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 multi-shell 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 sub-serving 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.
Highlights
White matter abnormalities of the human brain are implicated in typical aging and neurodegenerative diseases
Descriptive statistics of demographic characteristics and neuropsychological assessments are summarized for amnestic mild cognitive impairment (aMCI) patients and in healthy controls (HC) in Table 1. aMCI and HC participants did not differ significantly in age, sex, years of education, intracranial brain volume (ICV) or white matter hyperintensity volume (WMHV). aMCI patients demonstrated significantly lower scores in Logical Memory II-Delayed Recall (LM-II), Mini-Mental State Examination (MMSE), and Symbol Digit Modalities Test (SDMT) assessments compared to HC, but List Sorting Working Memory (LSWM) and Rey's Auditory Verbal Learning Test (RAVLT) scores did not differ significantly between groups
Amnestic Mild Cognitive Impairment was associated with alterations in tissue properties at specific locations along three white matter tracts considered crucial for memory: the right cingulum cingulate, right cingulum hippocampus and anterior corpus callosum (CC)
Summary
White matter abnormalities of the human brain are implicated in typical aging and neurodegenerative diseases. When quantified, these white matter abnormalities could plausibly be used for the early identification of individuals at higher risk of developing AD and to plan for early intervention before substantial neurological compromise. Major fiber tracts such as the corpus callosum (CC), inferior fronto-occipital fasciculus (IFOF), and posterior cingulum bundle have shown disruptions in white matter integrity in aMCI patients as well as in AD5,8,9. These white matter tracts interconnect frontal, parietal and medial temporal regions and are thought to carry signals that contribute to executive control and memory processes. They have reported higher degrees of aberrant functional connectivity patterns in aMCI in the posterior cingulate cortex (PCC) in the absence of grey matter atrophy[12], white matter degeneration in the tracts that sub-serve a part of the connection between the hippocampus and PCC5, as well as fiber density reduction in aMCI patients in the posterior white matter cingulum bundle[9]
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