Individuals in the highest quartile of accelerated biological aging had a higher risk of dementia compared to those in the lowest quartile (HR: 1.145).
Accelerated biological aging, as measured by , is associated with an increased incidence of dementia.
Biologically older individuals have a higher risk of dementia than biologically younger individuals (HR: 1.069).
Individuals with biologically younger and high APOE ε4-related genetic risk have a greater risk of dementia than those who are biologically older with the same genetic risk (HR: 3.048 vs. HR: 2.765).
Among biologically younger individuals, those with a high (PRS) exhibit a 72.7% increased risk of dementia (HR: 1.727) compared to those with a low PRS.
Biologically older individuals with a high PRS have a 58.7% increased risk of dementia (HR: 1.587) compared to those with a low PRS.
Negative interactions between accelerated biological aging and APOE ε4-related genetic risk as well as PRS suggest that biological aging may influence genetic susceptibility to dementia.
Simplified
BACKGROUND: Accelerated biological aging has been verified to be a critical risk factor for a number of age-related diseases, but its role in dementia remained unclear. Whether it modified the effects of genetic factors was also unknown. This study evaluated the associations between accelerated biological aging and dementia and the moderating role of accelerated biological aging in the genetic susceptibility to the disease.
METHODS: We included 200,731 participants in the UK biobank. Nine clinical blood biomarkers and chronological age were used to calculate Phenotypic age acceleration (), which is a novel indicator for accelerated biological aging. The associations of PhenoAgeAccel with dementia, both young-onset and late-onset dementia, were assessed by Cox proportional hazard models. Apolipoprotein E (APOE) alleles and polygenic risk scores () were used to evaluate the genetic risk of dementia. The interactions between genetic susceptibility and biological aging were tested on both multiplicative and additive scales.
RESULTS: These findings showed individuals who were in the highest quartile of PhenoAgeAccel had a higher risk with incidence of dementia compared to individuals in the lowest quartile of PhenoAgeAccel (HR: 1.145 (95% CI: 1.050, 1.249)). Individuals with biologically older had a higher risk of dementia than individuals with biologically younger (HR: 1.069 (95% CI: 1.004, 1.138)). Furthermore, compared to individuals with biologically younger and low APOE ε4-related genetic risk, individuals with biologically younger and high APOE ε4-related genetic risk (HR:3.048 (95% CI: 2.811, 3.305)) had a higher risk of dementia than individuals with biologically older and high APOE ε4-related genetic risk (HR: 2.765 (95% CI: 2.523, 3.029)). Meanwhile, referring to low dementia PRS and biologically younger, the risk of dementia increased by 72.7% (HR: 1.727 (95% CI: 1.538, 1.939) in the biologically younger and high PRS group and 58.7% (HR: 1.587 (95% CI: 1.404, 1.793) in the biologically older and high PRS group, respectively. The negative interactions between PhenoAgeAccel with APOE ε4 and PRS were also tested on the additive scale.
CONCLUSIONS: Accelerated biological aging could bring the extra risk of dementia but attenuate the effects of genetic risk on dementia. These findings provide insights for precise prevention and intervention of dementia.
Key numbers
1.145
Increase in dementia risk
Hazard Ratio for highest vs. lowest quartile of
3.048×
Higher risk for biologically younger individuals
Hazard Ratio for biologically younger with high APOE ε4-related risk
1.727
Increase in dementia risk with high
Hazard Ratio for biologically younger with high
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