Subject-specific multiporoelastic model for exploring the risk factors associated with Dementia

Alzheimer’s disease (AD) is the most common form of dementia, a clinical syndrome of progressive deterioration of cognitive abilities and ordinary daily functioning. In its early stage, AD may present itself as mild cognitive impairment (MCI), a state between normal aging and dementia. MCI is characterized by objective cognitive impairment relative to the person’s age, with concern about the cognitive symptoms in a person with essentially normal functional activities who does not have dementia. Evidence suggests that in many cases, AD has a vascular component, caused by impaired cerebral perfusion, which may be promoted by cardiovascular risk factors (CRF). CRFs are known to be strongly influenced by lifestyle. In order to develop an understanding of the exact nature of such a hypothesis, a biomechanical understanding of the influence of lifestyle factors is pursued. We introduce a novel consolidated pipeline within the European VPH-DARE@IT project that integrates three key components: a 3D multiporoelastic-based model of cerebral parenchyma; an accurate, fully automated image-based model personalization workflow (subject-specific meshes, permeability tensor maps); and a subject-specific boundary condition model (blood flow variability). The subject-specific datasets used in the modelling were collected as part of prospective data collection. The size of this database is 104 participants (52 controls and 52 MCI cases). Subject-specific characterization of 24-hour blood flow variability was obtained through a combination of ambulatory blood pressure measurements, clinical ultrasound flow measurements, and mathematical modelling. For the latter, a lumped parameter circulation model is used to simulate continuous arterial blood flow and translate spot measurements collected at finite intervals to continuous waveforms of arterial blood flow. The preliminary cases simulated involved both male and female control and MCI cases. Smokers and non-smokers during two states of activity (high and low) were investigated within this cohort. Results showed variations in clearance of CSF/ISF, elevated parenchymal tissue displacement and CSF/ISF accumulation and drainage in the MCI cases.