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Joan T. Moroney, MD, MRCPI; Ming-Xin Tang, PhD; Lars Berglund, MD; Scott Small, MD; Carole Merchant, MD; Karen Bell, MD; Yaakov Stern, PhD; Richard Mayeux, MD, MSc

JAMA. 1999;282:254-260.

Context  Next to Alzheimer disease, vascular dementia is the second most common form of dementia in the elderly, yet few specific risk factors have been identified.

Objective  To investigate the relationship of plasma lipids and lipoproteins to dementia with stroke.

Design and Setting  Prospective longitudinal community-based study over a 7-year period (1991-1998).

Participants  A total of 1111 nondemented participants (mean [SD] age, 75.0 [5.9] years) were followed up for an average of 2.1 years (range, 1-7.8 years).

Main Outcome Measure  Incident dementia with stroke according to standardized criteria, by baseline levels of total plasma cholesterol and triglycerides, low-density lipoprotein (LDL) cholesterol, LDL levels corrected for lipoprotein(a), high-density lipoprotein cholesterol, lipoprotein(a), and apolipoprotein E genotype.

Results  Two hundred eighty-six (25.7%) of the 1111 subjects developed dementia during follow-up; 61 (21.3%) were classified as having dementia with stroke and 225 (78.7%) as having probable Alzheimer disease. Levels of LDL cholesterol were significantly associated with an increased risk of dementia with stroke. Compared with the lowest quartile, the highest quartile of LDL cholesterol was associated with an approximately 3-fold increase in risk of dementia with stroke, adjusting for vascular risk factors and demographic variables (relative risk [RR], 3.1; 95% confidence interval [CI], 1.5-6.1). Levels of LDL corrected for lipoprotein(a) were an even stronger predictor of dementia with stroke in the adjusted multivariate analysis. Compared with the lowest quartile, the RR of dementia with stroke for the highest quartile of lipoprotein(a)–corrected LDL cholesterol was 4.1 (95% CI, 1.8-9.6) after adjusting for vascular factors and demographic variables. Lipid or lipoprotein levels were not associated with the development of Alzheimer disease in our cohort.

Conclusions  Elevated levels of LDL cholesterol were associated with the risk of dementia with stroke in elderly patients. Further study is needed to determine whether treatment of elevated LDL cholesterol levels will reduce the risk of dementia with stroke.

Author Affiliations: Gertrude H. Sergievsky Center (Drs Moroney, Tang, Small, Merchant, Bell, Stern, and Mayeux), Taub Center for Alzheimer's Disease Research (Drs Stern and Mayeux), the Divisions of Biostatistics (Dr Tang) and Epidemiology (Dr Mayeux), School of Public Health, and the Departments of Neurology (Drs Moroney, Small, Merchant, Bell, Stern, and Mayeux), Psychiatry (Drs Stern and Mayeux), and Medicine (Dr Berglund), Columbia University, College of Physicians and Surgeons and Columbia-Presbyterian Medical Center, New York, NY.

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