Co-STAR: Cognition in the Study of Tamoxifen and Raloxifene

• Sponsor: Wake Forest University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00687102
• Collaborator: National Institute on Aging (NIA) (NIH)
• Enrollment: 1,498
• Locations: 134
• Arms: 2
• Duration (Months): 77
• Patients Per Site: 11.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Cognition; Aging	Drug: tamoxifen; Drug: raloxifene	Phase 3

Detailed Description

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) NCT00003906, 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1498 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Effects of Selective Estrogen Receptor Modulators on Cognitive Aging: Cognition in the Study of Tamoxifen and Raloxifene
• Study Start Date: Oct 1, 2001
• Actual Primary Completion Date: Mar 1, 2008
• Actual Study Completion Date: Mar 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Star participants assigned to Tamoxifen Participants in the parent study, STAR assigned to Tamoxifen who were 65 or older at time of enrollment.	Drug: tamoxifen; oral tamoxifen plus placebo daily for 5 years; Other Names: Nolvadex
Experimental: Star participants assigned to Raloxifene Participants in the parent study, STAR assigned to Raloxifene who were 65 or older at time of enrollment.	Drug: raloxifene; oral raloxifene plus placebo daily for 5 years; Other Names: Evista, Keoxifene

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline on the the Benton Visual Retention Test Scores by Treatment Group [Baseline and 3 Years]

   Mean Change From Baseline on the Benton Visual Retention (BVRT) Test scores. Adjusted for age, ethnicity, education, and baseline measure, for participants with true baseline measures. The BVRT measures short term visual memory and visuo-constructional abilities. Each of 10 designs was presented one at a time for 10 seconds, and immediately after the design was withdrawn, the participant was instructed to draw it from memory on a blank sheet of paper. The score on the BVRT is the total number of errors, 0-26 represents the total number of theoretically possible errors. Lower score denotes better outcomes.

2. Mean Change From Baseline on the the California Verbal Learning Test Scores by Treatment Group [Baseline and 3 Years]

   Adjusted for age, ethnicity, education, and baseline measure, for participants with true baseline measures. The experimenter reads a list of 16 nouns aloud, at one-second intervals, in fixed order, over 3 learning trials (list A) . After each trial, the subject is asked to recall as many words as they can in any order (i.e., free recall) given a score 0-16 each. Total range as the sum of the 3 learning trials: 0 - 48. Participants were asked to recall a second interference list (List B) with a score range of 0-16. Free recall of list A are tested immediately after list B (short-delay) Total range 0- 16 , and again after 20 minutes (long-delay) 0-16. Each part of the scale is reported separately as Total List A trials, Total List B trials, Short-delay free recall, and Long-delay free recall.

Secondary Outcome Measures

1. Mean Change From Baseline on the Letter Fluency and Semantic Fluency Scores by Treatment Group [Baseline and 3 Years]

   Mean Change From Baseline on the Letter Fluency Test scores. Adjusted for age, ethnicity, education, and baseline measure, for participants with true baseline measures. Measures cognitive function. In this test, the participant names as many words as possible in 1 minute, beginning with each letter for letter fluency (F, A, and S) and category for semantic fluency (fruits and vegetables). To score the administrator, counts up the total number letters or words that the individual is able to produce. The score minimum would be 0 and the maximum would be the total of correct items named within 1 minute. Higher scores represent better outcomes.

2. Mean Change From Baseline on Digit Span Test Scores by Treatment Group [Baseline and 3 Years]

   Mean Change From Baseline on the Digit Span Test - Digits Forward and Digits backward Test scores. Adjusted for age, ethnicity, education, and baseline measure, for participants with true baseline measures. Measures reasoning, verbal ability, and memory. The participant is asked to provide immediate recall of a series of digits in forward and backward sequences. The individual's score is the total number of items correctly repeated forwards or backwards. Total range 0 - 14, higher results denotes a better outcome.

