Bone mineral density and the risk of incident dementia: A meta‐analysis

Abstract

BackgroundIt is not known whether bone mineral density (BMD) measured at baseline or as the rate of decline prior to baseline (prior bone loss) is a stronger predictor of incident dementia or Alzheimer's disease (AD).MethodsWe performed a meta‐analysis of three longitudinal studies, the Framingham Heart Study (FHS), the Rotterdam Study (RS), and the Rush Memory and Aging Project (MAP), modeling the time to diagnosis of dementia as a function of BMD measures accounting for covariates. We included individuals with one or two BMD assessments, aged ≥60 years, and free of dementia at baseline with follow‐up available. BMD was measured at the hip femoral neck using dual‐energy X‐ray absorptiometry (DXA), or at the heel calcaneus using quantitative ultrasound to calculate estimated BMD (eBMD). BMD at study baseline (“baseline BMD”) and annualized percentage change in BMD prior to baseline (“prior bone loss”) were included as continuous measures. The primary outcome was incident dementia diagnosis within 10 years of baseline, and incident AD was a secondary outcome. Baseline covariates included age, sex, body mass index, ApoE4 genotype, and education.ResultsThe combined sample size across all three studies was 4431 with 606 incident dementia diagnoses, 498 of which were AD. A meta‐analysis of baseline BMD across three studies showed higher BMD to have a significant protective association with incident dementia with a hazard ratio of 0.47 (95% CI: 0.23–0.96; p = 0.038) per increase in g/cm2, or 0.91 (95% CI: 0.84–0.995) per standard deviation increase. We observed a significant association between prior bone loss and incident dementia with a hazard ratio of 1.30 (95% CI: 1.12–1.51; p < 0.001) per percent increase in prior bone loss only in the FHS cohort.ConclusionsBaseline BMD but not prior bone loss was associated with incident dementia in a meta‐analysis across three studies.

Evaluating the effect of rapamycin treatment in Alzheimer's Disease and aging usingin vivoimaging: the ERAP phase IIa clinical study protocol

“…For example, preclinical data support a beneficial effect of rapamycin (or it's analogous) on periodontitis (10), retinal pathologies (11,12), atherosclerosis (13,14); cardiac dysfunction (15,16), and bone mass loss (17,18). Such diseases are commonly manifested with increasing age and are considered frequent comorbidities to AD (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31).…”