A Polygenic Risk Score for Hand Grip Strength is Associated with Cognitive Function in Mid‐to‐Late Life Adults
Bibliographic record
Abstract
Abstract Background Lower muscular fitness is a risk factor for Alzheimer’s disease (AD). Hand grip strength (HGS) specifically ‐ a proxy for muscular fitness ‐ is a heritable predictor of cognitive decline in aging adults. However, the genetic component of HGS has not yet been explored with respect to cognitive decline. Therefore, we examined the association between a polygenic risk score (PRS) for hand grip strength (HGS) and cognitive function in mid‐to‐late life individuals. Method We accessed data for 22,759 unrelated adults of European ancestry (ages 45‐86) from the Canadian Longitudinal Study on Aging (CLSA), calculating a PRS for HGS using the PRS‐CS‐Auto method and summary statistics from Willems et al., 2017. Linear models were used to test for PRS effects on baseline memory and executive function t‐scores, co‐varying for physical activity and other lifestyle and demographic factors. We also explored interactions with measured hand grip strength, physical activity level, sex, and age. Finally, we tested if our HGS‐PRS was able to significantly augment the predictive performance of a benchmark AD‐PRS, calculated using summary statistics from Bellenguez et al., 2022. Result A higher HGS‐PRS was associated with better global cognitive performance (p = 6.05e‐08). This effect remained significant after controlling for a full set of covariates, including cardiovascular fitness, physical activity, and lean muscle mass (p = 3.14e‐05). Interaction models revealed that age, sex, measured grip strength, and level of physical activity did not change the relationship between HGS‐PRS and cognition. Finally, when assessing whether the HGS‐PRS could augment the predictive performance of an established AD‐PRS, we found significant improvements to models of memory (p = .0035), executive function (p = 7.13e‐06), and global cognition (p = 3.07e‐06). While statistically significant, the additional variance explained in cognition was very small (improvement in R2∼0.1%). Conclusion Genetic predisposition for greater HGS is significantly associated with better cognitive performance in mid‐late life, regardless of sex, fitness, or levels of physical activity. It is therefore possible that direct mind‐muscle connections account for this observation, rather than indirect effects of active lifestyle. Further analyses on longitudinal cognitive outcomes and intermediate brain functional phenotypes are warranted.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".