3. Mean Change From Baseline on Card Rotations Test Scores by Treatment Group [Baseline and 3 Years]

   Mean Change From Baseline on the Card Rotations Test scores. Adjusted for age, ethnicity, education, and baseline measure, for participants with true baseline measures. Measures the ability to mentally manipulate figures in two and three-dimensions. On each of 28 trials, participants view sample line drawings of a geometric figure and 8 alterations representing 2 or 3-dimensional rotations of the drawing. Participants are asked to identify alternatives that show the sample in 2-D but not in 3-D. Total range 0 - 160 and the number of incorrect/correct responses is measure. Higher number of correct answers is a better outcome.

4. Mean Change From Baseline on the Finger Tapping Test Scores by Treatment Group [Baseline and 3 Years]

   Mean Change From Baseline on the the Finger Tapping Test scores. Adjusted for age, ethnicity, education, and baseline measure, for participants with true baseline measures. Measures motor speed, coordination, attention, alertness, slowing of responses, and motor control. In this test of motor speed and dexterity participants are asked to depress a lever as many times as possible in each of 7, 10-second trials, first with the right hand and next with the left hand. The highest and lowest scores are dropped; the score is the average of the remaining five trials for each hand.Higher scores represent better outcomes.

5. Mean Change From Baseline on the Positive and Negative Affect Schedule Scores by Treatment Group [Baseline and 3 Years]

   Mean Change From Baseline on the Positive and Negative Affect Schedule (PANAS). Adjusted for age, ethnicity, education, and baseline measure, for participants with true baseline measures. Measures positive and negative affect. Mood is assessed with the PANAS, a list of ten pleasant mood states (e.g., interested, proud, inspired) and ten unpleasant mood states (e.g., irritable, guilty, jittery). Respondents are asked to rate on a 5-point scale (1 being "very slightly or not at all" and 5 being "extremely") the extent to which they have experienced each mood during a specific time frame. Ratings for each item can range from 0 to 4 with total scores for positive affect and negative affect subscales ranging from 0 to 40. For positive affect, higher scores denote higher levels of positive affect and for negative affect, lower scores denote lower levels of negative affect.

