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Updated: Oct 23, 2026
Evaluation of the Cognitive Performance of Hypertensive Patients with Silent Cerebrovascular Lesions
Published on: April 23, 2021
Effect of thrombin inhibition in vascular dementia and silent cerebrovascular disease. An MR spectroscopy study
Insights
Thrombin inhibition improved cerebral metabolism in patients with silent cerebrovascular disease (CVD) and peripheral arterial occlusive disease (PAOD). This suggests thrombin plays a role in vascular dementia and its precursors, with potential for clinical improvement.
Area of Science:
- Neuroscience
- Vascular Biology
- Biochemistry
Background:
- Silent cerebrovascular disease (CVD) is linked to stroke and vascular dementia.
- Increased thrombin generation is observed in silent CVD patients.
Purpose of the Study:
- To investigate the effect of thrombin inhibition on cerebral metabolism and function.
- To assess outcomes in peripheral arterial occlusive disease (PAOD) patients with or without silent CVD.
Main Methods:
- Proton MR spectroscopy assessed cerebral biochemical compounds in 17 PAOD patients (12 with advanced CVD, 5 without).
- Argatroban (a thrombin inhibitor) was administered intravenously for 7 days.
- Measurements were taken before and after treatment in deep white matter and cerebellar regions.
Main Results:
- Deep white matter N-acetylaspartate (NAA) to creatine (Cre) ratio was lower in advanced CVD patients.
- Argatroban therapy significantly increased the NAA/Cre ratio in these patients.
- Two vascular dementia patients showed clinical improvement and increased NAA/Cre ratios.
Conclusions:
- Increased thrombin generation may contribute to vascular dementia and its predisposing conditions.
- Thrombin inhibition could disrupt this cycle and improve clinical outcomes.
- Targeting thrombin offers a potential therapeutic strategy for cerebrovascular disorders.
Background And Purpose:
Silent cerebrovascular disease (CVD) has been proposed as a predisposing condition for clinically overt stroke and vascular dementia. Recently, we found increased thrombin generation in silent CVD patients. Here, we report the effect of thrombin inhibition using a potent selective thrombin inhibitor on the cerebral metabolism and function in peripheral arterial occlusive disease (PAOD) patients with or without silent CVD.
Methods:
We examined 17 mild chronic PAOD patients, including 2 cases of vascular dementia. We divided the patients into 2 groups: 1 was the advanced CVD group with multiple lacunar infarction and/or advanced periventricular hyperintensity detected by brain MRI (n=12), and the other was the no CVD group that had none of these abnormalities (n=5). We assessed the cerebral biochemical compounds in the deep white matter area and cerebellar hemisphere (8 cm3) by proton MR spectroscopy before and after infusion of argatroban (10 mg/d IV) over 2 hours for 7 days.
Results:
The ratio of N-acetylasparate (NAA) to total creatine (Cre) in the deep white matter area was significantly lower in the advanced CVD group than in the no CVD group, whereas there were no significant differences in this ratio in the cerebellar hemisphere between the 2 groups. In the former group, this decreased NAA/Cre ratio significantly increased after argatroban therapy, whereas there was no change in the latter group. The 2 patients with vascular dementia showed clinical improvement with marked increases in the NAA/Cre ratio and mini-mental score.
Conclusions:
These results suggest that increased thrombin generation may have some pathophysiological roles in developing vascular dementia and its chronic predisposing conditions. Thrombin inhibition may break this vicious cycle and lead to clinical improvement.
