a symptomatic macrohaemorrhage through microinfarction, white-matter injury, impaired vascular reactivity, and combined Alzheimer pathology. The profile is not sufficiently specific to separate CAA from other SVD or Alzheimer disease clinically. The impairment is common and has a measurable shape. In a prospective cohort comparing 34 CAA participants with 16 Alzheimer disease, 69 MCI and 27 ischaemic-stroke participants, CAA mean z-scores fell below test norms for memory (−0.44 ± 1.03, P=0.02), executive function (−1.14 ± 1.07, P<0.001) and processing speed (−1.06 ± 1.12, P<0.001); 27 of 34 (79%) met criteria for mild cognitive impairment. Executive scores were as low as in Alzheimer disease while memory was relatively preserved, and processing speed and executive scores were below those of ischaemic-stroke controls; lower processing speed tracked WMH volume, and there was no association with APOE ε4 (Case 2016, PMID 27338926). The profile is a vascular one, which is the argument against treating CAA cognition as an Alzheimer phenotype with extra bleeding.

A CAA diagnosis should therefore integrate lesion distribution and competing biomarkers (Charidimou 2022, PMID 35841910). Plasma Aβ42/40 is lower and p-tau-181 and NfL higher in Boston v2.0 CAA than in healthy controls; a three-marker combination reached AUC 0.90 (0.80–0.95) in a 45 vs 47 case-control sample, which is not yet diagnostic validity (Muir 2025, PMID 40156276).

Two phenotypes, split by APOE allele

CAA is not one disease with variable severity; the haemorrhagic and non-haemorrhagic forms differ genetically and pathologically. Among 105 patients with pathologically confirmed CAA and MRI (54 presenting with symptomatic lobar ICH, 51 without), neuritic plaques were present in >90% of both groups, but neurofibrillary tangles were far commoner in the non-haemorrhagic group (87% vs 42%, P<0.0001). APOE ε4 carriage was higher in the non-haemorrhagic group (85.7% vs 53.9%, P=0.035) with a trend toward more ε2 in the haemorrhagic group (48.7% vs 21.4%, P=0.075), and disseminated cortical superficial siderosis occurred in 33.3% of the ICH group versus 5.9% without (P<0.0001), associating with ε2 (OR 5.83, 95% CI 1.49–22.82, P=0.011) and not with ε4 (Charidimou 2015, PMID 25716356).

Collaborative meta-analysis across 13 studies — 7 memory-clinic cohorts (n=2,587), 5 symptomatic CAA cohorts (n=402), 1 population study (n=1,379) — confirms the allele split: ε2+ genotypes carried OR 2.42 (95% CI 1.48–3.95) for cortical superficial siderosis, strongest for disseminated siderosis in symptomatic CAA, while ε4+ showed no overall association and was associated with siderosis only in the memory-clinic setting (OR 2.10, 1.11–3.99); ε2/ε2 and ε2/ε4 were the most consistently associated genotypes (Charidimou 2019, PMID 31243071). The mechanistic reading is that ε2 promotes vasculopathic change and vessel fragility — the bleeding phenotype — while ε4 promotes amyloid deposition itself. Two consequences follow: a single "APOE risk" statement is wrong for CAA, and the marker that best predicts ICH recurrence within a randomized trial (siderosis, see below) is the marker most tied to ε2.

Does CAA cause dementia independently?

The evidence points two ways and the difference is methodological rather than semantic.

In the ACT autopsy cohort (848 participants, mean age at death 86.7, 57.6% female), CAA was present in 38.0% and dementia in 45.3%. Dementia was commoner with CAA (53.7% vs 40.1%; age-sex-adjusted OR 1.57, 95% CI 1.18–2.10), but the association lost significance after adjustment for CERAD neuritic-plaque score (OR 1.27, 0.93–1.71) and reversed toward null after adjustment for Braak stage (OR 0.96, 0.69–1.33). Formal mediation gave natural indirect effects of OR 1.25 (1.13–1.37) for CERAD and 1.63 (1.38–1.88) for Braak, mediating 53% and 111% of the total association respectively (Sin 2024, PMID 39481068). On that analysis, CAA has essentially no dementia effect independent of Alzheimer neuropathology.

The Rush/MARS analysis above reaches a compatible but more specific conclusion — CAA interacts with plaque burden, and tau mediates the CAA–cognition association only among participants with higher neuritic plaque burden (Rabin 2022, PMID 35759327). Read together: CAA appears to act by amplifying the amyloid-to-tau step rather than by adding an independent vascular insult, and a mediation proportion above 100% in the ACT data is a warning that CAA and Braak stage are too collinear at this age for observational adjustment to separate them. Neither study can exclude an independent CAA effect through microinfarction and white-matter injury, which neither measured directly.

