Dementia incidence and predictors in cerebral amyloid angiopathy patients without intracerebral hemorrhage

Cerebral amyloid angiopathy (CAA) is a common cause of cognitive impairment in older individuals. This study aimed to investigate predictors of dementia in CAA patients without intracerebral hemorrhage (ICH). A total of 158 non-demented patients from the Stroke Service or the Memory Clinic who met the modified Boston Criteria for probable CAA were included. At baseline, neuroimaging markers, including lobar microbleeds (cerebral microbleeds (CMBs)), white matter hyperintensities (WMH), cortical superficial siderosis (cSS), magnetic resonance imaging (MRI)-visible centrum semiovale perivascular spaces (CSO-PVS), lacunes, and medial temporal atrophy (MTA) were assessed. The overall burden of small vessel disease (SVD) for CAA was calculated by a cumulative score based on CMB number, WMH severity, cSS presence and extent and CSO-PVS severity. The estimated cumulative dementia incidence at 1 year was 14% (95% confidence interval (CI): 5%–23%), and 5 years 73% (95% CI: 55%, 84%). Age (hazard ratio (HR) 1.05 per year, 95% CI: 1.01–1.08, p = 0.007), presence of MCI status (HR 3.40, 95% CI: 1.97–6.92, p < 0.001), MTA (HR 1.71 per point, 95% CI: 1.26–2.32, p = 0.001), and SVD score (HR 1.23 per point, 95% CI: 1.20–1.48, p = 0.030) at baseline were independent predictors for dementia conversion in these patients. Cognitive deterioration of CAA patients appears attributable to cumulative changes, from both vasculopathic and neurodegenerative lesions.

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Advances in cerebral amyloid angiopathy imaging

Therapeutic Advances in Neurological Disorders ◽

10.1177/1756286419844113 ◽

2019 ◽

Vol 12 ◽

pp. 175628641984411 ◽

Cited By ~ 2

Author(s):

Szu-Ju Chen ◽

Hsin-Hsi Tsai ◽

Li-Kai Tsai ◽

Sung-Chun Tang ◽

Bo-Chin Lee ◽

...

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Small Vessel Disease ◽

Imaging Techniques ◽

White Matter Hyperintensity ◽

Superficial Siderosis ◽

Clinical Aspects ◽

Amyloid Angiopathy ◽

Perivascular Spaces ◽

Imaging Studies ◽

Cerebral Amyloid

Cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease caused by β -amyloid (Aβ) deposition at the leptomeningeal vessel walls. It is a common cause of spontaneous intracerebral hemorrhage and a frequent comorbidity in Alzheimer’s disease. The high recurrent hemorrhage rate in CAA makes it very important to recognize this disease to avoid potential harmful medication. Imaging studies play an important role in diagnosis and research of CAA. Conventional computed tomography and magnetic resonance imaging (MRI) methods reveal anatomical alterations, and remains as the most reliable tool in identifying CAA according to modified Boston criteria. The vascular injuries of CAA result in both hemorrhagic and ischemic manifestations and related structural changes on MRI, including cerebral microbleeds, cortical superficial siderosis, white matter hyperintensity, MRI-visible perivascular spaces, and cortical microinfarcts. As imaging techniques advance, not only does the resolution of conventional imaging improve, but novel skills in functional and molecular imaging studies also enable in vivo analysis of vessel physiological changes and underlying pathology. These modern tools help in early detection of CAA and may potentially serve as sensitive outcome markers in future clinical trials. In this article, we reviewed past studies of CAA focusing on utilization of various conventional and novel imaging techniques in both research and clinical aspects.

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Cerebral amyloid angiopathy severity is linked to dilation of juxtacortical perivascular spaces

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x15620434 ◽

2015 ◽

Vol 36 (3) ◽

pp. 576-580 ◽

Cited By ~ 33

Author(s):

Susanne J van Veluw ◽

Geert Jan Biessels ◽

Willem H Bouvy ◽

Wim GM Spliet ◽

Jaco JM Zwanenburg ◽

...

