Aging acceleration, not chronological age, is associated with cognitive performance in older adults: A cross-sectional study on the protective role of physical activity.

Cognitive decline in older adults is a growing public health concern, and traditional measures such as chronological age are insufficient for accurately assessing cognitive function. Phenotypic age (PhenoAge) and phenotypic age acceleration (PhenoAgeAccel), which reflect biological age and aging acceleration, may be better predictors of cognitive decline. Additionally, physical activity (PA) has been recognized for its protective effects on aging and cognitive health. This study explored the role of PhenoAge and PhenoAgeAccel in cognitive performance and investigated whether PA moderates this relationship. We used data from the National Health and Nutrition Examination Survey, which analyzed 1298 participants aged 60 years and older. PhenoAge was calculated using 10 biomarkers, and PhenoAgeAccel was derived as the difference between chronological age and PhenoAge. Cognitive performance was assessed using the Digit Symbol Substitution Test. The relationship between PhenoAge, PhenoAgeAccel, and low cognitive performance was analyzed using weighted logistic regression models. Subgroup and sensitivity analyses were conducted, and the interactions between PhenoAgeAccel and PA were evaluated. Both PhenoAge and PhenoAgeAccel scores were significantly associated with low cognitive performance. The highest quartiles of PhenoAge (odds ratio = 3.22, P = .025) and PhenoAgeAccel (odds ratio = 2.31, P = .022) were associated with higher odds of low cognitive performance. By contrast, chronological age did not show a significant relationship with cognitive performance. PA was found to moderate the association between PhenoAgeAccel and cognitive performance (P for interaction = .045). Higher levels of PA attenuated the impact of PhenoAgeAccel on cognitive decline. Receiver operating characteristic curve analysis showed that PhenoAge (area under the curve [AUC] = 0.562), PhenoAgeAccel (AUC = 0.589), and chronological age (AUC = 0.513) were significantly different. In conclusion, PhenoAgeAccel and PA are significant predictors of cognitive decline, with PA offering a protective effect against the impact of accelerated aging on cognition.