Low bone mineral density (BMD) has been associated with a greater risk for cognitive decline, possibly as a marker for low estrogen exposure, ill health, weight loss, or other conditions. The phenotype apolipoprotein E (ApoE) e4 allele, which is highly correlated with cognitive decline, also has been associated with low BMD, accelerated bone loss, and fracture risk. Lui and colleagues investigated the question of whether the rate of bone loss is associated with subsequent cognitive decline and whether this association is mediated through the ApoE genotype.

The participants were 4,462 ambulatory, community-dwelling women 65 years and older who were enrolled in an ongoing prospective study. Change in total hip BMD was measured for a period of about three and one half years, with cognitive decline measured in the subsequent four years. Measurement modalities were dual-energy x-ray absorptiometry and a modified Mini-Mental State Examination. ApoE testing was done on 1,750 women at enrollment.

Percentage loss of total hip BMD was associated with subsequent cognitive decline. After adjustment for education, age, history of stroke, impaired functional status, body mass index, and smoking status, the association between hip-bone loss and cognitive decline was attenuated but still statistically significant (odds ratio, 1.4). After adjustment for the above confounders, women in the highest quartile of percentage hip BMD were 1.4 times more likely to have cognitive decline than women in the lowest quartile.

Of the 883 women with an ApoE phenotype, 13.1 percent (n = 116) had an e4 allele. Initially, these women had cognitive scores similar to those in women without an e4 allele, but subsequently they showed greater cognitive decline. The relationship between hip-bone loss and cognitive decline in ApoE and e4-variant women was similar to that of the entire study group.

The authors conclude that women with more rapid hip-bone loss have increased rates of cognitive decline, an association that is independent of age, education, history of stroke, impaired functional status, estrogen use, years since menopause, depression, alcohol use, history of heart attack, exercise, and ApoE phenotype. Adjusting for or excluding past or current estrogen users did not modify this association. Bone loss may be a marker for a process that causes cognitive decline.