Mild Cognitive Impairment is Associated With White Matter Integrity Changes in Late-Myelinating Regions Within the Corpus Callosum

Stricker, Nikki H.; Salat, David H.; Kuhn, Taylor; Foley, Jessica; Price, J. Waide; Westlye, Lars T.; Esterman, Michael; McGlinchey, Regina E.; Milberg, William; Leritz, Elizabeth C.

doi:10.1177/1533317515578257

Cited by 19 publications

(21 citation statements)

References 77 publications

(227 reference statements)

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“…In line with this model, Stricker et al . found reduced FA in late-myelinating regions within the corpus callosum and in the body of the corpus callosum in MCI compared to healthy elderly controls36. Our finding of greater FA reductions and RD increases in AD in the genu of the corpus callosum as compared to the splenium (may be seen in Fig.…”

Section: Discussionsupporting

confidence: 58%

Dissociable diffusion MRI patterns of white matter microstructure and connectivity in Alzheimer’s disease spectrum

Doan

Engvig

Persson

et al. 2017

Sci Rep

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Recent efforts using diffusion tensor imaging (DTI) have documented white matter (WM) alterations in Alzheimer’s disease (AD). The full potential of whole-brain DTI, however, has not been fully exploited as studies have focused on individual microstructural indices independently. In patients with AD (n = 79), mild (MCI, n = 55) and subjective (SCI, n = 30) cognitive impairment, we applied linked independent component analysis (LICA) to model inter-subject variability across five complementary DTI measures (fractional anisotropy (FA), axial/radial/mean diffusivity, diffusion tensor mode), two crossing fiber measures estimated using a multi-compartment crossing-fiber model reflecting the volume fraction of the dominant (f1) and non-dominant (f2) diffusion orientation, and finally, connectivity density obtained from full-brain probabilistic tractography. The LICA component explaining the largest data variance was highly sensitive to disease severity (AD < MCI < SCI) and revealed widespread coordinated decreases in FA and f1 with increases in all diffusivity measures in AD. Additionally, it reflected regional coordinated decreases and increases in f2, mode and connectivity density, implicating bidirectional alterations of crossing fibers in the fornix, uncinate fasciculi, corpus callosum and major sensorimotor pathways. LICA yielded improved diagnostic classification performance compared to univariate region-of-interest features. Our results document coordinated WM microstructural and connectivity alterations in line with disease severity across the AD continuum.

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Section: Discussionsupporting

confidence: 58%

Dissociable diffusion MRI patterns of white matter microstructure and connectivity in Alzheimer’s disease spectrum

Doan

Engvig

Persson

et al. 2017

Sci Rep

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“…Loss of neural integrity in this region has also been linked to neurocognitive disorders, including Alzheimer's disease (Alves et al, 2012; Di Paola et al, 2010). It is thought to be a late myelinating region of the corpus callosum that is composed of long, small diameter, thinly myelinated and easily damaged commissural fibers that transmit information relatively slowly across the hemispheres (Aboitiz et al, 1992; Kochunov et al, 2007, 2012; Pfefferbaum et al, 2000; but see: Stricker et al, 2015). …”

Section: Discussionmentioning

confidence: 99%

Accelerated DNA methylation age: Associations with PTSD and neural integrity

Wolf

Logue

Hayes

et al. 2016

Psychoneuroendocrinology

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Background Accumulating evidence suggests that post traumatic stress disorder (PTSD) may accelerate cellular aging and lead to premature morbidity and neurocognitive decline. Methods This study evaluated associations between PTSD and DNA methylation (DNAm) age using recently developed algorithms of cellular age by Horvath (2013) and Hannum et al. (2013). These estimates reflect accelerated aging when they exceed chronological age. We also examined if accelerated cellular age manifested in degraded neural integrity, indexed via diffusion tensor imaging. Results Among 281 male and female veterans of the conflicts in Iraq and Afghanistan, DNAm age was strongly related to chronological age (rs ~.88). Lifetime PTSD severity was associated with Hannum DNAm age estimates residualized for chronological age (β = .13, p= .032). Advanced DNAm age was associated with reduced integrity in the genu of the corpus callosum (β = −.17, p= .009) and indirectly linked to poorer working memory performance via this region (indirect β = − .05, p= .029). Horvath DNAm age estimates were not associated with PTSD or neural integrity. Conclusions Results provide novel support for PTSD-related accelerated aging in DNAm and extend the evidence base of known DNAm age correlates to the domains of neural integrity and cognition.

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“…Lesion or transection, depending on the specific anatomical localization, may lead to reduced processing speed, difficulty with visuospatial processing, dysnomia, and other cognitive impairments [33]. Alterations in corpus callosum microstructure have been shown to correlate with age-related reductions in processing speed [40], and are associated with other cognitive disorders such as MCI, traumatic brain injury, and Alzheimer’s [41–43]. …”

Section: Discussionmentioning

confidence: 99%

Regional susceptibility to dose-dependent white matter damage after brain radiotherapy

Connor

Karunamuni

McDonald

et al. 2017

Radiotherapy and Oncology

103

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Background and Purpose Regional differences in sensitivity to white matter damage after brain radiotherapy (RT) are not well-described. We characterized the spatial heterogeneity of dose-response across white matter tracts using diffusion tensor imaging (DTI). Materials and Methods Forty-nine patients with primary brain tumors underwent MRI with DTI before and 9–12 months after partial-brain RT. Maps of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were generated. Atlas-based white matter tracts were identified. A secondary analysis using skeletonized tracts was also performed. Linear mixed-model analysis of the relationship between mean and max dose and percent change in DTI metrics was performed. Results Tracts with the strongest correlation of FA change with mean dose were the fornix (−0.46 percent/Gy), cingulum bundle (−0.44 percent/Gy), and body of corpus callosum (−0.23 percent/Gy), p<.001. These tracts also showed dose-sensitive changes in MD and RD. In the skeletonized analysis, the fornix and cingulum bundle remained highly dose-sensitive. Maximum and mean dose were similarly predictive of DTI change. Conclusions The corpus callosum, cingulum bundle, and fornix show the most prominent dose-dependent changes following RT. Future studies examining correlation with cognitive functioning and potential avoidance of critical white matter regions are warranted.

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Mild Cognitive Impairment is Associated With White Matter Integrity Changes in Late-Myelinating Regions Within the Corpus Callosum

Cited by 19 publications

References 77 publications

Dissociable diffusion MRI patterns of white matter microstructure and connectivity in Alzheimer’s disease spectrum

Dissociable diffusion MRI patterns of white matter microstructure and connectivity in Alzheimer’s disease spectrum

Accelerated DNA methylation age: Associations with PTSD and neural integrity

Regional susceptibility to dose-dependent white matter damage after brain radiotherapy

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