Abstract:
BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.
journal_name
Circulationjournal_title
Circulationauthors
Smit RA,Trompet S,Sabayan B,le Cessie S,van der Grond J,van Buchem MA,de Craen AJ,Jukema JWdoi
10.1161/CIRCULATIONAHA.115.020627subject
Has Abstractpub_date
2016-07-19 00:00:00pages
212-21issue
3eissn
0009-7322issn
1524-4539pii
CIRCULATIONAHA.115.020627journal_volume
134pub_type
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