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Lower cardiac output is associated with neurodegeneration among older adults with normal cognition but not mild cognitive impairment

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Abstract

Subclinical cardiac dysfunction is associated with smaller total brain volume on magnetic resonance imaging (MRI). To study whether cardiac output relates to regional measurements of grey and white matter structure, older adults (n = 326) underwent echocardiogram to quantify cardiac output (L/min) and brain MRI. Linear regressions related cardiac output to grey matter volumes measured on T1 and white matter hyperintensities assessed on T2-FLAIR. Voxelwise analyses related cardiac output to diffusion tensor imaging adjusting for demographic, genetic, and vascular risk factors. Follow-up models assessed a cardiac output x diagnosis interaction with stratification (normal cognition, mild cognitive impairment). Cardiac output interacted with diagnosis, such that lower cardiac output related to smaller total grey matter (p = 0.01), frontal lobe (p = 0.01), and occipital lobe volumes (p = 0.01) among participants with normal cognition. When excluding participants with cardiovascular disease and atrial fibrillation, associations emerged with smaller parietal lobe (p = 0.005) and hippocampal volume (p = 0.05). Subtle age-related cardiac changes may disrupt neuronal homeostasis and impact grey matter integrity prior to cognitive impairment.

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Abbreviations

AD:

Alzheimer’s disease

APOE:

Apolipoprotein E

CBF:

Cerebral blood flow

CSF:

Cerebrospinal fluid

CVD:

Cardiovascular disease

DTI:

Diffusion tensor imaging

eMCI:

Early mild cognitive impairment

FLAIR:

Fluid attenuated inversion recovery

FSL:

FMRIB Software Library

FSRP:

Framingham Stroke Risk Profile

LVH:

Left ventricular hypertrophy

MCI:

Mild cognitive impairment

MNI:

Montreal Neurological Institute

MRI:

Magnetic resonance imaging

NC:

Normal cognition

ROI:

Region of interest

VMAP:

Vanderbilt Memory & Aging Project

WMH:

White matter hyperintensities

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Acknowledgments

The authors would like to thank the dedicated Vanderbilt Memory & Aging Project participants, their loved ones, and the devoted staff and trainees who contributed to recruitment, screening, and enrollment of the baseline cohort.

Funding

This research was supported by the Vanderbilt Alzheimer's Disease Research Center (P20-AG068082 [ALJ]), Alzheimer’s Association (IIRG-08-88733 [ALJ]), the National Institutes of Health (R01-AG034962 [ALJ], R01-AG056534 [ALJ], R01-NS100980 [ALJ], K24-AG046373 [ALJ], Paul B. Beeson Career Development Award in Aging K23-AG045966 [KAG], K01-AG049164 [TJH], K12-HL109019 [DKG], K23-HL128928 [DKG], F30-AG064847 [EEM], T32-GM007347 [EEM], F31-AG066358 (CWB), T32-AG058524 (CWB) UL1-TR000445, and S10-OD023680), and the Vanderbilt Memory & Alzheimer’s Center.

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Authors and Affiliations

  1. Vanderbilt Memory & Alzheimer’s Center, Vanderbilt University Medical Center, 1207 17th Avenue South, Suite 204, Nashville, TN, 37212, USA

    Elizabeth E. Moore, Dandan Liu, Corey W. Bown, Hailey A. Kresge, Kimberly R. Pechman, L. Taylor Davis, Katherine A. Gifford, Timothy J. Hohman & Angela L. Jefferson

  2. Medical Scientist Training Program, School of Medicine, Vanderbilt University, Nashville, TN, USA

    Elizabeth E. Moore

  3. Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA

    Dandan Liu

  4. Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    Deepak K. Gupta, Lisa A. Mendes, Thomas J. Wang & Angela L. Jefferson

  5. Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA

    Kimberly R. Pechman, Katherine A. Gifford, Timothy J. Hohman & Angela L. Jefferson

  6. Department of Radiology & Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA

    L. Taylor Davis & Bennett A. Landman

  7. Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA

    Adam W. Anderson & Bennett A. Landman

  8. Department of Electrical Engineering and Computer Science, Vanderbilt University, Nashville, TN, USA

    Bennett A. Landman

Authors
  1. Elizabeth E. Moore
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  2. Dandan Liu
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  14. Angela L. Jefferson
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Contributions

Author contributions included conception and study design (EEM, ALJ, KAG, and TJH), data collection or acquisition (EEM, CWB, HAK, DKG, KRP, LAM, LTD, AWA, TJW, and BAL), statistical analysis (DL, TJH, and ALJ), interpretation of results (EEM, CWB, HAK, TJH, and ALJ), drafting the manuscript work or revising it critically for important intellectual content (EEM and ALJ) and approval of final version to be published and agreement to be accountable for the integrity and accuracy of all aspects of the work (All authors).

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Correspondence to Angela L. Jefferson.

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Moore, E.E., Liu, D., Bown, C.W. et al. Lower cardiac output is associated with neurodegeneration among older adults with normal cognition but not mild cognitive impairment. Brain Imaging and Behavior 15, 2040–2050 (2021). https://doi.org/10.1007/s11682-020-00398-0

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