Spatial Gradient of Microstructural Changes in Normal-Appearing White Matter in Tracts Affected by White Matter Hyperintensities in Older Age

Abstract

Brain white matter hyperintensities (WMH), common in older adults, may contribute to cortical disconnection and cognitive dysfunction. The presence of WMH within white matter (WM) tracts indicates underlying microstructural WM changes that may also affect the normal-appearing WM (NAWM) of a tract. We performed an exploratory study using diffusion magnetic resonance imaging of 52 healthy participants from the Lothian Birth Cohort 1936 (age 72.2 ± 0.7 years) selected to include a range of WMH burden, to quantify microstructural changes of tracts intersecting WMH. We reconstructed tracts using automated tractography and identified intersections with WMH. Tissue volumes and water diffusion tensor parameters (mean diffusivity (MD) and fractional anisotropy (FA)) were established for tract-WMH and tract-NAWM. MD and FA were also measured for tract-NAWM at 2 mm incremental distances from the tract-WMH edge, and from the edge of nearby, non-intersecting, WMH. We observed microstructural changes in tract-WMH suggestive of tissue damage. Tract-NAWM also showed a spatial gradient of FA and MD abnormalities, which diminished with distance from the tract-WMH. Nearby WMH lesions, not directly crossed by the tract, also affected tract microstructure with a similar pattern. Additionally, both FA and MD changes in tract-NAWM were predicted by FA and MD changes respectively in tract-WMH. FA was also predicted by tract-WMH overlap volume, whereas MD was better predicted by whole-brain WMH load. These results suggest that tract-NAWM microstructure is affected by the pathological process underlying WMH, when WMH are either within or near to the tract. The changes in NAWM tract tissue may indicate future lesion progression and may play an important role in cognitive ageing.

Tract-defined regional white matter hyperintensities and memory

“…We suggest our findings of the impact of tract-defined WMH on memory performance is partially explained by the previously proposed concept of “disconnection” (Lockhart et al., 2012; Munoz Maniega et al., 2019; O'Sullivan et al., 2001; Ritchie et al., 2015), which may mediate the effect of tract WMH on cognitive performance. Neuroimaging studies suggest that long-term memory is dependent on multiple cortical and subcortical regions, which are integrated via neural networks (Charlton et al., 2010; Grady et al., 2003; Ranganath et al., 2005).…”

“…Our unexpected finding regarding the relationship between WMH in projection white matter tracts, particularly the relationship between corticospinal tract and memory, deviates from previous DTI studies, which suggested a role of the corticospinal tract in sensorimotor functions rather than cognitive functions (Carter et al., 2012; Karahan et al., 2019). A plausible explanation of the relationship between corticospinal tract WMH and memory may simply be due to the tract's proximity to the lateral ventricles, where periventricular WMH reside and are known to be associated to memory (Munoz Maniega et al., 2019; Smith et al., 2011).…”

Brain network reorganisation and spatial lesion distribution in systemic lupus erythematosus

“…A study in 52 normal individuals at the beginning of the 8th decade of life observed that despite WMH having similar effects on tract infrastructure, whether they be intersecting or nearby, differences in tract water diffusion properties around WMH suggest that tract degeneration may propagate along the white matter tract for intersecting WMH, while in some areas of the brain there is a larger and more localized accumulation of axonal damage in tract tissue nearby a non-connected WMH. 47 This study also complements findings by other studies in smaller SLE samples, which found altered structural network parameters in SLE patients 13,14 compared to controls, with only few differences in functional hub measures. 14…”

Cerebral Immunohistochemical Characterization of the H2S and the Oxytocin Systems in a Porcine Model of Acute Subdural Hematoma

“…Furthermore, the adult pig and human brain are composed of 60% white matter, in contrast to <12% in the adult rat brain ( 5 ). This may be crucial for translation since white matter is more prone to develop edema and thus aggravates the pressure-induced trauma in the cerebrum ( 2 , 6 ).…”