title: Higher Visit-to-Visit Low-Density Lipoprotein Cholesterol Variability Is Associated With Lower Cognitive Performance, Lower Cerebral Blood Flow, and Greater White Matter Hyperintensity Load in Older Subjects.
abstract: Recently, it was shown that intraindividual variation in low-density lipoprotein cholesterol (LDL-C) predicts both cerebrovascular and cardiovascular events. We aimed to examine whether this extends to cognitive function and examined possible pathways using a magnetic resonance imaging substudy.
  
  
  
  We investigated the association between LDL-C variability and 4 cognitive domains at month 30 in 4428 participants of PROSPER (PROspective Study of Pravastatin in the Elderly at Risk). Additionally, we assessed the association of LDL-C variability with neuroimaging outcomes in a subset of 535 participants. LDL-C variability was defined as the intraindividual standard deviation over 4 postbaseline LDL-C measurements, and all analyses were adjusted for mean LDL-C levels and cardiovascular risk factors.
  
  
  
  Higher LDL-C variability was associated with lower cognitive function in both the placebo and pravastatin treatment arms. Associations were present for selective attention (P=0.017 and P=0.11, respectively), processing speed (P=0.20 and P=0.029), and memory (immediate recall, P=0.002 and P=0.006; delayed recall, P=0.001 and P≤0.001). Furthermore, higher LDL-C variability was associated with lower cerebral blood flow in both trial arms (P=0.031 and P=0.050) and with greater white matter hyperintensity load in the pravastatin arm (P=0.046). No evidence was found for interaction between LDL-C variability and pravastatin treatment for both cognitive and magnetic resonance imaging outcomes.
  
  
  
