Publications by authors named "Charidimou A"
Background And Objectives: There is a clear need to characterize and validate molecular biomarkers of cerebral amyloid angiopathy (CAA), in an effort to improve diagnostics, especially in the context of patients with Alzheimer disease (AD) receiving immunotherapies (for whom underlying CAA is the driver of amyloid-related imaging abnormalities). We performed an updated meta-analysis of 5 core CSF biomarkers (Aβ42, Aβ40, Aβ438, total tau [T-tau], and phosphorylated tau [P-tau]) to assess which of these are most altered in sporadic CAA.
Methods: We systematically searched PubMed for eligible studies reporting data on CSF biomarkers reflecting APP metabolism (Aβ42, Aβ40, Aβ38), neurodegeneration (T-tau), and tangle pathology (P-tau), in symptomatic sporadic CAA cohorts (based on the Boston criteria) vs control groups and/or vs patients with AD.
Objective: Elevated levels of anti-amyloid-β (anti-Aβ) autoantibodies in cerebrospinal fluid (CSF) have been proposed as a diagnostic biomarker for cerebral amyloid angiopathy-related inflammation (CAA-RI). We aimed to independently validate the immunoassay for quantifying these antibodies and evaluate its diagnostic value for CAA-RI.
Methods: We replicated the immunoassay to detect CSF anti-Aβ autoantibodies using CSF from CAA-RI patients and non-CAA controls with unrelated disorders and further characterized its performance.
Article Synopsis
- Lecanemab, an amyloid-targeting immunotherapy for Alzheimer’s, shows promise but comes with potential risks for patients.
- An interprofessional team at a medical center developed resources like patient handouts and documentation templates to aid in the infusion process of lecanemab.
- The team plans to share these developed resources and processes with other healthcare settings to improve implementation and monitoring.
Article Synopsis
- Cerebral amyloid angiopathy (CAA) is a progressive condition in the elderly that leads to brain bleeding and cognitive issues, often mistaken for other diseases like Alzheimer's.
- Amyloid-β-related angiitis (ABRA) is a severe form of vasculitis linked to CAA that can be fatal without treatment, making early diagnosis critical, as common treatments for other conditions may worsen CAA.
- A case study showed that high-field 7T MR imaging can reveal subtle brain hemorrhages not seen in lower-field imaging, highlighting its potential to improve early diagnosis of CAA and ABRA.
Background And Objectives: Updated criteria for the clinical-MRI diagnosis of cerebral amyloid angiopathy (CAA) have recently been proposed. However, their performance in individuals without symptomatic intracerebral hemorrhage (ICH) presentations is less defined. We aimed to assess the diagnostic performance of the Boston criteria version 2.
View Article and Find Full Text PDFNontraumatic intracerebral hemorrhage is an important health issue. Although common causes such as hypertension and cerebral amyloid angiopathy predominantly affect the elderly, there exists a spectrum of uncommon etiologies that contribute to the overall incidence of intracerebral hemorrhage. The identification of these rare causes is essential for targeted clinical management, informed prognostication, and strategic secondary prevention where relevant.
View Article and Find Full Text PDFCerebral microbleeds (CMBs) detected on blood-sensitive magnetic resonance imaging sequences are usually a sign of an underlying cerebral small vessel disease such as sporadic cerebral amyloid angiopathy or sporadic nonamyloid small vessel pathology (eg, arteriolosclerosis). Much of the enduring interest in CMBs relates to their high prevalence (partly due to the widespread use of magnetic resonance imaging) in the context of stroke, cognitive impairment and in healthy individuals, and the clinical uncertainties created about the safety of antithrombotic medications due to their association with both future hemorrhagic and ischemic stroke. Historically, the research literature overwhelmingly emphasized the future hemorrhagic risk associated with CMBs, potentially leading to unnecessary withholding of treatments proven effective at preventing thrombosis, such as anticoagulants in patients with atrial fibrillation who happened to have some microbleeds.
View Article and Find Full Text PDFIntroduction: Long-term systolic blood pressure variability (BPV) has been proposed as a novel risk factor for dementia, but the underlying mechanisms are largely unknown. We aimed to investigate the association between long-term blood pressure variability (BPV), brain injury, and cognitive decline in patients with mild cognitive symptoms and cerebral amyloid angiopathy (CAA), a well-characterized small-vessel disease that causes cognitive decline in older adults.
Methods: Using a prospective memory clinic cohort, we enrolled 102 participants, of whom 52 with probable CAA.
Article Synopsis
- The study aimed to determine if pre-existing cerebral small vessel disease (cSVD), including cerebral microbleeds (CMBs), is linked to symptomatic intracerebral hemorrhage (sICH) in patients with acute ischemic stroke undergoing endovascular therapy (EVT).
