CAA - Cerebral Amyloid Angiopathy, Cerebral Amyloid Angiopathy
Conditions
Keywords
Cerebral Amyloid Angiopathy, CAA, plasma biomarkers, cerebrospinal fluid biomarkers
Brief summary
Cerebral amyloid angiopathy (CAA) is a microangiopathy characterized by the progressive deposition of β-amyloid in cerebral vessel walls, contributing to intracerebral hemorrhages, cognitive decline, and other clinical manifestations. Despite recent advances in diagnosis and understanding, many pathogenic, prognostic, and therapeutic aspects remain unclear. Study Objective: PRIORITY is a prospective observational study aimed at identifying clinical, neuroradiological, and biochemical biomarkers that could improve early diagnosis, risk stratification, and the identification of personalized therapeutic targets for CAA.
Detailed description
PRIORITY is a prospective, single-center observational study conducted at the Fondazione IRCCS Istituto Neurologico Carlo Besta in Milan. It will consecutively enroll patients over 18 years of age with possible or probable cerebral amyloid angiopathy (CAA), symptomatic or asymptomatic, with or without histological confirmation. Diagnosis will follow the updated Boston criteria 2.0, and a brain MRI is mandatory for inclusion. The study duration is 36 months, with clinical and neuroimaging assessments at baseline (T0), 12 months (T1), and 24 months (T2). CSF analysis will be performed at T0; plasma biomarkers (via ELISA and SIMOA) will be assessed at all time points. Lipid profiles will be analyzed using mass spectrometry with both untargeted and targeted lipidomic approaches (e.g., sphingolipidomics). The comprehensive clinical and biological dataset will be used to develop a machine learning-based predictive model to support diagnostic, prognostic, and therapeutic decision-making in CAAThe study duration is 36 months, with clinical and neuroimaging assessments at baseline (T0), 12 months (T1), and 24 months (T2). CSF analysis will be performed at T0; plasma biomarkers (via ELISA and SIMOA) will be assessed at all time points. Lipid profiles will be analyzed using mass spectrometry with both untargeted and targeted lipidomic approaches (e.g., sphingolipidomics).
Interventions
None listed
Sponsors
Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* patients of either sex over 18 years of age; * patients with possible and probable symptomatic or asymptomatic CAA with or without histological demonstration (modified Boston criteria); * patients who have had at least one brain MRI.
Exclusion criteria
* patients who have contraindications to undergoing brain MRI (e.g., pacemaker, incompatible mechanical valves, claustrophobia); * patients who have contraindications to or refuse to undergo lumbar puncture; * patients who are unable to provide informed consent for the study due to aphasic or cognitive impairment; * patients who are pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Progression of CAA | Baseline (T0), 12 months (T1), 24 months (T2). | Evaluation of the natural progression of cerebral amyloid angiopathy (CAA) through clinical assessments. At baseline, clinical data (e.g., history of stroke, a diagnosis of dementia, presence of seizures, gait disturbances, vascular risk factors, prior brain injury/surgery, family history, medications…) recorded in a binary (yes/no) scale, indicating the presence or absence of each condition or risk factor, will be collected for each patient. During follow-up, new clinical events (e.g., number of new ICH-intracerebral hemorrhages, number of new ischemic stroke, presence of seizures, presence of TFNEs, cognitive status, death) will be recorded and compared with T0. |
| Radiological Progression of CAA | Baseline (T0), 12 months (T1), 24 months (T2). | Evaluation of the natural progression of cerebral amyloid angiopathy (CAA) through neuroimaging markers (MRI). MRI assessment at baseline will include T1, T2, FLAIR, T2\*, GRE, SWI, and DWI sequences. Imaging will be assessed using STRIVE (Standards for Reporting Vascular Changes on Neuroimaging) criteria, with standardized rating scales for: number of Microbleeds (Microbleed Anatomical Rating Scale - MARS); presence of Lobar ICH- intracerebral hemorrhages; presence of Superficial siderosis; presence of White matter lesions (Fazekas scale: o to 3 scores, where 0 means absence of white matter lesions and 3 large presence of them); presence of Perivascular spaces (CSO-PVS); presence of Cortical microinfarcts; presence of Global cortical atrophy; presence of Subarachnoid haemorrhage. Follow-up includes repeated MRI with the same sequences. MRI changes will be evaluated with the same standardized rating scales for progression or appearance of the same parameters evaluated in T0. |
| Identification of Protein and Lipid Biomarkers | Baseline (T0), 12 months (T1), 24 months (T2). | Analysis of cerebrospinal fluid and plasma to identify protein (e.g., concentrations in pg/mL of total Tau, p-Tau, Aβ42/Aβ40, NfL, GFAP) and lipid (qTOF-MS) signatures associated with CAA progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive Decline Assessment | Baseline (T0), 12 months (T1), 24 months (T2). | Longitudinal evaluation of cognitive functions and disability to correlate with disease progression. A neuropsychological evaluation will be performed using the Montreal Cognitive Assessment (MoCA) test, scores range from 0 to 30, with lower scores indicating greater cognitive impairment. |
| Development of a Predictive Model for Disease Progression | 24 months (T2). | Development and validation of machine learning models (e.g., Random Forest, Decision Trees) to predict disease progression. Performance metrics include accuracy, sensitivity, specificity, PPV, NPV, and AUC based on integrated clinical, imaging, and biomolecular data. |
| Hemorrhagic and Non-Hemorrhagic Event Incidence | 24 months (T2) | Monitoring of symptomatic and asymptomatic cerebral hemorrhages, as well as other vascular events, to determine risk factors. |
| Therapeutic Target Identification | 24 months (T2) | Identification of potential molecular targets for future therapeutic interventions based on CSF and plasma biomarker analysis. |
| Functional assessment | Baseline (T0), 12 months (T1), 24 months (T2) | Disability will be assessed with the modified Rankin Scale (mRS, scores ranges from 0 - no symptoms - to 6 - death). |
Countries
Italy
Outcome results
None listed