AUTHOR=Liu Hai-yan , Zhang Yi-Jing , Zhang Wen-you 

TITLE=Exploring the association of physical activity on cognitive function in older adults from observational and genetic insights: a combined NHANES and Mendelian randomization study

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=16

YEAR=2024

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2024.1418455

DOI=10.3389/fnagi.2024.1418455

ISSN=1663-4365

ABSTRACT=<sec id="sec1"><title>Background</title><p>Cognitive function (<italic>CF</italic>) deterioration is a pressing concern in geriatric research. This study aimed to explore the relationship between physical activity (PA) and <italic>CF</italic> in older adults.</p></sec><sec id="sec2"><title>Methods</title><p>This study adopted a dual approach, employing both observational and genetic approaches through data from the National Health and Nutrition Examination Survey (NHANES) 2011–2014 and Mendelian Randomization (MR) analysis. For the NHANES component, PA levels were evaluated using the Global Physical Activity Questionnaire, and <italic>CF</italic> was assessed via standardized tests. Multivariate regression, threshold effect analysis, smoothing curve fitting, and subgroup analyses were conducted to examine the association between PA and <italic>CF.</italic> In parallel, MR methods, using genetic variants as instrumental variables, assessed the causal impact of PA on <italic>CF</italic> and related conditions such as Alzheimer’s disease and dementia.</p></sec><sec id="sec3"><title>Results</title><p>Observational findings from NHANES demonstrated a positive correlation between PA and <italic>CF</italic>, notably among female participants. The detailed analysis identified specific thresholds of PA that correlate with cognitive enhancements. However, MR results did not support a significant causal relationship between PA and <italic>CF</italic> or dementia-related outcomes, indicating an absence of a direct genetic basis for the observational associations.</p></sec><sec id="sec4"><title>Conclusion</title><p>Although observational data from NHANES suggest that PA is positively associated with <italic>CF</italic> in older adults, particularly among women, MR analysis did not confirm these findings as causally related. The discrepancy highlights the complexity of the PA-<italic>CF</italic> relationship and underscores the need for further research. These results emphasize the potential of PA as a modifiable risk factor for <italic>CF</italic>, though causal effects remain to be definitively established.</p></sec>