Bone Mineral Density May Predict Risk for All-Cause Dementia in Older Adults

Low bone mineral density, specifically at the femoral neck, may be a significant risk factor for dementia in older adults.

Older adults with low bone mineral density may be at an elevated risk for developing dementia, according to study findings published in Neurology.

Previous studies have indicated a link between low bone mineral density and structural brain changes, memory loss and silent infarcts, and dementia. However, any causal relationship remains unclear. Numerous links between bone density and cognitive loss may include endocrine dysfunction, changes in daily habits, cellular processes of brain and bone, and fractures.

As a step toward clarifying these relationships, researchers aimed to establish more clearly the time course of onset of dementia, including Alzheimer disease (AD), with respect to low bone mineral density status.

Researchers analyzed prospective data from 2 cohorts of community-dwelling adults, with a median age of 72.3 years, from the Rotterdam Study. A total of 3,651 participants (58% women) without dementia underwent baseline bone density scans, yielding bone mineral density scores of the hip, femoral neck, spine, and total skeletal system. They also completed cognitive assessment tests at baseline, between the years 2002 and 2005, and at 4- to 5-year follow-up visits, until either censoring in January 2020, loss to follow-up, diagnosis of dementia, or death.

Nevertheless, as an indicator of dementia risk, intervening in BMD may improve clinical care of these persons, especially considering the multi-comorbidities and polypharmacy that are highly preventive in this group.

During this period, the researchers examined relationships between bone mineral density and diagnosis of dementia (all-cause and AD), via Cox proportional hazards regression analysis and Kaplan-Meier estimation. They controlled for covariables including age, sex, genetic risk for dementia via apolipoprotein E (APOE) assay, physical activity, and cardiometabolic data.

Of the total cohort sample, 18.8% developed dementia, which included 76.7% with AD. Low baseline bone mineral density at the femoral neck was associated with all-cause dementia (hazard ratio [HR], 1.43; 95% CI, 1.19-1.72) and AD specifically (HR, 1.52; 95% CI, 1.20-1.92) during the first 10 years and over the entire follow-up period (HRall-cause, 1.12; 95% CI, 1.02-1.23; HRAlz, 1.14, 95% CI, 1.02-1.28).

Low total-body bone mineral density was associated with all-cause dementia diagnosis only in the first 10 years. This attenuation of effect over time suggested that bone mineral density loss, rather than causative, was either coincident with dementia or caused partly by brain or behavioral changes occurring in dementia.

The Kaplan-Meier analysis confirmed shorter survival of dementia-free status (for both all-cause dementia and AD diagnoses) in the lowest tertile of bone mineral density, particularly of the femoral neck.

In stratified analyses, these relationships remained only for men and for non-carriers of the APOE-ε4 allele.

Strengths of this study included long follow-up time and high statistical power. Limitations included lack of experimental control individuals in this observational design, and a largely white, European study population older than 70 years of age.

“Nevertheless, as an indicator of dementia risk, intervening in BMD [bone mineral density] may improve clinical care of these persons, especially considering the multi-comorbidities and polypharmacy that are highly preventive in this group,” the researchers acknowledged.

This article originally appeared on Neurology Advisor


Xiao T, Ghatan S, Mooldijk SS, et al. Association of bone mineral density and dementia: the Rotterdam study. Neurology. Published online March 22, 2023. doi:10.1212/WNL.0000000000207220