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

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 as...

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Main Authors: Eugene S. J. Tan, Saima Hilal, Siew Pang Chan, Ming Ann Sim, Mitchell K. P. Lai, Joyce Chong, Caroline Robert, Hazliza Hazli, Lingli Gong, Josephine Lunaria Berboso, Narayanaswamy Venketasubramanian, Boon‐Yeow Tan, A. Mark Richards, Christopher Chen, Lieng‐Hsi Ling
Format: Article
Language:English
Published: Wiley 2025-04-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.123.036931
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author Eugene S. J. Tan
Saima Hilal
Siew Pang Chan
Ming Ann Sim
Mitchell K. P. Lai
Joyce Chong
Caroline Robert
Hazliza Hazli
Lingli Gong
Josephine Lunaria Berboso
Narayanaswamy Venketasubramanian
Boon‐Yeow Tan
A. Mark Richards
Christopher Chen
Lieng‐Hsi Ling
author_facet Eugene S. J. Tan
Saima Hilal
Siew Pang Chan
Ming Ann Sim
Mitchell K. P. Lai
Joyce Chong
Caroline Robert
Hazliza Hazli
Lingli Gong
Josephine Lunaria Berboso
Narayanaswamy Venketasubramanian
Boon‐Yeow Tan
A. Mark Richards
Christopher Chen
Lieng‐Hsi Ling
author_sort Eugene S. J. Tan
collection DOAJ
description 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.
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spelling doaj-art-632d2b884cf04dd6a4e8c265b0e18d3d2025-08-20T03:47:44ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-04-0114810.1161/JAHA.123.036931Left Atrial Myocardial Mechanics: Association With Cognitive Dysfunction, Cerebrovascular Disease, and Circulating BiomarkersEugene S. J. Tan0Saima Hilal1Siew Pang Chan2Ming Ann Sim3Mitchell K. P. Lai4Joyce Chong5Caroline Robert6Hazliza Hazli7Lingli Gong8Josephine Lunaria Berboso9Narayanaswamy Venketasubramanian10Boon‐Yeow Tan11A. Mark Richards12Christopher Chen13Lieng‐Hsi Ling14National University Heart Centre Singapore SingaporeMemory Aging and Cognition Center National University Health System Singapore SingaporeYong Loo Lin School of Medicine National University of Singapore Singapore SingaporeYong Loo Lin School of Medicine National University of Singapore Singapore SingaporeMemory Aging and Cognition Center National University Health System Singapore SingaporeMemory Aging and Cognition Center National University Health System Singapore SingaporeYong Loo Lin School of Medicine National University of Singapore Singapore SingaporeNational University Heart Centre Singapore SingaporeYong Loo Lin School of Medicine National University of Singapore Singapore SingaporeYong Loo Lin School of Medicine National University of Singapore Singapore SingaporeRaffles Neuroscience Centre Singapore SingaporeSt. Luke’s Hospital Singapore SingaporeNational University Heart Centre Singapore SingaporeMemory Aging and Cognition Center National University Health System Singapore SingaporeNational University Heart Centre Singapore SingaporeBackground 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.https://www.ahajournals.org/doi/10.1161/JAHA.123.036931atrial fibrosisatrial straincerebrovascular diseasecognitive impairmentdementia
spellingShingle Eugene S. J. Tan
Saima Hilal
Siew Pang Chan
Ming Ann Sim
Mitchell K. P. Lai
Joyce Chong
Caroline Robert
Hazliza Hazli
Lingli Gong
Josephine Lunaria Berboso
Narayanaswamy Venketasubramanian
Boon‐Yeow Tan
A. Mark Richards
Christopher Chen
Lieng‐Hsi Ling
Left Atrial Myocardial Mechanics: Association With Cognitive Dysfunction, Cerebrovascular Disease, and Circulating Biomarkers
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
atrial fibrosis
atrial strain
cerebrovascular disease
cognitive impairment
dementia
title Left Atrial Myocardial Mechanics: Association With Cognitive Dysfunction, Cerebrovascular Disease, and Circulating Biomarkers
title_full Left Atrial Myocardial Mechanics: Association With Cognitive Dysfunction, Cerebrovascular Disease, and Circulating Biomarkers
title_fullStr Left Atrial Myocardial Mechanics: Association With Cognitive Dysfunction, Cerebrovascular Disease, and Circulating Biomarkers
title_full_unstemmed Left Atrial Myocardial Mechanics: Association With Cognitive Dysfunction, Cerebrovascular Disease, and Circulating Biomarkers
title_short Left Atrial Myocardial Mechanics: Association With Cognitive Dysfunction, Cerebrovascular Disease, and Circulating Biomarkers
title_sort left atrial myocardial mechanics association with cognitive dysfunction cerebrovascular disease and circulating biomarkers
topic atrial fibrosis
atrial strain
cerebrovascular disease
cognitive impairment
dementia
url https://www.ahajournals.org/doi/10.1161/JAHA.123.036931
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