Atrial function: Association with cerebrovascular disease and cognitive dysfunction

Abstract Background The relationships of left atrial (LA) dysfunction with cognition are poorly understood. We investigated the associations of LA function with cognitive impairment, etiologic‐subtype (neurodegenerative vs. vascular[VCI]), neuroimaging markers of cerebrovascular disease (CeVD) and circulating biomarkers, in subjects without AF. Method In this prospective cohort study of subjects recruited from memory clinics with brain magnetic resonance imaging (MRI), neuropsychological assessments, circulating biomarker measurements, LA strain (reservoir [LASr], conduit [LAScd], contractile) was determined using 2D speckle‐tracking echocardiography. VCI was defined as vascular dementia or cognitive impairment no dementia(CIND)/Alzheimer’s dementia with significant CeVD, and neurodegenerative defined as CIND/dementia without significant CeVD on neuroimaging. Result Among 251 subjects (age 75±8years, 59% female, 178(71%) had cognitive impairment (37% dementia, 14% moderate CIND, 20% mild CIND), of which 58% were VCI and 42% neurodegenerative. LAScd was the only LA strain parameter independently associated with more severe (moderate CIND/dementia vs. mild CIND/no cognitive impairment) grades of cognitive impairment (lowest vs. highest tertile: adjusted odds ratio[AOR] 2.50, p=0.015), and worse MMSE scores, visuomotor construction and memory on neuropsychological testing (p<0.05). LAScd was independently associated with VCI (vs. neurodegeneration) (lowest vs. highest tertile: AOR 3.16, p=0.006), and showed no associations with markers of neurodegeneration, including circulating pTau‐181 and strictly lobar cerebral microbleeds (p>0.05). LAScd and LASr were both associated with increased burden of CeVD including intracranial stenoses, cortical infarcts, lacunes, cerebral microinfarcts, microbleeds and white matter hyperintensities and correlated with cardiac‐specific biomarkers (p<0.05), but LAScd correlated additionally with a broader range of circulating biomarkers reflecting inflammation, neurotrophic processes and neuronal damage (p<0.05). Conclusion Reduced LA conduit function was associated with more severe cognitive impairment, primarily due to CeVD. LA strain, particularly LAScd, may be a useful biomarker of cognitive impairment in at‐risk subjects without AF.