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Zaldy Sy Tan, MD, MPH; Sudha Seshadri, MD; Alexa Beiser, PhD; Yuqing Zhang, DSc; David Felson, MD; Marian T. Hannan, DSc; Rhoda Au, PhD; Philip A. Wolf, MD; Douglas P. Kiel, MD, MPH

Arch Neurol. 2005;62:107-111.

Background  Some, but not all, studies have suggested that estrogen replacement therapy has a beneficial effect on cognition in postmenopausal women. Bone mineral density (BMD) is a potential surrogate marker for cumulative estrogen exposure and has been associated with cognitive performance and risk of cognitive deterioration.

Objective  To examine whether low BMD in elderly individuals is associated with an increased risk of developing Alzheimer disease (AD).

Design, Setting, and Participants  Community-based prospective cohort study of 987 subjects (610 women) who were cognitively intact and had baseline BMD measured at the femoral neck, the trochanter, and the radial shaft between 1988 and 1989.

Main Outcome Measures  Incidence of AD and all-cause dementia during an 8-year follow-up period.

Results  Women in the lowest quartile of femoral neck BMD had more than twice the incidence of AD (hazard ratio, 2.04; 95% confidence interval, 1.11-3.75) and all-cause dementia (hazard ratio, 2.01; 95% confidence interval, 1.16-3.49) compared with those in higher quartiles after adjusting for age, sex, apolipoprotein E 4, baseline homocysteine level, education, estrogen use, smoking, and stroke. A similar but statistically nonsignificant relationship was observed between BMD of the femoral trochanter and AD, while no such relationship was seen between radial BMD and AD or all-cause dementia. In men, there was a trend toward an inverse relationship between BMD and the risk of AD, but the relationship was not statistically significant at any of the 3 sites.

Conclusions  Low femoral neck BMD was associated with approximately 2 times the risk of AD and all-cause dementia in women but not men, suggesting the possibility that cumulative estrogen exposure may influence the risk of developing AD. Additional studies are needed to confirm this correlation.

Author Affiliations: Division on Aging, Harvard Medical School (Drs Tan, Hannan, and Kiel); Departments of Neurology (Drs Seshadri, Au, and Wolf) and Medicine (Drs Seshadri, Zhang, and Felson), Boston University School of Medicine; Department of Biostatistics, Boston University School of Public Health (Dr Beiser); Hebrew Rehabilitation Center for Aged Research and Training Institute (Drs Tan, Hannan, and Kiel); and Division of Gerontology, Beth Israel Deaconess Medical Center (Drs Tan, Hannan, and Kiel); Boston, Mass.

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