The older population-autopsy evidence, however, found an interaction large enough that mediation framing may understate the clinical stake. In 211 Japanese-American men from the Honolulu-Asia Aging Study with antemortem Cognitive Abilities Screening Instrument scores and blinded neuropathology, CAA was present in at least one neocortical area in 44.1%, and its presence tracked higher neurofibrillary-tangle and neuritic-plaque counts and APOE ε4. Adjusted for age at death, interval to death, education, plaque and tangle counts, infarcts, haemorrhage and APOE, the CAA × Alzheimer-disease interaction on mean CASI was significant: against non-demented men without CAA, CASI was 16.6% lower in Alzheimer disease without CAA and 45.9% lower in Alzheimer disease with CAA (Pfeifer 2002, PMID 12058090). A near-tripling of the cognitive deficit when CAA accompanies Alzheimer pathology is not well described by saying CAA has "no independent effect" — the honest statement is that CAA's effect is conditional on Alzheimer pathology being present, which is the same structure Rabin later found for tau.

The monogenic model: HCHWA-D

Dutch-type hereditary cerebral haemorrhage with amyloidosis is CAA without the vascular-risk-factor background, and it is markedly worse. Comparing 58 HCHWA-D patients with 316 sporadic CAA patients over a mean 5 ± 4 years (1,550 person-years), HCHWA-D patients had fewer cardiovascular risk factors (≥1 risk factor in 24% vs 70%), presented a mean 18 years younger (54 vs 72), and had a recurrent ICH incidence of 20.9 versus 8.9 per 100 person-years (adjusted HR 2.8, 95% CI 1.6–4.9, P<0.001) with long-term mortality HR 2.8 (1.5–5.2, P=0.001), despite near-identical 90-day mortality (14% vs 15%) (van Etten 2016, PMID 27590282). Because most HCHWA-D patients have no conventional vascular risk factors, the accelerated recurrence is attributable to vascular amyloid itself — which makes it the cleanest available human model for testing amyloid-directed prevention of haemorrhage, in the same way CADASIL serves for ischaemic small-vessel disease.

Blood pressure after a lobar haemorrhage

This is the one modifiable exposure with a large observational effect in lobar ICH specifically. Among 1,145 ICH survivors followed a median 36.8 months at a single tertiary centre (505 lobar, 640 non-lobar; 102 and 44 recurrences), adequate BP control was achieved consistently by only 43.2%. Recurrence rates were 84 per 1,000 person-years with inadequate versus 49 per 1,000 with adequate control for lobar ICH, and 52 versus 27 for non-lobar. Modelling BP control as time-varying gave HR 3.53 (95% CI 1.65–7.54) for lobar and 4.23 (1.02–17.52) for non-lobar recurrence; each 10 mm Hg of follow-up systolic pressure carried HR 1.33 (1.02–1.76) for lobar and 1.54 (1.03–2.30) for non-lobar recurrence, while diastolic pressure predicted only non-lobar recurrence (Biffi 2015, PMID 26325559). It is observational and single-centre, with BP partly self-reported, and the authors call for randomized trials of stricter control in ICH survivors — which have still not reported. Given a 23% pooled recurrence rate and no antithrombotic strategy of proven net benefit, blood-pressure control is the intervention with the best risk-benefit case in CAA even though it has never been randomized in this population.

CAA-related inflammation/amyloid-β-related angiitis can cause subacute cognitive change, seizures, headache, focal deficits, and asymmetric vasogenic edema. Chung et al. described a characteristic clinical–radiologic syndrome and proposed diagnostic criteria, noting that immunosuppressive response is common and that selected patients may be treated without biopsy (Chung 2011, PMID 20935328).

In 48 consecutive CAA-ri episodes (mean follow-up 2.7 years), 33 (69%) received corticosteroids, 6 (13%) cyclophosphamide, 2 (4%) mycophenolate, and 14 (29%) no treatment. Immunosuppression versus none was associated with clinical improvement (32/34 [94%] vs 7/14 [50%]; OR 16.0, 95% CI 2.72–94.1), radiographic improvement (24/28 [86%] vs 4/14 [29%]; OR 15.0, 3.12–72.1), and lower recurrence (9/34 [26%] vs 10/14 [71%]; HR 0.19, 0.07–0.48) (Regenhardt 2020, PMID 32568365). This is observational, indication-confounded evidence, not a randomized effect size.

