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By Kristina Fiore, Staff Writer, MedPage Today
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

Left ventricular ejection fraction (LVEF) may play a role in cognitive aging, but that role is not a simple matter of impaired LVEF, researchers found.

Patients in lowest quartile of LVEF performed significantly worse on several cognitive tests than patients in middle quintiles, but there was no linear association since U-shaped curves also showing an association between the highest LVEF levels and cognitive aging, Angela Jefferson, PhD, of Boston University, and colleagues reported online in the American Journal of Cardiology.

Jefferson and colleagues called these findings "unexpected."

Heart failure is a known risk factor for Alzheimer's disease and cerebrovascular disease. But even in the absence of end-stage heart disease, it's thought that LVEF may have an affect on brain aging.

To test their hypothesis that lower LVEF was associated with cognitive and neuroimaging markers of preclinical Alzheimer's disease, Jefferson and colleagues looked at data from the Framingham Offspring Study, an offshoot of the Heart study.

They analyzed brain MRI and cardiac MRI studies as well as the results of neuropsychological examinations for 1,114 patients -- mean age 67 -- who didn't have stroke or dementia.

Multivariate analyses revealed overall that LVEF wasn't associated with any brain variable.

However, there were several U-shaped associations when LVEF levels were separated into quintiles.

Patients in the first quintile, or those with the lowest LVEF values, had lower mean cognitive performance on several cognitive tests, including the Visual Reproduction Delayed Recall and the Hooper Visual Organization Test, compared with patients in the middle quintiles (P<0.001 for both).

But the researchers noted that there were no differences among groups on any of the brain MRI variables.

Unexpectedly, they said, patients in the highest quintile of LVEF values also had lower mean performance on cognitive tests, including the Logical Memory Delayed Recall (P=0.03), the Visual Reproduction Delayed Recall (P=0.03), the Trail Making Test (P=0.02), and the Hooper Visual Organization Test (P=0.02).

Jefferson and colleagues reported that the associations were similar even after excluding prevalent cardiovascular disease.

"The observation that a lower LVEF is associated with abnormal brain changes extends previous research examining patients with severe cardiomyopathies, which reported that a reduced LVEF was associated with memory, reasoning, and sequencing impairments," they wrote.

"While healthy LVEFs may be good for brain health, very high LVEFs may correspond to subtle cognitive impairment," they wrote, adding that the finding may also be a sign of another pathologic process such as anemia or thyroid disease.

The study was limited by its use of observational, cross-sectional data, which cannot establish causality. The study may also be limited in generalizability, because the cohort was predominantly white and middle-aged to elderly.

Still, they concluded that "in the absence of clinical heart failure and prevalent cardiovascular disease, our findings suggest that lower LVEFs are also related to abnormal brain aging."