Original ArticlesIncreased Atherogenic Lipoproteins are Associated With Cognitive Impairment: Effects of Statins and Subclinical AtherosclerosisCarlsson, Cynthia M. MD, MS* †; Nondahl, David M. MS‡; Klein, Barbara E. K. MD, MPH‡; McBride, Patrick E. MD, MPH, FACC§; Sager, Mark A. MD*; Schubert, Carla R. MS‡; Klein, Ronald MD, MPH‡; Cruickshanks, Karen J. PhD‡ ∥Author Information *Section of Geriatrics and Gerontology, Department of Medicine ‡Department of Ophthalmology and Visual Sciences §Section of Cardiovascular Medicine, Department of Medicine ∥Department of Population Health Sciences; University of Wisconsin School of Medicine and Public Health †Veterans Affairs Geriatric Research, Education and Clinical Center (GRECC), Madison, WI Supported by NIH grants AG11099 (Dr Cruickshanks) and EY06594 (Drs Ronald Klein and Barbara Klein). Dr Carlsson was supported in part through NIA grant 1K23 AG021605 and the Beeson Career Development Award (1K23 AG026752, a grant jointly funded by NIA, the John A. Hartford Foundation, Atlantic Philanthropies, and the Starr Foundation). This is Madison VA Geriatric Research, Education and Clinical Center (GRECC) manuscript No. 2007-08. Reprints: Cynthia M. Carlsson, MD, MS, Section of Geriatrics and Gerontology, University of Wisconsin School of Medicine and Public Health, VA Geriatric Research, Education and Clinical Center (GRECC) (11G), 2500 Overlook Terrace, Madison, WI 53705 (e-mail: firstname.lastname@example.org). Received for publication November 30, 2007; accepted June 14, 2008 Alzheimer Disease & Associated Disorders: January-March 2009 - Volume 23 - Issue 1 - p 11-17 doi: 10.1097/WAD.0b013e3181850188 Buy Metrics Abstract Hypercholesterolemia increases the risk for dementia. Some studies suggest that statins may protect cognition, but findings are conflicting. Unmeasured confounders, including high-density lipoprotein (HDL) cholesterol or subclinical atherosclerosis, may have influenced prior study outcomes. In older adults participating in a population-based cohort study (n=1711, aged 65 to 97 y), we investigated the relationships of total and HDL cholesterol levels, statin use, and carotid intima-media thickness with the prevalence of cognitive impairment. In adjusted models, participants in the highest quartile of non-HDL (total−HDL) cholesterol had an increased odds of cognitive impairment compared with those in the lowest quartile [odds ratio (OR): 2.06, 95% confidence interval (CI): 1.07-3.98]. Statin use was associated with lower odds of cognitive impairment in unadjusted models (OR: 0.57, 95% CI: 0.36-0.89), but this relationship was not significant after adjusting for vascular and lifestyle factors (OR: 0.84, 95% CI: 0.47-1.49). In this analysis of older adults, increased atherogenic lipoproteins were associated with impaired cognition. Statin use was related to many factors that both negatively and positively affect cognition, but was not associated with better cognitive function. These results suggest that confounding by indication may explain the contradictory findings in studies assessing the association of statins with cognition. Randomized-controlled clinical trials and longitudinal studies are necessary to determine if statins protect against cognitive decline. © 2009 Lippincott Williams & Wilkins, Inc.