Recurrence risk and what predicts it

CAA-related intracerebral haemorrhage recurs at a rate that dominates every management decision on this page. Pooling 30 studies, the recurrence rate was 23% (95% CI 18–28%), with extreme heterogeneity (I²=96.7%). Predictors with pooled odds ratios were previous ICH (OR 2.03, 95% CI 1.50–2.75), baseline ICH volume (OR 1.01 per unit, 95% CI 1.00–1.02), convexity subarachnoid haemorrhage (OR 3.05, 95% CI 1.86–4.99), cortical superficial siderosis (OR 2.04, 95% CI 1.46–2.83), disseminated siderosis (OR 3.21, 95% CI 2.25–4.58), and centrum-semiovale perivascular-space severity (OR 1.67, 95% CI 1.14–2.45) (Jia 2023, PMID 38020625).

The siderosis signal predates that pooling by a decade and is unusually consistent. In a European multicentre cohort of 118 Boston-criteria CAA patients (104 with baseline symptomatic lobar ICH) followed a median 24 months, 4-year ICH risk was 25% without siderosis, 28.9% with focal siderosis, and 74% (95% CI 44.1–95.7) with disseminated siderosis (log-rank P=0.0031), with adjusted HR 2.53 (1.05–6.15) for any siderosis and 3.16 (1.35–7.43) for disseminated siderosis after accounting for ≥2 microbleeds and age (Charidimou 2013, PMID 24107862). The risk is also front-loaded: among 292 consecutive survivors of CAA-related lobar ICH aged ≥55, 21 (7%) had a recurrence within 6 months, and disseminated siderosis on MRI (HR 3.92, 95% CI 1.38–11.17) and acute convexity subarachnoid haemorrhage on CT (HR 3.48, 1.13–10.73) independently predicted it after adjustment for age and prior ICH (Roongpiboonsopit 2016, PMID 27694268). This six-month estimate is relevant to antithrombotic restart timing, but observational data cannot determine an individual restart decision; CT can identify one of the reported predictors.

The strongest independent confirmation comes from within a randomized trial. In the prespecified imaging subanalysis of PRESTIGE-AF (313 of 319 participants with adequate imaging, median age 79, MRI in 170), over a median 1.4 years, recurrent ICH was not associated with lobar versus non-lobar haematoma location or with the overall category of probable CAA (both P>0.2) — but was strongly associated with cortical superficial siderosis (HR 7.7, 95% CI 1.4–42.2) and chronic intracerebral macrohaemorrhages on MRI (HR 9.1, 95% CI 1.8–46.8), while non-lobar ICH predicted ischaemic stroke (HR 9.1, 95% CI 1.2–67.7) (Fandler-Höfler 2025, PMID 41197104). Only 13 recurrent ICH and 22 ischaemic strokes occurred, so the intervals are very wide. Still, the direction is consistent and clinically pointed: the diagnostic category "probable CAA" did not stratify recurrence risk, whereas one specific marker within it did. This argues for siderosis-based rather than criteria-based risk communication.

Risk stratification where MRI is unavailable

Most of the world diagnoses lobar ICH on CT. An individual-patient-data meta-analysis of eight cohorts from six countries tested whether the Edinburgh CT-only and CT-APOE criteria predict recurrence. In the primary two-stage analysis (562 patients, three European cohorts, 69 recurrences over 1,381 person-years), 5-year recurrence was 48/307 (16%) in the intermediate/high-risk group versus 21/255 (8%) in the low-risk group (adjusted subdistribution HR 1.79, 95% CI 1.05–3.05; P=0.032). In the pooled one-stage analysis (1,620 patients, 171 recurrences over 3,208 person-years), cumulative 5-year recurrence rose across strata: 45/727 (12%) low risk, 54/513 (16%) intermediate (aSHR 1.68, 95% CI 1.21–2.32), and 72/380 (26%) high risk (aSHR 2.97, 95% CI 1.50–5.89). Adding APOE genotype to CT gave a 3-year recurrence of 34/320 (15%) in the high-risk group versus 14/322 (8%) in the low-risk group (aSHR 2.22, 95% CI 1.36–3.61) (Rodrigues 2025, PMID 40975099). A CT-based criterion set that separates 12% from 26% five-year recurrence closes part of the equity gap that MRI-dependent criteria create.

