Microstructural Changes Of White Matter Lesions And Its Correlation With Cognitive Functions

Objectives:Although white matter hyperintensities(WMLs)are commonly seen via MRI in the elderly,little is known about the cumulative spatial distribution and underlying microstructural changes of WMLs,which is critical for understanding the mechanisms of cognitive impairment.In addition,the critical stage,in which cognition and brain microstructure are damaged,has not been fully determined.Methods:Participants(n=321)were community-dwelling and non-demented elderly(mean age 66±7 years)from the Beijing Ageing Brain Rejuvenation Initiative Study.All participants underwent T1-and T2-weighted fluid-attenuated inversion recovery(T2w-FLAIR)and diffusion tensor MRI scanning,as well as a battery of neuropsychological tests.Lesions were both qualitatively(Fazekas scale)assessed and segmented on fluid-attenuated inversion recovery images.Voxel-and atlas-based analyses of the whole-brain white matter integrity were assessed.Results:WMLs of the same stages were found to occur uniformly with a specific pattern of lesions,which originally presented in periventricular areas with several foci in the subcortical white matter in patients with mild WMLs(Fazekas 1&2);this distribution then further extended to the corpus callosum and occipitotemporal regions in patients with moderate WMLs(Fazekas 3&4)and eventually involved the superior frontal and occipital lobes in patients with severe WMLs(Fazekas 5&6).In our results,the integrity of white matter was relatively maintained in Fazekas 1&2 groups,and presented significant impairments in the anterior corona radiata posterior thalamic radiation and superior fronto-occipital fasciculus(p<0.05 after Bonferroni correction)in Fazekas 3,which then spread to the whole brain above Fazekas scale 4.The severity of WMLs had a significant negative association with the performance of working memory(r=-0.144,p=0.022)and episodic memory(r=-0.127,p=0.045)after adjustment for vascular risk factors.More importantly,we found that Fazekas scale 3 might be a crucial watershed point,as a significant decline in white matter integrity and cognitive function can begin to be seen at that level.The microstructural integrity of the superior cerebellar peduncle and left posterior thalamic radiation showed the highest relation with episodic memory,and the middle cerebellar peduncle showed the highest relation with working memory.Conclusions:These results support that WMLs mainly affect memory in the non-demented elderly,independent of age and vascular risk factors,and the effect may potentially be influenced by tract-specific WM abnormalities.Fazekas scale 3 might be the critical value that predicts a future decline in cognition.