- Researchers analyzed data from 445 patients who had pre-treatment MRIs, finding that CMBs were present in only 15.7%, but did not significantly correlate with the occurrence of sICH (p=0.805).
- The only factors showing a significant association with increased risk of sICH were the Alberta Stroke Program Early CT Score (ASPECTs) and the status of collateral circulation, suggesting that CMBs should not restrict patient eligibility
Article Synopsis
- The Boston criteria v2.0 help diagnose cerebral amyloid angiopathy (CAA) using non-invasive methods, incorporating new MRI features for improved accuracy.
- A study analyzed 134 participants with in vivo MRI and pathology data to compare diagnostic yields between the updated and earlier Boston criteria.
- The findings showed that the v2.0 criteria had better sensitivity (38.8%) compared to versions 1.0 and 1.5, and true-positive cases had more strictly cortical lobar microbleeds than false-positive cases.
Background And Objectives: Accumulating evidence suggests that gray matter atrophy, often considered a marker of Alzheimer disease (AD), can also result from cerebral small vessel disease (CSVD). Cerebral amyloid angiopathy (CAA) is a form of sporadic CSVD, diagnosed through neuroimaging criteria, that often co-occurs with AD pathology and leads to cognitive impairment. We sought to identify the role of hippocampal integrity in the development of cognitive impairment in a cohort of patients with possible and probable CAA.
View Article and Find Full Text PDFArticle Synopsis
- A 79-year-old woman with Alzheimer's participated in a Phase III trial for a drug called lecanemab, but was placed in the placebo group before later receiving the active drug during an extension phase.
- After her third infusion, she experienced a seizure and MRI scans showed significant brain swelling and increased microhemorrhages.
- Despite aggressive treatment, she worsened and died 5 days later, with autopsy results revealing severe cerebral amyloid-related inflammation and extensive brain damage linked to factors like the APOE4 gene.
Background And Purpose: Cortical superficial siderosis (cSS) is a key neuroimaging marker of cerebral amyloid angiopathy (CAA) detected on blood-sensitive magnetic resonance imaging (MRI). We aimed to assess cSS in advanced CAA patients and explore differences in its evaluation between susceptibility weighted imaging (SWI) and gradient recalled echo-T2* (GRE-T2*).
Materials And Methods: Neuroimaging data gathered from a prospective cohort of CAA patients with probable or definite CAA were retrospectively analyzed by two independent raters.
Background: Updated criteria for the clinical-MRI diagnosis of cerebral amyloid angiopathy (CAA) have recently been proposed. However, their performance in individuals without intracerebral hemorrhage (ICH) or transient focal neurological episodes (TFNE) is unknown. We assessed the diagnostic performance of the Boston criteria version 2.
View Article and Find Full Text PDFPerivascular spaces (PVS) visible on brain MRI signal cerebral small vessel disease (CSVD). The coexistence of PVS with other CSVD manifestations likely increases the risk of adverse neurological outcomes. We related PVS to other CSVD manifestations and brain volumes that are markers of vascular brain injury and neurodegeneration.
View Article and Find Full Text PDFBackground: Neurofilament light chain (NfL) is a marker of neuronal injury. Perivascular spaces (PVS) visible on magnetic resonance imaging (MRI) represent cerebral small vessel disease (CSVD) but their role as markers of neuronal injury needs further clarification.
Objective: To relate PVS burden according to brain topography and plasma NfL.
Background And Objectives: Hematoma expansion (HE) is a major determinant of neurologic deterioration and poor outcome in intracerebral hemorrhage (ICH) and represents an appealing therapeutic target. We analyzed the prognostic effect of different degrees of HE.
Methods: This was a retrospective analysis of patients with ICH admitted at 8 academic institutions in Italy, Germany, Canada, China, and the United States.
Objective: To determine whether MRI-based cerebral small vessel disease (cSVD) burden predicts treatment-induced aphasia recovery in chronic stroke patients above and beyond initial aphasia severity and stroke-lesion volume.
Design: Retrospective. Four cSVD neuroimaging markers were rated using validated visual scales: white matter hyperintensities, enlarged perivascular spaces, lacunes, and global cortical atrophy.
We studied the association between inflammatory biomarkers and magnetic resonance imaging (MRI) visible perivascular spaces (PVS) in Framingham Heart Study participants free of stroke and dementia. PVS in the basal ganglia (BG) and centrum semiovale (CSO) were rated with validated methods and categorized based on counts. A mixed score of high PVS burden in neither, one or both regions was also evaluated.
View Article and Find Full Text PDFA leading cause of white matter (WM) injury in older individuals is cerebral small vessel disease (SVD). Cerebral SVD is the most prevalent vascular contributor to cognitive impairment and dementia. Therapeutic progress for cerebral SVD and other WM disorders depends on the development and validation of neuroimaging markers suitable as outcome measures in future interventional trials.
View Article and Find Full Text PDF