Background and Purpose-Recent investigations have suggested an important role of statins in the prevention of stroke and dementia independent of their lipid-lowering properties. Using transcranial Doppler sonography (TCD), we examined acetazolamide reactivity as a marker of cerebral vasoreactivity in patients with subcortical small-vessel disease before and after pravastatin treatment. Methods-In 16 patients (mean age 68Ϯ10 years) with subcortical small-vessel disease, cerebral vasomotor reactivity was tested using TCD insonating the middle cerebral artery. Cerebral blood flow velocity (CBFV) increase after bolus injection of 1 g acetazolamide was determined before and after 2-month treatment with pravastatin sodium 20 mg daily. Results-Relative CBFV increase was significantly greater after pravastatin treatment (41.9Ϯ23.7% versus 55.7Ϯ18. 3%, Pϭ0.004). Comparison of CBFV at rest before and after treatment with pravastatin did not show significant differences.There was a strong negative correlation between the pravastatin-induced enhancement of vasomotor reactivity and the pretreatment CBFV increase (␤ϭϪ0. 64, Pϭ0.019). No associations were found between the effect of pravastatin on vasomotor reactivity and pretreatment levels or changes of LDL cholesterol. ecent studies have demonstrated a significant reduction of risk for ischemic stroke in patients with coronary heart disease treated with ␤-hydroxy-␤-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins). 1 In addition, these agents may also prevent vascular dementia. 2 Current evidence suggests that the beneficial effects of statins on the vascular system seem to be mediated not only by their lipid-lowering properties but also by improving vascular endothelial function. They are known to activate endothelial nitric oxide synthase (eNOS) 3 and thereby propagate NOdependent vasodilation. In patients with cerebral small-vessel disease, impaired vasoregulation of the subcortical microvasculature may be an important pathogenetic mechanism, leading to white matter hypoperfusion, recurrent lacunar infarctions, and vascular dementia. Accordingly, reduced vasomotor reactivity as measured by transcranial Doppler (TCD) has been shown to correlate with the severity of leukoencephalopathy seen on MRI. 4,5 The purpose of the present pilot study was to investigate the effects of statin treatment on vasomotor reactivity in patients with cerebral small-vessel disease. Conclusions-This Subjects and MethodsWe prospectively studied 16 patients (9 men, 7 women; mean age 68Ϯ10 years) with subcortical small-vessel disease, defined by periventricular or subcortical white matter lesions on fluid-attenuated inversion recovery (FLAIR)-weighted MRI in addition to one or more of the following criteria: Ն1 ischemic events consistent with transient ischemic attack or lacunar infarction, history of cognitive decline, gait instability, and symptomatic epileptic seizure with no evident cause other than cerebral small-vessel disease. Exclusion criteria were previous statin treatm...

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BackgroundLithium augmentation of antidepressants is an effective strategy in treatment-resistant depression. The proteohormone ghrelin is thought to be involved in the pathophysiology of depression. The purpose of this study was to investigate the association of treatment response with the course of ghrelin levels during lithium augmentation.MethodGhrelin serum concentrations and severity of depression were measured in 85 acute depressive patients before and after 4 weeks of lithium augmentation.ResultsIn a linear mixed model analysis, we found a significant effect of response*time interaction (F1.81=9.48; P=.0028): under treatment, ghrelin levels increased in nonresponders and slightly decreased in responders to lithium augmentation. The covariate female gender had a significant positive effect (F1.83=4.69; P=.033), whereas time, response, appetite, and body mass index (kg/m2) did not show any significant effect on ghrelin levels (P>.05).ConclusionThis is the first study showing that the course of ghrelin levels separates responders and nonresponders to lithium augmentation. Present results support the hypothesis that ghrelin serum concentrations might be involved in response to pharmacological treatment of depression.