Genetic predisposition to hand grip strength predicts cognitive decline.

Area of Science:

• Neuroscience
• Genetics
• Gerontology

Background:

• Hand grip strength (HGS) is a known predictor of cognitive decline in aging populations.
• Understanding the direct and indirect mechanisms linking HGS and cognition is crucial for developing interventions.

Purpose of the Study:

• To investigate the genetic predisposition for HGS and its association with cognitive performance and neuropathology in aging.
• To explore potential mediating roles of physical activity in the HGS-cognition relationship.

Main Methods:

• Calculated a polygenic risk score for HGS (PRS_HGS) in two independent aging cohorts (n=25,227).
• Utilized cross-sectional and longitudinal modeling to assess PRS_HGS effects on cognitive performance and postmortem neuropathology.
• Performed mediation analyses incorporating physical activity data.

Main Results:

• Higher PRS_HGS was significantly associated with better global cognitive performance in both cohorts.
• PRS_HGS improved the predictive performance of an Alzheimer's disease polygenic risk score.
• No significant association was found between PRS_HGS and postmortem neuropathology markers.
• Physical activity showed only partial and inconsistent mediation of PRS_HGS effects on cognition.

Conclusions:

• Genetic predisposition for greater hand grip strength is linked to better cognitive performance in late life.
• This association appears independent of Alzheimer's disease-related neuropathology.
• The findings suggest a direct genetic influence of HGS on cognitive function, with limited mediation by physical activity.