Biomarkers

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.