Specific White Matter Tracts and Diffusion Properties Predict Conversion From Mild Cognitive Impairment to Alzheimer’s Disease

Abstract

Identifying biomarkers that can assess the risk of developing Alzheimer’s Disease (AD) remains a significant challenge. In this study, we investigated the integrity levels of brain white matter in 34 patients with mild cognitive impairment (MCI) who later converted to AD and 53 stable MCI patients. We used diffusion tensor imaging (DTI) and automated fiber quantification to obtain the diffusion properties of 20 major white matter tracts. To identify which tracts and diffusion measures are most relevant to AD conversion, we used support vector machines (SVMs) to classify the AD conversion and non-conversion MCI patients based on the diffusion properties of each tract individually. We found that diffusivity measures from seven white matter tracts were predictive of AD conversion with axial diffusivity being the most predictive diffusion measure. Additional analyses revealed that white matter changes in the central and parahippocampal terminal regions of the right cingulate hippocampal bundle, central regions of the right inferior frontal occipital fasciculus, and posterior and anterior regions of the left inferior longitudinal fasciculus were the best predictors of conversion from MCI to AD. An SVM based on these white matter tract regions achieved an accuracy of 0.75. These findings provide additional potential biomarkers of AD risk in MCI patients.

Age-dependent microstructure alterations in 5xFAD mice by high-resolution diffusion tensor imaging

“…Alzheimer's disease is classically considered a disease of gray matter; however, white matter abnormalities have been widely reported in the brains of incipient and mildly afflicted individuals (Sachdev et al, 2013). Advanced neuroimaging studies demonstrate that patients with preclinical AD have widespread white matter abnormalities at a stage similar to those reported in AD (Marquez and Yassa, 2019;Stone et al, 2021). White matter abnormalities, particularly axonal transport deficiencies, are also important components of AD (Klok et al, 2018).…”

Disrupted Value-Directed Strategic Processing in Individuals with Mild Cognitive Impairment: Behavioral and Neural Correlates

“…A diffusion tensor imaging study has also shown that preferential recall of high-value words in older adults was dependent on the integrity of the inferior fronto-occipital fasciculus, a tract associated with semantic memory performance and retrieval of semantic information [ 82 ]. These regions and tracts have been shown to be altered in individuals with MCI compared to CNCs [ 83 , 84 , 85 , 86 , 87 , 88 ]. Examining the links between neurophysiological alterations in alpha band and the neural substrates that support value-directed strategic processing in MCI will advance our theoretical understanding of value-directed strategic processing.…”

Neuroimaging of Mouse Models of Alzheimer’s Disease

“…MR imaging of brain networks, both structural (diffusion tensor; DTI) and functional (resting state fMRI; rsfMRI), has been utilized in the assessment of human AD. DTI lends itself to the assessment of regional microstructural integrity (or lack thereof) and is particularly well suited to the evaluation of white matter integrity [ 43 ]. In neurodegenerative diseases, such as AD, DTI has been especially useful in assessing gray and white matter brain pathology, as recently reviewed [ 44 ].…”

“…These decrements in white matter were associated with amyloid PET imaging of the fornix. Emerging studies using DTI have identified a group of white matter tracts that are predictive for conversion to AD from MCI [ 43 ].…”