Vascular Alteration and Evolution of Cognitive Impairment

Background: The role of arterial hypertension and vascular alterations in the development of cognitive decline is a major issue in both research and clinical practice. In a recently published cross-sectional study (Kearney-Schwartz, Rossignol et al. 2009), conducted on the "ADELAHYDE" cohort comprised of older hypertensive patients with memory complaints, the investigators showed the association of arterial changes (hypertrophy and arterial stiffness, endothelial dysfunction) with cognitive functions and/or white matter hyperintensities on MRI. A longitudinal study is the only means to confirm the role of vascular factors in the evolution of cognitive function and onset of dementia. Objectives: i) Primary: To establish, in the "ADELAHYDE" cohort, the relationship between vascular alterations assessed at baseline during the cross-sectional study (hypertrophy and arterial stiffness, endothelial dysfunction) and the evolution of cognitive function (primary study endpoint) over a 8-year follow-up period; ii) Secondary a) To investigate the evolution of white matter hyperintensities on MRI (secondary study endpoint) as a function of peripheral vascular status, and especially of endothelial function. b) Determine the role of genetic factors and biomarkers of oxidative stress (from DNA and serum biobanks collected at the first visit) in the evolution of cognitive functions and white matter hyperintensities. Methods: Prospective longitudinal single center study. All patients (378 subjects) who participated in the baseline cross-sectional study conducted between 2001 and 2005, will be reconvened at the Clinical Investigation Centre (CIC) of Nancy. As in the cross-sectional study, the following will be assessed in this longitudinal phase: pulse wave velocity (PWV), carotid ultrasonography, flow-mediated dilation, brain MRI with semi-quantification of white matter hyperintensities, cognitive function evaluation and measurement of various biomarkers of endothelial function. Expected fallouts: A major benefit of this project is that this cohort has already been explored in terms of cognitive function, arterial properties and neurovascular imaging (MRI). Thus, the programmed reconvening of these subjects for this project in 2011 will enable us to identify the role of vascular alterations in the evolution of cognitive function and leucoaraiosis in this population at high risk of dementia over a period of at least 8 years. Finally, it could pave the way for further investigations, notably in the field of cognitive impairment prevention, aimed at reducing or delaying the onset of dementia by acting on the "vascular factor", which is potentially modifiable.