Cardiometabolic diseases ( CMD), a group of diseases including type 2 diabetes (T2D), heart disease (HD), and stroke, are a growing challenge in our aging society. With increasing life expectancy and continued advances in the treatment of cardiovascular disease and diabetes, people with CMD are living longer and are increasingly likely to develop more than one of these conditions during their lifetime. . Cardiometabolic multimorbidity, that is, the coexistence of two or more CMDs, has been associated with mortality and other negative health outcomes and affects approximately 30% of older adults.
Type 2 diabetes (T2D), heart disease (HD), and stroke are well-established individual risk factors but only a few studies have addressed the relationship between cardiometabolic multimorbidity and dementia . It is currently unclear how dementia risk is affected by the timing of CMD development across the adult lifespan, given the variability of CMDs as chronic diseases with a potentially long time course. Furthermore, although CMDs may be related to dementia through several biologically plausible pathways, our understanding of the mechanisms underlying this association is still limited.
Goals
Cardiometabolic diseases (CMD), including diabetes, heart disease, and stroke, are established risk factors for dementia, but their combined impact has only recently been investigated. This study aimed to examine the association between dementia and cardiometabolic multimorbidity in middle and older age and explore the role of genetic background in this association.
Methods and results
Within the Swedish Twin Registry, 17,913 people without dementia aged ≥60 years were followed for 18 years . Cardiometabolic diseases (CMD) [including age of onset in mid (60) or late (≥60) life] and dementia were determined from medical records. Cardiometabolic multimorbidity was defined as having ≥2 CMD.
Cox regression was used to estimate the CMD-dementia association in (i) a classic cohort study design and (ii) a co-twin study design involving 356 monozygotic and dizygotic pairs. By comparing the strength of the association in the two designs, the contribution of genetic background was estimated.
At baseline, 3312 (18.5%) participants had 1 CMD and 839 (4.7%) had ≥2 CMD. During the follow-up period, 3020 participants developed dementia . In the classic cohort design, the hazard ratio (95% confidence interval) for dementia was 1.42 (1.27–1.58) for 1 CMD and 2.10 (1.73–2 . 57) for ≥2 CMD. The risk of dementia was higher in middle age compared to CMD in old age.
In the co-twin design, the CMD-dementia association was attenuated among monozygotic [0.99 (0.50–1.98)] but not dizygotic [1.55 (1.15–2.09)] twins, suggesting that the association was due in part to factors genetic factors common to both CMD and dementia.
Conclusions To our knowledge, this study is the first to demonstrate that CMDs, particularly when they develop in middle age, increase the risk of dementia, including AD and vascular dementia. These findings add to growing evidence of a connection between cardiometabolic multimorbidity and forms of vascular and neurodegenerative dementia and highlight the need for special monitoring of people who develop T2D, HD or stroke in midlife to reduce risk. of developing dementia in old age. Using a twin study design, we also provide evidence that genetic background may underpin the association between cardiometabolic disease and dementia. Our findings call for the identification of these common genes for both CMD and dementia in future studies. |
