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Abstract
Rationale
Cognitive decline and dementia have been reportedly linked to atherosclerosis, the main cause of cardiovascular disease. Cohort studies identifying early brain alterations associated with subclinical atherosclerosis are warranted to understand the potential of prevention strategies before cerebral damage becomes symptomatic and irreversible.
Methods & designThe Progression of Early Subclinical Atherosclerosis (PESA) study is a longitudinal observational cohort study that recruited 4,184 asymptomatic middle-aged individuals (40-54 years) in 2010 in Madrid (Spain) to thoroughly characterize subclinical atherosclerosis development over time. In this framework, the PESA-Brain study has been designed to identify early structural, functional and vascular brain changes associated with midlife atherosclerosis and cardiovascular risk factors. The PESA-Brain study targets 1,000 participants at the 10-year follow-up PESA visit and consists of thorough neuropsychological testing, advanced multimodal neuroimaging, and quantification of blood-based neuropathological biomarkers.
Primary hypothesisWe hypothesize that, in middle-age, the presence of cardiovascular risk factors and a high burden of subclinical atherosclerosis will be associated with structural, functional and vascular brain alterations, greater amyloid burden and subtle cognitive impairment. We further hypothesize that the link between subclinical atherosclerosis and poor brain health in midlife will be mediated by cerebrovascular pathology and intracranial atherosclerosis.
Enrollment datesThe PESA-Brain study started in October 2020 and is estimated to be completed by December 2024.
ConclusionThis study is in a unique position to unveil novel relationships between cardiovascular and brain alterations in the health-to-disease transition, which may have important implications for interventional and therapeutic approaches.
ClinicalTrials.gov identifier: NCT01410318.
Details
1 Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
2 Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; Icahn School of Medicine at Mount Sinai, New York, US
3 Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; Cardiology Department, University Hospital La Moraleja, Madrid, Spain; CIBER de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
4 Health Research Institute, Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain; CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
5 Philips Healthcare Iberia, Spain
6 Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; CIBER de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Health Research Institute, Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
7 Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain
8 Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; Health Research Institute, Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain; Centro Internacional de Neurociencia Cajal - Consejo Superior de Investigaciones Científicas (CINC-CSIC), Madrid, Spain