title: Bone mineral density and the risk of Alzheimer disease.
abstract: 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).
  
  
  METHODS
  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.
  
  
  METHODS
  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 epsilon4, 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.
authors.affiliation: Division on Aging, Harvard Medical School, Beth Israel Deaconess Medical Center, 110 Francis Street, Boston, MA 02215, USA. ztan@hms.harvard.edu
authors.forename: Zaldy Sy
authors.initials: ZS
authors.lastname: Tan
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
authors.forename: Alexa
authors.initials: A
authors.lastname: Beiser
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Zhang
authors.forename: David
authors.initials: D
authors.lastname: Felson
authors.forename: Marian T
authors.initials: MT
authors.lastname: Hannan
authors.forename: Rhoda
authors.initials: R
authors.lastname: Au
authors.forename: Philip A
authors.initials: PA
authors.lastname: Wolf
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Kiel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000503:physiopathology*; D015519:Bone Density / Q000502:physiology*; D001842:Bone and Bones / Q000378:metabolism; D005260:Female; D005269:Femur / Q000378:metabolism; D005272:Femur Neck / Q000378:metabolism; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D015233:Models, Statistical; D011446:Prospective Studies; D012189:Retrospective Studies; D012306:Risk; D012307:Risk Factors; D012737:Sex Factors