• California Verbal Learning Test (CVLT) [ Time Frame: Baseline and annually up to 4 years post treatment ] [ Designated as safety issue: No ]
• Benton Visual Retention Test (BVRT) Form D [ Time Frame: Baseline and annually up to 4 years post treatment ] [ Designated as safety issue: No ]

• Modified Mini-Mental State Exam [ Time Frame: Baseline and annually up to 4 years post treatment ] [ Designated as safety issue: No ]
• Prospective Memory Test [ Time Frame: Baseline and annually up to 4 years post treatment ] [ Designated as safety issue: No ]
• Primary Mental Abilities Vocabulary Test [ Time Frame: Baseline and annually up to 4 years post treatment ] [ Designated as safety issue: No ]
• Card Rotations Test [ Time Frame: Baseline and annually up to 4 years post treatment ] [ Designated as safety issue: No ]
• Finger Tapping Test [ Time Frame: Baseline and annually up to 4 years post treatment ] [ Designated as safety issue: No ]
• CVLT Long Delay Recall and Recognition Trials [ Time Frame: Baseline and annually up to 4 years post treatment ] [ Designated as safety issue: No ]
• Letter (F,A,S) and Semantic (fruits, vegetables) Fluency Tests [ Time Frame: Baseline and annually up to 4 years post treatment ] [ Designated as safety issue: No ]
• Digit Span [ Time Frame: Baseline and annually up to 4 years post treatment ] [ Designated as safety issue: No ]
• Positive and Negative Affect Scale (PANAS) [ Time Frame: Baseline and annually up to 4 years post treatment ] [ Designated as safety issue: No ]
• Geriatric Depression Scale (GDS) [ Time Frame: Baseline and annually up to 4 years post treatment ] [ Designated as safety issue: No ]
• Women's Health Initiative (WHI) Sleep Disturbance Measure Version 5 [ Time Frame: Baseline and annually up to 4 years post treatment ] [ Designated as safety issue: No ]
• Menopausal Symptoms Checklist Version 5 [ Time Frame: Baseline and annually up to 4 years post treatment ] [ Designated as safety issue: No ]

The purpose of this study is to assess the effects of tamoxifen and raloxifene on cognitive aging in selected cognitively-healthy women.

Recent reports indicate that hormone therapy (HT) may have a protective effect on the aging brain. Although previous studies have examined the effects of HT on age-related cognitive changes, there is little information on the effect of a new class of estrogenic agents, selective estrogen receptor modulators (SERMs), on cognitive aging. The two most commonly prescribed SERMs are tamoxifen, for treatment and prevention of breast cancer, and raloxifene, for maintaining bone density. In the face of potential widespread use of SERMs in healthy women, information on the effects of these agents on memory and other cognitive functions is essential.

The principal goals of Co-STAR are to compare the effects of tamoxifen and raloxifene

• on age-associated declines in measures of verbal and nonverbal memory in women over age 65
• other cognitive abilities and mood
• with those resulting from more common forms of HT, specifically ET (conjugated equine estrogen) and ET plus progesterone

Co-STAR results will be compared to results from the Women's Health Initiative Study of Cognitive Aging (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. A comparison of the Co-STAR treatment groups with the group of WHISCA participants receiving placebo will provide insights into the effects of SERMs relative to no treatment. A comparison of the Co-STAR treatment groups with WHISCA treatment groups receiving ET or ET plus progesterone will provide insights into the effects of SERMs relative to common HT treatments.

Co-STAR participants will be recruited from The National Cancer Institute's (NCI) Study of Tamoxifen and Raloxifene (STAR), a multi-center, 5-year, randomized clinical trial among 22,000 women at increased risk for breast cancer, to compare the effects of tamoxifen and raloxifene on risk for breast cancer.

• Cognition
• Aging

• Drug: tamoxifen
• Drug: raloxifene

• Experimental: tamoxifen
• Experimental: raloxifene

• Maki PM, Zonderman AB, Resnick SM. Enhanced verbal memory in nondemented elderly women receiving hormone-replacement therapy. Am J Psychiatry. 2001 Feb;158(2):227-33.
• Resnick SM, Metter EJ, Zonderman AB. Estrogen replacement therapy and longitudinal decline in visual memory. A possible protective effect? Neurology. 1997 Dec;49(6):1491-7.
• Resnick SM, Maki PM, Golski S, Kraut MA, Zonderman AB. Effects of estrogen replacement therapy on PET cerebral blood flow and neuropsychological performance. Horm Behav. 1998 Oct;34(2):171-82.

Inclusion Criteria:

• Women enrolled in STAR trial at a site participating in Co-STAR
• 65 years of age or older
• Have been randomized into STAR but have not started taking the study drug OR enrolled in STAR for a minimum of one year
• Have not been diagnosed with dementia
• Have signed a separate consent document for the Co-STAR Study
• Previous diagnoses of chronic neurologic disease (Parkinson's disease, stroke, epilepsy, multiple sclerosis), history of head injury, depression, alcohol addiction, drug addiction, and other neurologic or psychiatric conditions will be recorded but will not serve as exclusion factors for this study

Exclusion Criteria:

• Not enrolled in the STAR Trial
• Younger than 65 years of age
• Diagnosed with dementia