Low Cardiac Index Is Associated With Incident Dementia and Alzheimer Disease: The Framingham Heart Study
Open accessAbstract
Background—: Cross-sectional epidemiological and clinical research suggests that lower cardiac index is associated with abnormal brain aging, including smaller brain volumes, increased white matter hyperintensities, and worse cognitive performances. Lower systemic blood flow may have implications for dementia among older adults. Methods and Results—: A total of 1039 Framingham Offspring Cohort participants free of clinical stroke, transient ischemic attack, and dementia formed our sample (age, 69±6 years; 53% women). Multivariable-adjusted proportional hazard models adjusting for Framingham Stroke Risk Profile score (age, sex, systolic blood pressure, antihypertensive medication, diabetes mellitus, cigarette smoking, cardiovascular disease history, atrial fibrillation), education, and apolipoprotein E4 status related cardiac magnetic resonance imaging–assessed cardiac index (cardiac output divided by body surface area) to incident all-cause dementia and Alzheimer disease (AD). Over the median 7.7-year follow-up period, 32 participants developed dementia, including 26 cases of AD. Each 1-SD unit decrease in cardiac index increased the relative risk of both dementia (hazard ratio [HR]=1.66; 95% confidence interval [CI], 1.11–2.47; P =0.013) and AD (HR=1.65; 95% CI, 1.07–2.54; P =0.022). Compared with individuals with normal cardiac index, individuals with clinically low cardiac index had a higher relative risk of dementia (HR=2.07; 95% CI, 1.02–4.19; P =0.044). If participants with clinically prevalent cardiovascular disease and atrial fibrillation were excluded (n=184), individuals with clinically low cardiac index had a higher relative risk of both dementia (HR=2.92; 95% CI, 1.34–6.36; P =0.007) and AD (HR=2.87; 95% CI, 1.21–6.80; P =0.016) compared with individuals with normal cardiac index. Conclusion—: Lower cardiac index is associated with an increased risk for the development of dementia and AD.
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Sensitivity analysis excluded participants with prevalent mild cognitive impairment to address reverse causality.
“To address the possibility of reverse causality from mild cognitive impairment affecting social relationships before diagnosis of dementia, sensitivity analysis was performed by excluding participants with prevalent mild cognitive impairment [34].”
From Associations between social relationship measures, serum brain-derived neurotrophic factor, and risk of stroke and dementia (2017) · cites this paper as [34]
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- Authors
- Jefferson, A. L., Beiser, A. S., Himali, J. J., Seshadri, S., O’Donnell, C. J., Manning, W. J., Wolf, P. A., Au, R., & Benjamin, E. J.
- Affiliations
- Boston University (US)
- ORCID
- Venue
- Circulation
- Published
- 2015-04-14
- Volume
- 131
- Issue
- 15
- Pages
- 1333-1339
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC4398627
- OpenAlex
- W2074874117
- Cited by
- 169
- References
- 51
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 6 · 2023: 18 · 2022: 15 · 2021: 14 · 2020: 19 · 2019: 14 · 2018: 16 · 2017: 16 · 2016: 21 · 2015: 4 · 2013: 1
- FWCI
- 15.41
- 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 (HL092577, AG028321, AG033040, AG031287, AG08122, AG030962, NS017950, HL070279, AG16495, IIRG-08-88733, AG033193)
- National Institutes of Health (n01hc25195-41-0-1)
- National Institute on Aging (AG034962, P30AG010129, AG-16495, K24AG046373, K23AG030962, R01AG031287, AG031287, AG030962, R01AG028321, AG08122, AG033193, R01AG033040, AG046373, R01AG016495, AG 033040, AG-028321, R01AG033193, R01AG008122, R01AG034962)
- National Heart, Lung, and Blood Institute (HC25195, HL111516, HL070279, R01HL070279, R01HL111516, N01-HC-025195, HL092577, R01HL092577)
- National Institute of Neurological Disorders and Stroke (NS017950, R01NS017950)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD083211)
- 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
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- cardiac output, dementia, Alzheimer's disease, incident dementia, brain aging, cerebral blood flow, cardiovascular disease, atrial fibrillation, Framingham Offspring cohort, older adults
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Cardiac Output, Low, Cross-Sectional Studies, Dementia, Female, Follow-Up Studies, Humans, Male, Massachusetts, Middle Aged, Risk Factors, Incidence
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