Association of Echocardiographic Measures of Left Atrial Function and Size with Incident Dementia

Wendy Wang, Michael J Zhang, Riccardo M. Inciardi, Faye L. Norby, Michelle C. Johansen, Romil Parikh, Jeremy R. Van't Hof, Alvaro Alonso, Elsayed Z. Soliman, Thomas H. Mosley, Rebecca F. Gottesman, Amil M. Shah, Scott D. Solomon, Lin Yee Chen

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Importance: Atrial myopathy-characterized by alterations in left atrial (LA) function and size-is associated with ischemic stroke, independent of atrial fibrillation (AF). Electrocardiographic markers of atrial myopathy are associated with dementia, but it is unclear whether 2-dimensional echocardiographic (2DE)-defined LA function and size are associated with dementia. Objective: To examine the association of LA function and size with incident dementia. Design, Setting, and Participants: The Atherosclerosis Risk in Communities (ARIC) study is a community-based prospective cohort. An exploratory, retrospective analysis was conducted. ARIC centers are located in Forsyth County, North Carolina; Jackson, Mississippi; Washington County, Maryland; and suburban Minneapolis, Minnesota. For this analysis, visit 5 (2011-2013) served as the baseline. Participants without prevalent AF and stroke and who had 2DEs in 2011-2013 were included and surveilled through December 31, 2019. Exposures: LA function (reservoir strain, conduit strain, contractile strain, emptying fraction, passive emptying fraction, and active emptying fraction), and LA size (maximal and minimal volume index) as evaluated by 2DE. Main Outcomes and Measures: Dementia cases were identified using in-person and phone cognitive assessments, hospitalization codes, and death certificates. Cox proportional hazards models were used. Results: Among 4096 participants (mean [SD] age, 75 [5] years; 60% women; 22% Black individuals), 531 dementia cases were ascertained over a median follow-up of 6 years. Dementia incidence for the lowest LA quintile was 4.80 for reservoir strain, 3.94 for conduit strain, 3.29 for contractile strain, 4.20 for emptying fraction, 3.67 for passive emptying fraction, and 3.27 for active emptying fraction per 100 person-years. After full-model adjustments, there were statistically significant associations between measures of LA function and dementia; the hazard ratios (HRs) from the lowest vs highest quintile for reservoir strain were 1.98 (95% CI, 1.42-2.75); for conduit strain, 1.50 (95% CI, 1.09-2.06); for contractile strain, 1.57 (95% CI, 1.16-2.14); for emptying fraction, 1.87 (95% CI, 1.31-2.65); and for active emptying fraction, 1.43 (95% CI, 1.04-1.96). LA passive emptying fraction was not significantly associated with dementia (HR, 1.26 [95% CI, 0.93-1.71]). Dementia incidence for the highest LA maximal volume index quintile was 3.18 per 100 person-years (HR for highest vs lowest quintile, 0.77 [95% CI, 0.58-1.02]) and for the highest minimal volume index quintile was 3.50 per 100 person-years (HR for the highest vs lowest quintile, 0.95 [95% CI, 0.71-1.28]). Both measures were not significantly associated with dementia. These findings were robust to sensitivity analyses that excluded participants with incident AF or stroke. Conclusions and Relevance: In this exploratory analysis of a US community-based cohort, several echocardiographic measures of lower LA function were significantly associated with an increased risk of subsequent dementia. Measures of LA size were not significantly associated with dementia risk. These findings suggest that impaired LA function may be a risk factor associated with dementia.

Original languageEnglish (US)
Pages (from-to)1138-1148
Number of pages11
Issue number12
StatePublished - Mar 22 2022

Bibliographical note

Funding Information:
Communities study has been funded in whole or in part by grants HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, and HHSN268201700004I from the NHLBI; neurocognitive data collection by grants U01 2U01HL096812, 2U01HL096814, 2U01HL096899, 2U01HL096902, and 2U01HL096917 from the NHLBI, NINDS, National Institute on Aging (NIA), and National Institute on Deafness and Other Communication Disorders; R01-HL70825 for previous brain magnetic resonance imaging examinations from the NHLBI; T32GM132063 from the National Institute of General Medical Sciences (Wang); P30AG066511 from the NIA and K24HL148521 from the NHLBI (Alonso); R01HL126637, R01HL141288, and K24HL155813 from the NHLBI (Chen); and R01HL135008, R01HL143224, R01HL150342, R01HL148218, K24HL152008 from the NHLBI (Shah).

Funding Information:
receiving grants from the American Heart Association during the conduct of the study. Dr Mosley reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study. Dr Gottesman reported receiving grants from the NIH and serving as an associate editor of Neurology. Dr Shah reported receiving grants from Philips Ultrasound and Novartis, both to Brigham and Women’s Hospital; serving on the advisory boards of Philips Ultrasound and Janssen and as a consultant to Edwards Life Sciences. Dr Solomon reported receiving grants to his institution from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lilly, Mesoblast, MyoKardia, National Heart, Lung, and Blood Institute (NHLBI), Neurotronik, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI, outside scope of manuscript and serving as a consultant to Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi Sankyo, GlaxoSmithKline, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and PureHealth, outside the submitted work. No other disclosures were reported.

Publisher Copyright:
© 2022 American Medical Association. All rights reserved.


  • Aged
  • Aged, 80 and over
  • Atrial Function, Left
  • Dementia/diagnostic imaging
  • Echocardiography
  • Female
  • Heart Atria/anatomy & histology
  • Humans
  • Incidence
  • Male
  • Organ Size
  • Retrospective Studies

PubMed: MeSH publication types

  • Journal Article


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