6. Mean Change From Baseline on the Geriatric Depression Scale Scores by Treatment Group [Baseline and 3 Years]

   Mean Change From Baseline on the Geriatric Depression Scale. Adjusted for age, ethnicity, education, and baseline measure, for participants with true baseline measures. Measures depression in older adults. Mood is also assessed with the 15-item short form of the GDS which measures non-somatic features of depressed mood. Participants indicate the presence or absence of each symptom. The GDS-SF score is the total number of positive depressive items. Score range is 0-15, with 0-4 denoting better outcomes and a score of 5 and above denoting worse outcomes (depression).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CCOP Western Regional	Phoenix	Arizona	United States	85006
2	Arizona Cancer Center	Tucson	Arizona	United States	85719
3	Naval Hospital Camp Pendleton	Camp Pendleton	California	United States	92055
4	City of Hope National Medical Center	Duarte	California	United States	91010
5	Hematology Oncology Consultants	Duarte	California	United States	91010
6	Southern Nevada Cancer Research Foundation	Duarte	California	United States	91010
7	Virginia K. Crosson Cancer Center	Fullerton	California	United States	92835
8	Glendale Memorial Hospital Comprehensive Cancer Center	Glendale	California	United States	91204
9	Valley Tumor Medical Group	Lancaster	California	United States	93534
10	Kaiser Permanente Division of Research	Oakland	California	United States	94612
11	Ventura County Hematology-Oncology Specialists	Oxnard	California	United States	93030
12	North Valley Breast Clinic	Redding	California	United States	96001
13	Kaiser Permanente Oncology Research	San Diego	California	United States	92120
14	Naval Medical Center San Diego	San Diego	California	United States	92134
15	Cancer Foundation of Santa Barbara	Santa Barbara	California	United States	93105
16	Kaiser Permanente, Woodland Hills	Woodland Hills	California	United States	91367
17	Penrose Cancer Center	Colorado Springs	Colorado	United States	80907
18	Colorado Cancer Research Program	Denver	Colorado	United States	80224
19	St. Mary-Corwin Medical Center	Pueblo	Colorado	United States	81004
20	Hartford Hospital	Hartford	Connecticut	United States	06102
21	The Hospital of Central Connecticut	New Britain	Connecticut	United States	06050
22	Lawrence & Memorial Hospital	New London	Connecticut	United States	06320
23	Christiana Care Health Services	Newark	Delaware	United States	19718
24	Washington Cancer Institute	Washington	District of Columbia	United States	20010
25	Lakeland Regional Cancer Center	Lakeland	Florida	United States	33805
26	H. Lee Moffitt Cancer Center and Research Center	Tampa	Florida	United States	33612
27	Memorial Medical Center	Savannah	Georgia	United States	31403
28	University of Hawaii, Honolulu	Honolulu	Hawaii	United States	96813
29	Rush-Presbyterian-St. Luke's Medical Center	Chicago	Illinois	United States	60612
30	SwedishAmerican Hospital Regional Cancer Ctr	Rockford	Illinois	United States	61104
31	Carle Cancer Center	Urbana	Illinois	United States	61801
32	Center for Cancer Care at Goshen Health Systems	Goshen	Indiana	United States	46526
33	Community Hospital	Munster	Indiana	United States	46321
34	CCOP,Northern Indiana Research Consortium	South Bend	Indiana	United States	46601
35	Genesis Medical Center	Davenport	Iowa	United States	52803
36	Finely Hospital, Wendt Regional Cancer Center	Dubuque	Iowa	United States	52001
37	Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
38	Ochsner Cancer Institute	New Orleans	Louisiana	United States	70121
39	The Harry and Jeanette Weinberg Cancer Institute at Franklin Square	Baltimore	Maryland	United States	21237
40	Boston Medical Center	Boston	Massachusetts	United States	02118
41	Berkshire Hematology Oncology, P.C.	Pittsfield	Massachusetts	United States	01201
42	Genesys Hurley Cancer Institute	Ann Arbor	Michigan	United States	48106
43	Genesys Regional Medical Center	Ann Arbor	Michigan	United States	48106
44	Oakwood Healthcare System	Ann Arbor	Michigan	United States	48106
45	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
46	St. John Hospital and Medical Center	Ann Arbor	Michigan	United States	48106
47	Battle Creek Health Systems	Battle Creek	Michigan	United States	49016
48	Henry Ford Health System	Detroit	Michigan	United States	48202
49	McLaren Regional Medical Center	Flint	Michigan	United States	48532
50	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan	United States	49503
51	Kalamazoo	Kalamazoo	Michigan	United States	49007
52	Michigan State University	Lansing	Michigan	United States	48910
53	Marquette General Hospital	Marquette	Michigan	United States	49855
54	Mercy Memorial Hospital Cancer Center	Monroe	Michigan	United States	48162
55	William Beaumont Hospital	Royal Oak	Michigan	United States	48073
56	St. Luke's Hospital	Duluth	Minnesota	United States	55802
57	Duluth Clinic	Duluth	Minnesota	United States	55805
58	Hennepin Consortium	Minneapolis	Minnesota	United States	55415
59	Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
60	Hematology & Oncology Associates Ltd	Tupelo	Mississippi	United States	38801
61	Ellis Fischel Cancer Center	Columbia	Missouri	United States	65203
62	St John's Regional Medical Center Cancer Center	Joplin	Missouri	United States	64804
