Dutch type (HCHWA-D) Hereditary cerebral hemorrhage with amyloidosis Hereditary Cerebrale Amyloïd Angiopathie (hCAA)
Conditions
Interventions
None listed
Sponsors
Leids Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Symptomatic HCHWA-D patients: * HCHWA-D with a genetic-based diagnosis * One or more radiological confirmed hemorrhages * Ability and willingness to provide written informed consent * Age: older than 18 years;Control subjects: * Age and gender matched with the HCHWA-D subjects, older than 18 years * Ability and willingness to provide written informed consent
Exclusion criteria
Exclusion criteria: * Presence of other known cerebrovascular diseases not related to CAA: diabetes, hypertension, overt atherosclerotic disease * Contra indications to MR imaging * Contra indications to CO2 stimulation * Severe physical restriction / inability to be scanned, such as weight above 120 kg.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The first set of main study parameters are related to the cerebrovascular reactivity (CVR) measurements with MRI (without using contrast agents) and consist of: * cerebrovascular reactivity to visual stimuli: Cerebrovascular blood flow change * cerebrovascular CO2 reactivity: Cerebrovascular blood flow change / mmHg CO2 change Oxygenation signal change / mmHg CO2 change The second set main study parameters are related to the dynamic cerebrovascular autoregulation (CA) and cerebral vasomotor reactivity (CVMR) measurements and consist of: * Hemodynamic parameters measured by finger plethysmography with a finger cuff: Blood pressure Heart rate Stroke volume Cardiac output Systemic vascular resistance * Cerebral parameters measured by means of transcranial Doppler Cerebral blood flow velocity (CBFv) * Respiratory parameters measured through a nasal cannula using a capnograph End-tidal CO2 | — |
Secondary
| Measure | Time frame |
|---|---|
| The other study parameters collected during this study are related to the clinical characteristics of the study populations: date of birth, gender, arterial oxygen saturation, presence of other comorbidities, current/past medication use, daily intake of alcohol/drugs/caffeine, smoking status, body weight and neurologic history. These data will be collected through questionnaires as screening and, if necessary and the subject gives permission, through the patient*s health records at the hospital, and will also be administered on the day of scanning. Furthermore, subjects will undergo a neurological and physical examination and take neurological and cognitive tests to evaluate cognitive functioning, speed of processing, mental flexibility, executive functioning, aphasia, memory, anxiety and depression. Anatomical MRI-scans will be used for the post-processing of the images. Standard laboratory blood tests will provide the measurement of hemoglobin, hematocrit, HbA1C, plasma creatinine, glucose, cholesterol (total, HDL and LDL), leukocyte and thrombocyte count and Apoe to get insight in the vascular risk factors that might be associated with microvascular function and to detect diabetes. Furthermore, if subject gives permission for taking additional blood, these samples will be used for discovery of novel biomarkers related to the vascular dysfunction seen in CAA. Studies will include identification of dysregulated pathways (inflammatory and oxidative stress pathways are of particular interest) at the gene and the protein levels. Focus will be on biomarkers for endothelial function (like VCAM, ICAM), blood-brain barrier integrity (MMP2, MMP9, s100b) and vascular mural cell function (for example PDGFR*). Results will be correlated with findings from ongoing RNA-sequencing project on post-mortem brain tissue. This pilot study on blood biomarkers is a first step before screening larger biobank samples like the ones from the EDAN study. This addi | — |
Countries
Netherlands
Outcome results
None listed