Lower left atrial function associated with higher risk for dementia

Echocardiographic measures of lower left atrial function were significantly associated with an increased risk of subsequent dementia, experts reported in JAMA.

“Although the evidence linking atrial myopathy to adverse cardiovascular outcomes is compelling, less is known about the association of atrial myopathy with dementia,” Wendy Wang, MPH, a research assistant at the University of Minnesota School of Public Health, and colleagues wrote.

To assess whether a correlation exists between left atrial function and size and dementia, Wang and colleagues conducted an exploratory, retrospective analysis of a four-state Atherosclerosis Risk in Communities cohort study. Participants without prevalent atrial fibrillation and stroke and who underwent two-dimensional echocardiograms between 2011 and 2013 (considered baseline for the study) were monitored through Dec. 31, 2019.

A total of 4,096 participants were included (mean age, 75 years; 60% women; 22% Black), and over the 6-year median follow-up period, 531 dementia cases were identified.

For all left atrial function measures, the incidence of dementia was highest in the lowest quintile: 4.8, reservoir strain; 3.94, conduit strain; 3.29, contractile strain; 4.2, emptying fraction; 3.67, passive emptying fraction; and 3.27, active emptying fraction per 100 person-years.

Following full-model adjustments, there were significant associations between the highest and lowest quintiles for measures of left atrial function and dementia, including reservoir strain (HR = 1.98; 95% CI, 1.42-2.75), conduit strain (HR = 1.5; 95% CI, 1.09-2.06), contractile strain (HR = 1.57; 95% CI, 1.16-2.14), emptying fraction (HR = 1.87; 95% CI, 1.31-2.65) and active emptying fraction (HR = 1.43; 95% CI, 1.04-1.96). Passive emptying fraction was not associated with dementia, the authors noted (HR = 1.26; 95% CI, 0.93-1.71).

Left atrial size was not significantly associated with incident dementia, after full-model adjustment comparing the highest and lowest quintiles of maximal left atrial volume index (HR = 0.77; 95% CI, 0.58-1.02) and minimal volume index (HR = 0.95; 95% CI, 0.71-1.28).

Dementia incidence for the highest maximal volume index quintile was 3.18 per 100 person-years and 3.5 per 100 person-years for the highest minimal volume index. Both measures were not associated with dementia.

“To our knowledge, this is the first study to report an independent association between echocardiographic measures of [left atrial] function with dementia,” the authors wrote. “By interrogating a comprehensive set of [left atrial] function measures — quantified by speckle tracking and volumetric analysis — this study advances the field by linking [left atrial] function measures to dementia risk for the first time.”

In related editorial, Shyam Prabhakaran, MD, MS, of the department of neurology at the University of Chicago, and Philip Greenland, MD, of the department of preventative medicine at Northwestern University, state that Wang and colleagues’ study “introduces some interesting concepts regarding the mechanisms by which atrial myopathy, however defined, may contribute to dementia risk.”

Prabhakaran and Greenland wrote that although Wang and colleagues used echocardiographic measures, there are more advanced imaging tools available to assess left atrial flow patterns and areas of atrial blood stasis.

“Given the exploratory nature of the study findings, prospective validation in other cohorts is clearly necessary,” Prabhakaran and Greenland wrote. “In addition to identification of the precise biomarkers of atrial myopathy, randomized clinical trials testing treatments in patients with atrial myopathy could further establish a causal effect on dementia.”

References:

Prabhakaran S, Greenland P. JAMA. 2022;doi:10.1001/jama.2022.2374.

Wang W, et al. JAMA. 2022;doi:10.1001/jama.2022.2518.