63	Alvin J Siteman Cancer Center at Barnes-Jewish Hosp & Washington U Sch of Med	Saint Louis	Missouri	United States	63110
64	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
65	Cancer Research for the Ozarks	Springfield	Missouri	United States	65804
66	St John's Health System	Springfield	Missouri	United States	65804
67	Montana Cancer Consortium	Billings	Montana	United States	59101
68	Great Falls Clinic, LLP	Great Falls	Montana	United States	59405
69	Good Samaritan Health Systems	Kearney	Nebraska	United States	68848
70	Cancer Resource Center	Lincoln	Nebraska	United States	68510
71	Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
72	Methodist Cancer Center, Omaha	Omaha	Nebraska	United States	68114
73	Riverview Medical Center	Red Bank	New Jersey	United States	07701
74	Roswell Park/Western New York STAR Consortium	Buffalo	New York	United States	14263
75	Bassett Healthcare	Cooperstown	New York	United States	13326
76	Hematology-Oncology Associates of CNY	East Syracuse	New York	United States	13057
77	Vassar Brothers Hospital	Poughkeepsie	New York	United States	12601
78	University of Rochester Cancer Center	Rochester	New York	United States	14642
79	University Healthcare System	Syracuse	New York	United States	13202
80	Presbyterian Hospital	Charlotte	North Carolina	United States	28204
81	Blumenthal Cancer Center	Charlotte	North Carolina	United States	28231
82	Duke University Medical Center	Durham	North Carolina	United States	27710
83	Cape Fear Valley Medical Center	Fayetteville	North Carolina	United States	28302
84	Gaston Memorial Hospital	Gastonia	North Carolina	United States	28054
85	Southeastern Medical Oncology Center	Goldsboro	North Carolina	United States	27534
86	East Carolina University	Greenville	North Carolina	United States	27834
87	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina	United States	28791
88	Forsyth Regional Cancer Center	Winston-Salem	North Carolina	United States	27103
89	Wake Forest University School of Medicine	Winston-Salem	North Carolina	United States	27157
90	Kaiser Permanente Ohio	Bedford	Ohio	United States	44146
91	Ireland Cancer Center at Case Western Reserve University	Cleveland	Ohio	United States	44106
92	CCOP Columbus	Columbus	Ohio	United States	43215
93	Lima Memorial Hospital	Lima	Ohio	United States	45807
94	Fulton County Health Center	Toledo	Ohio	United States	43623
95	Toledo Community Hospital Oncology Program	Toledo	Ohio	United States	43623
96	Columbia River Oncology Program	Portland	Oregon	United States	97225
97	Kaiser Permanente Center for Health Research (Oncology Research)	Portland	Oregon	United States	97227
98	UPMC/UPCI/Magee Women's Hospital	Pittsburgh	Pennsylvania	United States	15213
99	Mercy Cancer Center, Scranton	Scranton	Pennsylvania	United States	18501
100	York Cancer Center	York	Pennsylvania	United States	17403
101	Roper Hospital	Charleston	South Carolina	United States	29401
102	Palmetto Richland Memorial Hospital	Columbia	South Carolina	United States	29203
103	Cancer Centers of the Carolinas	Greenville	South Carolina	United States	29605
104	Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
105	Sioux Valley Clinic Oncology	Sioux Falls	South Dakota	United States	57104
106	Thompson Cancer Survival Center	Knoxville	Tennessee	United States	37916
107	Don and Sybil Harrington Cancer Center	Amarillo	Texas	United States	79106
108	Methodist Hospitals of Dallas	Dallas	Texas	United States	75203
109	Presbyterian Hospital of Dallas	Dallas	Texas	United States	75231
110	Baylor-Sammons Cancer Center	Dallas	Texas	United States	75246
111	UT Southwestern Center for Breast Care	Dallas	Texas	United States	75390
112	Baylor Medical Center at Garland	Garland	Texas	United States	75042
113	Breast Care Center at Baylor College of Medicine/Methodist Hospital	Houston	Texas	United States	77030
114	University of Texas M. D. Anderson Cancer Center	Houston	Texas	United States	77030
115	Wilford Hall Medical Center	Lackland Air Force Base	Texas	United States	78236
116	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas	United States	79401
117	Southwest Cancer Center	Lubbock	Texas	United States	79415
118	Baylor Regional Medical Center	Plano	Texas	United States	75093
119	Scott and White Hospital	Temple	Texas	United States	76508
120	Huntsman Cancer Institute at the University of Utah	Salt Lake City	Utah	United States	84112
121	Danville Hematology & Oncology, Inc.	Danville	Virginia	United States	24541
122	Olympic Hematology and Oncology Associates	Bremerton	Washington	United States	98310
123	Benaroya Research Institute at Virginia Mason	Seattle	Washington	United States	98101
124	Swedish Medical Center	Seattle	Washington	United States	98104
125	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
126	Yakima Valley Memorial Hospital/North Star Lodge Cancer Center	Yakima	Washington	United States	98902
127	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
128	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N4N2
129	UBC-Vancouver Hospital & Health Science Center	Vancouver	British Columbia	Canada	V6K2B5
130	CancerCare Manitoba	Winnepeg	Manitoba	Canada	R3EOV9
131	Women's Breast Health Centre	Ottawa	Ontario	Canada	K1Y4K7
132	Thunder Bay Regional Health Sciences Centre, Regional Cancer Care Clinical Trials	Thunder Bay	Ontario	Canada	P7B6V4
133	North York General Hospital	Toronto	Ontario	Canada	M5S1B6
134	Women's College Hospital	Toronto	Ontario	Canada	M5S1B6

