EMBARGOED FOR RELEASE UNTIL 4:00 P.M. ET, WEDNESDAY, SEPTEMBER 17, 2025
MINNEAPOLIS — A new study suggests that physical frailty may contribute to the development of dementia. The study was published on September 17, 2025, in Neurology®, the medical journal of the American Academy of Neurology.
Physical frailty is defined as having three or more of these five symptoms: often feeling tired; little or no physical activity; slow walking speed; low grip strength; and unintentional weight loss.
“We’ve known that frailty is associated with a higher risk of dementia, but our study provides evidence that frailty may be an actual cause of dementia,” said study author Yacong Bo, PhD, of Zhengzhou University in China. “On the other hand, despite this new evidence, we can’t rule out the possibility that frailty is instead a marker of the early changes in the disease process.”
The study involved 489,573 people with an average age of 57 who were followed for an average of 14 years. A total of 4.6% of the participants met the definition for frailty, with three or more of the symptoms. Another 43.9% who had one or two symptoms were categorized as pre-frailty and 51.5% had no symptoms and were categorized as not frail.
During the study, 8,900 people developed dementia. A total of 4.6% of those with frailty developed dementia, compared to 2.2% of those with pre-frailty and 1.3% of those without frailty.
After researchers adjusted for other factors that could affect the risk of dementia, such as age, education level and physical activity, they found that the people who met the definition for frailty were nearly three times more likely to develop dementia than those who had no symptoms of frailty. Those categorized as pre-frailty were 50% more likely to develop dementia.
People with frailty who also had genes linked to dementia were nearly four times more likely to develop dementia than those without frailty or the genetic risk.
The researchers also analyzed the data and found evidence suggesting that frailty may potentially be a factor in causing dementia.
“These findings reinforce the importance of identifying and managing frailty as a strategy for preventing dementia,” Bo said.
Looking at the data from the other direction, the researchers found that dementia is unlikely to increase the risk of frailty.
The researchers also looked at brain imaging and biological biomarkers and found that people with frailty were more likely to have changes in their brain structure related to dementia.
“These biomarkers may be a mechanism underlying the pathway from frailty to dementia,” said Bo.
A limitation of the study was that four of the five symptoms of frailty were reported by the participants, so they may not have provided accurate information.
The study was supported by the Chinese National Health Commission Key Laboratory of Birth Defects Prevention, Henan Key Laboratory of Population Defects Prevention, the Chinese International Postdoctoral Exchange Fellowship Program and the Henan Medical Science and Technology Research Program.
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Neurology