• To assess the effects of tamoxifen and raloxifene on cognitive aging in selected nondemented women. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  
• Co-STAR will compare the effects of tamoxifen and raloxifene on age-associated declines in measures of verbal and nonverbal memory in women over age 65 within the context of a randomized clinical trial. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  

• Co-STAR will compare these effects on other cognitive abilities and mood. Co-STAR will involve collection of longitudinal data on cognitive aging in a subset of STAR volunteers allowing a comparison of the two agents. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  
• to compare the cognitive effects of tamoxifen and raloxifene with those resulting from more common forms of HT, specifically ET and ET plus progesterone within the context of an observational trial. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  

Insights into the neural underpinnings of HT effects were gained in neuroimaging studies among a subset of BLSA volunteers. HT users and nonusers showed different patterns of regional cerebral blood flow during verbal and figural memory tasks in brain regions subserving memory functions. Though suggestive, these observational studies may be limited by the "healthy user bias," the tendency for HT users to be healthier and better educated than nonusers. To address those limitations, investigators at the BLSA and Wake Forest University School of Medicine initiated the Women's Health Initiative Study of Cognitive Aging or WHISCA, a study involving 6-year longitudinal assessment of cognitive outcomes in 2969 women randomly assigned to receive active treatment (Premarin or Premarin plus medroxyprogesterone acetate) or placebo. WHISCA is an ancillary study to the Women's Health Initiative Memory Study (WHIMS) and is the largest randomized trial of hormone therapy on cognitive outcomes. WHISCA will provide invaluable data on the effects of estrogen treatments on cognitive aging.

Cognition in the Study of Tamoxifen and Raloxifene (Co-STAR), sponsored and conducted in collaboration with the National Institute on Aging (NIA), is in response to the unique opportunity afforded by the STAR Trial, sponsored by the NCI and coordinated by the National Surgical Adjuvant Breast and Bowel Project (NSABP). Co-STAR studies the effects of tamoxifen and raloxifene on cognitive aging in selected non-demented women. As an ancillary study to STAR, Co-STAR will focus on the acquisition of data on verbal and non-verbal memory, and will also assess other cognitive abilities and mood, in STAR participants randomized to either tamoxifen or raloxifene. The assessments involve a battery of cognitive tests that have been shown in previous observational studies in the BLSA to be reliable longitudinally and sensitive to the effects of age and hormone treatment. Co-STAR will contrast the relative effects of tamoxifen and raloxifene across this battery of tests, with measures of verbal and non-verbal memory defining its two primary outcome measures. Co-STAR data will provide unique information about the effects of SERMs on age- associated cognitive decline. The methods employed in Co-STAR will parallel those used in WHISCA to allow comparisons between the two treatment groups in Co-STAR (tamoxifen and raloxifene) and the three treatment groups in WHISCA (placebo, estrogen therapy [ET], and ET plus progesterone).