On 1 November, Dr. Juul Rasmussen, Prof. Ruth Frikke-Schmidt and colleagues published an article in the European Heart Journal, showing that a healthy cardiovascular lifestyle can reduce the chances of developing dementia even in the presence of genetic risk alleles such as ApoE4.
The e4 allele of the ApoE gene (often termed ApoE4) is the most well-established genetic risk factor for dementia, increasing the risk of developing late-onset Alzheimer’s disease (AD) almost 8-fold. Conversely, the e2 allele of ApoE has been shown to confer protection against the development of AD and dementia. At highest risk of dementia and AD are individuals who carry two e4 alleles, with people who carry two e2 alleles sitting at the other end of the genetic risk spectrum. Alongside ApoE, several other genetic risk alleles have recently been identified through genome-wide association studies (GWAS). While clinical trials such as FINGER and PreDIVA show that many dementias may be prevented by changes in lifestyle habits, it is not yet fully understood whether, when and how these interventions should be targeted at groups with genetic risk factors for AD and dementia.
To address this question, the researchers calculated 10-year absolute risk scores for all-cause dementia combining cardiovascular risk factors and genetics, by analyzing data from over 61,000 participants in two Danish cohort studies: the Copenhagen General Population Study and the Copenhagen City Heart Study. Stratifying individuals based on their genetic risk, the researchers calculated hazard ratios across ages based on genetic risk and combined with hypertension status, smoking, physical activity, education and alcohol intake. There were some differences based on sex: for women, the modifiable risk factors with highest impact on dementia risk were diabetes, smoking and low education; whereas for men, diabetes, low physical activity and low education conferred the greatest risk of all-cause dementia. Importantly, individuals with fewer modifiable risk factors (e.g no diabetes, no smoking and high education) had a reduced risk of developing dementia, even on a high-risk genetic background – indicating that a healthy cardiovascular lifestyle can confer substantial benefits even in the presence of genetic risk.