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Kristine Yaffe, MD; Elizabeth Barrett-Connor, MD; Feng Lin, MS; Deborah Grady, MD

Arch Neurol. 2002;59:378-384.

Background  Few strategies are available for the prevention of cognitive impairment in elderly persons. Serum lipoprotein levels may be important predictors of cognitive function, and drugs that lower cholesterol may be effective for the prevention of cognitive impairment.

Objective  To determine whether serum lipoprotein levels, the 4-year change in serum lipoprotein levels, and the use of statin drugs are associated with cognition in older women without dementia.

Design, Setting, and Participants  An observational study of 1037 postmenopausal women with coronary heart disease enrolled in the Heart and Estrogen/progestin Replacement Study (participants at 10 of 20 centers).

Main Outcome Measure  The Modified Mini-Mental State Examination was administered at the end of the study after 4 years of follow-up. Women whose score was less than 84 points (>1.5 SDs below the mean) were classified as having cognitive impairment. Lipoprotein levels (total, high-density lipoprotein, and low-density lipoprotein [LDL] cholesterol and triglycerides) were measured at baseline and at the end of the study; statin use was documented at each visit.

Results  Compared with women in the lower quartiles, women in the highest LDL cholesterol quartile at cognitive testing had worse mean ± SD Modified Mini-Mental State Examination scores (93.7 ± 6.0 vs 91.9 ± 7.6; P = .002) and an increased likelihood of cognitive impairment (adjusted odds ratio, 1.76; 95% confidence interval, 1.04-2.97). A reduction in the LDL cholesterol level during the 4 years tended to be associated with a lower odds of impairment (adjusted odds ratio, 0.61; 95% confidence interval, 0.36-1.03) compared with women whose levels increased. Higher total and LDL cholesterol levels, corrected for lipoprotein(a) levels, were also associated with a worse Modified Mini-Mental State Examination score and a higher likelihood of impairment, whereas high-density lipoprotein cholesterol and triglyceride levels were not associated with cognition. Compared with nonusers, statin users had higher mean ± SD Modified Mini-Mental State Examination scores (92.7 ± 7.1 vs 93.7 ± 6.1; P = .02) and a trend for a lower likelihood of cognitive impairment (odds ratio, 0.67; 95% confidence interval, 0.42-1.05), findings that seemed to be independent of lipid levels.

Conclusions  High LDL and total cholesterol levels are associated with cognitive impairment, and lowering these lipoprotein levels may be a strategy for preventing impairment. The association between statin use and better cognitive function in women without dementia requires further study.

From the Departments of Psychiatry (Dr Yaffe), Neurology (Dr Yaffe), Epidemiology and Biostatistics (Drs Yaffe and Grady and Ms Lin), and Medicine (Dr Grady), University of California, San Francisco; the San Francisco VA Medical Center, San Francisco (Drs Yaffe and Grady); and the Department of Community and Family Medicine, University of California San Diego, La Jolla (Dr Barrett-Connor).

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