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Impact of Cardiovascular Risk Factors and Genetics on 10-Year Risk of Dementia
Quick Takes
- Dementia is a highly prevalent disease that is expensive to society, and up to one-third of dementia cases may be preventable.
- This study seeks to determine what risk factors best predict development of dementia, knowledge which may allow targeting of resources to individuals at highest risk.
- In this large prospective cohort study, the most influential potentially modifiable risk factors for development of dementia in men and women were diabetes, low education, and smoking.
Study Questions:
What socioeconomic, genetic, and modifiable risk factors best predict development of dementia?
Methods:
This is a prospective cohort study enrolling 61,664 Danish subjects aged 20-100 years. Individuals were selected randomly for this study. Cardiovascular risk factors were recorded at baseline. The endpoint of dementia was derived from national registries. Genotyping (which included apolipoprotein E (APOE) genotype and number of genome-wide association studies [GWAS] risk alleles) was available for 53,546 (87%) individuals. GWAS risk allele number was stratified (8-17, 18-19, 20-21, or 22-31). Age was stratified by decade (50-59, 60-69, 70-79, and 80-100). The outcome of interest was 10-year absolute risk scores (presented at percentages) for all-cause dementia.
Results:
Of the 61,664 subjects, 2,158 (3.5%) received a diagnosis of dementia during a median follow-up of 10 years. For women, the modifiable risk factors with the highest hazard ratios for all ages were diabetes, smoking, and low education. For men, these were diabetes, low physical activity, and low education. The 10-year absolute risk of all-cause dementia increased with increasing age, APOE ɛ4 genotype, number of GWAS risk alleles, diabetes, low education, and smoking. The highest 10-year absolute risk scores of all-cause dementia were seen in women with smoking, diabetes, low education, APOE ɛ44 genotype, and 22-31 GWAS risk alleles and were 6%, 23%, 48%, and 66% in those aged 50-59, 60-69, 70-79, and 80-100, respectively. The highest 10-year absolute risk scores of all-cause dementia were seen in men with smoking, diabetes, low education, APOE ɛ44 genotype, and 22-31 GWAS risk alleles and were 5%, 19%, 42%, and 60%, respectively.
Conclusions:
In this large prospective cohort study, the risk of all-cause dementia increased with increasing age, APOE ɛ44 genotype, number of GWAS risk alleles, diabetes, low education, and smoking.
Perspective:
The prevalence of dementia is increasing given our aging population, and no available curative treatments exist. Some estimates suggest that up to one-third of dementia may be preventable with cardiovascular risk factor modification. Given the scale of this disease and the need to concentrate resources most effectively, the authors sought to determine the risk factors that best predict which individuals will develop dementia and would presumably benefit the most from preventative interventions. In present day, where genotyping is not widely available to most patients, the results of this study chiefly suggest a role for aggressive society-based interventions to prevent diabetes and smoking.
Clinical Topics: Dyslipidemia, Prevention, Lipid Metabolism, Smoking
Keywords: Alleles, Apolipoprotein E4, Apolipoproteins E, Cardiovascular Diseases, Diabetes Mellitus, Genome-Wide Association Study, Genotype, Primary Prevention, Risk Factors, Smoking
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