Association Between Phenoage With Cognitive Function and Cerebrospinal Fluid Biomarkers of Alzheimer's Disease Pathology: The CABLE Study.

Biological age, reflecting an individual's physiological state and function, may vary more or less than chronological age. This study aimed to probe the association between biological age (phenoage) with cognitive function and pathological biomarkers of Alzheimer's disease (AD) in cerebrospinal fluid (CSF). All population were recruited from the Chinese Alzheimer's Biomarker and Lifestyle (CABLE) study. Multiple linear regression models were utilized to analyze the correlation between phenoage with cognitive function, as well as CSF AD biomarkers. Stratified analyses were conducted by age, gender, APOE ε4 allele status, and age acceleration (AA). Sensitivity analyses were performed to ensure the robustness of the results. Mediation analyses were employed to explore the relationship between phenoage, CSF AD pathological biomarkers, and cognitive function. Our research sample consisted of 337 individuals, with a mean age of 64.06 years, of whom 39.8% were female. The study found that higher phenoage was significantly associated with poorer cognitive function, including lower MMSE scores (β = -0.024, p < 0.001) and MoCA-B scores (β = -0.020, p < 0.001). Besides, higher phenoage was also remarkably correlated with increased CSF AD pathologies, including increased t-tau (β = 0.020, p < 0.001), p-tau181 (β = 0.013, p = 0.005) and p-tau181/Aβ42 ratio (β = 0.012, p = 0.008). Stratified analysis revealed that the association between phenoage and cognitive function was more pronounced in the middle-aged group and among APOE ε4 allele noncarriers. Furthermore, mediation analysis revealed that tau pathologies partially mediated the relationship between phenoage and cognitive decline. Our study demonstrates that biological age (phenoage), determined by chronological age and nine aging-related variables, is correlated with cognitive function and CSF AD pathological biomarkers. Phenoage could offer a novel strategy for the prevention of Alzheimer's disease.