How CAA drives cognitive decline: through tau, not directly

The mechanism linking CAA to dementia has been resolved further than the rest of this page's uncertainty would suggest. Across 1,722 autopsied participants from the Rush Memory and Aging Project, Religious Orders Study, and Minority Aging Research Study (mean age at baseline 80.2, at death 89.5; 68% female), CAA interacted with neuritic plaque burden — more severe CAA plus higher plaque burden produced greater tau burden and faster cognitive decline than either alone — and causal mediation analysis showed that tau mediated the CAA–cognition association among participants with higher neuritic plaque burden (Rabin 2022, PMID 35759327). CAA is therefore not simply an additive vascular insult; it appears to accelerate the amyloid-to-tau step. This is the strongest available mechanistic argument that CAA belongs on the Alzheimer side of the border as much as the vascular side, and it predicts that anti-amyloid therapy in CAA-heavy patients could in principle help cognition while simultaneously raising ARIA risk (see below) — a tradeoff no trial has tested prospectively.

Iatrogenic CAA: a transmissible phenotype

A CAA phenotype exists that has nothing to do with ageing, and its existence changes what the disease is understood to be. Three patients presenting with early-onset symptomatic amyloid-β CAA had all been exposed in childhood to cadaveric dura — two by neurosurgical grafting, one by tumour embolization — providing in-vivo clinical and neuroimaging evidence that CAA can follow transmission of amyloid-β seeds present in cadaveric tissue (Banerjee 2019, PMID 30597599). Proposed criteria require a documented intervention with transmission potential (cadaveric dura, or instrumentation of brain or spinal cord) followed by an appropriate latency, usually three to four decades.

The initial cases were all young, which made the diagnosis relatively easy. That has changed: five cases of possible iatrogenic CAA have now been reported in adults aged 65 and over, all with prior neurosurgery and latencies of 30–39 years, with cadaveric dura confirmed in one and highly likely in the rest (Panteleienko 2024, PMID 38511868). In that age group iatrogenic and sporadic CAA are not separable on imaging or presentation, only on history; case reports cannot establish the true frequency. A surgical history from the era of cadaveric dura grafting therefore deserves asking about in a CAA workup. The reports provide a documented acquired-transmission model and support seeded, progressive vascular amyloid deposition after a decades-long latency.

Antithrombotic decisions

Cerebral microbleeds predict higher intracranial-haemorrhage risk during anticoagulation, but atrial fibrillation also creates preventable ischaemic-stroke risk. In 1,552 AF-stroke patients, CMB presence raised ICH odds (OR 2.68, 1.19–6.01) and ≥5 CMBs raised them further (OR 5.50, 2.07–14.66); annual ICH incidence rose from 0.30% without CMBs to 0.81% with any CMB and 2.48% with ≥5 (Charidimou 2017, PMID 29117953). Later meta-analysis in anticoagulated AF after stroke similarly found higher ICH with baseline CMBs, especially ≥5, and higher ICH than recurrent ischaemic stroke after anticoagulation in that selected literature (Zhao 2024, PMID 38560733). Observational comparisons cannot fully eliminate confounding by indication (Cheng 2021, PMID 31616992).

Decision input Favors haemorrhage concern Favors ischaemic prevention
MRI numerous lobar microbleeds, siderosis small infarcts/embolic pattern
Clinical history prior lobar ICH or TFNE prior embolic stroke
Etiology probable CAA high-risk AF
Modifiers uncontrolled BP, falls high CHA₂DS₂-VASc factors

Left atrial appendage occlusion is the most-discussed way out of the dilemma, and the evidence for it in this specific population is observational and small. Pooling a multicentre cohort with two published series gives 102 patients with CAA-related symptomatic ICH and atrial fibrillation treated with LAAO (mean age 76.2±8.0, 74.6% male), followed a median 9.4 months (IQR 4.2–20.6). Post-procedural antithrombotics were single antiplatelet (73.0%), dual antiplatelet (16.2%), or a DOAC (10.8%) for a median 42 days. Complications were uncommon (transient arrhythmia 2.1%, non-life-threatening tamponade 2.1%). Pooled incidence was 5.16 per 100 patient-years for ischaemic stroke (95% CI 1.36–17.48) and 2.73 per 100 patient-years for ICH (95% CI 0.41–13.94) (Thiankhaw 2025, PMID 39694822). Both intervals span an order of magnitude on ~100 patients and under a year of median follow-up; the authors call explicitly for randomized comparison against long-term DOAC. LAAO in CAA is a plausible strategy with no controlled evidence, not an established one.

