Asthana S, Baker LD, Craft S, Stanczyk FZ, Veith RC, Raskind MA, Plymate SR. High-dose estradiol improves cognition for women with AD: results of a randomized study. Neurology. 2001 Aug 28;57(4):605-12. PubMed Abstract

REAGENTS/MATERIAL:
Twenty postmenopausal women were recruited for the study. All women had dementia of mild to moderate severity, and presented with the characteristic clinical features of AD. Using a double-blind, parallel-group design, subjects were randomized to receive either 0.10 mg/ day of 17b-estradiol or a placebo by a skin patch (Estraderm; CibaGeigy Corp., Summit, NJ) for 8 weeks. After the week 8 evaluation, treatment was discontinued and subjects were followed for an additional 2 months. The patches were changed every 3 days and plasma estradiol levels at the time of testing were used to assess compliance. Following tests were administered: Stroop Color Word Interference Test, Trail-Making Test, Treisman Visual Search, Buschke Selective Reminding Test, Story Recall, Figure Copy/ Memory, Visual Paired-Associates, Oculomotor Delayed Response, and Semantic memory. Estradiol and estrone were extracted from serum using ethyl acetate hexane (2:3), and then subjected to Celite column chromatography. Procedural losses were followed by the addition of tritiated internal standards to each sample before the extraction step. Sensitivity for the estradiol assay was 8 pg/mL, whereas that for the estrone assay was 15 pg/mL. The intra-assay and interassay coefficients of variation for estradiol and estrone ranged from 9 to 15%. Free and total IGF-I, IGF-II, and IGFBP-3 were measured by highly specific enzyme-linked immunosorbent assays, using reagents obtained from the Diagnostics Systems Laboratories (Webster, TX).

FUTURE DIRECTION:
Clinical study evaluating the relationship between estrogen-induced alterations in the IGF system and cognitive function for subjects with AD will be important in the future to explore one potential mechanism underlying estrogen’s beneficial effect on cognition.