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Cardiorespiratory capacity correlates with cerebral blood flow, white matter hyperintensities, and cognition in preclinical Alzheimer's disease

  • Elizabeth A. Boots
    Affiliations
    Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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  • Stephanie A. Schultz
    Affiliations
    Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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  • Jennifer M. Oh
    Affiliations
    Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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  • Ryan J. Dougherty
    Affiliations
    University of Wisconsin-Madison, Madison, WI, USA
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  • Dorothy Farrar Edwards
    Affiliations
    Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    University of Wisconsin-Madison, Madison, WI, USA

    Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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  • Jean A. Einerson
    Affiliations
    University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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  • Claudia E. Korcarz
    Affiliations
    University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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  • Howard A. Rowley
    Affiliations
    University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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  • Barbara B. Bendlin
    Affiliations
    Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison, WI, USA
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  • Sanjay Asthana
    Affiliations
    Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison, WI, USA
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  • Mark A. Sager
    Affiliations
    Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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  • Bruce P. Hermann
    Affiliations
    Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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  • Sterling C. Johnson
    Affiliations
    Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison, WI, USA
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  • James H. Stein
    Affiliations
    University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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  • Dane B. Cook
    Affiliations
    University of Wisconsin-Madison, Madison, WI, USA
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  • Ozioma C. Okonkwo
    Affiliations
    Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison, WI, USA
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      Background

      Cerebral hypoperfusion and white matter hyperintensities (WMHs), indicators of poor vascular health, are often observed in Alzheimer’s disease (AD). Physical fitness improves vascular health and is protective against AD, yet little research has examined the influence of fitness on cerebral blood flow (CBF) and WMHs in individuals at-risk for AD. Therefore, the objective of this study was to determine whether cardiorespiratory capacity is associated with increased CBF in AD-related brain regions, decreased WMHs, and better cognitive performance in a middle-aged cohort at-risk for AD.

      Methods

      105 cognitively-healthy adults from the Wisconsin Registry for Alzheimer’s Prevention (age=64.06±5.90 years) participated in this study. Participants performed graded treadmill exercise testing, and peak oxygen consumption (VO2peak, ml/kg/min) was used as the index for cardiorespiratory capacity. Participants underwent comprehensive cognitive testing, T1-weighted and T2 FLAIR structural MRI scanning, and CBF assessments using pseudocontinuous ASL. CBF values were sampled from regions implicated in AD using the Alzheimer’s Disease Neuroimaging Initiative FDG Meta-ROI suite that includes the left and right angular and temporal gyri, posterior cingulate, and a composite ROI. Total WMHs were quantified using Lesion Segmentation Toolbox, and adjusted for intracranial volume in analyses. Linear regression, adjusted for relevant covariates, was used to examine relationships between VO2peak, CBF, WMHs, and cognition.

      Results

      Higher VO2peak was associated with greater CBF in the left (p=.047) and right (p=.006) angular gyri, right temporal cortex (p=.019), and the composite ROI (p=.011). VO2peak was also associated with better cognitive performance in Speed & Flexibility (p=.020), a composite measure consisting of Trails A&B and the Stroop Color-Word Test Interference Trial. VO2peak was not associated with WMHs (p=.931), however VO2peak did modify the association between age and WMHs such that more fit individuals had fewer WMHs with increasing age compared to their less fit peers (p=.046; Figure).

      Conclusions

      Higher cardiorespiratory capacity is associated with greater CBF in key AD brain regions, better executive function, and modifies the relationship between age and WMH burden in a cohort at-risk for AD. This suggests that participation in regular exercise may increase brain vascular health and cognitive function, thereby decreasing future risk for AD.
      Figure thumbnail fx1
      FigureHigh cardiorespiratory capacity modifies the detrimental effects of age on white matter lesion burden.
      Adjusted means and standard errors are displayed from the analysis modeling total white matter lesion volume as a function of age, sex, peak effort attainment, intracranial volume, VO2peak, and a VO2peak*age interaction. The V02peak*age interaction term was the effect of primary interest.
      VO2peak and age were included as continuous variables in the analysis, but for graphing purposes we chose two anchor points (i.e., ± 1 SD) to represent Low vs. High VO2peak and Young vs. Old age.
      VO2peak = peak oxygen consumption (ml/kg/min).