A genetic predisposition to strong grip strength is associated with better cognitive health in older adults. Researchers recently discovered that people born with DNA traits that favor muscle strength tend to decline mentally more slowly as they age. According to a recent study published in Neurobiology of Aging, this relationship operates independently of how much people exercise.
Loss of motor function, including basic physical movements and muscle control, often precedes decline in cognitive function. Medical professionals frequently measure hand grip strength using simple hand-held devices as an easy indicator of a person’s overall vitality. Decreased grip strength is known to be a risk factor for developing memory impairment and Alzheimer’s disease later in life.
The biological reasons behind this relationship remain a subject of debate. One common explanation revolves around general health. People who stay fit may simply be more physically active, which supports heart health and brain function over time. In this perspective, lifestyle choices are the main bridge between a strong body and a sharp mind.
Another explanation suggests a more direct biological connection between muscles and the brain. Producing a strong physical grip requires coordinated signals from the nervous system. As we age, changes in these neural pathways can lead to both muscle weakness and cognitive impairment.
Several lines of evidence indicate physiological interactions between tissue types. Skeletal muscle secretes certain proteins that travel through the bloodstream and influence learning and neuroadaptation in the brain. In this scenario, genetic profiles that protect muscle mass or nervous system integrity may directly maintain cognitive function.
To investigate this connection, Rachel Berkovich and Daniel Felski, along with a team of colleagues at the University of Toronto, Center for Addiction and Mental Health, and Rush University Medical Center, turned to genetic data. They wanted to see whether innate genetic predispositions to grip strength could predict cognitive outcomes. They also wanted to see if this genetic link existed before lifestyle factors such as exercise came into play.
Polygenic risk scores are tools that sum up the estimated impact of thousands of small genetic variations across a person’s DNA sequence. Many physiological traits are not controlled by a single gene, but rather by small contributions from a myriad of scattered genetic markers. By calculating this summary score, researchers can assess an individual’s genetic likelihood of developing a particular physical characteristic.
The research team created a genetic score for hand grip strength in more than 25,000 adults. Participants were from two separate aging studies: the Canadian Longitudinal Study on Aging, the Religious Order Study, and the Rush Memory and Aging Project. Using two large groups allowed the researchers to look for patterns that held true across different demographics and testing methods.
The Canadian study included more than 23,000 mostly healthy adults in middle to late adulthood, allowing the researchers to observe early changes in memory and thinking. The Rush Project tracked about 2,000 elderly people, including Catholic nuns and priests, in the United States. These elderly participants underwent detailed annual cognitive testing and consented to brain donation after death.
First, the researchers verified that the genetic tool worked as intended. In both study groups, people with higher genetic scores for hand grip strength also recorded stronger physical grip strength when gripping the test device. This confirmed that the genetic overview accurately reflected real-world physical characteristics.
Next, the team looked at cognitive abilities. In both the Canadian and Rush groups, those with higher genetic scores for hand grip strength performed better on global cognitive tests. This test score association remained even after researchers took into account age, gender, BMI, and risk of cardiovascular disease.
The researchers also tracked changes in memory and thinking skills over time. In the Rasch study, which followed participants for up to 21 years, those in the top third of genetic grip strength scores experienced slower cognitive decline than those in the bottom third. This difference represented a 20% improvement in cognitive function that was maintained over the study period.
In the Canadian group, genetic scores did not predict long-term changes in cognitive speed or memory. The researchers suggested that this discrepancy may be due to the Canadian participants being relatively young and healthy. The short follow-up period in the Canadian group may also have made slow changes in mental acuity difficult to detect.
The team then determined whether the cognitive benefits were simply due to physical activity. They used a statistical model to test whether the association between genetic scores and cognitive health was primarily driven by reported exercise habits. The analysis showed that physical activity did not act as a mediating factor.
Rather, actual physical fitness and lean muscle mass played a larger role in linking genetic scores to cognitive outcomes. This suggests that genetic predisposition to muscle strength influences cognitive aging primarily through direct biological pathways related to muscle function, rather than through behavioral choices such as deciding to exercise.
Rush’s research also included brain dissections, allowing the researchers to look for physical signs of Alzheimer’s disease. These signs include the accumulation of misfolded proteins known as amyloid plaques and tau tangles. They also checked for evidence of microinfarcts, which are small strokes that can damage brain tissue over time.
Genetic scores for hand grip strength showed no association with any of the 12 postmortem brain lesions measured. The lack of association with traditional indicators of dementia suggests that entirely different biological mechanisms are at work. Genetic predispositions for muscle strength may reflect a form of overall biological resilience that protects the brain without altering the typical buildup of plaques and tangles.
The researchers also tested grip strength scores alongside established genetic scores for Alzheimer’s disease risk. Medical professionals are increasingly focusing on hereditary Alzheimer’s disease risk to identify patients who may benefit from early intervention. However, these genetic models are still incomplete and only capture a portion of a person’s total risk.
Adding the grip strength variable improved the accuracy of the baseline Alzheimer’s disease prediction model. This combined approach demonstrated stronger associations with cognitive outcomes than Alzheimer’s disease scores alone. Future clinical models may incorporate physical trait genetics to more accurately assess cognitive status.
Despite the large sample size, the researchers found some limitations in their data. Measures of physical activity rely on self-reported questionnaires that cover only the past few weeks and may not accurately capture a person’s lifelong exercise habits. A lifetime history of physical activity can help us pinpoint how behavioral factors relate to genetic predisposition over decades.
Additionally, the analysis focused only on individuals of European descent. Studies involving more diverse genetic backgrounds will be needed to confirm whether these relationships hold globally across diverse populations.
Future research will need to identify the precise biological networks linking muscle and cognitive health. The researchers are now investigating other possible biological markers, such as specific brain structures visible on brain scans or circulating immune system proteins. The discovery of specific metabolic and neural pathways linking muscle function and brain health could ultimately lead to new strategies to slow memory loss.
The study, “Genetic predisposition to grip strength predicts cognitive decline,” was authored by Rachel Bercovitch, Earvin S. Tio, Rajith Wickramatunga, Melissa Misztal, Kristina Gicas, Philip L. De Jager, Julie A. Schneider, Aron S. Buchman, David A. Bennett, Tarek Rajji, James L. Kennedy, and Daniel Felsky.
