Dataset Information

Index event of cerebral amyloid angiopathy (CAA) determines long-term prognosis and recurrent events (retrospective analysis and clinical follow-up).

ABSTRACT:

Background

The modified Boston criteria (mBC) define the probability for the diagnosis of cerebral amyloid angiopathy (CAA). Its initial clinical presentation differs from asymptomatic cerebral microbleedings (cMBs), acute ischemic stroke (AIS), cortical hemosiderosis (cSS), to lobar ICH (lICH).

Methods

Retrospective analyses and clinical follow-ups of individuals with at least mBC "possible" CAA from 2005 to 2018.

Results

149 patients were classified in subgroups due to the index event: lICH (n = 91), AIS (n = 32), > 3 cMBs only (n = 16) and cSS (n = 10). Patients in the lICH subgroup had a significantly higher percentage of single new lICHs compared to other groups, whereas patients in the AIS-group had a significantly higher percentage of multiple new AIS. cMBs as index event predisposed for AIS during follow up (p < 0.0016). Patients of the cMBs- or cSS-group showed significantly more TFNEs (transient focal-neurological episodes) and lower numbers of asymptomatic patients (for epilepsy and TFNEs) at the index event than patients with lICH or AIS (p < 0.0013). At long-term follow-up, the cMBs- and cSS-group were characterized by more TFNEs and fewer asymptomatic patients.

Conclusions

A new classification system of CAA should add subgroups according to the initial clinical presentation to the mBCs allowing individual prognosis, acute treatment and secondary prophylaxis.

SUBMITTER: Wagner A

PROVIDER: S-EPMC8474746 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

Index event of cerebral amyloid angiopathy (CAA) determines long-term prognosis and recurrent events (retrospective analysis and clinical follow-up).

Wagner Andrea A Groetsch Christiane C Wilfling Sibylle S Schebesch Karl-Michael KM Kilic Mustafa M Nenkov Marjan M Wendl Christina C Linker Ralf A RA Schlachetzki Felix F

Neurological research and practice 20210927 1

<h4>Background</h4>The modified Boston criteria (mBC) define the probability for the diagnosis of cerebral amyloid angiopathy (CAA). Its initial clinical presentation differs from asymptomatic cerebral microbleedings (cMBs), acute ischemic stroke (AIS), cortical hemosiderosis (cSS), to lobar ICH (lICH).<h4>Methods</h4>Retrospective analyses and clinical follow-ups of individuals with at least mBC "possible" CAA from 2005 to 2018.<h4>Results</h4>149 patients were classified in subgroups due to th ...[more]

PMID: 34565480

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Project description:Cerebral amyloid angiopathy (CAA) involves cerebrovascular amyloid deposition and is classified into several types according to the amyloid protein involved. Of these, sporadic amyloid β-protein (Aβ)-type CAA is most commonly found in older individuals and in patients with Alzheimer's disease (AD). Cerebrovascular Aβ deposits accompany functional and pathological changes in cerebral blood vessels (CAA-associated vasculopathies). CAA-associated vasculopathies lead to development of hemorrhagic lesions [lobar intracerebral macrohemorrhage, cortical microhemorrhage, and cortical superficial siderosis (cSS)/focal convexity subarachnoid hemorrhage (SAH)], ischemic lesions (cortical infarction and ischemic changes of the white matter), and encephalopathies that include subacute leukoencephalopathy caused by CAA-associated inflammation/angiitis. Thus, CAA is related to dementia, stroke, and encephalopathies. Recent advances in diagnostic procedures, particularly neuroimaging, have enabled us to establish a clinical diagnosis of CAA without brain biopsies. Sensitive magnetic resonance imaging (MRI) methods, such as gradient-echo T2(*) imaging and susceptibility-weighted imaging, are useful for detecting cortical microhemorrhages and cSS. Amyloid imaging with amyloid-binding positron emission tomography (PET) ligands, such as Pittsburgh Compound B, can detect CAA, although they cannot discriminate vascular from parenchymal amyloid deposits. In addition, cerebrospinal fluid markers may be useful, including levels of Aβ40 for CAA and anti-Aβ antibody for CAA-related inflammation. Moreover, cSS is closely associated with transient focal neurological episodes (TFNE). CAA-related inflammation/angiitis shares pathophysiology with amyloid-related imaging abnormalities (ARIA) induced by Aβ immunotherapies in AD patients. This article reviews CAA and CAA-related disorders with respect to their epidemiology, pathology, pathophysiology, clinical features, biomarkers, diagnosis, treatment, risk factors, and future perspectives.

