Reduced heart function might be associated with signs of preclinical brain aging, based on a review of data from the observational Framingham Heart Study.
Investigators led by Angela Jefferson, Ph.D., of Boston University found that cardiac output, adjusted for body size, was significantly associated with the rate of change in brain volume as the study participants aged. The findings were published online Aug. 4 in the journal Circulation.
Because initial research studies on the effects of cardiac output on brain aging were conducted on small samples of referred patients with clinical cardiovascular disease (CVD) and were not systematically adjusted for environmental risk factors known to contribute to both central nervous system and myocardial injury, Dr. Jefferson and her colleagues sought to determine if the relationship existed in patients who were free of clinical dementia or stroke. Based on previous findings from animal and clinical studies, they “hypothesized that MRI-assessed cardiac function is associated with cognitive and neuroimaging markers of preclinical Alzheimer’s disease and cerebrovascular disease.”
The investigators reviewed brain and heart MRI data from 1,504 adults aged 34-84 years, excluding individuals with a documented history of clinical stroke, transient ischemic attack, or dementia. The average age of the study group was 61 years, and 54% were women. In the ongoing study, participants are assessed every 4-8 years (Circulation 2010 Aug. 2 [doi:10.1161/circulationaha.109.905091]).
Low cardiac index (defined as less than 2.5 L/min per m2) was identified in 415 individuals (28%) after the exclusion of 112 individuals with prevalent cardiovascular disease.
The researchers found that for every one standard deviation increase in cardiac index, the total brain volume (measured as a percentage of total cranial volume) increased by 0.30%. Cardiac index also increased as lateral ventricular volume decreased, but this relationship was not significant when individuals with CVD were excluded.
In a post hoc analysis, the researchers compared cardiac index tertiles and changes in brain volume. They used the highest tertile as the referent, given that higher cardiac index values reflect healthier heart function.
Individuals in the middle tertile for cardiac index had an average total brain volume that was 0.35% less than that of those in the top tertile. Those in the bottom tertile had average total brain volume of 0.36% less than that of those in the top tertile. These changes corresponded to an average difference in brain aging of 1.9 years (a total brain volume decrease of 0.19% per 1-year increase in age).
Cardiac index as a continuous variable was not significantly related to any of the neuropsychological factor scores. But low executive function and information processing nearly reached statistical significance in association with low cardiac index.
The association between cardiac index and brain volume was significantly stronger among adults who were younger than 60 years, compared with older adults, and in men compared with women. However, the association was not significantly modified by apolipoprotein E e4 allele status.
The results were limited by the observational nature of the study, which cannot establish causality. However, the findings were consistent with the hypothesis that decreasing cardiac function is associated with accelerated brain aging, and suggest that low and low-normal cardiac index values might be related to brain health, as measured by brain volume, the investigators said.
In an accompanying editorial, Dr. Clinton B. Wright and Dr. Ralph L. Sacco of the department of neurology at the University of Miami noted that the cross-sectional nature of the study prevented the identification of a causal relationship, which means that brain volume differences might be due to normal aging or other underlying processes that could contribute to dementia. However, they pointed out that the fact that the relationship between brain volume and cardiac index was modified by younger age and male sex strengthens the results (Circulation 2010 Aug. 4 [doi:10.1161/circulationaha.110.970301]).
None of the investigators or editorialists had financial conflicts to disclose. The research was supported in part by grants from the National Heart, Lung and Blood Institute’s Framingham Heart Study.