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Small Vessel Disease ◽

Amyloid Β ◽

Amyloid Angiopathy ◽

Perivascular Spaces ◽

Resonance Imaging ◽

Centrum Semiovale ◽

Tissue Sections ◽

Cortical Areas ◽

Cerebral Amyloid

Perivascular spaces are an emerging marker of small vessel disease. Perivascular spaces in the centrum semiovale have been associated with cerebral amyloid angiopathy. However, a direct topographical relationship between dilated perivascular spaces and cerebral amyloid angiopathy severity has not been established. We examined this association using post-mortem magnetic resonance imaging in five cases with evidence of cerebral amyloid angiopathy pathology. Juxtacortical perivascular spaces dilation was evaluated on T2 images and related to cerebral amyloid angiopathy severity in overlying cortical areas on 34 tissue sections stained for Amyloid β. Degree of perivascular spaces dilation was significantly associated with cerebral amyloid angiopathy severity (odds ratio = 3.3, 95% confidence interval 1.3–7.9, p = 0.011). Thus, dilated juxtacortical perivascular spaces are a promising neuroimaging marker of cerebral amyloid angiopathy severity.

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Abstract 36: The Boston Criteria V2.0 for Cerebral Amyloid Angiopathy: Updated Criteria and Multicenter MRI-Neuropathology Validation

Stroke ◽

10.1161/str.52.suppl_1.36 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Andreas Charidimou ◽

Gregoire Boulouis ◽

Matthew Frosch ◽

Jean-Claude Baron ◽

Marco Pasi ◽

...

Keyword(s):

White Matter ◽

Intracerebral Hemorrhage ◽

Diagnostic Accuracy ◽

Cerebral Amyloid Angiopathy ◽

Brain Mri ◽

Amyloid Angiopathy ◽

Perivascular Spaces ◽

Validation Sample ◽

Temporal Validation ◽

Cerebral Amyloid

Introduction: The Boston criteria are used worldwide for in vivo diagnosis of cerebral amyloid angiopathy (CAA). Given substantial advances in CAA research, we aimed to update the Boston criteria and externally validate their diagnostic accuracy across the spectrum of CAA-related presentations and across international sites. Methods: As part of an International CAA Association multicenter study, we identified patients age 50 or older with potential CAA-related clinical presentations (spontaneous intracerebral hemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathologic assessment for the diagnosis of CAA. We derived Boston criteria v2.0 by selecting MRI features to optimize diagnostic specificity and sensitivity in a pre-specified derivation sample (Boston cases 1994 to 2012, n=159), then externally validated in pre-specified temporal (Boston cases 2012-2018, n=59) and geographical (non-Boston cases 2004-2018; n=123) validation samples and compared their diagnostic accuracy to the currently used modified Boston criteria. Results: Based on exploratory analyses in the derivation sample, we derived provisional criteria for probable CAA requiring presence of at least 2 strictly lobar hemorrhagic lesions (intracerebral hemorrhage, cerebral microbleed, or cortical superficial siderosis focus) or at least 1 strictly lobar hemorrhagic lesion and 1 white matter characteristic (severe degree of visible perivascular spaces in centrum semiovale or white matter hyperintensities multispot pattern). Sensitivity/specificity of the criteria were 74.8/84.6% in the derivation sample, 92.5/89.5% in the temporal validation sample, 80.2/81.5% in the geographic validation sample, and 74.5/95.0% in cases across all samples with autopsy as the diagnostic gold standard. The v2.0 criteria for probable CAA had superior accuracy to the currently modified Boston criteria (p<0.005) in the autopsied cases. Conclusion: The Boston criteria v.2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their high specificity. Validation of the criteria across independent patient settings firmly supports their adoption into clinical practice and research.

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White Matter Perivascular Spaces Are Related to Cortical Superficial Siderosis in Cerebral Amyloid Angiopathy

Stroke ◽

10.1161/strokeaha.114.005568 ◽

2014 ◽

Vol 45 (10) ◽

pp. 2930-2935 ◽

Cited By ~ 32

Author(s):

Andreas Charidimou ◽

Rolf H. Jäger ◽

Andre Peeters ◽

Yves Vandermeeren ◽

Patrice Laloux ◽

...

