Tractography of the external capsule and cognition: A diffusion MRI study of cholinergic fibers.

INTRODUCTION: White matter changes (WMC) in the cholinergic tracts contribute to executive dysfunction in the context of cognitive aging. WMC in the external capsule have been associated with executive dysfunction. The objectives of this study were to: 1) Characterize the lateral cholinergic tracts (LCT) and the superior longitudinal fasciculus (SLF). 2) Evaluate the association between diffusion measures within those tracts and cognitive performance. METHODS: Neuropsychological testing and high angular resolution diffusion imaging (HARDI) of 34 healthy elderly participants was done, followed by anatomically constrained probabilistic tractography reconstruction robust to crossing fibers. The external capsule was manually segmented on a mean T1 image then merged with an atlas, allowing extraction of the LCT. Diffusion tensor imaging (DTI) and HARDI-based measures were obtained. RESULTS: Correlations between diffusion measures in the LCT and the time of completion of Stroop (left LCT radial and medial diffusivity), the Symbol Search score (right LCT apparent fiber density) and the motor part of Trail-B (left LCT axial and radial diffusivity) were observed. Correlations were also found with diffusion measures in the SLF. WMC burden was low, and no correlation was found with diffusion measures or cognitive performance. DISCUSSION: DTI and HARDI, with isolation of strategic white matter tracts for cognitive functions, represent complimentary tools to better understand the complex process of brain aging.

White Matter Hyperintensities in Mild Cognitive Impairment and Lower Risk of Cognitive Decline.

BACKGROUND: White matter hyperintensities (WMH) may have a different impact on cognitive decline depending on strategic localization. OBJECTIVE: The goal of this study is to assess the impact of global and cholinergic WMH on cognitive decline of mild cognitive impairment (MCI) patients in the ADNI-1 dataset. METHODS: This is a retrospective analysis of data from a natural history study. MRI scans (T2 and PD sequences) were assessed with two visual scales: 1) The Cholinergic Pathways HyperIntensities Scale (CHIPS) score, designed to assess WMH in the cholinergic tracts, and 2) the Age-Related White Matter Changes Scale (ARWMC), a scale to assess the global WMH burden. All subjects underwent standardized neuropsychological testing. RESULTS: Subjects included 310 individuals with MCI. Analysis showed no association between WMH at baseline and conversion from MCI to Alzheimer's disease (AD), either for the global WMH burden or WMH within the cholinergic pathways. However, ARWMC scores had a significant confounding effect (p = 0.03) on conversion to dementia (hazard ratio of 0.37) among MCI subjects with low executive functions. CONCLUSION: We found no association between the burden of WMH at baseline in MCI and conversion to AD over 3 years. However, a higher global WMH burden appears to reduce the risk of conversion to AD in subjects with low executive functions. These results suggest that higher WMH burden in MCI individuals may be associated with a more gradual cognitive decline or stabilization, compared to a low WMH burden.