Loss of white matter integrity mediates the association between cortical cerebral microinfarcts and cognitive dysfunction:, 2024, Huang et al

Loss of white matter integrity mediates the association between cortical cerebral microinfarcts and cognitive dysfunction: A longitudinal study
Jiannan Huang; Megan Oh; Caroline Robert; Xiangyuan Huang; Marco Egle; Daniel J Tozer; Christopher Chen; Saima Hilal

Cortical cerebral microinfarcts (CMIs) are associated with loss of white matter (WM) integrity and cognitive impairment in cross-sectional studies, while further investigation using longitudinal datasets is required. This study aims to establish the association between cortical CMIs and WM integrity assessed by diffusion-tensor imaging (DTI) measures and to investigate whether DTI measures mediate the relationship between cortical CMIs and cognitive decline.

Cortical CMIs were graded on 3T MRI. DTI measures were derived from histogram analysis of mean diffusivity (MD) and fractional anisotropy (FA). Cognitive function was assessed using a neuropsychological test battery. Linear mixed-effect models were employed to examine associations of cortical CMIs with longitudinal changes in DTI measures and cognitive function.

Final analysis included 231 patients (71.14 ± 7.60 years). Presence of cortical CMIs at baseline was associated with longitudinal changes in MD median and peak height and FA median and peak height, as well as global cognition (b = -0.50, 95%CI: -0.91, -0.09) and executive function (b = -0.77, 95%CI: -1.25, -0.28). MD median mediated the cross-sectional association between cortical CMIs and global cognition.

Further studies are required to investigate whether cortical CMIs and loss of WM integrity are causally related or if they are parallel mechanisms that contribute to cognitive decline.

Link | PDF (Journal of Cerebral Blood Flow & Metabolism, paywall)

 

A rapid bullet-point precis.

NAWM = normal appearing white matter (search), CMI = cortical microinfarct, DTI = diffusion tensor imaging (search), WHM = white matter hyperintensities (search), MD = mean diffusivity (search), FA = fractional anisotropy (search)

 

The key points would seem to be that cortical microinfarcts associate with both —

• cognitive dysfunction / executive dysfunction
• disruption of white matter microstructure and function

And that the evidence of white matter damage can be shown when it otherwise looks normal (NAWM, "all tests are normal"). In this scenario of cerebral small vessel ischaemic disease, the suggestion is that a microinfarct in the cortex (grey matter) can have remote effects on white matter — "existing evidence has shown that cortical CMIs can disrupt WM connectivity through mechanisms involving inflammation, oxidative damage, and blood-brain barrier leakage".

So, could you have disrupted white matter connectivity for other upstream reasons, but still leading to similar inflammation, oxidative damage, and blood-brain barrier leakage?