Low HDL, high LDL linked to cerebral amyloidosis

A low level of HDL cholesterol and a high level of LDL cholesterol was associated with elevated cerebral amyloid-beta in a small sample of elderly individuals with high vascular risk, representing one of the best efforts yet to determine the link between cholesterol and susceptibility to brain amyloidosis seen in Alzheimer’s disease.

Epidemiologic literature has suggested that higher cholesterol values, particularly at midlife, are associated with an increased risk of Alzheimer’s disease, said at the annual meeting of the American Academy of Neurology.

In addition, a number of large observational studies have found a substantial reduction in Alzheimer’s disease risk associated with statin use, though randomized controlled trials have been negative, said the associate director of the University of California, Davis, Alzheimer’s disease research center.

In an effort to investigate the relationship between cholesterol levels and contemporaneous cerebral amyloid-beta, studied were 66 men and women in the Aging Brain study. The mean age of the 66 study participants was 78 years, and 44 (67%) had a history of stroke or TIA, myocardial infarction, and/or coronary artery bypass grafting. Nearly half (31) had a Clinical Dementia Rating (CDR) score of 0 (normal), and of the remaining 35 individuals, 32 had score of 0.5 (mild cognitive impairment) and 3 had a score of 1 (demented).

The researchers assayed fasting HDL and LDL cholesterol and triglycerides and used 11-C labeled Pittsburgh compound B (PIB) PET to measure cerebral amyloid-beta. The primary predictors were total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides. Secondary measures included VLDL cholesterol, apolipoprotein A-I, and apolipoprotein B. Apolipoprotein A-I is the primary protein of HDL cholesterol; it’s involved in reverse cholesterol transport. Apolipoprotein B is thought to be the atherogenic constituent of LDL cholesterol.

In a multiple regression model that adjusted for age and sex, both HDL and LDL cholesterol had significant, independent effects on the PIB index. Specifically, lower HDL and higher LDL were both associated, while adding apo E-epsilon 4 status to the model left the association essentially unchanged. Apo E-epsilon 4 had an independent effect on PIB in the expected direction.

Nearly three-quarters of subjects (71%) were on cholesterol-lowering drugs and 65% were on a statin. When the investigators adjusted the model for cholesterol treatment, it did not modify the results. “We modeled this in a number of ways and the treatment effects were not significant.” The apolipoprotein A-l and apolipoprotein B effects mirrored the effects of HDL and LDL.