IHD leads to poor brain health regardless of WMH

31 May 2023

It is well known that traditional cardiovascular (CV) risk factors cause cerebrovascular events.1 Stroke is the first widely examined measure of vascular brain health as it can be quantified and clinically confirmed with neuroimaging.1 Advancement in brain imaging technology allows for a better understanding of the impacts of other vascular risk factors like white matter hyperintensity (WMH) or the downstream impacts of vascular brain health like dementia.1 Recently, the effects of ischemic heart disease (IHD) have been revealed to be an independent risk factor for brain aging and dementia, highlighting the importance of IHD prevention in delaying brain deterioration.2 

IHD has been linked with brain structure abnormalities in both the white and grey matter independent of aging.2 These abnormalities are often noted before the clinical onset of dementia and are predictive of cognitive decline.1 Identifying and quantifying such changes may help the development of preventative measures or even guide treatment.2 A recent study using the United Kingdom Biobank (UKB) data set has investigated the relationship between IHD and brain aging.2 Further associations of IHD with dementia were also investigated.2 

Participants were adults aged 40-69 years with brain imaging-derived phenotypes (IDPs) available.2 Patients with a history of mental health, neurological disorders, or dementia that could affect cognitive function were excluded from the analysis.2 They were subsequently divided into 2 groups, i.e., with prevalent IHD (n=1,341) and without prevalent IHD (n=35,237).2 Patients with IHD were older (59.2 vs. 54.6 years old) and most were males (71.4% vs. 46.3%)2 Their brain scans also showed significantly lower volumes of most brain structures and increased WMH.2 Logistical regression was used to analyze the changes in brain age and incident dementia.2 For every unit increase in brain age, the odds of dementia were increased by 13% (OR=1.13; 95% CI: 0.04-1.22; p=0.002).2 The results were consistent when adjusted for sex and age.2 

Data from the non-IHD group were used to model brain age and estimate the brain age of IHD patients.2 A significant (p<0.001) difference between the estimated brain age and the chronological brain age in the IHD group and non-IHD group was found at 6.96 and 4.69 years, respectively.2 The estimated brain age was found to be independent of the actual age of participants in both cohorts, showing that the results were not confounded by the baseline age difference.2 Further analysis found that IHD had both a direct effect (β=6.41) and an indirect effect mediated by WMH (β=0.11) on brain age (p<0.001). However, the significance of the WMH-mediated effect was lost when adjusted for covariates.2 This suggested that there are other non-WMH mechanisms in which IHD increases brain aging.2 Possible mechanisms include ischemic brain injury, blood-brain barrier (BBB) alterations, and various biological pathways, including oxidative stress, immune responses, and endothelial dysfunction.2 

Besides, the association of other vascular risk factors with brain age was also investigated.2 Diabetes was found to be associated with increased brain age in both the IHD and non-IHD cohorts, respectively (β=1.3; p<0.001 and β=2.06; p<0.001).2 The Body Mass Index (BMI) (β=0.1; p=0.003) and waist-hip ratio (β=8.02; p<0.001) as measures of adiposity were also associated with increased brain age in the IHD population.2 These results suggested that insulin resistance and increased systemic inflammation might have roles in subclinical brain damage.2 Additionally, in the non-IHD population, cardiovascular magnetic resonance (CMR) imaging revealed significant associations across many parameters, but the significance was lost in the IHD group despite a similar direction of the association.2 It is noted that in the non-IHD group, accelerated brain aging did not translate into an increased risk of dementia.2 

Further research is required to study the associations of how genetic factors or early brain developments affect brain structures.2 However, brain age can be used as an effective means to communicate the risk in age and promote healthy lifestyle to patients, particularly the younger population.2 

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