Frederick Naftolin, MD, PhD; S. Mitchell Harman, MD, PhD
Potential Conflicts of Interest: None disclosed.
Naftolin F, Harman SM. Preventing Alzheimer Disease and Cognitive Decline. Ann Intern Med. 2011;154:211-212. doi: 10.7326/0003-4819-154-3-201102010-00015
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Published: Ann Intern Med. 2011;154(3):211-212.
TO THE EDITOR:
The National Institutes of Health (NIH) State-of-the-Science Conference Panel statement (1) suggesting that estrogen and progesterone may contribute to causation of Alzheimer disease has raised concern and elicited alarmed calls from patients regarding their future. We believe that the panel's conclusion is erroneous because it is based solely on the outcome of the Women's Health Initiative (WHI) trial's substudy WHIMS (Women's Health Initiative Memory Study), which had the same risk value as that shown in the NIH statement (2).
WHIMS had an inappropriate experimental construction using age-driven postrandomization apportionment of participants. Because of this, WHIMS was limited to women older than 65 years at randomization. This choice of participants was arbitrary and did not include women who might have received hormones for an interval sufficient for prevention of dementia. Rather, these participants were chosen because only an older population could furnish the number of events that would offer statistical significance among treatment groups. The WHIMS participants were not representative of women who usually initiate menopausal hormone therapy. Furthermore, they did not undergo neurologic examinations before inclusion in the WHI trial or WHIMS. We have previously commented on problems with this design strategy (3, 4).
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