Effect of raloxifene on prevention of dementia and cognitive impairment in older women: the Multiple Outcomes of Raloxifene Evaluation (MORE) randomized trial.
OBJECTIVE
This investigation examined whether raloxifene, a selective estrogen receptor modulator, affects the risk for Alzheimer's disease.


METHODS
The Multiple Outcomes of Raloxifene Evaluation was a randomized, placebo-controlled trial among postmenopausal women with osteoporosis. The effect of raloxifene (60 or 120 mg/day) on vertebral fractures was the primary outcome. Development of mild cognitive impairment and dementia was a secondary outcome. Women were given clinical and cognitive evaluations at baseline and annually. After 3 years, among the 5,386 women enrolled at participating sites, those who had clinical symptoms of dementia or scored in the lowest 10th percentile on cognitive screening were evaluated by a blinded dementia specialist and had brain scans and laboratory tests to evaluate dementia etiology. Dementia was diagnosed by a blinded adjudication committee.


RESULTS
Of the 5,386 women, 5,153 (95.7%) were classified as cognitively normal, 181 (3.4%) had mild cognitive impairment, and 52 (1.0%) had dementia, 36 with Alzheimer's disease. Compared to those taking placebo, women receiving 120 mg/day of raloxifene had a 33% lower risk of mild cognitive impairment (relative risk, 0.67; 95% confidence interval [CI], 0.46-0.98) and somewhat lower risks of Alzheimer's disease (relative risk=0.52, 95% CI=0.22-1.21) and any cognitive impairment (relative risk=0.73, 95% CI=0.53-1.01). Risks of mild cognitive impairment, Alzheimer's disease, and any impairment were not significantly different in the group taking 60 mg/day of raloxifene.


CONCLUSIONS
Raloxifene at a dose of 120 mg/day, but not 60 mg/day, resulted in reduced risk of cognitive impairment in postmenopausal women.
Yaffe
Kristine
K
Department of Psychiatry, University of California, San Francisco, Box 181, 4150 Clement St., San Francisco, CA 94121, USA. kyaffe@itsa.ucsf.edu
Krueger
Kathryn
K
Cummings
Steven R
SR
Blackwell
Terri
T
Henderson
Victor W
VW
Sarkar
Somnath
S
Ensrud
Kristine
K
Grady
Deborah
D
D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000517:prevention & control / Q000523:psychology; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D015897:Comorbidity; D003704:Dementia / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D005260:Female; D015577:Geriatric Assessment; D006801:Humans; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000453:epidemiology / Q000523:psychology; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use*; D018570:Risk Assessment; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016103:Spinal Fractures / Q000517:prevention & control; D016896:Treatment Outcome
D010919:Placebos; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride