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Frailty and the Risk of Age-Related Macular Degeneration: A Prospective Cohort and Mendelian Randomization Study
Xinyu Zhu1,2, Yikeng Huang1,2, Li Liang1,2
1Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background:
Both frailty and age-related macular degeneration (AMD) are related to aging and may share some common mechanisms. We aimed to examine the observational and causal association between frailty and the risk of AMD.
Methods:
We included 320 810 participants free of AMD at baseline from the UK Biobank. Frailty phenotypes were defined according to 5 components: weight loss, exhaustion, slow gait speed, low grip strength, and low physical activity. Cox proportional hazard models were used to evaluate the association between frailty phenotype and the risk of AMD. A causal relationship between frailty phenotype and AMD was examined using 2-sample Mendelian randomization (MR) analysis.
Results:
During a median follow-up of 12.81 years, 7 222 AMD cases were documented. After adjusting for confounding factors, compared with nonfrail participants, both pre-frail and frail participants were significantly associated with an increased risk of AMD (hazard ratio [HR] 1.17, [95% confidence interval {CI}: 1.11, 1.23] for pre-frailty and HR 1.55 [95% CI: 1.40, 1.73] for frailty). With each 1-point increase in frailty phenotype score, the risk of AMD increased by 14%. Results from the 2-sample MR analysis supported the potential causal effect of frailty phenotype on AMD.
Conclusions:
Our findings suggested that frailty assessment may help identify at-risk populations and serve as a potential strategy for early prevention and management of AMD.
Insights
Frailty is linked to an increased risk of age-related macular degeneration (AMD). Frailty assessment may aid in identifying individuals at risk for AMD, supporting early prevention strategies.
Area of Science:
- Gerontology
- Ophthalmology
- Public Health
Background:
- Frailty and age-related macular degeneration (AMD) are common aging-related conditions.
- Shared underlying biological mechanisms may link frailty and AMD.
- The relationship between frailty and AMD risk requires further investigation.
Purpose of the Study:
- To examine the observational association between frailty and AMD risk.
- To investigate the potential causal relationship between frailty and AMD.
Main Methods:
- Utilized UK Biobank data from 320,810 participants without AMD at baseline.
- Defined frailty phenotypes using five components: weight loss, exhaustion, slow gait speed, low grip strength, and low physical activity.
- Employed Cox proportional hazard models and 2-sample Mendelian randomization (MR) analysis.
Main Results:
- Over 12.81 years, 7,222 AMD cases were identified.
- Pre-frail and frail individuals had significantly increased AMD risk (HR 1.17 and 1.55, respectively).
- Each 1-point increase in frailty score correlated with a 14% higher AMD risk; MR analysis supported causality.
Conclusions:
- Frailty is a significant risk factor for developing AMD.
- Frailty assessment can identify populations at higher risk for AMD.
- Identifying frailty may enable early prevention and management of AMD.
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