BACKGROUND: Cerebral amyloid angiopathy-related inflammation (CAA-ri) derives from inflammatory response to β-amyloid (Aβ) protein deposition within the cerebral blood vessel walls. We report a case that accentuates those clinical and imaging features that can contribute to raise suspicion for the condition and lead to early treatment initiation.
METHODS: A 72-year-old man was referred with one-month history of cognitive decline along with behavioral alterations. Brain MRI showed fluid attenuated inversion recovery (FLAIR) asymmetrical multifocal white matter hyperintensities (WMHs) along with multiple cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS) on T2*-weighted gradient-recalled echo (T2*-GRE) images. Metabolic, infectious, and neoplastic causes were excluded, and subsequently corticosteroids were administered to the patient resulting in clinical recovery. Imaging on follow-up disclosed remission of WMHs, while CMBs load increased significantly.
CONCLUSIONS: Clinical neurologists\' acquaintance with the clinical and imaging features of CAA-ri allows prompt diagnosis and medication initiation, that is essential for a conceivably treatable condition.

Anderson-Fabry disease (AFD) is a genetic sphingolipidosis involving virtually the entire body. Among its manifestation, the involvement of the central and peripheral nervous system is frequent. In recent decades, it has become evident that, besides cerebrovascular damage, a pure neuronal phenotype of AFD exists in the central nervous system, which is supported by clinical, pathological, and neuroimaging data. This neurodegenerative phenotype is often clinically characterized by an extrapyramidal component similar to the one seen in prodromal Parkinson\'s disease (PD). We analyzed the biological, clinical pathological, and neuroimaging data supporting this phenotype recently proposed in the literature. Moreover, we compared the neurodegenerative PD phenotype of AFD with a classical monogenic vascular disease responsible for vascular parkinsonism and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). A substantial difference in the clinical and neuroimaging features of neurodegenerative and vascular parkinsonism phenotypes emerged, with AFD being potentially responsible for both forms of the extrapyramidal involvement, and CADASIL mainly associated with the vascular subtype. The available studies share some limitations regarding both patients\' information and neurological and genetic investigations. Further studies are needed to clarify the potential association between AFD and extrapyramidal manifestations.

Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid protein in the walls of cerebral blood vessels. This deposition of amyloid causes damage to the cerebral vasculature, resulting in blood-brain barrier disruption, cerebral hemorrhage, cognitive decline, and dementia. The role of the immune system in CAA is complex and not fully understood. While the immune system has a clear role in the rare inflammatory variants of CAA (CAA related inflammation and Abeta related angiitis), the more common variants of CAA also have immune system involvement. In a protective role, immune cells may facilitate the clearance of beta-amyloid from the cerebral vasculature. The immune system can also contribute to CAA pathology, promoting vascular injury, blood-brain barrier breakdown, inflammation, and progression of CAA. In this review, we summarize the role of the immune system in CAA, including the potential of immune based treatment strategies to slow vascular disease in CAA and associated cognitive impairment, white matter disease progression, and reduce the risk of cerebral hemorrhage. HIGHLIGHTS: The immune system has a role in cerebral amyloid angiopathy (CAA) which is summarized in this review. There is an inflammatory response to beta-amyloid that may contribute to brain injury and cognitive impairment. Immune cells may facilitate the clearance of beta-amyloid from the cerebral vasculature. Improved understanding of the immune system in CAA may afford novel treatment to improve outcomes in patients with CAA.

The Boston criteria v2.0 for cerebral amyloid angiopathy (CAA) incorporated non-hemorrhagic imaging markers. Their prevalence and significance in patients with cognitive impairment remain uncertain.
We studied 622 memory clinic patients with available magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers. Two raters assessed non-hemorrhagic markers, and we explored their association with clinical characteristics through multivariate analyses.
Most patients had mild cognitive impairment; median age was 71 years and 50% were female. Using the v2.0 criteria, possible or probable CAA increased from 75 to 383 patients. Sixty-eight percent of the sample had non-hemorrhagic CAA markers, which were independently associated with age (odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.01-1.07), female sex (OR = 1.68, 95% CI = 1.11-2.54), and hemorrhagic CAA markers (OR = 2.11, 95% CI = 1.02-4.35).
Two-thirds of patients from a memory clinic cohort had non-hemorrhagic CAA markers, increasing the number of patients meeting the v2.0 CAA criteria. Longitudinal approaches should explore the implications of these markers, particularly the hemorrhagic risk in this population.
The updated Boston criteria for cerebral amyloid angiopathy (CAA) now include non-hemorrhagic markers. The prevalence of non-hemorrhagic CAA markers in memory clinic patients is unknown. Two-thirds of patients in our memory clinic presented non-hemorrhagic CAA markers. The presence of these markers was associated with age, female sex, and hemorrhagic CAA markers. The hemorrhagic risk of patients presenting these type of markers remains unclear.

