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Research ArticleResearch Article: New Research, Integrative Systems

Differential Effects of Aging on Regional Corpus Callosum Microstructure and the Modifying Influence of Pulse Pressure

Jessica N. Kraft, Stephanie Matijevic, David A. Hoagey, Kristen M. Kennedy and Karen M. Rodrigue
eNeuro 6 May 2024, 11 (5) ENEURO.0449-23.2024; https://doi.org/10.1523/ENEURO.0449-23.2024
Jessica N. Kraft
1Center for Vital Longevity, Department of Psychology, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, Texas 75235
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  • ORCID record for Jessica N. Kraft
Stephanie Matijevic
1Center for Vital Longevity, Department of Psychology, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, Texas 75235
2Department of Psychology, University of Arizona, Tucson, Arizona 85721
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David A. Hoagey
1Center for Vital Longevity, Department of Psychology, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, Texas 75235
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Kristen M. Kennedy
1Center for Vital Longevity, Department of Psychology, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, Texas 75235
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Karen M. Rodrigue
1Center for Vital Longevity, Department of Psychology, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, Texas 75235
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Article Figures & Data

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  • Figure 1.
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    Figure 1.

    Example of callosal subregion ROI tracts registered to a subject’s native b0 image. Color represents each callosal subregion tract fiber.

  • Figure 2.
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    Figure 2.

    Effects of age on regional tract FA across the corpus callosum segments.

  • Figure 3.
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    Figure 3.

    Effects of age on regional tract RD across corpus callosum segments.

  • Figure 4.
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    Figure 4.

    Effects of age on regional tract AD across corpus callosum segments.

  • Figure 5.
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    Figure 5.

    Circular barplot depicting an anteroposterior gradient of vulnerability to age across CC subregion tracts. Bar heights indicate the age–diffusion correlation for each metric, in each CC segment. Significant differences in age–diffusion associations were tested using Steiger’s Z tests. These associations differed significantly for FA between the genu and splenium, the genu and isthmus, the anterior midbody and splenium, the anterior midbody and isthmus, the posterior midbody and splenium (Steiger’s Z p < 0.001), and the posterior midbody and isthmus (p < 0.05). A similar stepwise pattern was found for RD: between the genu and isthmus, genu and splenium, anterior midbody and isthmus, anterior midbody and splenium, posterior midbody and splenium (p’s < 0.001), genu and posterior midbody, and isthmus and splenium (p’s < 0.05). Although weaker, this pattern exists for AD: between the genu and the splenium, the genu and the posterior midbody, the anterior midbody and splenium (p’s < 0.001), between the genu and isthmus, anterior midbody and isthmus, and anterior midbody and splenium (p’s < 0.05).

  • Figure 6.
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    Figure 6.

    A significant association between pulse pressure and radial diffusivity, controlling for age. Radial diffusivity across the corpus callosum segments combined increases as a function of increasing pulse pressure, beyond the effects of age on RD.

  • Figure 7.
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    Figure 7.

    Age–pulse pressure interaction on CC axial diffusivity. A, Simple slope plots illustrating the effects of pulse pressure on AD are dependent on age, with significance in middle-aged and older adults, where increasing pulse pressure is associated with increased axial diffusivity in the corpus callosum. B, Johnson–Neyman interval plot suggests that the significance range of the interaction begins at approximately the age of 60 years.

Tables

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    Table 1.

    Sample demographics and blood pressure measurements

    Demographic characteristics
    Number of participants174
    Age, mean ± SD53.56 ± 18.90
    Sex N (Male/Female)72/102
    Years of education, mean ± SD15.50 ± 2.50
    MMSE, mean ± SD29.02 ± 0.85
    CESD, mean ± SD4.32 ± 3.79
    BMI, mean ± SD27.30 ± 5.13
    Smokers, N (%)7 (4.07%)
    High cholesterol, N (%)36 (20.93%)
    Hypertensives, N (%)38 (21.84%)
    Systolic BP, mean ± SD126.37 ± 16.54
    Diastolic BP, mean ± SD75.26 ± 9.54
    Heart rate, mean ± SD68.43 ± 9.84
    Pulse pressure, mean ± SD51.11 ± 12.06
    Mean arterial BP, mean ± SD92.29 ± 10.93
    • MMSE, Mini-Mental Status Exam; CESD, Center for Epidemiological Studies Depression Scale; BMI, body mass index; BP, blood pressure.

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    Table 2.

    Regression model for age

    MetricPredictordf, dferrorSSFp
    FABetween subjects
     Age1, 1710.34777.867<0.001***
    Within subjects
     Subregion4, 6841.395476.799<0.001***
     Subregion x age4, 6840.04615.577<0.001***
    RDBetween subjects
     Age1, 1711.123105.901<0.001***
    Within subjects
     Subregion4, 6842.217395.324<0.001***
     Subregion x age4, 6840.12922.963<0.001***
    ADBetween subjects
     Age1, 1710.21510.2390.002**
    Within subjects
     Subregion4, 6841.970159.027<0.001***
     Subregion x age4, 6840.0725.818<0.001***
    • df, degrees of freedom; SS, sum of squares; FA, fractional anisotropy; RD, radial diffusivity; AD, axial diffusivity.

