title: Low cardiac index is associated with incident dementia and Alzheimer disease: the Framingham Heart Study.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  Lower cardiac index is associated with an increased risk for the development of dementia and AD.
authors.affiliation: From Vanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN (A.L.J.); Departments of Neurology (A.S.B., J.J.H., S.S., P.A.W., R.A.) and Medicine (E.J.B.), Boston University School of Medicine, Boston, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA (A.S.B., J.J.H., S.S., C.J.O., P.A.W., R.A., E.J.B.); Departments of Epidemiology (E.J.B.) and Biostatistics (A.S.B.), Boston University School of Public Health, Boston, MA; and Departments of Medicine (Cardiovascular Division) (W.J.M.) and Radiology (W.J.M.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. angela.jefferson@vanderbilt.edu.
authors.forename: Angela L
authors.initials: AL
authors.lastname: Jefferson
authors.affiliation: From Vanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN (A.L.J.); Departments of Neurology (A.S.B., J.J.H., S.S., P.A.W., R.A.) and Medicine (E.J.B.), Boston University School of Medicine, Boston, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA (A.S.B., J.J.H., S.S., C.J.O., P.A.W., R.A., E.J.B.); Departments of Epidemiology (E.J.B.) and Biostatistics (A.S.B.), Boston University School of Public Health, Boston, MA; and Departments of Medicine (Cardiovascular Division) (W.J.M.) and Radiology (W.J.M.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Alexa S
authors.initials: AS
authors.lastname: Beiser
authors.affiliation: From Vanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN (A.L.J.); Departments of Neurology (A.S.B., J.J.H., S.S., P.A.W., R.A.) and Medicine (E.J.B.), Boston University School of Medicine, Boston, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA (A.S.B., J.J.H., S.S., C.J.O., P.A.W., R.A., E.J.B.); Departments of Epidemiology (E.J.B.) and Biostatistics (A.S.B.), Boston University School of Public Health, Boston, MA; and Departments of Medicine (Cardiovascular Division) (W.J.M.) and Radiology (W.J.M.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Jayandra J
authors.initials: JJ
authors.lastname: Himali
authors.affiliation: From Vanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN (A.L.J.); Departments of Neurology (A.S.B., J.J.H., S.S., P.A.W., R.A.) and Medicine (E.J.B.), Boston University School of Medicine, Boston, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA (A.S.B., J.J.H., S.S., C.J.O., P.A.W., R.A., E.J.B.); Departments of Epidemiology (E.J.B.) and Biostatistics (A.S.B.), Boston University School of Public Health, Boston, MA; and Departments of Medicine (Cardiovascular Division) (W.J.M.) and Radiology (W.J.M.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
authors.affiliation: From Vanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN (A.L.J.); Departments of Neurology (A.S.B., J.J.H., S.S., P.A.W., R.A.) and Medicine (E.J.B.), Boston University School of Medicine, Boston, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA (A.S.B., J.J.H., S.S., C.J.O., P.A.W., R.A., E.J.B.); Departments of Epidemiology (E.J.B.) and Biostatistics (A.S.B.), Boston University School of Public Health, Boston, MA; and Departments of Medicine (Cardiovascular Division) (W.J.M.) and Radiology (W.J.M.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
authors.affiliation: From Vanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN (A.L.J.); Departments of Neurology (A.S.B., J.J.H., S.S., P.A.W., R.A.) and Medicine (E.J.B.), Boston University School of Medicine, Boston, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA (A.S.B., J.J.H., S.S., C.J.O., P.A.W., R.A., E.J.B.); Departments of Epidemiology (E.J.B.) and Biostatistics (A.S.B.), Boston University School of Public Health, Boston, MA; and Departments of Medicine (Cardiovascular Division) (W.J.M.) and Radiology (W.J.M.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Manning
authors.affiliation: From Vanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN (A.L.J.); Departments of Neurology (A.S.B., J.J.H., S.S., P.A.W., R.A.) and Medicine (E.J.B.), Boston University School of Medicine, Boston, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA (A.S.B., J.J.H., S.S., C.J.O., P.A.W., R.A., E.J.B.); Departments of Epidemiology (E.J.B.) and Biostatistics (A.S.B.), Boston University School of Public Health, Boston, MA; and Departments of Medicine (Cardiovascular Division) (W.J.M.) and Radiology (W.J.M.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Wolf
authors.affiliation: From Vanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN (A.L.J.); Departments of Neurology (A.S.B., J.J.H., S.S., P.A.W., R.A.) and Medicine (E.J.B.), Boston University School of Medicine, Boston, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA (A.S.B., J.J.H., S.S., C.J.O., P.A.W., R.A., E.J.B.); Departments of Epidemiology (E.J.B.) and Biostatistics (A.S.B.), Boston University School of Public Health, Boston, MA; and Departments of Medicine (Cardiovascular Division) (W.J.M.) and Radiology (W.J.M.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Rhoda
authors.initials: R
authors.lastname: Au
authors.affiliation: From Vanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN (A.L.J.); Departments of Neurology (A.S.B., J.J.H., S.S., P.A.W., R.A.) and Medicine (E.J.B.), Boston University School of Medicine, Boston, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA (A.S.B., J.J.H., S.S., C.J.O., P.A.W., R.A., E.J.B.); Departments of Epidemiology (E.J.B.) and Biostatistics (A.S.B.), Boston University School of Public Health, Boston, MA; and Departments of Medicine (Cardiovascular Division) (W.J.M.) and Radiology (W.J.M.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology*; D002303:Cardiac Output, Low / Q000150:complications*; D003430:Cross-Sectional Studies; D003704:Dementia / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008404:Massachusetts; D008875:Middle Aged; D012307:Risk Factors
keywords: Alzheimer disease; blood circulation; brain; cardiac output; dementia; hemodynamics