脳表ヘモジデリン沈着症

INTRODUCTION: Anti-amyloid therapies such as lecanemab require magnetic resonance imaging (MRI) screening to exclude patients with > 4 gradient-recalled echo (GRE)-detected microhemorrhages or any superficial siderosis (SS). Although GRE and susceptibility-weighted imaging (SWI) are both accepted, they differ in detection performance. METHODS: We retrospectively analyzed 224 eligibility MRIs with paired GRE and SWI from a single academic health system. Six neuroradiologists assessed a 20-scan reliability subset; the remaining 204 scans were assigned to one rater for hemorrhagic lesion detection and MRI-based eligibility classification. Interobserver reliability was calculated using intraclass correlation coefficients (ICCs), and sequence differences were evaluated using non-parametric tests. RESULTS: SWI detected more microhemorrhages than GRE (mean 1.24 vs. 0.67, p < 0.0001), identified eight additional SS cases, and showed higher interobserver agreement (ICC 0.951 vs. 0.764, p < 0.01). SWI classified more patients as MRI ineligible than GRE (26/204 [12.7%] vs. 11/204 [5.4%]). DISCUSSION: SWI identifies more exclusionary hemorrhagic findings and demonstrates greater reproducibility than GRE.

The prognostic implications of covert cerebral small vessel disease (SVD) in spontaneous intracerebral hemorrhage (ICH) remain unclear. We investigated associations of SVD markers with hematoma severity and functional outcomes in patients with ICH. SVD markers (white matter hyperintensities [WMH], cerebral microbleeds [CMBs], lacunes, and cortical superficial siderosis [cSS]) were assessed. Outcomes included hematoma volume, hematoma expansion, and disability or death (mRS4-6 at 90 days and 1 year). Of 1,660 patients who underwent MRI (mean age:70±13years, 43% female), 397 had lobar (143 CAA-related) and 1,263 had deep ICH. In lobar ICH, confluent WMH (β=-0.29, 95%CI-0.54 to -0.01) and mixed CMB (β=-0.72[-1.02 to -0.42]) were associated with smaller hematoma volume, and cSS was associated with hematoma expansion (OR, 1.97[1.03-3.79]). In deep ICH, confluent WMH (β=-0.25[-0.41 to -0.09]), ≥5mixed CMBs (β=-0.17[-0.34 to -0.01]), and lacune(β=-0.21[-0.34 to -0.06]) were associated with smaller hematoma volume. Confluent WMH and mixed CMBs were also associated with poor functional outcome at 90 days (aOR 1.71[1.16-2.51] and 1.52[1.02-2.24]) and 1 year (aOR, 1.56[1.06-2.23] and 1.42[1.01-1.99]), and incorporating these markers into established risk factors improved discrimination for 1-year functional outcome. Similar findings were observed in ICH etiology. Covert SVD markers are associated with hematoma severity and functional outcomes after ICH.