Keyword(s):

White Matter ◽

Cerebral Amyloid Angiopathy ◽

Superficial Siderosis ◽

Amyloid Angiopathy ◽

Perivascular Spaces ◽

Cerebral Amyloid ◽

Cortical Superficial Siderosis

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The Characteristics of Superficial Siderosis and Convexity Subarachnoid Hemorrhage and Clinical Relevance in Suspected Cerebral Amyloid Angiopathy

Cerebrovascular Diseases ◽

10.1159/000381223 ◽

2015 ◽

Vol 39 (5-6) ◽

pp. 278-286 ◽

Cited By ~ 27

Author(s):

Jun Ni ◽

Eitan Auriel ◽

Jenelle Jindal ◽

Alison Ayres ◽

Kristin M. Schwab ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Intracerebral Hemorrhage ◽

Cerebral Amyloid Angiopathy ◽

Epileptiform Activity ◽

Brain Mri ◽

Superficial Siderosis ◽

Amyloid Angiopathy ◽

Cerebral Bleeding ◽

Cerebral Amyloid

Background and Aims: Systematic studies of superficial siderosis (SS) and convexity subarachnoid hemorrhage (cSAH) in patients with suspected cerebral amyloid angiopathy (CAA) without lobar intracerebral hemorrhage (ICH) are lacking. We sought to determine the potential anatomic correlation between SS/cSAH and transient focal neurological episodes (TFNE) and whether SS/cSAH is predictor of future cerebral hemorrhagic events in these patients. Methods: We enrolled 90 consecutive patients with suspected CAA (due to the presence of strictly lobar microbleeds (CMBs) and/or SS/cSAH) but without the history of symptomatic lobar ICH who underwent brain MRI including T2*-weighted, diffusion-weighted imaging and fluid-attenuated inversion recovery sequences from an ongoing single center CAA cohort from 1998 to 2012. Evaluation of SS, cSAH and CMBs was performed. Medical records and follow-up information were obtained from prospective databases and medical charts. TFNE was defined according to published criteria and electroencephalogram reports were reviewed. Results: Forty-one patients (46%) presented with SS and/or cSAH. The prevalence of TFNE was significantly higher in those with SS/cSAH (61 vs. 10%; p < 0.001) and anatomically correlated with the location of cSAH, but not SS. The majority of TFNE in patients with SS/cSAH presented with spreading sensory symptoms. Intermittent focal slowing on electroencephalogram was present in the same area as SS/cSAH in 6 patients, but no epileptiform activity was found in any patients. Among those with available clinical follow-up (76/90 patients, 84%), ten patients with SS/cSAH (29%, median time from the scan for all patients with SS/cSAH: 21 months) had a symptomatic cerebral bleeding event on follow up (average time to events: 34 months) compared with only 1 event (2.4%, 25 months from the scan) in patients without SS/cSAH (time to event: 25 months) (p = 0.001). The location of hemorrhages on follow-up scan was not in the same location of previously noted SS/cSAH in 9 of 10 patients. Follow-up imaging was obtained in 9 of 17 patients with cSAH and showed evidence of SS in the same location as initial cSAH in all these 9 cases. Conclusions: SS/cSAH is common in patients with suspected CAA without lobar intracerebral hemorrhage and may have a significantly higher risk of future cerebral bleeding events, regardless of the severity of the baseline CMB burden. The findings further highlight a precise anatomical correlation between TFNE and cSAH, but not SS. Distinct from transient ischemic attack or seizure, the majority of TFNE caused by SS/cSAH appear to present with spreading sensory symptoms.

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Cortical superficial siderosis and intracerebral hemorrhage risk in cerebral amyloid angiopathy

Neurology ◽

10.1212/01.wnl.0000435298.80023.7a ◽

2013 ◽

Vol 81 (19) ◽

pp. 1666-1673 ◽

Cited By ~ 87

Author(s):

A. Charidimou ◽

A. P. Peeters ◽

R. Jager ◽

Z. Fox ◽

Y. Vandermeeren ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Cerebral Amyloid Angiopathy ◽

Superficial Siderosis ◽

Amyloid Angiopathy ◽

Hemorrhage Risk ◽

Cerebral Amyloid ◽

Cortical Superficial Siderosis

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Stopping “transient ischemic attacks” by antiplatelet withdrawal

Neurological Research and Practice ◽

10.1186/s42466-021-00117-0 ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Lina Palaiodimou ◽

Aikaterini Theodorou ◽

Stefanos Lachanis ◽

George P. Paraskevas ◽

Matilda Papathanasiou ◽

...

