Association between white-matter lesion volume and heart-rate variability: A comparison of T1w, T1w+T2w and T1w+FLAIR-based segmentations using FreeSurfer SAMSEG

Background Heart disease is a crucial risk factor for brain degeneration, but the specific mechanisms of this association are still under investigation. Notably, the development of white-matter lesions, a hallmark of cerebral small-vessel disease with connections to progressive neurodegeneration and cognitive decline, has been linked to cardiovascular disease. As such, measures of cardiovascular function such as heart-rate variability may represent accessible indicators of white-matter lesion burden. Methods This study used data from healthy adults drawn from the Leipzig Study for Mind-Body-Emotion Interactions (LEMON) dataset to examine heart function through measures of heart-rate variability, as well as their relationship to cerebral small-vessel disease as quantified through white-matter lesion volumes, using FreeSurfer SAMSEG. White-matter lesion volumes were segmented using 3-Tesla T1w+FLAIR, T1w+T2w or T1w images alone. Results Unadjusted exploratory results suggested that lower heart-rate variability was associated with higher lesion volume, a cerebral hallmark of hypertension. After controlling for the effect of age on lesion volume, low-frequency heart rate variability specifically was found to interact with age-related lesion volume. Moreover, we showed that the relationship between white-matter lesion volume and heart-rate variability is apparent using T1w+FLAIR or T1w+T2w based lesion estimates could be observed with T1w-based lesion estimation alone, opening new avenues for studying cerebral small-vessel disease. Discussion These results suggest heart rate variability as a factor in the translation between cardiovascular risk and white matter degeneration, as well as an accessible and non-invasive indicator of white-matter lesion burden and associated cognitive impairment in later life. The unique association between reduced low-frequency band heart-rate variability and age-related lesion burden may help to establish the link between autonomic control of cardiac function and brain health in aging.