Brain damage in patients with manifest arterial disease

Abstract

In this thesis we assessed whether the risk factors known to affect markers of brain damage in the general population, also effectuate brain damage in patients who already have symptomatic arterial disease.

We found that elevated levels of homocysteine were related to slightly lower global cognitive function. The results suggest that vascular mechanisms are not responsible for the relationship between homocysteine and cognitive function.

The relation between the metabolic syndrome or type 2 diabetes mellitus, and cognitive function was investigated. The analyses showed that global cognitive function was not affected more in patients with than in patients without the metabolic syndrome. Only the scores on visuoperception and construction were slightly lower. Adjustment for markers of macro- and microvascular disease, and of metabolic disease, did not attenuate the results. Cognition in patients with type 2 diabetes mellitus was similar to cognition in patients with the metabolic syndrome. This suggests that most of the relation between the metabolic syndrome and cognitive function in the general population is attributable to arterial disease.

We analysed the relation between four vascular growth factors and cognitive function. The presence of the communicating arteries in the circle of Willis was assessed, as a measure of presence of cerebral collateral vessels; also the total volume flow rate (tVFR) through both internal carotid arteries and the basilar artery was assessed. In patients with internal carotid artery stenosis, higher basic fibroblast growth factor (bFGF) levels were related to higher scores on cognitive function. This relation was weakened by adjustment for tVFR, suggesting a mediating effect. Furthermore, patients with higher vascular endothelial growth factor levels had slightly lower performance on visuoperception and construction. We concluded that bFGF seems the most promising of the four studied growth factors for future clinical studies.

Cognitive function was assessed in three categories of patients with manifest arterial disease: no stroke or TIA, and no silent infarcts; silent infarcts; or stroke or TIA at inclusion. While silent infarcts did not influence cognitive function in these patients, patients with stroke or TIA had lower scores than patients with symptoms elsewhere in the arterial tree. Thus, when patients already are vascular compromised, the presence of a silent brain infarct does not add to the cognitive dysfunction due to the arterial disease itself, while symptomatic cerebrovascular disease does affect cognitive function more severely.

Patients with manifest arterial disease did not have lower flow to the brain compared with the general population. Presence of diabetes mellitus was associated with lower total volume flow rate, as was increasing BMI. Patients with cerebrovascular disease had lower tVFR values than patients with symptomatic vascular disease elsewhere in the vascular tree.

We have reviewed the literature on the fetal type posterior (FTP) circle of Willis. In FTPs there is an embryonic derivation of the posterior cerebral artery from the internal carotid artery. Besides the fact that a larger area is thus dependent on the internal carotid artery, leptomeningeal vessels can not develop between the anterior and posterior circulation.

Patients with a bFTP circle of Willis did not have statistically significant different WML volumes than patients without an FTP in our study. These preliminary results will be followed by extended analyses in patients with a unilateral FTP and comparison of different techniques to assess WML.