Sponsors and Collaborators

• Wake Forest University
• National Institute on Aging (NIA)

Investigators

• Principal Investigator: Sally A. Shumaker, PhD, Wake Forest University Health Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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, 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.
• 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.

• Responsible Party: Wake Forest University
• ClinicalTrials.gov Identifier: NCT00687102
• Other Study ID Numbers: IA0132; 1R13AG020218-01; NCT00571857
• First Posted: May 30, 2008
• Last Update Posted: Sep 12, 2018
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Wake Forest University: breast cancer; Tamoxifen; Raloxifene; hormone therapy
• Additional relevant MeSH terms: Tamoxifen; Raloxifene Hydrochloride

Study Results

Participant Flow

Recruitment Details	Co-STAR enrolled 1,498 women assigned in the STAR trial aged 65 years and older and no diagnosis of dementia. All participants were fluent in English and provided written informed consent for the Co-STAR study. Enrollment began in October 2001, 18 months after STAR enrollment started and continued until the unmasking of STAR in June 2006.

Arm/Group Title	Star Participants Assigned to Tamoxifen	Star Participants Assigned to Raloxifene
Arm/Group Description	Participants in the parent study, STAR assigned to Tamoxifen who were 65 or older at time of enrollment. tamoxifen: oral tamoxifen plus placebo daily for 5 years	Participants in the parent study, STAR assigned to Raloxifene who were 65 or older at time of enrollment. raloxifene: oral raloxifene plus placebo daily for 5 years
Period Title: Overall Study
STARTED	733	765
COMPLETED	733	765
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Star Participants Assigned to Tamoxifen	Star Participants Assigned to Raloxifene	Total
Arm/Group Description	Participants in the parent study, STAR assigned to Tamoxifen who were 65 or older at time of enrollment. tamoxifen: oral tamoxifen plus placebo daily for 5 years	Participants in the parent study, STAR assigned to Raloxifene who were 65 or older at time of enrollment. raloxifene: oral raloxifene plus placebo daily for 5 years	Total of all reporting groups
Overall Participants	733	765	1498
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	733 100%	765 100%	1498 100%
Sex: Female, Male (Count of Participants)
Female	733 100%	765 100%	1498 100%
Male	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	685 93.5%	715 93.5%	1400 93.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	48 6.5%	50 6.5%	98 6.5%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline on the the Benton Visual Retention Test Scores by Treatment Group
Description	Mean Change From Baseline on the Benton Visual Retention (BVRT) Test scores. Adjusted for age, ethnicity, education, and baseline measure, for participants with true baseline measures. The BVRT measures short term visual memory and visuo-constructional abilities. Each of 10 designs was presented one at a time for 10 seconds, and immediately after the design was withdrawn, the participant was instructed to draw it from memory on a blank sheet of paper. The score on the BVRT is the total number of errors, 0-26 represents the total number of theoretically possible errors. Lower score denotes better outcomes.
Time Frame	Baseline and 3 Years

Outcome Measure Data

Analysis Population Description

Women who were randomly assigned in STAR were age 65 years and older, were not diagnosed with dementia, and were enrolled onto the Cognition in the Study of Tamoxifen and Raloxifene (Co-STAR) trial.