BACKGROUND AND OBJECTIVES: Cerebral amyloid angiopathy (CAA) is currently diagnosed using MRI-based Boston criteria. However, imaging markers represent downstream consequences of vascular injury and may not fully reflect disease severity. CSF biomarkers, particularly β-amyloid 1-42 (Aβ42) and β-amyloid 1-40 (Aβ40), may provide a more direct measure of vascular amyloid burden. We investigated the association between CSF biomarkers and hemorrhagic and nonhemorrhagic MRI markers of disease severity in probable CAA. METHODS: We conducted a retrospective multicenter cohort study including consecutive patients diagnosed with probable CAA according to Boston criteria v2.0 at 2 tertiary centers (2014-2023) who underwent lumbar puncture (LP) as part of clinical evaluation. CSF Aβ42, Aβ40, total tau, and phosphorylated-tau 181 (p-tau181) were measured using standardized immunoassays. MRI markers included lobar cerebral microbleeds (CMBs), cortical superficial siderosis (cSS), white matter hyperintensity burden, Fazekas score, and enlarged perivascular spaces in the centrum semiovale. Multivariable linear regression models were adjusted for age, sex, MRI sequence type, and delay between onset and LP. False discovery rate correction was applied for multiple testing. We also used principal component analysis to explore associations between MRI and CSF biomarkers. RESULTS: A total of 102 patients were included (mean age at LP 72.0 ± 7.5 years; 65% male). Initial presentations were cognitive impairment in 53%, intracerebral hemorrhage in 34%, and transient focal neurologic episodes in 13%. Lower CSF Aβ40 and Aβ42 levels were significantly associated with greater cSS burden (standardized β -0.49 [95% CI -0.8 to -0.17], p = 0.002 and -0.42 [-0.73 to -0.11], p = 0.007, respectively) and higher Fazekas score (β -0.18 [-0.33 to -0.03], p = 0.02 and -0.23 [-0.38 to -0.08], p = 0.002) but not with CMB count. No significant association was found between tau species and MRI markers. Associations remained significant after stratification by CSF Aβ42/Aβ40-defined Alzheimer-like profile. DISCUSSION: In probable CAA, lower CSF Aβ40 and Aβ42 levels are associated with established MRI markers of disease severity, independently of clinical presentation and concomitant Alzheimer-like profile. These findings suggest that CSF Aβ levels may reflect vascular amyloid burden rather than downstream neurodegeneration. Prospective longitudinal studies are needed to determine their prognostic value.

Although radiological severity thresholds for amyloid-related imaging abnormalities with hemosiderin deposition (ARIA-H) were developed using 2-dimensional acquisitions of T2*-weighted gradient-recalled echo (T2*GRE) MRI in pivotal anti-amyloid trials, adoption of well established 3D susceptibility-weighted imaging (SWI) in ARIA-H monitoring in clinical practice represents a reasonable long-term direction for clinical practice. SWI provides documented higher sensitivity and comparable or superior inter-rater reliability compared with conventional T2*GRE for detecting cerebral microbleeds and cortical superficial siderosis, the two key imaging manifestations of ARIA-H. Moreover, SWI is already incorporated into most contemporary dementia MRI protocols, offering important practical and logistical advantages. Available preliminary evidence suggests that the downstream clinical impact of detecting a few additional microbleeds or areas of siderosis may remain modest for most patients. Earlier and more reliable detection could potentially enhance safety by identifying individuals at higher risk of ARIA-H before treatment initiation. The critical requirements are transparency regarding sequence choice and consistency within individual patients over time.

INTRODUCTION: Incident microhemorrhages and superficial siderosis are hemorrhagic magnetic resonance imaging (MRI) abnormalities relevant to amyloid-related imaging abnormalities with hemosiderin deposition (ARIA-H) risk stratification, but evidence exploring their short-term dynamic predictors remains limited. METHODS: We analyzed longitudinal MRI data from the A4 study, constructing a discrete person-interval dataset for modeling the short-term risk of incident hemorrhagic MRI abnormalities. Models incorporated baseline covariates, alongside dynamic variables of recent microhemorrhage accumulation and current microhemorrhage burden. The outcome was defined as two or more new microhemorrhages or one or more new superficial siderosis between consecutive MRI scans. RESULTS: Among 1069 participants (3647 intervals), 171 hemorrhagic events occurred. Both current burden (time-to-event: odds ratio [OR] 1.37, 95% confidence interval [CI] 1.09-1.73; all-event: OR 1.24, 95% CI: 1.04-1.49) and recent microhemorrhage accumulation were independently associated with an increased risk of hemorrhagic events (time-to-event: OR 1.83, 95% CI 1.01-3.30; all-event: OR 1.43, 95% CI: 1.00-2.04). DISCUSSION: Temporal imaging variables may provide independent prognostic information beyond baseline risk, supporting a dynamic model of hemorrhagic risk in Alzheimer's disease. CLINICAL TRIAL REGISTRATION: Clinical trial of Solanezumab for older individuals who may be at risk for memory loss (A4) (NCT02008357).