Microstructural Tissue Changes in Alzheimer Disease Brains: Insights from Magnetization Transfer Imaging.

BACKGROUND AND PURPOSE: Reductions in magnetization transfer ratio have been associated with brain microstructural damage. We aim to compare magnetization transfer ratio in global and regional GM and WM between individuals with Alzheimer disease and healthy control participants to analyze the relationship between magnetization transfer ratio and cognitive functioning in Alzheimer disease. MATERIALS AND METHODS: In this prospective study, participants with Alzheimer disease and a group of age-matched healthy control participants underwent clinical examinations and 3T MR imaging. Magnetization transfer ratios were determined in the cortex, AD-signature regions, normal-appearing WM, and WM hyperintensities. RESULTS: Seventy-seven study participants (mean age ± SD, 72 ± 8 years; 47 female) and 77 age-matched healthy control participants (mean age ± SD, 72 ± 8 years; 44 female) were evaluated. Magnetization transfer ratio values were lower in patients with Alzheimer disease than in healthy control participants in all investigated regions. When adjusting for atrophy and extent of WM hyperintensities, significant differences were seen in the global cortex (OR = 0.47; 95% CI: 0.22, 0.97; P = .04), in Alzheimer disease-signature regions (OR = 0.31; 95% CI: 0.14, 0.67; P = .003), in normal-appearing WM (OR = 0.59; 95% CI: 0.39, 0.88; P = .01), and in WM hyperintensities (OR = 0.18; 95% CI: 0.09, 0.33; P ≤ .001). The magnetization transfer ratio in these regions was an independent determinant of AD. When correcting for atrophy and WM hyperintensity extent, lower GM magnetization transfer ratios were associated with poorer global cognition, language function, and constructional praxis. CONCLUSIONS: Alzheimer disease is associated with magnetization transfer ratio reductions in GM and WM regions of the brain. Lower magnetization transfer ratios in the entire cortex and AD-signature regions contribute to cognitive impairment independent of brain atrophy and WM damage.

Lower Magnetization Transfer Ratio in the Forceps Minor Is Associated with Poorer Gait Velocity in Older Adults.

BACKGROUND AND PURPOSE: Gait disturbances in the elderly are disabling and a major public health issue but are poorly understood. In this multimodal MR imaging study, we used 2 voxel-based analysis methods to assess the voxelwise relationship of magnetization transfer ratio and white matter hyperintensity location with gait velocity in older adults. MATERIALS AND METHODS: We assessed 230 community-dwelling participants of the Austrian Stroke Prevention Family Study. Every participant underwent 3T MR imaging, including magnetization transfer imaging. Voxel-based magnetization transfer ratio-symptom mapping correlated the white matter magnetization transfer ratio of each voxel with gait velocity. To assess a possible relationship between white matter hyperintensity location and gait velocity, we applied voxel-based lesion-symptom mapping. RESULTS: We found a significant association between the magnetization transfer ratio within the forceps minor and gait velocity (ß = 0.134; 95% CI, 0.011-0.258; P = .033), independent of demographics, general physical performance, vascular risk factors, and brain volume. White matter hyperintensities did not significantly change this association. CONCLUSIONS: Our study provides new evidence for the importance of magnetization transfer ratio changes in gait disturbances at an older age, particularly in the forceps minor. The histopathologic basis of these findings is yet to be determined.

Decreased T1 contrast between gray matter and normal-appearing white matter in CADASIL.

BACKGROUND AND PURPOSE: CADASIL is the most frequent hereditary small-vessel disease of the brain. The clinical impact of various MR imaging markers has been repeatedly studied in this disorder, but alterations of contrast between gray matter and normal-appearing white matter remain unknown. The aim of this study was to evaluate the contrast alterations between gray matter and normal-appearing white matter on T1-weighted images in patients with CADASIL compared with healthy subjects. MATERIALS AND METHODS: Contrast between gray matter and normal-appearing white matter was assessed by using histogram analyses of 3D T1 high-resolution MR imaging in 23 patients with CADASIL at the initial stage of the disease (Mini-Mental State Examination score > 24 and modified Rankin scale score ≤ 1; mean age, 53.5 ± 11.1 years) and 30 age- and sex-matched controls. RESULTS: T1 contrast between gray matter and normal-appearing white matter was significantly reduced in patients compared with age- and sex-matched controls (patients: 1.35 ± 0.08 versus controls: 1.43 ± 0.04, P < 10(-5)). This reduction was mainly driven by a signal decrease in normal-appearing white matter. Contrast loss was strongly related to the volume of white matter hyperintensities. CONCLUSIONS: Conventional 3D T1 imaging shows significant loss of contrast between gray matter and normal-appearing white matter in CADASIL. This probably reflects tissue changes in normal-appearing white matter outside signal abnormalities on T2 or FLAIR sequences. These contrast alterations should be taken into account for image interpretation and postprocessing.