Arm/Group Title	Star Participants Assigned to Tamoxifen	Star Participants Assigned to Raloxifene
Arm/Group Description	Participants in the parent study, STAR assigned to Tamoxifen who were 65 or older at time of enrollment. tamoxifen: oral tamoxifen plus placebo daily for 5 years	Participants in the parent study, STAR assigned to Raloxifene who were 65 or older at time of enrollment. raloxifene: oral raloxifene plus placebo daily for 5 years
Measure Participants	83	93
Mean (Standard Error) [Number of errors]	-0.73 (0.34)	-1.41 (0.32)

2. Primary Outcome

Title	Mean Change From Baseline on the the California Verbal Learning Test Scores by Treatment Group
Description	Adjusted for age, ethnicity, education, and baseline measure, for participants with true baseline measures. The experimenter reads a list of 16 nouns aloud, at one-second intervals, in fixed order, over 3 learning trials (list A) . After each trial, the subject is asked to recall as many words as they can in any order (i.e., free recall) given a score 0-16 each. Total range as the sum of the 3 learning trials: 0 - 48. Participants were asked to recall a second interference list (List B) with a score range of 0-16. Free recall of list A are tested immediately after list B (short-delay) Total range 0- 16 , and again after 20 minutes (long-delay) 0-16. Each part of the scale is reported separately as Total List A trials, Total List B trials, Short-delay free recall, and Long-delay free recall.
Time Frame	Baseline and 3 Years

Outcome Measure Data

Analysis Population Description

Women who were randomly assigned in STAR were age 65 years and older, were not diagnosed with dementia, and were enrolled onto the Cognition in the Study of Tamoxifen and Raloxifene (Co-STAR) trial.

Arm/Group Title	Star Participants Assigned to Tamoxifen	Star Participants Assigned to Raloxifene
Arm/Group Description	Participants in the parent study, STAR assigned to Tamoxifen who were 65 or older at time of enrollment. tamoxifen: oral tamoxifen plus placebo daily for 5 years	Participants in the parent study, STAR assigned to Raloxifene who were 65 or older at time of enrollment. raloxifene: oral raloxifene plus placebo daily for 5 years
Measure Participants	83	93
Total List A trials	-3.31 (0.50)	-1.89 (0.48)
Total List B trials	-1.56 (0.19)	-1.74 (0.18)
Short-delay free recall	-0.96 (0.25)	-0.36 (0.24)
Long-delay free recall	-0.23 (0.25)	0.10 (0.24)

3. Secondary Outcome

Title	Mean Change From Baseline on the Letter Fluency and Semantic Fluency Scores by Treatment Group
Description	Mean Change From Baseline on the Letter Fluency Test scores. Adjusted for age, ethnicity, education, and baseline measure, for participants with true baseline measures. Measures cognitive function. In this test, the participant names as many words as possible in 1 minute, beginning with each letter for letter fluency (F, A, and S) and category for semantic fluency (fruits and vegetables). To score the administrator, counts up the total number letters or words that the individual is able to produce. The score minimum would be 0 and the maximum would be the total of correct items named within 1 minute. Higher scores represent better outcomes.
Time Frame	Baseline and 3 Years

Outcome Measure Data

Analysis Population Description

Women who were randomly assigned in STAR were age 65 years and older, were not diagnosed with dementia, and were enrolled onto the Cognition in the Study of Tamoxifen and Raloxifene (Co-STAR) trial.

Arm/Group Title	Star Participants Assigned to Tamoxifen	Star Participants Assigned to Raloxifene
Arm/Group Description	Participants in the parent study, STAR assigned to Tamoxifen who were 65 or older at time of enrollment. tamoxifen: oral tamoxifen plus placebo daily for 5 years	Participants in the parent study, STAR assigned to Raloxifene who were 65 or older at time of enrollment. raloxifene: oral raloxifene plus placebo daily for 5 years
Measure Participants	83	93
Letter Fluency	1.29 (0.75)	1.51 (0.71)
Semantic Fluency	-.51 (.50)	-.56 (.47)

4. Secondary Outcome

Title	Mean Change From Baseline on Digit Span Test Scores by Treatment Group
Description	Mean Change From Baseline on the Digit Span Test - Digits Forward and Digits backward Test scores. Adjusted for age, ethnicity, education, and baseline measure, for participants with true baseline measures. Measures reasoning, verbal ability, and memory. The participant is asked to provide immediate recall of a series of digits in forward and backward sequences. The individual's score is the total number of items correctly repeated forwards or backwards. Total range 0 - 14, higher results denotes a better outcome.
Time Frame	Baseline and 3 Years

Outcome Measure Data

Analysis Population Description

Women who were randomly assigned in STAR were age 65 years and older, were not diagnosed with dementia, and were enrolled onto the Cognition in the Study of Tamoxifen and Raloxifene (Co-STAR) trial.

