Abstract Body (Do not enter title and authors here): Introduction: Dementia has been strongly linked with cardiovascular disease, but the relationship between cardiovascular disease and brain health at subclinical stages remains uncertain. We explored the relationships between subclinical cardiac dysfunction, defined by echocardiography and cardiac biomarkers, and novel neurobiomarkers associated with dementia in older adults.

Methods: We included 962 Cardiovascular Health Study participants free of previous stroke, transient ischemic attack, atrial fibrillation, heart failure, or myocardial infarction. We analyzed cross-sectional associations with serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) using linear regression. Subclinical cardiac measures included echocardiographic left atrial reservoir strain, left ventricular average longitudinal strain, early diastolic strain rate of the left ventricle, decreased left ventricular ejection fraction, average E/e’, percent predicted left ventricular mass, and left atrial diameter and circulating N-terminal pro-brain-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT).

Results: Among 844 participants with NT-proBNP/hs-cTnT values, hs-cTnT was significantly associated with NfL, even after mutual adjustment for NT-proBNP (β=0.24, 95% CI: (0.10, 0.40); p=0.001. NT-proBNP was also associated with NfL (β=0.005, 95% CI: (0.000, 0.010), p=0.04), although this association was modestly attenuated and not nominally significant after adjustment for hs-cTnT (β=0.004, 95% CI: (-0.001, 0.010), p=0.08). No significant associations were observed for either circulating marker with GFAP, nor were echocardiographic variables associated with NfL or GFAP.

Conclusions: In older adults with no clinically identified cardiovascular disease, subclinical cardiac dysfunction identified through hs-cTnT and, to a lesser degree, NT-proBNP was linked to higher levels of NfL, a marker of brain injury. This novel insight suggests that long-term prevention of even subclinical cardiac disease could also lead to better brain health.