title: Lack of effect of pravastatin on cerebral blood flow or parenchymal volume loss in elderly at risk for vascular disease.
abstract: OBJECTIVE
  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<0.001), which was not different between the treatment groups (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.
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: V Hester
authors.initials: VH
authors.lastname: ten Dam
authors.forename: Frieke M A
authors.initials: FM
authors.lastname: Box
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: de Craen
authors.forename: Dominique M J
authors.initials: DM
authors.lastname: van den Heuvel
authors.forename: Edward L E M
authors.initials: EL
authors.lastname: Bollen
authors.forename: Heather M
authors.initials: HM
authors.lastname: Murray
authors.forename: Mark A
authors.initials: MA
authors.lastname: van Buchem
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
authors.forename: Gerard Jan
authors.initials: GJ
authors.lastname: Blauw
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D001776:Blood Circulation Time; D001783:Blood Flow Velocity; D001794:Blood Pressure; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002339:Carotid Arteries / Q000473:pathology; D002560:Cerebrovascular Circulation; D002784:Cholesterol / Q000378:metabolism; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D017035:Pravastatin / Q000627:therapeutic use*; D011446:Prospective Studies; D012984:Software; D013997:Time Factors
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D017035:Pravastatin