Association of serum 25(OH)D3 and cognitive levels with biological aging in the elderly: a cross-sectional study

Abstract

Background: Biological aging, a fundamental process affecting health and longevity, is pivotal to understanding the physiological decline associated with aging. Serum vitamin D3 deficiency and cognitive impairment are common health issues among older adults. However, the joint associations of serum vitamin D levels and cognitive impairment with biological aging remain poorly understood. This study aims to evaluate the independent and combined associations of serum vitamin D3 and cognitive impairment with biological aging in older adults.

Methods: This cross-sectional study included adults aged 60 years and older from the 2011-2014 National Health and Nutrition Examination Survey (NHANES). Biological aging was measured using Phenotypic Age calculated from biomarkers. Cognitive performance was assessed using the Centre for the Establishment of a Registry for Alzheimer's Disease (CERAD) test, the Animal Fluency test (AFT), and the Digit Symbol Substitution test (DSST). Multivariable regression and restricted cubic spline models were used to examine the relationships between serum 25(OH)D3 levels, cognitive performance, and biological aging.

Results: After adjusting for all covariates, individuals in the highest quartile of cognitive performance had a reduced risk of biological aging compared to those in the lowest quartile (CERAD: OR 0.91; 95% CI, 0.57-1.46; AFT: OR 0.48; 95% CI, 0.29-0.82; DSST: OR 0.43; 95% CI, 0.24-0.77). A U-shaped relationship was observed between serum 25(OH)D3 levels and biological aging. Combined analyses revealed that individuals with both low serum 25(OH)D3 and low cognitive performance had the highest risk of biological aging across all cognitive tests (CERAD: OR 1.43; 95% CI, 1.02-1.98; AFT: OR 1.70; 95% CI, 1.24-2.32; DSST: OR 1.67; 95% CI, 1.22-2.27). Notably, in the DSST, individuals with normal serum 25(OH)D3 levels and normal cognitive performance showed a reduction in Phenotypic Age by 2.40 years (p < 0.01).

Conclusion: In older adults, low serum 25(OH)D3 levels combined with low cognitive performance are strongly associated with an increased risk of biological aging.

Keywords: NHANES; biological aging; cognition; older adult; phenotypic age; serum 25(OH)D3.

Figure 1

Flow chart for subject selection. NHANES, National Health and Nutrition Examination Survey.

Figure 2

The relationship between 25(OH)D3 levels and biological aging, estimated using restricted cubic splines. The left side shows the odds ratio of 25(OH)D3 in the logistic regression, while the right side shows the $\beta$ coefficient of 25(OH)D3 in the linear regression. Data was adjusted for age, sex, race, education, marital status, BMI, PIR, PA, smoke status, alcohol status, diabetes, HBP and cognition level (animal fluency). All estimates accounted for complex survey design.

Figure 3

Joint association of 25(OH)D3 levels and cognitive status with biological aging among participants.

Figure 4

Subgroup analysis of the association between cognitive status (animal fluency) with biological aging. Adjusted for age, sex, race, education, marital status, BMI, PIR, PA, smoke status, alcohol status, diabetes, and HBP. All estimates accounted for complex survey designs.