Project description:Integrating cerebrospinal fluid-biomarkers into diagnostic workup of patients with sporadic cerebral amyloid angiopathy may support early and correct identification. We aimed to identify and validate clinical- and cerebrospinal fluid-biomarkers for in vivo diagnosis of cerebral amyloid angiopathy. This observational cohort study screened 2795 consecutive patients admitted for cognitive complaints to the academic departments of neurology and psychiatry over a 10-year period (2009-2018). We included 372 patients with available hemosiderin-sensitive MR imaging and cerebrospinal fluid-based neurochemical dementia diagnostics, i.e. Aβ40, Aβ42, t-tau, p-tau. We investigated the association of clinical- and cerebrospinal fluid-biomarkers with the MRI-based diagnosis of cerebral amyloid angiopathy, applying confounder-adjusted modelling, receiver operating characteristic and unsupervised cluster analyses. We identified 67 patients with cerebral amyloid angiopathy, 76 patients with Alzheimer's disease, 75 patients with mild cognitive impairment due to Alzheimer's disease, 76 patients with mild cognitive impairment with unlikely Alzheimer's disease and 78 healthy controls. Patients with cerebral amyloid angiopathy showed a specific cerebrospinal fluid pattern: average concentration of Aß40 [13 792 pg/ml (10 081-18 063)] was decreased compared to all controls (P < 0.05); Aß42 [634 pg/ml (492-834)] was comparable to Alzheimer's disease and mild cognitive impairment due to Alzheimer's disease (P = 0.10, P = 0.93) but decreased compared to mild cognitive impairment and healthy controls (both P < 0.001); p-tau [67.3 pg/ml (42.9-91.9)] and t-tau [468 pg/ml (275-698)] were decreased compared to Alzheimer's disease (P < 0.001, P = 0.001) and mild cognitive impairment due to Alzheimer's disease (P = 0.001, P = 0.07), but elevated compared to mild cognitive impairment and healthy controls (both P < 0.001). Multivariate modelling validated independent clinical association of cerebral amyloid angiopathy with older age [odds-ratio: 1.06, 95% confidence interval (1.02-1.10), P < 0.01], prior lobar intracerebral haemorrhage [14.00 (2.64-74.19), P < 0.01], prior ischaemic stroke [3.36 (1.58-7.11), P < 0.01], transient focal neurologic episodes (TFNEs) [4.19 (1.06-16.64), P = 0.04] and gait disturbance [2.82 (1.11-7.15), P = 0.03]. For cerebrospinal fluid-biomarkers per 1 pg/ml, both lower Aß40 [0.9999 (0.9998-1.0000), P < 0.01] and lower Aß42 levels [0.9989 (0.9980-0.9998), P = 0.01] provided an independent association with cerebral amyloid angiopathy controlled for all aforementioned clinical confounders. Both amyloid biomarkers showed good discrimination for diagnosis of cerebral amyloid angiopathy among adjusted receiver operating characteristic analyses (area under the receiver operating characteristic curves, Aß40: 0.80 (0.73-0.86), P < 0.001; Aß42: 0.81 (0.75-0.88), P < 0.001). Unsupervised Euclidian clustering of all cerebrospinal fluid-biomarker-profiles resulted in distinct segregation of cerebral amyloid angiopathy patients from all controls. Together, we demonstrate that a distinctive set of cerebrospinal fluid-biomarkers effectively differentiate cerebral amyloid angiopathy patients from patients with Alzheimer's disease, mild cognitive impairment with or without underlying Alzheimer's disease, and healthy controls. Integrating our findings into a multiparametric approach may facilitate diagnosing cerebral amyloid angiopathy, and may aid clinical decision-making, but warrants future prospective validation.

Dataset Information

Index event of cerebral amyloid angiopathy (CAA) determines long-term prognosis and recurrent events (retrospective analysis and clinical follow-up).

Background

Methods

Results

Conclusions

Publications

Index event of cerebral amyloid angiopathy (CAA) determines long-term prognosis and recurrent events (retrospective analysis and clinical follow-up).

Similar Datasets

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