The selective estrogen receptor modulator drug raloxifene showed no cognitive benefits for women with Alzheimer’s disease, results from a pilot study published in Neurology indicate
“If there are cognitive effects in this population, these effects are likely to be no more than small,” said Victor W. Henderson, MD, MS, from the Departments of Health Research and Policy and Neurology and Neurological Sciences at Stanford University, in a press release. He noted that the study was not designed to detect whether raloxifene had small effects on patients or not, as in the range provided by approved Alzheimer’s therapies such as donepezil or memantine.
Estrogen has been of interest as a potential treatment for women with Alzheimer’s disease, but relatively small trials have failed to confirm any benefit. Raloxifene, an oral selective estrogen receptor modulator (SERM), is an approved treatment for osteoporosis in postmenopausal women, and has not been previously tested as a potential Alzheimer’s treatment.
For the study, researchers randomized 42 women with an average age of 76 (range 68-84) with mild to moderate dementia from Alzheimer’s to either receive high-dose (120 mg) oral raloxifene or a placebo once daily for 12 months. Memory and cognitive functions were assessed at the beginning of the study and at 3, 6, 9, and 12 months to determine their score on the Alzheimer’s Disease Assessment Scale, cognitive subscale (ADAS-cog). Caregivers were asked about their burden and distress at the beginning, middle, and end of the study.
The researchers found no significant difference in ADAS-cog scores in the raloxifene group compared with the placebo group at 12 months (standardized difference 0.03, 95% confidence interval -0.39 to 0.44, 2-tailed P = 0.89), nor were there significant differences reported in caregiver burden or distress. These results could, however, be valuable to future clinical trials.
“The essentially null effect of raloxifene on the primary outcome implies a low likelihood of positive results but does not exclude the possibility of modest cognitive benefit or harm,” the researchers wrote. “The upper tail of the 95% CI represents a small (0.2 ≤ SD < 0.5) effect but corresponds to about 5 points on the ADAS-cog, a difference that — despite weak evidence for validity — falls within a commonly accepted range of clinical relevance. The ADAS-cog is a common endpoint in Alzheimer treatment trials, but it is possible that other neuropsychological outcomes could be more sensitive to any cognitive effect of raloxifene.”
- Henderson VW, Ala T, Sainani KL, et al. Raloxifene for women with Alzheimer disease: A randomized controlled pilot trial. Neurology. 2015; 2015;85:1-8.