Cardiac Index Is Associated With Brain Aging: The Framingham Heart Study
Open accessAbstract
Background— Cardiac dysfunction is associated with neuroanatomic and neuropsychological changes in aging adults with prevalent cardiovascular disease, theoretically because systemic hypoperfusion disrupts cerebral perfusion, contributing to subclinical brain injury. We hypothesized that cardiac function, as measured by cardiac index, would be associated with preclinical brain magnetic resonance imaging (MRI) and neuropsychological markers of ischemia and Alzheimer disease in the community. Methods and Results— Brain MRI, cardiac MRI, neuropsychological, and laboratory data were collected on 1504 Framingham Offspring Cohort participants free of clinical stroke, transient ischemic attack, or dementia (age, 61±9 years; 54% women). Neuropsychological and brain MRI variables were related to cardiac MRI–assessed cardiac index (cardiac output/body surface area). In multivariable-adjusted models, cardiac index was positively related to total brain volume ( P =0.03) and information processing speed ( P =0.02) and inversely related to lateral ventricular volume ( P =0.048). When participants with clinically prevalent cardiovascular disease were excluded, the relation between cardiac index and total brain volume remained ( P =0.02). Post hoc comparisons revealed that participants in the bottom cardiac index tertile (values <2.54) and middle cardiac index tertile (values between 2.54 and 2.92) had significantly lower brain volumes ( P =0.04) than participants in the top cardiac index tertile (values >2.92). Conclusions— Although observational data cannot establish causality, our findings are consistent with the hypothesis that decreasing cardiac function, even at normal cardiac index levels, is associated with accelerated brain aging.
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Reduced cardiac output is associated with executive dysfunction (mainly sequencing and planning difficulties) and regional WMLs adjacent to subcortical nuclei.
“Specifically, reduced cardiac output has been associated with executive dysfunction (mainly sequencing and planning difficulties)381 and regional WMLs adjacent to the subcortical nuclei.382”
From Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association (2011) · cites this paper as [382]
The Discussion reports that, among older adults with cardiovascular disease, reduced cardiac output was associated with executive dysfunction and white matter hyperintensities. It does not specify sequencing or planning difficulties, or locate the lesions adjacent to subcortical nuclei. The paper’s own Results found only a borderline association with a combined executive-function/information-processing score. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn the Framingham Heart Study sample of more than 1500 participants, higher levels of cardiac output were associated with increased cognitive processing speed in older adulthood.
“In the Framingham Heart Study sample of more than 1500 participants (Jefferson et al., 2010), higher levels of cardiac output, one of the primary cardiovascular determinants of challenge states, was associated with increased cognitive processing speed in older adulthood.”
From More than a feeling: A unified view of stress measurement for population science (2018) · cites this paper as Jefferson et al., 2010
The Abstract’s Methods and Results section identifies 1,504 Framingham participants, and the Results link low cardiac index to poorer performance on a processing-speed test. But the Results also state that cardiac index as a continuous measure was unrelated to neuropsychological factor scores; the reported finding concerns a low cardiac-index cutoff, not a general association between higher cardiac output and faster processing in older adults. (LLM, conf=0.88)
Experimental — accuracy not yet measured
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- Authors
- Jefferson, A. L., Himali, J. J., Beiser, A. S., Au, R., Massaro, J. M., Seshadri, S., Gona, P., Salton, C. J., DeCarli, C., O'Donnell, C. J., Benjamin, E. J., Wolf, P. A., & Manning, W. J.
- Affiliations
- Boston University (US)
- From the Department of Neurology (A.L.J., J.J.H., A.S.B., R.A., S.S., P.A.W.), Alzheimer’s Disease Center (A.L.J., S.S.), Whitaker Cardiovascular Institute (A.L.J., E.J.B.), and Department of Medicine (A.L.J., E.J.B.), Boston University School of Medicine, Boston, Mass; Department of Biostatistics, Boston University School of Public Health, Boston, Mass (J.J.H., A.S.B., J.M.M., P.G.); National Heart, Lung and Blood Institute’s Framingham Heart Study, Framingham, Mass (J.J.H., A.S.B., R.A., J.M.M., S...
- ORCID
- Venue
- Circulation
- Published
- 2010-08-17
- Volume
- 122
- Issue
- 7
- Pages
- 690-697
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC2929763
- OpenAlex
- W2121884189
- Cited by
- 256
- References
- 47
- Citations by year
- 2026: 15 · 2025: 17 · 2024: 12 · 2023: 12 · 2022: 15 · 2021: 20 · 2020: 16 · 2019: 17 · 2018: 14 · 2017: 16 · 2016: 15 · 2015: 15 · 2014: 16 · 2013: 18 · 2012: 12
- FWCI
- 12.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Alzheimer's Association
- National Institutes of Health (n01hc25195-41-0-1)
- National Institute on Aging (AG021028, P30AG010129, AG-16495, K23AG030962, R01AG021028, R01AG031287, AG031287, AG030962, R01AG028321, AG010129, AG08122, AG033193, R01AG033040, AG027480, R01AG016495, AG 033040, P30AG013846, AG-028321, R03AG027480, R01AG033193, R01AG008122)
- National Heart, Lung, and Blood Institute (HL-076784, HC25195, HL070279, R01HL070279, N01-HC-025195, R01HL076784)
- National Institute of Neurological Disorders and Stroke (NS017950, R01NS017950)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- cardiac index, brain aging, cardiac output, cerebral hypoperfusion, total brain volume, lateral ventricular volume, processing speed, cardiovascular disease, Alzheimer's disease, ischemia, Framingham Offspring cohort, cardiac MRI, brain MRI
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Brain, Cardiovascular Diseases, Cross-Sectional Studies, Female, Health Status Indicators, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Cohort Studies
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