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Meta-Analysis
. 2024 Jan;72(1):194-200.
doi: 10.1111/jgs.18638. Epub 2023 Nov 7.

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

Christine W Lary  1   2 , Samuel Ghatan  3 , Meghan Gerety  4 , Alexandra Hinton  2 , Archana Nagarajan  1   2   5 , Clifford Rosen  2 , Ryan D Ross  6 , David A Bennett  7 , Anita L DeStefano  8 , Mohammad A Ikram  3 , Fernando Rivadeneira  3 , Douglas P Kiel  9   10 , Sudha Seshadri  11   12 , Alexa Beiser  8   12
Affiliations
Meta-Analysis

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

Christine W Lary et al. J Am Geriatr Soc. 2024 Jan.

Abstract

Background: It 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).

Methods: We 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.

Results: The 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.

Conclusions: Baseline BMD but not prior bone loss was associated with incident dementia in a meta-analysis across three studies.

Keywords: Alzheimer's disease; BMD; bone loss; dementia; osteoporosis.

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Conflict of interest statement

Conflicts of Interest

DPK serves on scientific advisory boards for Pfizer and Solarea Bio, has received royalty payments from Wolters Kluwer for authoring a chapter in UpToDate on Falls, and received grant funding through a grant to his Institute by the Dairy Council, Amgen, and Radius Health. An earlier version of this work was presented at the ASBMR annual meeting in Austin, TX Sept 9–12, 2022, and has been submitted as an abstract to the 8th Annual Skeletal Research Symposium on Monday May 8th, 2023 in Boston, MA.

Figures

Figure 1:
Figure 1:. Study Design.
BMD (bone mineral density) of the hip femoral neck or heel calcaneus was collected at one or two timepoints with the second (Framingham Heart Study, Rotterdam Study) or only (Memory and Aging Project) timepoint serving as study baseline. Participants were ≥60 and free of dementia at baseline and followed for ten years for incident dementia or Alzheimer’s Disease. The time between BMD measurements was roughly 4 years for the Rotterdam Study and 8 years for the Framingham Heart Study.
See this image and copyright information in PMC

References

    1. Zhou R, Deng J, Zhang M, Zhou HD, Wang YJ. Association between bone mineral density and the risk of Alzheimer’s disease. J Alzheimers Dis 2011;24(1):101–8. doi:10.3233/JAD-2010-101467 - DOI - PubMed
    1. Tan ZS, Seshadri S, Beiser A, et al. Bone mineral density and the risk of Alzheimer disease. Arch Neurol Jan 2005;62(1):107–11. doi:10.1001/archneur.62.1.107 - DOI - PubMed
    1. Stefanidou M, O’Donnell A, Himali JJ, et al. Bone Mineral Density Measurements and Association With Brain Structure and Cognitive Function: The Framingham Offspring Cohort. Alzheimer Dis Assoc Disord May 11 2021;doi:10.1097/WAD.0000000000000453 - DOI - PMC - PubMed
    1. Lui LY, Stone K, Cauley JA, Hillier T, Yaffe K. Bone loss predicts subsequent cognitive decline in older women: the study of osteoporotic fractures. J Am Geriatr Soc Jan 2003;51(1):38–43. doi:10.1034/j.1601-5215.2002.51007.x - DOI - PubMed
    1. Yaffe K, Browner W, Cauley J, Launer L, Harris T. Association between bone mineral density and cognitive decline in older women. J Am Geriatr Soc Oct 1999;47(10):1176–82. - PubMed

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