Abstract Body (Do not enter title and authors here): Background
People with established cardiovascular disease (CVD) are at risk of early cognitive decline, and neurodegenerative diseases such as dementia. White matter hyperintensities (WMH) of presumed vascular origin are associated with progressive cerebrovascular disease and risk factors for CVD. The shared risk factors include blood pressure, sedentary lifestyle, genomic risk factors like APOE4 mutations. The extent to which common risk factors explain the co-occurrence of CVD and neurological diseases is unclear.

Purpose
To determine the extent of which CMR measurements associated with WMH independent of known cerebrovascular risk factors.

Methods
Cardiac and brain MRI images were analysed for 33,198 UK biobank participants. WMH analysis included 5 brain regions (Frontal, Parietal, Temporal, Occipital, Basal Ganglia and Thalami) and total brain WMH volume. Cardiac traits included stroke volumes, atrial volumes, ejection fractions (EF) of right and left chambers, left ventricular (LV) strain, LV wall thickness and aortic areas. Multivariable regression analysis was carried out, where each cardiac trait was regressed on each brain region and adjusted for demographics, cardiac risk factors, family history of disease and socioeconomic factors. Results were evaluated against a multiple testing correct p-value threshold of 0.05, reflecting the number of principle components(n=10) necessary to explain at least 90% of the cardiac trait variability.
Results
Higher values of 7 cardiac traits (LV end stroke volume, aortic areas, mid and basal wall thickness) associated with higher WMH volumes for all brain regions. Conversely three traits (LV ejection fraction, descending aorta distensibility and RV ejection fraction) associated positively with lower WMH volumes for all brain regions. LV cardiac output and maximum LAV only associated with frontal lobe WMH volumes. Associations on APOE- ε4 carriership, a known risk factor of Alzheimer’s disease, showed negative association in homozygous carriers between aortic distensibility of the ascending and descending aorta and higher WMH volumes in the frontal and occipital lobes.

Conclusions
This study offers insight into WMH burden in a large population of adults. Using cardiac traits as surrogate markers of different cardiac disease could explain how cardiac functionality defines WMH volume distribution and subsequently the wider relationship between cardiovascular and cerebrovascular disease.