  We found that higher visit-to-visit variability in LDL-C, independently of mean LDL-C levels and statin treatment, is associated with lower cognitive performance, lower cerebral blood flow, and greater white matter hyperintensity load.
authors.affiliation: From Department of Cardiology (R.A.J.S., S.T., J.W.J.), Section of Gerontology and Geriatrics, Department of Internal Medicine (R.A.J.S., S.T., B.S., A.J.M.d.C.), Department of Radiology (B.S., J.v.d.G., M.A.v.B.), Department of Clinical Epidemiology (S.l.C.), Department of Medical Statistics and Bioinformatics (S.l.C.), and Einthoven Laboratory for Experimental Vascular Medicine (J.W.J.), Leiden University Medical Center, Leiden, The Netherlands; and Interuniversity Cardiology Institute Netherlands, Utrecht, The Netherlands (J.W.J.).
authors.forename: Roelof A J
authors.initials: RA
authors.lastname: Smit
authors.affiliation: From Department of Cardiology (R.A.J.S., S.T., J.W.J.), Section of Gerontology and Geriatrics, Department of Internal Medicine (R.A.J.S., S.T., B.S., A.J.M.d.C.), Department of Radiology (B.S., J.v.d.G., M.A.v.B.), Department of Clinical Epidemiology (S.l.C.), Department of Medical Statistics and Bioinformatics (S.l.C.), and Einthoven Laboratory for Experimental Vascular Medicine (J.W.J.), Leiden University Medical Center, Leiden, The Netherlands; and Interuniversity Cardiology Institute Netherlands, Utrecht, The Netherlands (J.W.J.).
authors.forename: Stella
authors.initials: S
authors.lastname: Trompet
authors.affiliation: From Department of Cardiology (R.A.J.S., S.T., J.W.J.), Section of Gerontology and Geriatrics, Department of Internal Medicine (R.A.J.S., S.T., B.S., A.J.M.d.C.), Department of Radiology (B.S., J.v.d.G., M.A.v.B.), Department of Clinical Epidemiology (S.l.C.), Department of Medical Statistics and Bioinformatics (S.l.C.), and Einthoven Laboratory for Experimental Vascular Medicine (J.W.J.), Leiden University Medical Center, Leiden, The Netherlands; and Interuniversity Cardiology Institute Netherlands, Utrecht, The Netherlands (J.W.J.).
authors.forename: Behnam
authors.initials: B
authors.lastname: Sabayan
authors.affiliation: From Department of Cardiology (R.A.J.S., S.T., J.W.J.), Section of Gerontology and Geriatrics, Department of Internal Medicine (R.A.J.S., S.T., B.S., A.J.M.d.C.), Department of Radiology (B.S., J.v.d.G., M.A.v.B.), Department of Clinical Epidemiology (S.l.C.), Department of Medical Statistics and Bioinformatics (S.l.C.), and Einthoven Laboratory for Experimental Vascular Medicine (J.W.J.), Leiden University Medical Center, Leiden, The Netherlands; and Interuniversity Cardiology Institute Netherlands, Utrecht, The Netherlands (J.W.J.).
authors.forename: Saskia
authors.initials: S
authors.lastname: le Cessie
authors.affiliation: From Department of Cardiology (R.A.J.S., S.T., J.W.J.), Section of Gerontology and Geriatrics, Department of Internal Medicine (R.A.J.S., S.T., B.S., A.J.M.d.C.), Department of Radiology (B.S., J.v.d.G., M.A.v.B.), Department of Clinical Epidemiology (S.l.C.), Department of Medical Statistics and Bioinformatics (S.l.C.), and Einthoven Laboratory for Experimental Vascular Medicine (J.W.J.), Leiden University Medical Center, Leiden, The Netherlands; and Interuniversity Cardiology Institute Netherlands, Utrecht, The Netherlands (J.W.J.).
authors.forename: Jeroen
authors.initials: J
authors.lastname: van der Grond
authors.affiliation: From Department of Cardiology (R.A.J.S., S.T., J.W.J.), Section of Gerontology and Geriatrics, Department of Internal Medicine (R.A.J.S., S.T., B.S., A.J.M.d.C.), Department of Radiology (B.S., J.v.d.G., M.A.v.B.), Department of Clinical Epidemiology (S.l.C.), Department of Medical Statistics and Bioinformatics (S.l.C.), and Einthoven Laboratory for Experimental Vascular Medicine (J.W.J.), Leiden University Medical Center, Leiden, The Netherlands; and Interuniversity Cardiology Institute Netherlands, Utrecht, The Netherlands (J.W.J.).
authors.forename: Mark A
authors.initials: MA
authors.lastname: van Buchem
authors.affiliation: From Department of Cardiology (R.A.J.S., S.T., J.W.J.), Section of Gerontology and Geriatrics, Department of Internal Medicine (R.A.J.S., S.T., B.S., A.J.M.d.C.), Department of Radiology (B.S., J.v.d.G., M.A.v.B.), Department of Clinical Epidemiology (S.l.C.), Department of Medical Statistics and Bioinformatics (S.l.C.), and Einthoven Laboratory for Experimental Vascular Medicine (J.W.J.), Leiden University Medical Center, Leiden, The Netherlands; and Interuniversity Cardiology Institute Netherlands, Utrecht, The Netherlands (J.W.J.).
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: de Craen
authors.affiliation: From Department of Cardiology (R.A.J.S., S.T., J.W.J.), Section of Gerontology and Geriatrics, Department of Internal Medicine (R.A.J.S., S.T., B.S., A.J.M.d.C.), Department of Radiology (B.S., J.v.d.G., M.A.v.B.), Department of Clinical Epidemiology (S.l.C.), Department of Medical Statistics and Bioinformatics (S.l.C.), and Einthoven Laboratory for Experimental Vascular Medicine (J.W.J.), Leiden University Medical Center, Leiden, The Netherlands; and Interuniversity Cardiology Institute Netherlands, Utrecht, The Netherlands (J.W.J.).
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
mesh_terms: D000368:Aged; D001288:Attention; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000517:prevention & control; D002560:Cerebrovascular Circulation; D008078:Cholesterol, LDL / Q000097:blood*; D003072:Cognition Disorders / Q000097:blood*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D011939:Mental Recall; D017035:Pravastatin / Q000627:therapeutic use; D011379:Prognosis; D012959:Socioeconomic Factors; D066127:White Matter / Q000000981:diagnostic imaging*
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017035:Pravastatin
keywords: atherosclerosis; lipoproteins; magnetic resonance imaging