Summary Background Individual cardiometabolic disorders and genetic factors are associated with an increased risk of dementia; however, the relationship between dementia and cardiometabolic multimorbidity is unclear. We investigated whether cardiometabolic multimorbidity increases the risk of dementia, independently of genetic risk, and examined associated brain structural changes. Methods We examined genetic and health data from 203,038 UK Biobank participants of European ancestry, aged 60 years or older without dementia at baseline assessment (2006–10) and followed up to March 31, 2021 in England and Scotland and the February 28, 2018 in Wales, as well as brain structural data in a subsample of nested images of 12,236 participants. A cardiometabolic multimorbidity index comprising stroke, diabetes, and myocardial infarction (one point each) and a polygenic risk score for dementia (with low, intermediate, and high risk groups) were calculated for each participant. The main outcome measures were incident all-cause dementia and brain structural metrics. Results The risk of dementia associated with high cardiometabolic multimorbidity was three times higher than that associated with high genetic risk (hazard ratio [HR] 5.55, 95% CI 3.39–9.08, p<0.0001 and 1.68, 1·53–1·84, p<0·0001, respectively). Participants with high genetic risk and a cardiometabolic multimorbidity index of two or more had an increased risk of developing dementia (HR 5·74, 95% CI 4·26–7·74, p<0·0001), in comparison with those with low genetic risk and without cardiometabolic conditions. Fundamentally, we found no interaction between cardiometabolic multimorbidity and polygenic risk (p=0·18). Cardiometabolic multimorbidity was independently associated with more extensive and widespread brain structural changes, including lower hippocampal volume (F2, 12,110 = 10·70; p<0·0001) and total gray matter volume (F2, 12,236 = 55·65; p< 0·0001). Interpretation Cardiometabolic multimorbidity was independently associated with dementia risk and wide differences in brain imaging to a greater extent than genetic risk. Targeting cardiometabolic multimorbidity could help reduce the risk of dementia, independent of genetic risk. |
Total hippocampal volume, total gray matter volume, and white matter hyperintensity volume associated with CMI and polygenic risk Data are hippocampal brain volume, total gray matter, and white matter hyperintensities stratified by CMI and polygenic risk. Error bars represent SE. White matter hyperintensity volume was log-transformed due to skewed distribution. CMI=cardiometabolic multimorbidity index. PRS=polygenic risk score.
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Having multiple conditions that affect the heart is linked to a higher risk of dementia than having a high genetic risk, according to a large new study
Led by the University of Oxford and the University of Exeter, the study is among the largest ever conducted to examine the link between several heart-related conditions and dementia, and one of the few to look at the complex issue of multiple health conditions.
Published in The Lancet Healthy Longevity , the paper analyzed data from more than 200,000 people, aged 60 and over, and of European ancestry in the UK Biobank. The international research team identified those who had been diagnosed with cardiometabolic diseases such as diabetes, stroke or heart attack, or any combination of the three, and those who developed dementia.
Within this study population, the researchers found that the more of these three conditions a person had, the greater their risk of dementia. People who had all three conditions were three times more likely to develop dementia than people who had a high genetic risk.
Dr Xin You Tai, lead author and PhD student at the University of Oxford, said: "Dementia is a major global problem, with predictions that 135 million worldwide will have the devastating condition by 2050. We found that having Such heart-related conditions are linked to dementia risk to a greater extent than genetic risk. So whatever genetic risk you were born with, you can have a big impact on reducing dementia risk by taking care of your heart health. and metabolic throughout life.
The team, which included the universities of Glasgow and Michigan, found that almost 20,000 of the UK Biobank participants they studied had been diagnosed with one of the three conditions. Just over 2,000 had two conditions and 122 had all three.
Lead author Professor David Llewellyn, professor of clinical epidemiology and clinical health at the University of Exeter, said: “Many studies look at the risk of a single condition in relation to dementia, but health is more complex than that. We know that many patients actually have a variety of conditions. “Our study tells us that for people who are diagnosed with diabetes, stroke or heart attack , it is particularly important to take care of their health and make sure they receive the right treatment, to prevent further problems and reduce the risk of dementia.”
The team divided the 200,000 participants into three genetic risk categories, from highest to lowest, based on a comprehensive risk score that reflects multiple genetic risk traits relevant to people of European ancestry. They also had brain imaging data from more than 12,000 participants and found widespread brain damage for those with more than one cardiometabolic condition. In contrast, high genetic risk was linked to impairment only in specific parts of the brain.
Study co-author Dr. Kenneth M. Langa, professor of medicine at the University of Michigan and Veteran Affairs Ann Arbor Healthcare System, said, “Our research indicates that protecting the heart throughout life likely also has significant benefits for brain. To take care of your heart, you can exercise regularly, eat a healthy diet, and do everything you can to ensure your blood pressure, blood sugar, and cholesterol levels are within guidelines.”
Dr Sara Imarisio, head of research at Alzheimer’s Research UK, said: "The evidence is clear that what is good for the heart is also good for the head. A person’s risk of developing dementia is a complex mix of your age, your genes, and aspects of your lifestyle. In this study, researchers analyzed data from a population aged 60 and older , including whether they had particular heart conditions, information about their genetics, and how they affected their risk of developing dementia. They found that people with multiple heart conditions were even more likely to develop dementia than people who had a higher risk of Alzheimer’s disease due to their genetics.
“These findings reiterate the importance of treating the causes of poor heart health, not only for its own sake, but also for the added benefit in terms of reducing the number of cases of dementia. From the generosity of our supporters who allowed us to fund this work, to the selflessness of the volunteers who made it possible, we want to thank you, without you research like this cannot be carried out.
“If anyone is concerned about their heart or brain health, talk to their doctor.”
Added value of this study With the largest known sample to date addressing this issue, this study expands existing knowledge by examining the association between multiple established cardiometabolic conditions and the risk of developing dementia, as well as the possible interaction with genetic risk in people aged 60 years. or more. The risk associated with developing dementia in participants with cardiometabolic multimorbidity of stroke, myocardial infarction, and diabetes was more than three times greater than the risk of developing dementia in participants with high genetic risk. We found no interaction between cardiometabolic multimorbidity and genetic risk for both dementia risk and structural brain health. Implications of all available evidence Our results suggest the importance of targeting cardiometabolic multimorbidity to reduce dementia risk, regardless of predetermined genetic risk. These findings have important implications for clinical practice and public health initiatives in dementia prevention and care. |
