Intrinsic Capacity, Polygenic Risk Score, APOE Genotype, and Risk of Dementia: A Prospective Cohort Study Based on
Mengtong Sun1, Qida He1, Na Sun1
1From the Department of Epidemiology and Biostatistics, School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu, China.
Neurology
|June 6, 2024
Summary
Intrinsic capacity (IC) is linked to increased dementia risk. Low IC combined with genetic predisposition significantly elevates the risk for dementia, including Alzheimer's and vascular dementia.
Area of Science:
- Gerontology and Public Health
- Neuroscience and Neurology
- Genetics and Epidemiology
Background:
- The World Health Organization introduced intrinsic capacity (IC) as a new metric for healthy aging.
- The association between intrinsic capacity and dementia incidence, including subtypes, remains largely unexplored.
- Understanding this relationship is crucial for developing targeted interventions.
Purpose of the Study:
- To investigate the relationship between intrinsic capacity (IC) and the incidence of dementia and its subtypes.
- To determine if genetic susceptibility to dementia can be modified by an individual's intrinsic capacity.
- To analyze the combined impact of IC and genetic risk on dementia development.
Main Methods:
- A large cohort study utilizing data from 366,406 UK Biobank participants (2006-2010).
- Calculation of a comprehensive IC deficit score based on 7 factors across 4 IC domains.
- Application of Cox proportional hazards models to assess the association between IC deficit score and dementia incidence.
Main Results:
- A total of 5,207 dementia cases were identified, including 2,186 Alzheimer's disease and 1,175 vascular dementia cases.
- Individuals with a higher IC deficit score (4+) exhibited a significantly elevated risk of dementia (HR 2.17).
- The combination of high polygenic risk score (PRS) and high IC deficit score (4+) resulted in a substantially increased dementia risk (HR 8.11), observed for all-cause, Alzheimer's, and vascular dementia.
Conclusions:
- Intrinsic capacity (IC) is significantly associated with an increased risk of developing dementia.
- The risk of dementia is particularly pronounced in individuals with low intrinsic capacity who also have a genetic predisposition.
- These findings highlight the importance of maintaining intrinsic capacity for dementia prevention, especially in genetically susceptible individuals.
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