Focal white matter disruptions along the cingulum tract explain cognitive decline in amnestic mild cognitive impairment (aMCI)

Abstract

White matter abnormalities of the human brain are implicated in typical aging and neurodegenerative diseases. However, our understanding of how fine-grained changes in microstructural properties along white matter tracts are associated with memory and cognitive decline in normal aging and mild cognitive impairment remains elusive. We quantified tract profiles with a newer method that can reliably measure fine-grained changes in white matter properties along the tracts using advanced multishell diffusion magnetic resonance imaging in 25 patients with amnestic mild cognitive impairment (aMCI) and 23 matched healthy controls (HC). While the changes in tract profiles were parallel across aMCI and HC, we found a significant focal shift in the profile at specific locations along major tracts subserving memory in aMCI. Particularly, our findings depict white matter alterations at specific locations on the right cingulum cingulate, the right cingulum hippocampus and anterior corpus callosum (cc) in aMci compared to Hc. notably, focal changes in white matter tract properties along the cingulum tract predicted memory and cognitive functioning in aMci. the results suggest that white matter disruptions at specific locations of the cingulum bundle may be a hallmark for the early prediction of Alzheimer's disease and a predictor of cognitive decline in aMci. Mild Cognitive Impairment (MCI) is a condition characterized by cognitive impairment while retaining intact functioning in everyday life 1. Individuals with the amnestic subtype of MCI (aMCI), are classified as having progressive memory deficits, which are either isolated or associated with other cognitive domain impairments. Individuals with aMCI are at increased risk for developing Alzheimer's disease and in some cases, may be in the prodromal stage of Alzheimer's disease 2. There is increasing evidence showing that the estimated prevalence of aMCI in population-based studies ranges from 8.4 to 25.2% for individuals 65-85 years old 3. Despite intense efforts to develop effective medications and pharmacological interventions, there is currently no cure for Alzheimer's disease (AD). A non-invasive, objective biomarker capable of predicting AD before the onset of more severe cognitive symptoms is therefore crucial for implementing early AD interventions. Previous research has shown that changes in white matter tissue properties are highly relevant to cognitive decline associated with aging. Apolipoprotein E4 (APOE4), the most prevalent genetic risk factor for AD, codes for a protein involved in white matter myelination 4. Individuals with aMCI typically exhibit more white matter tissue changes related to demyelination compared to controls 5,6. aMCI patients also show decreased fractional anisotropy (FA) and increased mean diffusivity (MD), which define the directional coherence and the magnitude of water molecule diffusion in white matter tracts, relative to controls 7. Cortical disconnections as a result of axonal demyelination may explain cognitive decline in aMCI and cou...

Tract-specific differences in white matter microstructure between young adult APOE ε4 carriers and non-carriers: A replication and extension study

“…In one region-of-interest (ROI) meta-analysis, for example, Yu et al (2017) identified robust alterations in PHCB microstructure (lower FA, higher MD) among individuals with aMCI. This is consistent with the notion that cingulum bundle alterations predict cognitive decline in aMCI, and may even predict conversion to AD ( Gozdas et al, 2020 ). Studies combining positron emission tomography and dMRI have also allowed PHCB changes to be linked directly to AD pathology.…”

Tract-specific white matter microstructure alterations among young adultAPOEε4 carriers: A replication and extension study

“…In one region-of-interest (ROI) meta-analysis, for example, Yu et al (2017) identified robust alterations in PHCB microstructure (lower FA, higher MD) among individuals with aMCI. This is congruent with the notion that cingulum bundle alterations predict cognitive decline in aMCI and may even predict conversion to AD (Gozdas et al, 2020). Studies combining positron emission tomography and dMRI have also allowed PHCB changes to be linked directly to AD pathology.…”

Association between real-time strategy video game learning outcomes and pre-training brain white matter structure: preliminary study

“…In this study, the white matter regions and tracts that were signi cantly associated with indicators of StarCraft II performance are involved in psychomotor functions 37 , set shifting ability42, and visually guided decisions and behavior 43,44 . It is worth mentioning that previous studies mostly used rather simple video games, such as Space Fortress 24 or Sushi-Go-Round 15 , where in our study we can see similar patterns yet on a more advanced RTS game.…”

“…where research shows that people with MCI tend to have lower FA within this region 37 . In the same study 37 across groups (aMCI and healthy controls), the analysis showed that the FA within cingulum hippocampus is positively associated with The Symbol Digit Modalities Test (SDMT), which assesses psychomotor speed 38 .…”