Associations between grip strength, brain structure, and mental health in > 40,000 participants from the UK Biobank

Abstract

Background: Grip strength is a widely used and well-validated measure of overall health that is increasingly understood to index risk for psychiatric illness and neurodegeneration in older adults. However, existing work has not examined how grip strength relates to a comprehensive set of mental health outcomes, which can detect early signs of cognitive decline. Furthermore, whether brain structure mediates associations between grip strength and cognition remains unknown.

Methods: Based on cross-sectional and longitudinal data from over 40,000 participants in the UK Biobank, this study investigated the behavioral and neural correlates of handgrip strength using a linear mixed effect model and mediation analysis.

Results: In cross-sectional analysis, we found that greater grip strength was associated with better cognitive functioning, higher life satisfaction, greater subjective well-being, and reduced depression and anxiety symptoms while controlling for numerous demographic, anthropometric, and socioeconomic confounders. Further, grip strength of females showed stronger associations with most behavioral outcomes than males. In longitudinal analysis, baseline grip strength was related to cognitive performance at ~9 years follow-up, while the reverse effect was much weaker. Further, baseline neuroticism, health, and financial satisfaction were longitudinally associated with subsequent grip strength. The results revealed widespread associations between stronger grip strength and increased grey matter volume, especially in subcortical regions and temporal cortices. Moreover, grey matter volume of these regions also correlated with better mental health and considerably mediated their relationship with grip strength.

Conclusions: Overall, using the largest population-scale neuroimaging dataset currently available, our findings provide the most well-powered characterization of interplay between grip strength, mental health, and brain structure, which may facilitate the discovery of possible interventions to mitigate cognitive decline during aging.

Keywords: Brain plasticity; Cognitive functioning; Grey matter volume; Grip strength; Mental health.

Fig. 1

Flowchart illustrating criteria for selection of samples as well as the four analyses performed in the current study. Using data from over 40,000 participants, we start by establishing how grip strength relates to a total of 30 mental health-related behavioral phenotypes. Based on longitudinal data, we further determine the directionality of these associations. We then investigate how grip strength is related to regional GMV and examine whether GMV mediates any associations between grip strength and mental health outcomes

Fig. 2

Associations between handgrip strength and 30 mental health-related outcomes. a Of the 30 behavioral phenotypes, 27 showed significant association with grip strength and in the expected direction after controlling for confounders: stronger muscular strength was associated with better cognitive performance, higher life satisfaction, greater subjective well-being, and lower depression and anxiety symptoms. Significance is shown as -log₁₀(FDR corrected P-value) and a value above 1.30 is considered statistically significant (-log₁₀(0.05) = 1.30). b When the analyses were stratified by gender, a respective of 29 and 20 behavioral outcomes showed significant association with grip strength in females and males. c Three examples of the longitudinal association between grip strength and behavioral outcomes were revealed by a classic two-wave cross-lagged panel model. For the reaction time test, we observed a significant bi-directional association, i.e., stronger grip strength at baseline was related to better performance on reaction time at the 9-year follow-up, while the reverse was weaker but also significant (FDR corrected P < 10⁻⁴); for pairs matching, greater grip strength predicts higher task performance, while the reverse was nonsignificant; For neuroticism, a higher neuroticism score was associated with weaker grip strength measured 9 years later, but the reverse was nonsignificant

Fig. 3

Regional distribution of associations between grey matter volume and grip strength. a The regional analysis revealed widespread significant associations between grip strength and grey matter volume after controlling for potential confounders. T-statistics are visualized here. b The associations remained significant (FDR corrected P < 0.01) after additionally controlling for total intracranial volume, implying that grip strength relates to region GMV independently of overall brain volume. Brain regions showing the highest correlations with grip strength primarily included the ventral striatum, hippocampus, thalamus, temporal pole, parahippocampal gyrus, temporal fusiform cortex, brain stem, pallidum, and putamen

Fig. 4

Regional distribution of associations between grey matter volume and cognitive function. a Significant associations were observed between behavioral phenotypes and regional grey matter volume after controlling for potential confounders (FDR corrected P < 0.01). The top 4 behavioral phenotypes showing the highest similarities of association map with grip strength were visualized here. b Comparison between GMV-grip strength and GMV-behavior association maps. The brain association map of grip strength was highly similar to that of the behavioral phenotypes regardless of whether the total intracranial volume was added as a covariate. The T-statistic map correlations reach statistical significance in 11 and 16 of all 30 behavioral outcomes in cases of including or not including the total intracranial volume as an additional covariate (*FDR corrected P < 0.05)

Fig. 5

Mediation effects of brain volume on the association between grip strength and behavioral outcomes. a Mediation effect of mean GMV on the association between grip strength and behavioral outcomes. The proportion of variance explained by the mediation as well as the lower and upper bound of 95% confidence interval was shown. b The top three behavioral phenotypes having the highest mediation effect size were numeric memory (proportion mediated = 21.83%; 95% CI = 13.80%~41.88%; bootstrapping test, FDR corrected P < 2 × 10⁻⁴), symbol-digit substitution: attempted (15.58%; 9.66%~29.87%; P < 2 × 10⁻⁴), and symbol-digit substitution: corrected (15.26%; 9.31%~29.51%; P < 2 × 10⁻⁴). a×b: the indirect effect; c: the total effect; c’: the direct effect