    • *p < 0.05, **p < 0.01, ***p < 0.001.

    • View popup
    Table 3.

    Associations between age and DTI metrics within CC segment tracts

    SegmentFARDAD
    Mean ± SDrMean ± SDrMean ± SDr
    Genu0.63 ± 0.04−0.628**0.49 ± 0.060.694**1.56 ± 0.070.387**
    Anterior Midbody0.63 ± 0.04−0.612**0.50 ± 0.070.677**1.60 ± 0.070.359**
    Posterior Midbody0.65 ± 0.05−0.515**0.48 ± 0.070.561**1.64 ± 0.090.136
    Isthmus0.63 ± 0.06−0.327**0.52 ± 0.090.405**1.69 ± 0.090.150*
    Splenium0.73 ± 0.03−0.232**0.38 ± 0.040.336**1.67 ± 0.100.023
    • Pearson’s correlations, *p < 0.05, **p < 0.01.

    • View popup
    Table 4.

    Regression model for age and pulse pressure

    MetricPredictordf, dferrorSSFp
    FABetween subjects
     Age1, 1700.16136.246<0.001***
     Pulse pressure1, 1700.0071.5520.215
    Within subjects
     Subregion4, 6801.395477.463<0.001***
     Subregion x age4, 6800.0248.312<0.001***
     Subregion x pulse pressure4, 6800.0041.2250.299
    RDBetween subjects
     Age1, 1700.45043.503<0.001***
     Pulse pressure1, 1700.0525.0490.026*
    Within subjects
     Subregion4, 6802.217395.128<0.001***
     Subregion x age4, 6800.06611.761<0.001***
     Subregion x pulse pressure4, 6800.0050.8930.433
    ADBetween subjects
     Age1, 1690.0391.9900.160
     Pulse pressure1, 1690.0201.0440.308
     Age x pulse pressure1, 1690.1879.6620.002*
    Within subjects
     Subregion4, 6761.299104.052<0.001***
     Subregion x age4, 6760.0262.0760.082
     Subregion x pulse pressure4, 6760.0060.5060.672
     Subregion x age x pulse pressure4, 6760.0010.0720.991
    • df, degrees of freedom; SS, sum of squares; FA, fractional anisotropy; RD, radial diffusivity; AD, axial diffusivity.

    • ↵* p < 0.05, **p < 0.01, ***p < 0.001.

    • View popup
    Table 5.

    Regression model for age and hypertension

    MetricPredictordf, dferrorSSFp
    FABetween subjects
     Age1, 1700.22350.505<0.001***
     Hypertension status1, 1700.0102.1500.144
    Within subjects
     Subregion4, 6800.739253.190<0.001***
     Subregion–age4, 6800.0269.074<0.001***
     Subregion–hypertension status4, 6800.0041.3280.258
    RDBetween subjects
     Age1, 1700.72469.037<0.001***
     Hypertension status1, 1700.0312.9190.089
    Within subjects
     Subregion4, 6801.162207.338<0.001***
     Subregion–age4, 6800.08314.868<0.001***
     Subregion–hypertension status4, 6800.0071.1710.318
    ADBetween subjects
     Age1, 1700.1044.9770.027*
     Hypertension status1, 1700.0331.5720.212
    Within subjects
     Subregion4, 6801.05384.801<0.001***
     Subregion–age4, 6800.0685.5060.001**
     Subregion–hypertension status4, 6800.0080.6580.621
    • df, degrees of freedom; SS, sum of squares; FA, fractional anisotropy; RD, radial diffusivity; AD, axial diffusivity.

    • ↵* p < 0.05, **p < 0.01, ***p < 0.001.

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Differential Effects of Aging on Regional Corpus Callosum Microstructure and the Modifying Influence of Pulse Pressure
Jessica N. Kraft, Stephanie Matijevic, David A. Hoagey, Kristen M. Kennedy, Karen M. Rodrigue
eNeuro 6 May 2024, 11 (5) ENEURO.0449-23.2024; DOI: 10.1523/ENEURO.0449-23.2024

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Differential Effects of Aging on Regional Corpus Callosum Microstructure and the Modifying Influence of Pulse Pressure
Jessica N. Kraft, Stephanie Matijevic, David A. Hoagey, Kristen M. Kennedy, Karen M. Rodrigue
eNeuro 6 May 2024, 11 (5) ENEURO.0449-23.2024; DOI: 10.1523/ENEURO.0449-23.2024
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Keywords

  • aging
  • corpus callosum
  • diffusion imaging
  • pulse pressure
  • vascular risk
  • white matter

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