Arm/Group Title	Star Participants Assigned to Tamoxifen	Star Participants Assigned to Raloxifene
Arm/Group Description	Participants in the parent study, STAR assigned to Tamoxifen who were 65 or older at time of enrollment. tamoxifen: oral tamoxifen plus placebo daily for 5 years	Participants in the parent study, STAR assigned to Raloxifene who were 65 or older at time of enrollment. raloxifene: oral raloxifene plus placebo daily for 5 years
Measure Participants	83	93
Digits Forward	-0.02 (0.18)	-0.08 (0.17)
Digits Backward	-0.16 (0.17)	-0.27 (0.16)

5. Secondary Outcome

Title	Mean Change From Baseline on Card Rotations Test Scores by Treatment Group
Description	Mean Change From Baseline on the Card Rotations Test scores. Adjusted for age, ethnicity, education, and baseline measure, for participants with true baseline measures. Measures the ability to mentally manipulate figures in two and three-dimensions. On each of 28 trials, participants view sample line drawings of a geometric figure and 8 alterations representing 2 or 3-dimensional rotations of the drawing. Participants are asked to identify alternatives that show the sample in 2-D but not in 3-D. Total range 0 - 160 and the number of incorrect/correct responses is measure. Higher number of correct answers is a better outcome.
Time Frame	Baseline and 3 Years

Outcome Measure Data

Analysis Population Description

Women who were randomly assigned in STAR were age 65 years and older, were not diagnosed with dementia, and were enrolled onto the Cognition in the Study of Tamoxifen and Raloxifene (Co-STAR) trial.

Arm/Group Title	Star Participants Assigned to Tamoxifen	Star Participants Assigned to Raloxifene
Arm/Group Description	Participants in the parent study, STAR assigned to Tamoxifen who were 65 or older at time of enrollment. tamoxifen: oral tamoxifen plus placebo daily for 5 years	Participants in the parent study, STAR assigned to Raloxifene who were 65 or older at time of enrollment. raloxifene: oral raloxifene plus placebo daily for 5 years
Measure Participants	83	93
Mean (Standard Error) [correct responses]	6.10 (1.97)	5.40 (1.86)

6. Secondary Outcome

Title	Mean Change From Baseline on the Finger Tapping Test Scores by Treatment Group
Description	Mean Change From Baseline on the the Finger Tapping Test scores. Adjusted for age, ethnicity, education, and baseline measure, for participants with true baseline measures. Measures motor speed, coordination, attention, alertness, slowing of responses, and motor control. In this test of motor speed and dexterity participants are asked to depress a lever as many times as possible in each of 7, 10-second trials, first with the right hand and next with the left hand. The highest and lowest scores are dropped; the score is the average of the remaining five trials for each hand.Higher scores represent better outcomes.
Time Frame	Baseline and 3 Years

Outcome Measure Data

Analysis Population Description

Women who were randomly assigned in STAR were age 65 years and older, were not diagnosed with dementia, and were enrolled onto the Cognition in the Study of Tamoxifen and Raloxifene (Co-STAR) trial.

Arm/Group Title	Star Participants Assigned to Tamoxifen	Star Participants Assigned to Raloxifene
Arm/Group Description	Participants in the parent study, STAR assigned to Tamoxifen who were 65 or older at time of enrollment. tamoxifen: oral tamoxifen plus placebo daily for 5 years	Participants in the parent study, STAR assigned to Raloxifene who were 65 or older at time of enrollment. raloxifene: oral raloxifene plus placebo daily for 5 years
Measure Participants	83	93
Fine Tapping, Dominant	0.26 (0.65)	-0.04 (0.63)
Fine Tapping, Non-Dominant	-0.18 (0.50)	-0.45 (0.48)

