Associations between T₁ white matter lesion volume and regional white matter microstructure in aging

Abstract

White matter lesions, typically manifesting as regions of signal intensity abnormality (WMSA) on MRI, increase in frequency with age. However, the role of this damage in cognitive decline and disease is still not clear, as lesion volume has only loosely been associated with clinical status. Diffusion tensor imaging (DTI) has been used to examine the quantitative microstructural integrity of white matter, and has applications in the examination of subtle changes to tissue that appear visually normal on conventional imaging. The primary goal of this study was to determine whether major macrostructural white matter damage, (total WMSA volume), is associated with microstructural integrity of normal appearing white matter, and if these macrostructual changes fully account for microstructural changes. Imaging was performed in 126 non-demented individuals, ages 43-85, with no history of cerebrovascular disease. Controlling for age, greater WMSA volume was associated with decreased FA in widespread brain regions. Patterns were similar for FA and radial diffusivity but in contrast, WMSA was associated with axial diffusivity in fewer areas. Age was associated with FA in several regions, and many of these effects remained even when controlling for WMSA volume, suggesting the etiology of WMSAs does not fully account for all age-associated white matter deterioration. These results provide evidence that WMSA volume is associated with the integrity of normal-appearing white matter. In addition, our results suggest that overt lesions may not account for the association of increasing age with decreased white matter tissue integrity.

What are White Matter Hyperintensities Made of?

“…Several reports indicate that the tissue structural and vascular changes spread further than the visible area of the WMH, rather than being confined to the visible WMH109,111,118–120 consistent with recent pathological reports 90. The changes radiate into normal-appearing white matter, particularly in the immediate peri-WMH tissue, indicating that the underlying pathology is a diffuse process affecting much of the white matter and even other parts of the brain, and that visible lesions, ie, the WMH, are probably only the “tip of the iceberg.”…”

Tract-Specific Fractional Anisotropy Predicts Cognitive Outcome in a Community Sample of Middle-Aged Participants with White Matter Lesions

“…7 However, WMLs may also influence reduction of FA in normal-appearing WM via processes such as diaschisis or Wallerian degeneration. 14 The exact temporal relation between WMLs and FA changes should be explored further.…”

Decoupling of structural and functional brain connectivity in older adults with white matter hyperintensities

“…We tested our hypothesis in clinically normal older adults with high white matter hypertensities (WMH) on MRI, a common marker of white matter injury (Hedden et al, 2014; Leritz et al, 2014; O'Sullivan et al, 2001; Vernooij et al, 2009). Given the potential complexity of the relationship, we focused our analysis on two well-described nodes of the DN network: the posterior cingulate cortex (PCC) and medial prefrontal cortex (MPFC), between which information is passed along the cingulum bundle.…”