Links between genetic factors, ROS and behavioural risk factor
Now let us try to establish a link between genetics, ROS, risk factors and cardiovascular pathology or more exactly with the neuro-psychiatric consequences of the cardiovascular diseases. All along life the vascular vessels alter their structure, simultaneously responding to both physical and chemical stresses (41): 1) to cope with mechanical stressors, the endothelium and smooth muscle cells respond with adaptive cellular modifications in relation to signalling pathways of mechano-transduction 2) on the other hand, chemical stress (particularly oxidative stress) provokes also genetic (see above the role of stress in telomere shortening), molecular and smooth cells alterations. Moreover, a new inflammatory hypothesis of vascular aging emphasizes that stress-induced vascular aging may be the primary event that underlies the general aging phenomenon of systemic dysfunction (41). Risk factors of the adulthood (sedentary, overweight, smoking, arterial “pulse” hypertension, dyslipidemia…) and pathology of aged persons (atrial fibrillation, myocardial infarction, stroke) contribute to increase the vascular damage and the blood flow changes. The relationships between heart, vessels and brain are too often forgotten. For the geriatricians, the fundamental consequences of the vascular damage and blood flow changes are not only purely cardio-vascular alterations, but also cerebral white matter lesions. Numerous brain damages are closely linked to cardio-vascular dysfunctions:
Stenosis or occlusion of small brain vessels can provoke sudden or more chronic ischemia resulting in small areas of necrosis, known as lacunar infarction)
- Arteriolosclerotic changes involve loss of auto regulation in the deep white matter and generate consequent cerebral blood flow fluctuations
Small vessel alterations are the causes of damage to the blood-brain barrier and chronic leakage of fluid and macromolecules in the white matter (42).
As mentioned above, the white matter lesions have important consequences on vascular vessels and blood flow changes. The cerebral white matter lesions can be found in few healthy aged persons but they essentially characterize depressed and demented elders. In depression, the white matter lesions are mainly located in the sub-cortical cortex, while in dementia (mainly vascular dementia but also Alzheimer disease) the lesions are located in the periventricular areas (43).
All these interacting factors (from genetics to biological damages - and risk profile) explain the complexity of aging and age-related disorders. For example, a 20-year follow-up of 2611 intact participants in the Framingham study with a mean age of 66 years at baseline, showed that the incidence of vascular or mixed dementia, between 65 and 100 years of age, accounted for 7.3 % in men and 16.9 % in women, while the Alzheimer disease (AD) incidence was around 25.5 % in men and 28.1 % in women (44). These data are significant because they stress the importance of an adequate cardiovascular prevention (not only in men but also in women) to avoid or postpone the emergence of vascular dementia and perhaps also certain AD. This example of cardio and cerebral vascular links could have been replaced by a lot of other age-related pathologies. The present choice was driven by the invaluable disability consequences of such pathologies.