Poor Bone Health a 'Robust' Dementia Risk Factor

Megan Brooks

March 23, 2023

Low bone mineral density (BMD), particularly at the femoral neck, emerged as a "robust" risk factor for dementia in older adults in the long-running Rotterdam Study.

After adjusting for relevant factors, those with the lowest, vs higher, BMD at the femoral neck had a twofold higher risk of developing dementia over 10 years.

"Our research has found a link between bone loss and dementia, but further studies are needed to better understand this connection between bone density and memory loss," study investigator Mohammad Arfan Ikram, MD, PhD, with Erasmus University Medical Center in Rotterdam, the Netherlands, said in a statement.

"It's possible that bone loss may occur already in the earliest phases of dementia, years before any clinical symptoms manifest themselves. If that were the case, bone loss could be an indicator of risk for dementia and people with bone loss could be targeted for screening and improved care," Ikram added.

The study was published online March 22 in Neurology.

Common Bedfellows

Low BMD and dementia commonly co-occur in the older population, with bone loss accelerating in dementia patients due to physical inactivity and poor nutrition. However, the extent to which bone loss already exists prior to the onset of dementia remains unclear.

The new findings are based on 3651 adults (mean age 72 years, 58% women) in the Rotterdam Study who were free of dementia between 2002 and 2005.

At that time, BMD at the femoral neck, lumbar spine, and total body were obtained using dual-energy radiography absorptiometry (DXA) and the trabecular bone score, which offers further details such as bone microarchitecture, was calculated. Participants were followed up until January 1, 2020.

Analyses were adjusted for age, sex, educational, physical activity, smoking status, body mass index, blood pressure, cholesterol, history of comorbidities (stroke and diabetes), and apolipoprotein E genotype.

During follow-up, 688 (19%) participants developed dementia, mostly Alzheimer's disease (77%).

Throughout the entire follow-up period, lower BMD at the femoral neck (per standard deviation), but not at other bone sites, correlated with a higher risk for all-cause dementia (hazard ratio [HR], 1.12; 95% CI, 1.02-1.23) and Alzheimer's disease (HR, 1.14; 95% CI, 1.02-1.28).

Within the first 10 years after baseline, the risk for dementia was greatest in individuals with the lowest BMD at the femoral neck (HR, 2.03; 95% CI, 1.39-2.96) and total body (HR, 1.42; 95% CI, 1.01-2.02) and lowest trabecular bone score (HR, 1.59; 95% CI, 1.11-2.28).

Only BMD at the femoral neck was related to incident all-cause dementia in the first 5 years of follow-up (HR, 2.13; 95% CI, 1.28-3.57).

These findings add "extra knowledge to previous findings that associations change with time, with the strength of the effect decreasing with increasing follow-up time," the investigators note.

They suggest that total BMD and trabecular bone score might occur as "prodromal features instead of causes of dementia and related toxic protein accumulation in the brain. In other words, persons with subclinical, incipient dementia may have poor bone health due to the dementia process instead of vice versa."

The investigators note further research that focuses on the predictive ability of BMD for dementia is necessary.

"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," they conclude.

Little Known Bone-Brain Axis to Blame?

Commenting for Medscape Medical News, Shaheen Lakhan, MD, a neurologist and researcher in Boston, Massachusetts, noted that "bone health is increasingly becoming front of mind in older adults. This study confirms an association between poor bone health — low bone mineral density and bone scores — and poor brain health."

However, it's unclear whether the link is causal — that is, whether poor bone health actually leads to poor brain health, and whether that can be staved off by directly supporting bone density," Lakhan told Medscape Medical News.

"The link may very well be the little known "brain-bone axis" — where our bones actually regulate our brain," he added.

"Take for example the bone-generated hormone osteocalcin that crosses the blood-brain-barrier and regulates brain functions like memory and cognition. Mice who don't express the osteocalcin gene or are injected with antibodies that block osteocalcin actually have poor memory and worse anxiety," Lakhan said.

"In any event, good bone health begins with heavy habits: a diet with plenty of calcium, vitamin D and protein; a regimen of not just cardio, but also weight-bearing exercises; and staying clear of smoking and heavy alcohol intake," he concluded.

The study was funded by Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organization for Scientific Research, the Netherlands Organization for Health Research and Development, the Research Institute for Diseases in the Elderly, the Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission and the Municipality of Rotterdam. Ikram and Lakhan report no relevant disclosures.

Neurology. Published online March 22, 2023. Full text

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