ARIA and anti-amyloid therapy

ARIA-E is FLAIR edema/effusion; ARIA-H is GRE/T2* microhaemorrhage or siderosis. The construct was defined for amyloid-modifying trials because of overlap with CAA imaging (Sperling 2011, PMID 21784348). In CLARITY-AD, lecanemab produced ARIA-E in 12.6% and infusion reactions in 26.4% of 898 treated participants (van Dyck 2023, PMID 36449413). In TRAILBLAZER-ALZ 2, donanemab produced ARIA-E in 205/860 (24.0%; 52 symptomatic) versus 18/876 (2.1%) on placebo (Sims 2023, PMID 37459141). Pre-existing CAA-like imaging, APOE genotype, dose, and anticoagulation are the main modifiers discussed in trial and consensus literature; drug-specific eligibility belongs in Alzheimer's disease.

Management framework

  • Control hypertension while avoiding symptomatic hypotension.
  • Characterize haemorrhage distribution with susceptibility-sensitive MRI.
  • Avoid reflex antiplatelet use for imaging-only disease.
  • Reassess anticoagulant indication and alternatives after lobar ICH or TFNE.
  • Treat acute ICH through established haemorrhage pathways (Greenberg 2022, PMID 35579034).
  • Investigate inflammatory presentations urgently.
  • Counsel that cognitive and haemorrhage risks share a vessel substrate.

The 2025 International CAA Association/WSO statement covers diagnosis, ICH-risk prediction, antithrombotics, vascular risk, CAA manifestations, and CAA-ri (Cordonnier 2025, PMID 40721902).

Open questions

  • How well do Boston v2.0 criteria perform in consecutive memory-clinic cohorts? (Switzer 2024, PMID 38710005)
  • Can fluid biomarkers distinguish clinically consequential CAA from Alzheimer disease? (Muir 2025, PMID 40156276)
  • What antithrombotic strategy maximizes net benefit across CAA severity? (Charidimou 2017, PMID 29117953)
  • Can ARIA risk models serve as validated measures of underlying CAA? (Sperling 2011, PMID 21784348; Cordonnier 2025, PMID 40721902)
  • Why did cortical superficial siderosis stratify ICH recurrence within a randomized trial when the diagnostic category "probable CAA" did not? (Fandler-Höfler 2025, PMID 41197104)
  • If tau mediates CAA-related cognitive decline, could anti-amyloid therapy help cognition in CAA while raising ARIA risk in the same patients? (Rabin 2022, PMID 35759327; Sperling 2011, PMID 21784348)
  • Should CT-based Edinburgh criteria replace MRI-dependent risk stratification where MRI is unavailable? (Rodrigues 2025, PMID 40975099)
  • Does left atrial appendage occlusion beat long-term DOAC in CAA-related ICH with atrial fibrillation? (Thiankhaw 2025, PMID 39694822)
  • Does CAA contribute to dementia independently of Alzheimer neuropathology, or is the association fully mediated by plaques and tangles? (Sin 2024, PMID 39481068; Rabin 2022, PMID 35759327)
  • Is CAA's cognitive effect independent, fully mediated by Alzheimer pathology, or conditional on it — given a 45.9% versus 16.6% CASI deficit for AD-with-CAA versus AD-alone? (Pfeifer 2002, PMID 12058090; Sin 2024, PMID 39481068)
  • If 79% of CAA patients meet MCI criteria with a vascular rather than Alzheimer profile, should cognitive assessment be routine in imaging-diagnosed CAA? (Case 2016, PMID 27338926)
  • How many older adults diagnosed with sporadic CAA in fact have iatrogenic disease from neurosurgery three to four decades earlier? (Panteleienko 2024, PMID 38511868; Banerjee 2019, PMID 30597599)
  • How should antithrombotic restart after lobar ICH incorporate the observed 7% six-month recurrence rate and its siderosis/cSAH predictors alongside longer-term estimates and ischaemic risk? (Roongpiboonsopit 2016, PMID 27694268; Jia 2023, PMID 38020625)
  • Should APOE ε2 rather than ε4 be the genotype reported when counselling about haemorrhage risk in CAA? (Charidimou 2019, PMID 31243071; Charidimou 2015, PMID 25716356)
  • Are haemorrhagic and non-haemorrhagic CAA distinct diseases requiring separate criteria rather than one criterion set with different sensitivities? (Charidimou 2015, PMID 25716356; Switzer 2024, PMID 38710005)
  • Would randomized intensive blood-pressure control reduce recurrence after lobar ICH, as the 84-vs-49 per 1,000 person-year observational gap implies? (Biffi 2015, PMID 26325559)
  • Can HCHWA-D serve as the trial population for amyloid-directed haemorrhage prevention, given a 20.9 per 100 person-year recurrence rate? (van Etten 2016, PMID 27590282)

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