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Low bone mineral density (BMD) may be predictive of who develops dementia, researchers reported.

In a study of community-dwelling older adults, every one standard deviation lower BMD at the femoral neck was linked with a 12% higher risk for developing all-cause dementia (HR 1.12, 95% CI 1.02-1.23), said Mohammad Arfan Ikram, MD, PhD, of Erasmus University Medical Center in Rotterdam, The Netherlands, and colleagues.

Each standard deviation lower for femoral neck BMD was also linked with a 14% higher risk for Alzheimer's disease during the 11-year follow-up (HR 1.14, 95% CI 1.02-1.28), the group wrote in .

When the researchers homed in on just the first decade of follow-up, older adults falling into the lowest tertile of BMD in the femoral neck had a twofold higher risk for dementia than those in the highest tertile (HR 2.03, 95% CI 1.39-2.96).

During the first 10 years, those in the lowest tertile for trabecular bone score and total body BMD also saw a significantly higher risk for developing all-cause dementia.

But when expanding out to the total follow-up period, only low femoral neck BMD was still significantly linked with dementia onset.

Looking more closely into this relationship, Ikram's group stratified data according to sex and APOE-e4 allele carriers -- a strong genetic risk factor for Alzheimer's disease. Here, they found that only men had a significantly higher risk for all-cause dementia linked with lower femoral neck BMD (HR 1.56, 95% CI 1.12-2.16) and not women. Likewise, only non-APOE-e4 carriers also saw this significant link (HR 1.36, 95% CI 1.04-1.76) and not carriers.

"Low bone density and dementia are two conditions that commonly affect older people simultaneously, especially as bone loss often increases due to physical inactivity and poor nutrition during dementia," noted Ikram in a statement. "However, little is known about bone loss that occurs in the period leading up to dementia. Our study found that bone loss indeed already occurs before dementia and thus is linked to a higher risk of dementia."

"Previous research has found factors like diet and exercise may impact bones differently as well as the risk of dementia," Ikram added. "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."

"It's possible that bone loss may occur already in the earliest phases of dementia, years before any clinical symptoms manifest themselves," he explained. "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."

The researchers added that suggested a link between low femoral neck BMD with structural brain changes, which may be a driving force behind the elevated dementia risk. These changes include declined white matter volume, increased white matter hyperintensity volume, occurrence of silent brain infarction, and progression of parenchymal atrophy.

"Potential pathophysiological mechanisms behind low bone mineral density being a prodrome of dementia might include the effect of amyloid-beta on suppressing osteoblast proliferation and enhancing osteoclast activity, and/or impact of systemic Wnt/Beta-catenin signaling deficits on impeding osteoblast differentiation and bone formation," the team also pointed out.

On top of that, it's possible that these individuals experienced some loss of cognition that subsequently lead to poorer dietary nutrition and lifestyle habits.

The research was conducted within the Rotterdam Study, an ongoing prospective population-based cohort study that started in 1990. The new analysis included a total of 3,651 older adults without dementia, all of whom were at least 45 years old (median 72.3); 57.9% were women. Participants underwent dual-energy x-ray absorptiometry scans at the femoral neck, the lumbar spine, and the total body, and dementia was assessed using the Mini-Mental State Examination and the Geriatric Mental Schedule.

During the median 11.1-year follow-up, 18.8% of participants developed incident dementia -- 76.7% of whom developed Alzheimer's disease. About 27% of all study participants were APOE-e4 carriers.

Across the board, women on average had lower BMD at every location compared with men: total body BMD (1.06 vs 1.20 g/cm² for men), femoral neck BMD (0.82 vs 0.92 g/cm²), lumbar spine BMD (1.04 vs 1.21 g/cm²), trabecular bone score (1.25 vs 1.33 mm^-1).

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