Bone Mineral Density Measurements and Association
With Brain Structure and Cognitive Function

Background: Bone mineral density (BMD) is a potential surrogate
marker of lifetime estrogen exposure previously linked to increased
risk of Alzheimer dementia among elderly women. We examine the
association between BMD in the “young old” with imaging biomarkers
of brain aging and cognitive performance.

Methods: Offspring participants (N=1905, mean age 66) of a population-
based cohort who had BMD, brain imaging and detailed
cognitive assessment were included in the study. Sex-stratified, linear,
and logistic regression models were used for analysis.

Results: Higher femoral neck BMD was associated with lower white
matter hyperintensity burden and better performance on Trails B-A in
both sexes, even after adjustment for cerebrovascular risk factors. Among
women, the positive association with Trails B-A performance was seen
only in APOE4 allele carriers. Higher BMD measurements were linked to
better visual reproductions test performance in men. Finally, among
women, higher femoral trochanter BMD was associated with better
logical memory and Hooper visual organization test performance.

Conclusion: Among the “young old,” higher BMD is associated
with less white matter hyperintensity burden and better, domainspecific,
cognitive performance. This suggests that lifetime estrogen
exposure may modulate the degree of cumulative vascular brain
injury independent of cerebrovascular risk factors.