Keyword(s):

Differential Diagnosis ◽

Cerebral Amyloid Angiopathy ◽

Brain Mri ◽

Superficial Siderosis ◽

Amyloid Angiopathy ◽

Perivascular Spaces ◽

The Past ◽

Cerebral Amyloid ◽

Ischemic Attack ◽

Cortical Superficial Siderosis

Abstract Introduction Transient ischemic attack (TIA) is considered to be an important risk factor for the development of ischemic stroke and requires complete etiopathogenic evaluation and prompt initiation of secondary prevention treatment. In addition, an accurate differential diagnosis should be performed in order to exclude other disorders mimicking TIA. Methods In this case report, we describe the clinical and neuroimaging evaluation and the differential diagnosis of a patient with suspected crescendo TIAs. Results A 79-year-old man presented with recurrent episodes of right-sided numbness over the past 7 months, despite different single and dual antiplatelet therapies that were sequentially prescribed for suspected TIAs. Brain MRI revealed cortical superficial siderosis, symmetrical periventricular leukoencephalopathy and enlarged perivascular spaces. Cerebral amyloid angiopathy was considered in the differential diagnosis of the patient. Antiplatelet withdrawal was recommended and led to complete remission of the patient’s transient focal neurological episodes (TFNE) that were initially misdiagnosed as TIAs. Discussion Cortical superficial siderosis has been implicated as a key neuroimaging feature of cerebral amyloid angiopathy, a diagnosis which can be supported by the additional radiological findings of symmetrical white matter hyperintensities and enlarged perivascular spaces. Antiplatelet treatment in patients with cortical superficial siderosis may increase the frequency and severity of TFNE, while it increases exponentially the risk of intracerebral hemorrhage. The present case highlights that recognition of cortical superficial siderosis is crucial in the management of patients presenting with transient focal neurological symptoms that can be misdiagnosed as recurrent TIAs.

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Abstract TP432: Predictors for Dementia Conversion in Cerebral Amyloid Angiopathy From a Stroke Unit

Stroke ◽

10.1161/str.48.suppl_1.tp432 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Li Xiong ◽

Raffaella Valenti ◽

Andreas Charidimou ◽

Gregoire Boulouis ◽

Duangnapa Roongpiboonsopit ◽

...

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Stroke Unit ◽

Cox Regression ◽

Superficial Siderosis ◽

P Value ◽

Amyloid Angiopathy ◽

Perivascular Spaces ◽

Cox Regression Analysis ◽

Cerebral Amyloid

Objective: Cerebral amyloid angiopathy (CAA) is increasing recognized as a cause of cognitive impairment and dementia in older individuals. This study aimed to investigate predictors of dementia, including imaging markers, in CAA patients from a stroke unit. Methods: A total of 71 non-demented patients from a stroke unit were included according to modified Boston Criteria for probable CAA with available cognitive follow up. These CAA patients included both patients with and patients without previous intracerebral hemorrhage (ICH). At baseline, neuroimaging markers, including lobar microbleeds (CMBs), white matter hyperintensities (WMH), cortical superficial siderosis (cSS) and MRI-visible centrum semiovale perivascular spaces (CSO-PVS) were assessed. The small vessel disease (SVD) score for CAA was calculated by the scores of CMBs, WMH, cSS and CSO-PVS. The association between these neuroimaging markers and dementia conversion was analyzed. Results: The median follow up time is 1.91 years (quartiles 1.14-4.23 years). Fourteen (19.72%) CAA patients developed dementia during follow up period. Thirty-seven CAA patients (52.11%) had previous symptomatic ICH. Age, lobar CMBs≥20 and SVD score were selected from the univariate Cox-regression analysis with p value less than 0.1 (Table1). In a backward stepwise multivariabte analysis including age, previous ICH history and either SVD score or number of CMBs, age and SVD score independently predicted dementia conversion (Table 1). The individual neuroimaging markers for SVD related brain damage (CSO-PVS, cSS, lobar MBs and WMH) did not predict dementia conversion for probable CAA patients. Conclusion: Our results demonstrate that cognitive deterioration of CAA patients appears attributed to cumulative CAA related vasculopathic changes.

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Small vessel disease burden in cerebral amyloid angiopathy without symptomatic hemorrhage

Neurology ◽

10.1212/wnl.0000000000003655 ◽

2017 ◽

Vol 88 (9) ◽

pp. 878-884 ◽

Cited By ~ 16

Author(s):

Gregoire Boulouis ◽

Andreas Charidimou ◽

Michael J. Jessel ◽

Li Xiong ◽

Duangnapa Roongpiboonsopit ◽

...

