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Tract Specific White Matter Lesion Load Affects White Matter Microstructure and Their Relationships with Functional Connectivity and Cognitive Decline

April 25, 2022

To better understand the processes of cognitive impairment, a team of UPMC and Pitt experts conducted a study that examined the effect of white matter hyperintensities (WMH) on white matter (WM) microstructural changes and its relationships with structural and functional connectivity to multiple cognitive domains.

Tae Kim, PhD, a faculty in the Department of Radiology, was lead author of the study. Contributing to this study were Beth E. Snitz, PhD, and Rebecca E. Roush, PhD, from the Department of Neurology and Yue-Fang Chang, PhD, from the Department of Neurological Surgery. 

WM in the brain is made up of bundles of myelinated fibers, also known as fiber tracts. Abnormalities in WM are referred to as lesions, which can appear as white matter hyperintensities (WMH) on T2-weighted magnetic resonance imaging (MRI). 

It is common for WMH to appear on MRIs of older adults as they continue to age. However, it is believed that a significant presence of WMH may likely be associated with a disruption in nerve signal and overall cognitive decline.

The research team hypothesized that the relationships among WMH, fiber density, structural connectivity, and functional connectivity were highly correlated, and that these changes are associated with cognitive performance.

Data was collected from 65 participants using a 3T Siemens Prisma MRI scanner with a 64-channel head coil. Participants underwent a multi-domain cognitive assessment, which evaluated memory, language, attention, executive functions, and visuospatial construction. The Montreal Cognitive Assessment (MoCA), a 30-question test that tells whether a person shows signs of dementia, was also administered as a global screening measure.

Results from the MRIs showed that the load of WMH lesions contributing to microstructural alterations (fiber density) is related to WM tract connectivity, but it is not directly associated with functional connectivity. The specific tracts of WMH, tract connectivity, and functional connectivity were differently associated with changes in specific cognitive performances, and alterations in these identified tracts may involve in specific cognitive deficits.1 

It should be noted that changes in each cognitive domain on WMH loads were mediated through different pathways of tract connectivity and functional connectivity. Therefore, specific cognitive deterioration may be affected by alterations in a set of different tracts that are differently associated with macrostructural, microstructural, and function changes.1

Ultimately, the evaluation of WMH and its effect on tracts allows for better understanding of the relationships between the multiple pathological changes occurring in older adults that lead to cognitive impairment.

Read the full study here.


1. Kim T, Aizenstein HJ, Snitz BE, Cheng Y, Chang YF, Roush RE, Huppert TJ, Cohen A, Doman J, Becker JT. Tract Specific White Matter Lesion Load Affects White Matter Microstructure and Their Relationships with Functional Connectivity and Cognitive Decline. Front Aging Neurosci. 2022 Feb 2;13:760663. doi: 10.3389/fnagi.2021.760663. PMID: 35185514; PMCID: PMC8848259.