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To the Editor: The study by Dr Mulnard and colleagues¹ investigated the role of estrogen replacement therapy (ERT) in the treatment of Alzheimer disease (AD). The conclusion that ERT produces no global changes in the cognition of women with AD is supported by the recent study by Henderson et al.² However, estrogen may affect cognition in a domain-specific manner. For instance, estrogen might specifically improve verbal explicit memory.³ To assess this effect, Mulnard et al used the Alzheimer's Disease Assessment Scale–Cognitive (ADAS-Cog), a broad test that reflects many more domains than verbal explicit memory, as well as other unpublished or little-used tests whose psychometric properties are unknown. This use of nonstandardized tests has been a problem in other studies of ERT.⁴

In another attempt to determine which specific domains were affected by estrogen treatment, the patients were tested on measures of attention (Letter Cancellation, Trail-Making Test A, and Digit Symbol). . . . [Full Text of this Article]

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