OBJECTIVE: Possible differences in the prevalence of cerebral amyloid angiopathy (CAA) in East-Asian compared to Western populations have received little attention, and results so far have been ambiguous. Our aim is to compare the prevalence of CAA neuropathology and magnetic resonance imaging markers of CAA in East-Asian and Western cohorts reflecting the general population, cognitively normal elderly, patients with Alzheimer\'s disease (AD), and patients with (lobar) intracerebral hemorrhage (ICH).
METHODS: We performed a systematic literature search in PubMed and Embase for original research papers on the prevalence of CAA and imaging markers of CAA published up until February 17th 2022. Records were screened by two independent reviewers. Pooled estimates were determined using random-effects models. We compared studies from Japan, China, Taiwan, South Korea (East-Asian cohorts) to studies from Europe or North America (Western cohorts) by meta-regression models.
RESULTS: We identified 12,257 unique records, and we included 143 studies on Western study populations and 53 studies on East-Asian study populations. Prevalence of CAA neuropathology did not differ between East-Asian and Western cohorts in any of the investigated patient domains. The prevalence of strictly lobar microbleeds was lower in East-Asian cohorts of population-based individuals (5.6% vs. 11.4%, P=0.020), cognitively normal elderly (2.6% vs. 11.4%, P=0.001), and patients with ICH (10.2% vs. 24.6%, P<0.0001). However, age was in general lower in the East-Asian cohorts.
CONCLUSIONS: The prevalence of CAA neuropathology in the general population, cognitively normal elderly, patients with AD, and patients with (lobar) ICH is similar in East-Asian and Western countries. In East-Asian cohorts reflecting the general population, cognitively normal elderly, and patients with ICH, strictly lobar microbleeds were less prevalent, likely due to their younger age. Consideration of potential presence of CAA is warranted in decisions regarding antithrombotic treatment and potential new anti-amyloid-β immunotherapy as treatment for AD in East-Asian and Western countries alike.

UNASSIGNED: Cerebral microbleeds (MBs) are recently described entity on magnetic resonance (MR) neuroimaging and are considered one of the markers of small vessel disease. We aimed to study the clinicoradiological features of cerebral MBs that were diagnosed in MR neuroimaging.
UNASSIGNED: We studied 109 South Indian patients, who presented to a tertiary care institution for MR neuroimaging with cerebral MBs as diagnosed on MR neuroimaging based on either the gradient T2* imaging or susceptibility-weighted imaging. The clinical details and coexisting MR features of infarcts, macrohemorrhages, lacunar infarcts, and white matter leukoaraiosis were evaluated and analyzed.
UNASSIGNED: Of 109 patients, 79 were males and 30 were females. Associated clinical comorbidities noted include hypertension (62.39%), diabetes (23.85%), and alcoholism (31.19%) apart from the history of anti-platelet/anti-coagulant usage (15.5%), previous cardiac disease (12.84%), and previous stroke/transient ischemic attacks (9.17%). Other co-existing neuroimaging abnormalities noted include cortical infarcts (27.52%), old hemorrhages (29.36%), lacunar infarcts (56.88%), and white matter leukaraiosis (67.89%).
UNASSIGNED: The clinicoradiological features of cerebral MBs in South Indian patients are similar to other Asian and Western studies with significant coexistence of clinical comorbidities and imaging features of small vessel changes. Further studies with a larger sample are needed to correlate the grade of MBs to the individual risk of these clinicoradiological characteristics.

UNASSIGNED: Efficiently and accurately detecting cerebral microbleeds (CMBs) is crucial for diagnosing dementia, stroke, and traumatic brain injury. Manual CMB detection, however, is time-consuming and error-prone. This study evaluates a novel artificial intelligence (AI) software designed for the automated detection of CMBs using susceptibility weighted imaging (SWI).
UNASSIGNED: The SWI data from 265 patients, 206 of whom had a history of stroke and others of whom presented a variety of other medical histories, including hypertension, diabetes, hyperlipidemia, cerebral hemorrhage, intracerebral vascular malformations, tumors, and inflammation, collected between January 2015 and December 2018, were analyzed. Two independent radiologists initially reviewed the images to identify and count the number of CMBs. Subsequently, the images were processed using an automatic CMB detection software. The generated reports were then reviewed by the radiologists. A final consensus between the two radiologists, obtained after a second review of the images, was used to compare results obtained from the initial manual detection and those of the automatic CMB detection software. The differences of detection sensitivity and precision for patients with or without CMBs and for individual CMBs between the radiologist and the automatic CMB detection software were compared using Pearson chi-squared tests.
UNASSIGNED: A total of 1,738 CMBs were detected among 148 patients (71.4±10.7 years, 100 males) from the analyzed SWI data. While the radiologists identified 139 cases with CMBs, the automatic CMB detection software detected 145 cases. Nevertheless, there was no statistical difference in the sensitivity and specificity of the automatic CMB detection software compared to manual detection in determining patients with CMBs (P=0.656 and P=0.212, chi-square test). However, the radiologist identified 93 patients without CMBs, while the automatic CMB detection software detected 121 patients without CMBs, exhibiting a statistically significant difference (P=0.016, chi-square test). In terms of individual CMBs, the radiologists found 1,284, whereas the automatic CMB detection software detected 1,677 CMBs. The detection sensitivity for human versus the automatic CMB detection software were 75.5% and 96.5% respectively (P<0.001, chi-square test), while the precision rates were 92.2% and 86.0% (P<0.001, chi-square test), respectively. Notably, the radiologists were more likely to overlook CMBs when the number of CMBs was high (above 30).
UNASSIGNED: The automatic CMB detection software proved to be an effective tool for the detection and quantification of CMBs. It demonstrated higher sensitivity than the radiologists, especially in detecting minuscule CMBs and in cases with high CMB prevalence.

