Wendy Wang1, Michael J Zhang2, Riccardo M Inciardi3, Faye L Norby4, Michelle C Johansen5, Romil Parikh1, Jeremy R Van't Hof2, Alvaro Alonso6, Elsayed Z Soliman7, Thomas H Mosley8, Rebecca F Gottesman5,9, Amil M Shah10, Scott D Solomon10, Lin Yee Chen2. 1. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis. 2. Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis. 3. Institute of Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy. 4. Center for Cardiac Arrest Prevention, Department of Cardiology, Cedars-Sinai Smidt Heart Institute, Los Angeles, California. 5. Department of Neurology, Johns Hopkins University, Baltimore, Maryland. 6. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia. 7. Epidemiological Cardiology Research Center, Cardiovascular Medicine Section, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina. 8. The MIND Center, University of Mississippi Medical Center, Jackson. 9. Stroke Branch, National Institute of Neurological Disorders and Stroke Intramural Research Program, Bethesda, Maryland. 10. Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
Abstract
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.
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.
Authors: Regina Sorrentino; Roberta Esposito; Ciro Santoro; Andrea Vaccaro; Sara Cocozza; Maria Scalamogna; Maria Lembo; Federica Luciano; Alessandro Santoro; Bruno Trimarco; Maurizio Galderisi Journal: J Am Soc Echocardiogr Date: 2019-10-13 Impact factor: 5.251
Authors: Manuel Martínez-Sellés; M Esther Martínez-Larrú; Martin Ibarrola; Alba Santos; Pablo Díez-Villanueva; Antoni Bayés-Genis; Adrian Baranchuk; Antonio Bayés-de-Luna; Roberto Elosua Journal: Int J Cardiol Date: 2020-08-15 Impact factor: 4.164
Authors: W D Rosamond; A R Folsom; L E Chambless; C H Wang; P G McGovern; G Howard; L S Copper; E Shahar Journal: Stroke Date: 1999-04 Impact factor: 7.914
Authors: A Alonso; T H Mosley; R F Gottesman; D Catellier; A R Sharrett; J Coresh Journal: J Neurol Neurosurg Psychiatry Date: 2009-08-19 Impact factor: 10.154
Authors: Melinda C Power; Erin E Bennett; Robert W Turner; N Maritza Dowling; Adam Ciarleglio; M Maria Glymour; Kan Z Gianattasio Journal: JAMA Neurol Date: 2021-03-01 Impact factor: 18.302
Authors: Michael J Zhang; Faye L Norby; Pamela L Lutsey; Thomas H Mosley; Rebecca J Cogswell; Suma H Konety; Tze-Fan Chao; Amil M Shah; Scott D Solomon; Alvaro Alonso; Lin Y Chen Journal: J Am Heart Assoc Date: 2019-11-26 Impact factor: 5.501
Authors: Michelle C Johansen; Wendy Wang; Michael Zhang; David S Knopman; Chiadi Ndumele; Thomas H Mosley; Elizabeth Selvin; Amil M Shah; Scott D Solomon; Rebecca F Gottesman; Lin Yee Chen Journal: J Am Heart Assoc Date: 2022-08-10 Impact factor: 6.106