Left Atrial Myocardial Mechanics: Association With Cognitive Dysfunction, Cerebrovascular Disease, and Circulating Biomarkers

Abstract

Background: The relationship of left atrial (LA) strain with cognition in the absence of atrial fibrillation is poorly understood. We investigated the association of LA strain with cognitive impairment and its pathogenetic subtype (vascular [VCI] or neurodegenerative) and underlying mechanisms via associations with circulating and neuroimaging markers of cerebrovascular disease.

Methods and results: LA strain (reservoir, conduit [LAScd], contractile) was determined using speckle-tracking echocardiography in a prospective memory clinic cohort with brain magnetic resonance imaging, neuropsychological assessments, and circulating biomarker measurements. Cognitive impairment was classified as VCI or neurodegenerative in the presence or absence of significant cerebrovascular disease, respectively. Among 251 subjects (age 75±8 years, 59% women) without atrial fibrillation, 178 (71%) had cognitive impairment (20% mild, 14% moderate, 37% dementia); of these impairments, 58% were VCI and 42% neurodegenerative. Only LAScd was associated with more severe cognitive impairment (moderate/dementia versus none/mild, adjusted odds ratio [aOR] for lowest versus highest tertile >2) and specifically, with worse Mini-Mental State Examination score and memory on neuropsychological testing. LAScd was independently associated with VCI (versus neurodegenerative; aOR for lowest versus highest tertile, 4.22 [95% CI, 1.59-11.2]) and not with neurodegenerative markers (circulating pTau-181 [phosphorylated tau-181], isolated lobar cerebral microbleeds). Both LAScd and LA reservoir strain were associated with increased burden of cerebral small vessel disease on magnetic resonance imaging, but only LAScd correlated with circulating biomarkers, reflecting inflammation, neurotrophic processes, and neuronal damage.

Conclusions: Reduced LA strain was associated with cognitive impairment, primarily of vascular origin, and a higher burden of cerebral small vessel disease. LAScd may be a biomarker of VCI in at-risk subjects without atrial fibrillation.

Keywords: atrial fibrosis; atrial strain; cerebrovascular disease; cognitive impairment; dementia.

Figure 1. Atrial strain measurement by speckle‐tracking echocardiography.

The region of interest is delineated by the endocardial border of the LA during speckle‐tracking echocardiography (top left panel). The LA strain curve (right panel) has 3 phases: reservoir (LASr), conduit (LAScd), and contractile (LASct) strain. LASr is measured as the difference in strain values between mitral valve opening and LV end‐diastole, LAScd is measured as the difference in strain values at the onset of atrial contraction and mitral valve opening, and LASct is the difference in strain values at LV end‐diastole and onset of atrial contraction. LASr, LAScd, and LASct values represent the average of 12 segments in both 4‐ and 2‐chamber views. LA indicates left atrial; LAScd, left atrial conduit strain; LASct, left atrial contractrile strain; LASr, left atrial reservoir strain; and LV, left ventricular.

Figure 2. Flow diagram for study participants.

Of 272 participants in the cardiac substudy, 251 were included after excluding those with AF, uninterpretable LA strain images and incomplete neuropsychological assessment. AF indicates atrial fibrillation; CIND, cognitive impairment no dementia; LA, left atrial; NCI, no cognitive impairment; TTE, transthoracic echocardiography; and VCI, vascular cognitive impairment.

Figure 3. Association of LA mechanical function with CeVD and cognitive impairment.

Among patients without atrial fibrillation from a memory clinic, reduced LA conduit strain was associated with more severe cognitive impairment, primarily of a vascular basis, affecting memory in particular. Both LA reservoir and conduit strain showed significant associations with increased presence and burden of cerebrovascular disease on neuroimaging. CeVD indicates cerebrovascular disease; CMB, cerebral microbleed; CMI, cerebral microinfarct; LA, left atrial; and WMH, white matter hyperintensities.