Premium
P‐152: Human brain myelination and amyloid beta deposition in Alzheimer's disease
Author(s) -
Bartzokis George,
Lu Po H.,
Mintz Jim
Publication year - 2007
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2007.04.115
Subject(s) - myelin , neuroscience , human brain , amyloid (mycology) , amyloid beta , oligodendrocyte , biology , cognitive decline , in vivo , pathology , disease , medicine , central nervous system , genetics , dementia
jective: To evaluate whether estradiol-induced effects on cognitive function will be disturbed when cortisol levels are exogenously elevated in older postmenopausal women, and the effects of this manipulation on blood levels of beta-amyloid (A 40 & A 42) and insulin-like growth factors (IGFs). Methods: Forty subjects (56-84 yrs) were enrolled into a placebo-controlled, double blind, parallel-group design study and randomized to receive 0.10 mg/day of transdermal -estradiol or a placebo skin patch for 8 weeks. In the last 4 days of the trial, subjects were also randomized to receive 90 mg/day (30 mg TID) of oral hydrocortisone or matched placebo. Cognitive test scores and blood levels of estradiol, cortisol, insulin-like growth factors, and beta-amyloid (A 40 A 42) were quantified at baseline, and at weeks 4 and 8. Results: Estradiol and cortisol levels attained confirmed compliance. Relative to baseline, performance on the Stroop improved when estradiol was administered alone, and worsened when cortisol was administered alone. Co-administration obliterated each of these effects. For tasks of working memory and visual memory, estradiol alone benefited performance while co-administration of estradiol and cortisol had a deleterious effect. Verbal declarative memory improved with estradiol, regardless of whether cortisol was also administered. Cortisol increased plasma levels of IGF-I and A 42, but only when administered without estradiol. For A 40, estradiol administered alone increased levels, cortisol administered alone decreased levels and again, the combined regimen altered each of these effects. Conclusions: This is the first clinical study to document that elevated cortisol levels do in fact modulate biological and cognitive response to estradiol. The cognitive findings, with associated changes in beta-amyloid levels, begin to unmask an influential factor that might very well detract from a salutary response to estradiol for older postmenopausal women, and thereby account for inconsistent findings in estradiol intervention trials.