Lack of Effect of Pravastatin on Cerebral Blood Flow or Parenchymal Volume Loss in Elderly at Risk for Vascular Disease

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Abstract
Background and Purpose— Ageing is associated with a decline in cerebral blood flow. Animal studies have shown that cholesterol-lowering therapy with statins might preserve cerebral blood flow (CBF). We examined the effect of 40 mg pravastatin on the decline in CBF and brain volume in a subset of elderly subjects participating in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial. Methods— Randomization was not stratified according to whether or not subjects participated in the MRI substudy. In 391 men (n=226) and women (n=165) aged 70 to 82 years (mean±SD, 75±3.2), we measured total CBF (in mL/min) at baseline and after a mean±SD follow-up of 33±1.4 months with a gradient-echo phase-contrast MRI technique. Total CBF was defined as the summed flows in both internal carotid and vertebral arteries. Parenchymal volume (whole brain) was segmented with the use of in-house–developed semiautomatic software. Results— Total CBF significantly declined in the placebo-allocated group, from 521±83 to 504±92 mL/min ( P =0.0036) and in the pravastatin-allocated group from 520±94 to 506±92 mL/min ( P =0.018). This decline was not significantly different between treatment groups ( P =0.56). There was also a significant reduction in brain volume over time ( P P =0.47). When expressed per unit of parenchymal volume, the decline in CBF over time was no longer statistically significant. Conclusions— Elderly people at risk for cerebral vascular disease had a significant decline in CBF with increasing age that was explained by a concomitant reduction in brain volume. Treatment with 40 mg pravastatin daily had no beneficial effect on total CBF.