7. Secondary Outcome

Title	Mean Change From Baseline on the Positive and Negative Affect Schedule Scores by Treatment Group
Description	Mean Change From Baseline on the Positive and Negative Affect Schedule (PANAS). Adjusted for age, ethnicity, education, and baseline measure, for participants with true baseline measures. Measures positive and negative affect. Mood is assessed with the PANAS, a list of ten pleasant mood states (e.g., interested, proud, inspired) and ten unpleasant mood states (e.g., irritable, guilty, jittery). Respondents are asked to rate on a 5-point scale (1 being "very slightly or not at all" and 5 being "extremely") the extent to which they have experienced each mood during a specific time frame. Ratings for each item can range from 0 to 4 with total scores for positive affect and negative affect subscales ranging from 0 to 40. For positive affect, higher scores denote higher levels of positive affect and for negative affect, lower scores denote lower levels of negative affect.
Time Frame	Baseline and 3 Years

Outcome Measure Data

Analysis Population Description

Women who were randomly assigned in STAR were age 65 years and older, were not diagnosed with dementia, and were enrolled onto the Cognition in the Study of Tamoxifen and Raloxifene (Co-STAR) trial.

Arm/Group Title	Star Participants Assigned to Tamoxifen	Star Participants Assigned to Raloxifene
Arm/Group Description	Participants in the parent study, STAR assigned to Tamoxifen who were 65 or older at time of enrollment. tamoxifen: oral tamoxifen plus placebo daily for 5 years	Participants in the parent study, STAR assigned to Raloxifene who were 65 or older at time of enrollment. raloxifene: oral raloxifene plus placebo daily for 5 years
Measure Participants	83	93
PANAS-positive	-0.10 (0.06)	-0.04 (0.05)
PANAS-negative	0.00 (0.06)	-0.06 (0.05)

8. Secondary Outcome

Title	Mean Change From Baseline on the Geriatric Depression Scale Scores by Treatment Group
Description	Mean Change From Baseline on the Geriatric Depression Scale. Adjusted for age, ethnicity, education, and baseline measure, for participants with true baseline measures. Measures depression in older adults. Mood is also assessed with the 15-item short form of the GDS which measures non-somatic features of depressed mood. Participants indicate the presence or absence of each symptom. The GDS-SF score is the total number of positive depressive items. Score range is 0-15, with 0-4 denoting better outcomes and a score of 5 and above denoting worse outcomes (depression).
Time Frame	Baseline and 3 Years

Outcome Measure Data

Analysis Population Description

Women who were randomly assigned in STAR were age 65 years and older, were not diagnosed with dementia, and were enrolled onto the Cognition in the Study of Tamoxifen and Raloxifene (Co-STAR) trial.

Arm/Group Title	Star Participants Assigned to Tamoxifen	Star Participants Assigned to Raloxifene
Arm/Group Description	Participants in the parent study, STAR assigned to Tamoxifen who were 65 or older at time of enrollment. tamoxifen: oral tamoxifen plus placebo daily for 5 years	Participants in the parent study, STAR assigned to Raloxifene who were 65 or older at time of enrollment. raloxifene: oral raloxifene plus placebo daily for 5 years
Measure Participants	83	93
Mean (Standard Error) [units on a scale]	0.57 (0.19)	0.13 (0.18)

Adverse Events

Time Frame	4 years, 8 months
Arm/Group Title	Star Participants Assigned to Tamoxifen		Star Participants Assigned to Raloxifene
Arm/Group Description	Participants in the parent study, STAR assigned to Tamoxifen who were 65 or older at time of enrollment. tamoxifen: oral tamoxifen plus placebo daily for 5 years		Participants in the parent study, STAR assigned to Raloxifene who were 65 or older at time of enrollment. raloxifene: oral raloxifene plus placebo daily for 5 years
All Cause Mortality
	Star Participants Assigned to Tamoxifen		Star Participants Assigned to Raloxifene
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Star Participants Assigned to Tamoxifen		Star Participants Assigned to Raloxifene
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/733 (0%)		0/765 (0%)
Other (Not Including Serious) Adverse Events
	Star Participants Assigned to Tamoxifen		Star Participants Assigned to Raloxifene
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/733 (0%)		0/765 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.