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Small Vessel Disease ◽

Summary Score ◽

Small Vessel ◽

Amyloid Angiopathy ◽

Perivascular Spaces ◽

Cognitive Symptoms ◽

Vessel Disease ◽

Age Related ◽

Cerebral Amyloid

Objective:Cerebral amyloid angiopathy (CAA) is a common age-related small vessel disease (SVD). Patients without intracerebral hemorrhage (ICH) typically present with transient focal neurologic episodes (TFNEs) or cognitive symptoms. We sought to determine if SVD lesion burden differed between patients with CAA first presenting with TFNEs vs cognitive symptoms.Methods:A total of 647 patients presenting either to a stroke department (n = 205) or an outpatient memory clinic (n = 442) were screened for eligibility. Patients meeting modified Boston criteria for probable CAA were included and markers of SVD were quantified, including cerebral microbleeds (CMBs), perivascular spaces, cortical superficial siderosis (cSS), and white matter hyperintensities (WMHs). Patients were classified according to presentation symptoms (TFNEs vs cognitive). Total CAA-SVD burden was assessed using a validated summary score. Individual neuroimaging markers and total SVD burden were compared between groups using univariable and multivariable models.Results:There were 261 patients with probable CAA included. After adjustment for confounders, patients first seen for TFNEs (n = 97) demonstrated a higher prevalence of cSS (p < 0.0001), higher WMH volumes (p = 0.03), and a trend toward higher CMB counts (p = 0.09). The total SVD summary score was higher in patients seen for TFNEs (adjusted odds ratio per additional score point 1.46, 95% confidence interval 1.16–1.84, p = 0.013).Conclusions:Patients with probable CAA without ICH first evaluated for TFNEs bear a higher burden of structural MRI SVD-related damage compared to those first seen for cognitive symptoms. This study sheds light on neuroimaging profile differences across clinical phenotypes of patients with CAA without ICH.

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Hypertensive Arteriopathy and Cerebral Amyloid Angiopathy in Patients with Cognitive Decline and Mixed Cerebral Microbleeds

Journal of Alzheimer s Disease ◽

10.3233/jad-200992 ◽

2020 ◽

Vol 78 (4) ◽

pp. 1765-1774

Author(s):

Yuichiro Ii ◽

Hidehiro Ishikawa ◽

Hirofumi Matsuyama ◽

Akihiro Shindo ◽

Keita Matsuura ◽

...

Keyword(s):

White Matter ◽

Cerebral Amyloid Angiopathy ◽

Small Vessel Disease ◽

Cerebral Microbleeds ◽

White Matter Hyperintensity ◽

Superficial Siderosis ◽

Amyloid Angiopathy ◽

Age Related ◽

Cerebral Amyloid ◽

Occipital Lobes

Background: Hypertensive arteriopathy (HA) and cerebral amyloid angiopathy (CAA) may contribute to the development of mixed cerebral microbleeds (CMBs). Recently, the total small vessel disease (SVD) scores for HA and CAA were proposed, which are determined by a combination of MRI markers to reflect overall severity of these microangiopathies. Objective: We investigated whether or not total HA-SVD and CAA-SVD scores could be used to predict overlap of HA and CAA in patients with mixed CMBs. Methods: Fifty-three subjects with mixed CMBs were retrospectively analyzed. MRI markers (CMBs, lacunes, perivascular space, white matter hyperintensity [WMH] and cortical superficial siderosis [cSS]) were assessed. The HA-SVD score and CAA-SVD score were obtained for each subject. Anterior or posterior WMH was also assessed using the age-related white matter changes scale. Results: The two scores were positively correlated (ρ= 0.449, p < 0.001). The prevalence of lobar dominant CMB distribution (p < 0.001) and lacunes in the centrum semiovale (p < 0.001) and the severity of WMH in the parieto-occipital lobes (p = 0.004) were significantly higher in the high CAA-SVD score group. cSS was found in four patients with high CAA-SVD score who showed lobar-dominant CMB distribution and severe posterior WMH. Conclusion: Mixed CMBs are mainly due to HA. Assessing both two scores may predict the overlap of HA and CAA in individuals with mixed CMBs. Patients with a high CAA-SVD score may have some degree of advanced CAA, especially when lobar predominant CMBs, severe posterior WMH, lobar lacunes, or cSS are observed.

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