A position paper: based on observational data indicating an increased rate of altered blood chemistry requiring withdrawal from the Alzheimer's Disease Cholesterol-Lowering Treatment Trial (ADCLT)

J Mol Neurosci. 2003;20(3):407-10. doi: 10.1385/JMN:20:3:407.

Abstract

Recruitment for the inaugural double-blind placebo-controlled trial investigating a cholesterol-lowering treatment for benefit in Alzheimer's disease (AD) (ADCLT) ended after obtaining 98 informed consents. Suspension of recruitment of the ADCLT occurred in concert with initiation of two separate multicenter trials testing similar hypotheses. Although occurring at very low rates (<2%), altered-chemistry adverse events requiring discontinuation of therapy (withdrawal AEs) are not unexpected with use of cholesterol-lowering statins. We suggest that exceptionally close monitoring for altered chemistry among individuals with AD should be undertaken in future statin treatment trials, as limited data from the ADCLT indicate that chemically based withdrawal AEs could be more prevalent among female AD patients. There was no apparent correlation between the occurrence of withdrawal-AE incidence and lower body mass among the female AD trial subjects and, therefore, probably was not a dose-related resultant. This might indicate that cognitively intact elderly women at risk for heart disease and those with clinically documented AD should not be presumed to be pharmocodynamically equivalent. Lipid profiles obtained at screening in the ADCLT are consistent with a possible difference between patients with current AD and those at risk for heart disease. Elevated cholesterol, increased cholesterol/high-density lipid (HDL) ratios, and elevated triglycerides are routinely observed among those at risk for heart disease; however, among ADCLT study participants, only cholesterol levels were increased while cholesterol/HDL ratio and triglyceride levels remained within normal limits.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / etiology*
  • Alzheimer Disease / metabolism
  • Blood / drug effects*
  • Blood / metabolism
  • Blood Chemical Analysis
  • Coronary Disease / complications
  • Coronary Disease / drug therapy
  • Coronary Disease / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Hypercholesterolemia / complications*
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / metabolism
  • Hyperlipidemias / complications
  • Hyperlipidemias / drug therapy
  • Hyperlipidemias / metabolism
  • Male
  • Monitoring, Physiologic
  • Patient Dropouts / statistics & numerical data
  • Risk Factors
  • Sex Characteristics

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors