Penman, Alan D.

AbstractIntroductionExisting studies predominantly consider the association of late‐life lipid levels and subsequent cognitive change. However, midlife rather than late‐life risk factors are often most relevant to cognitive health.MethodsWe quantified the association between measured serum lipids in midlife and subsequent 20‐year change in performance on three cognitive tests in 13,997 participants of the Atherosclerosis Risk in Communities study.ResultsElevated total cholesterol, low‐density lipoprotein cholesterol, and triglycerides were associated with greater 20‐year decline on a test of executive function, sustained attention, and processing speed. Higher total cholesterol and triglycerides were also associated with greater 20‐year decline in memory scores and a measure summarizing performance on all three tests. High‐density lipoprotein cholesterol was not associated with cognitive change. Results were materially unchanged in sensitivity analyses addressing informative missingness.DiscussionElevated total cholesterol, low‐density lipoprotein cholesterol, and triglycerides in midlife were associated with greater 20‐year cognitive decline.

Alzheimer's disease (AD) is the most common form of dementia and is characterized by impairment in memory, behavioral changes, and gradual loss of autonomy. Since there is a long latent period prior to diagnosis, the aim of this study was to determine whether twenty single nucleotide polymorphisms identified in genome‐wide association analyses of AD are associated with cognitive change in 8,320 white and 2,039 African‐American middle‐aged adults enrolled in the prospective Atherosclerosis Risk in Communities (ARIC) study. Cognition was evaluated using the Delayed Word Recall Test (DWRT; verbal memory), Digit Symbol Substitution Test (DSST; processing speed), and Word Fluency Test (WFT; executive function). General linear models were used to assess mean differences in 6‐year change in test scores among individuals categorized by genotype after adjusting for age, gender, and years of education. Addition of the minor allele for rs670139 (MS4A4E), rs9331896 (CLU), and rs12155159 (NME8) was nominally associated with change on the DWRT, DSST, and WFT, respectively, in whites. The ZCWPW1(rs1476679) andCDS33(rs3865444) variants were nominally associated with change on the DWRT and WFT in African‐Americans. For rs670139 and rs9331896 the association was only significant in individuals bearing at least oneAPOEϵ4 allele in stratified analyses. An unweighted genetic risk score aggregating the risk alleles for 15 polymorphisms was not associated with change in cognitive function. Although the AD‐associated genetic variants appear to have small effects on early cognitive change, replication will be required to establish whether there is a discernible influence on cognitive status in midlife. © 2016 Wiley Periodicals, Inc.

Background and purposeTo evaluate the association between systolic, diastolic and pulse pressure, and increase in ventricular size (VS). Observations in laboratory animals suggest intraventricular pulse pressure (systolic–diastolic) may play a role in ventricular enlargement.MethodsInitial magnetic resonance (MR) scans and vascular risk factors evaluation were performed in 1812 Atherosclerosis Risk in Communities participants in 1994–1995. In 2004–2006, 1130 participants underwent repeat MR. VS was rated using a validated nine‐point scale. Multiple logistic regression analysis assessed association between blood pressure measures and pulse pressure, and the change between the MR scans of VS controlling for age, sex and race.ResultsAt baseline 1112 participants (385 black women, 200 black men, 304 white women and 223 white men) had a mean age of 61.7 ± 4.3 years. In adjusted models pulse pressure at baseline was associated with an increase in VS [odds ratio (OR) 1.19, 95% confidence interval (CI) 1.01–1.40], as was systolic pressure (OR 1.28, 95% CI 1.03–1.58).ConclusionsSystolic pressure and pulse pressure are associated with future development of increased VS. The findings are consistent with the animal literature that increased pulse pressure predisposes to risk of future increased VS. High pulse pressure might play a role in the pathogenesis of normal pressure hydrocephalus.