BACKGROUND: Strictly superficial cerebellar microbleeds and cerebellar superficial siderosis have been considered markers of advanced cerebral amyloid angiopathy (CAA), but there are few studies on cerebellar ischemic lesions in CAA. We investigated the presence of superficial small cerebellar infarct (SCI) ≤15 mm and its relation to magnetic resonance imaging (MRI) markers in patients with probable CAA.
METHODS: Eighty patients with probable CAA were retrospectively evaluated. The presence of superficial SCIs was examined, along with cerebellar microbleeds and cerebellar superficial siderosis, using 3-T MRI. Lobar cerebral microbleeds, cortical superficial siderosis (cSS), enlargement of the perivascular space in the centrum semiovale, and white matter hyperintensity were assessed and the total CAA-small vessel disease (SVD) score was calculated.
RESULTS: Nine of the 80 patients (11.3%) had a total of 16 superficial SCIs. By tentatively defining SCI <4 mm as cerebellar microinfarcts, 8 out of 16 (50%) superficial SCIs corresponded to cerebellar microinfarcts. The total CAA-SVD score was significantly higher in patients with superficial SCIs (p = 0.01). The prevalence of cSS (p = 0.018), cortical cerebral microinfarct (p = 0.034), and superficial cerebellar microbleeds (p = 0.006) was significantly higher in patients with superficial SCIs. The number of superficial cerebellar microbleeds was also significantly higher in patients with superficial SCIs (p = 0.001).
CONCLUSIONS: Our results suggest that in patients with CAA, superficial SCIs (including microinfarcts) on MRI may indicate more severe, advanced-stage CAA. These preliminary findings should be verified by larger prospective studies in the future.

The purpose of this study is to the relationship between peripheral apolipoproteins and cerebral small vessel disease (CSVD) imaging markers.
We reviewed the data of a population that above 40 years old with CSVD, while free of known dementia or acute stroke. We evaluated CSVD imaging markers, including white matter hyperintensities (WMHs), enlarged perivascular spaces (EPVS), lacunas, microbleeds by MRI scans, and measured peripheral apolipoproteins.
After adjusting for age, sex and vascular risk factors,1) apoB and apoB/apoA-1 were related to grade of EPVS in basal ganglia(apoB:r=0.196,p<0.001;apoB/apoA-1:r=0.208,p<0.001), apoE was related to grade of EPVS in centrum semiovale (r=0.125,p=0.040); 2) apoB(OR=1.739, 95%CI=1.357-2.061, p<0.001), apoB/apoA-1(OR=1.116, 95%CI=1.037-1.761, p=0.005) and apoE(OR=1.287, 95%CI=1.036-1.599, p=0.023) were independent factors of presence of severer EPVS in basal ganglia, apoE was an independent factor of presence of severer EPVS in centrum semiovale (OR=1.235, 95%CI=1.021-1.494, p=0.029).
Our findings demonstrated peripheral apolipoproteins, including apoB, apoB/apoA-1, and apoE, were independent factor for EPVS in CSVD.

Amyloidosis, including cerebral amyloid angiopathy, and markers of small vessel disease (SVD) vary across dominantly inherited Alzheimer\'s disease (DIAD) presenilin-1 (PSEN1) mutation carriers. We investigated how mutation position relative to codon 200 (pre-/postcodon 200) influences these pathologic features and dementia at different stages.
Individuals from families with known PSEN1 mutations (n = 393) underwent neuroimaging and clinical assessments. We cross-sectionally evaluated regional Pittsburgh compound B-positron emission tomography uptake, magnetic resonance imaging markers of SVD (diffusion tensor imaging-based white matter injury, white matter hyperintensity volumes, and microhemorrhages), and cognition.
Postcodon 200 carriers had lower amyloid burden in all regions but worse markers of SVD and worse Clinical Dementia Rating® scores compared to precodon 200 carriers as a function of estimated years to symptom onset. Markers of SVD partially mediated the mutation position effects on clinical measures.
We demonstrated the genotypic variability behind spatiotemporal amyloidosis, SVD, and clinical presentation in DIAD, which may inform patient prognosis and clinical trials.
Mutation position influences Aβ burden, SVD, and dementia. PSEN1 pre-200 group had stronger associations between Aβ burden and disease stage. PSEN1 post-200 group had stronger associations between SVD markers and disease stage. PSEN1 post-200 group had worse dementia score than pre-200 in late disease stage. Diffusion tensor imaging-based SVD markers mediated mutation position effects on dementia in the late stage.