Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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Gewählte Publikation:

Seiler, S.
Magnetization Transfer Imaging for Detection of Microstructural Brain Tissue Changes in Aging: Associations with Cognition and Gait Disturbances.
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Graz Medical University; 2016. pp. [OPEN ACCESS]


Autor*innen der Med Uni Graz:
Seiler Stephan
Ropele Stefan
Schmidt Reinhold

The present PhD thesis consists of 2 separate magnetic resonance imaging (MRI) studies that are based on each other. Our aims were to elaborate the role of microstructural brain tissue damage associated with cognitive performance (study #1) and gait disturbances (study #2). To accomplish this, we used Magnetization Transfer Imaging (MTI). MTI can detect microstructural brain tissue changes beyond what is visible on standard MRI and may be helpful in determining age-related cerebral damage. In study#1, we investigated the association between the magnetization transfer ratio (MTR) in gray and white matter and cognitive functioning in 355 participants of the Austrian Stroke Prevention Family Study (ASPS-Fam) aged 38 to 86 years. Every participant underwent 3T MRI including MTI. MTR maps were generated for the neocortex, deep gray matter structures, white matter hyperintensities, and normal appearing white matter. Adjusted mixed models determined whole brain and lobar cortical MTR to be directly and significantly related to performance on tests of memory, executive function and motor skills. There existed an almost linear dose-effect relationship. MTR of deep gray matter structures and normal appearing white matter correlated to executive functioning. All associations were independent of demographics, vascular risk factors, focal brain lesions and cortex volume. In study #2, we used voxel-based lesion symptom mapping (VLSM) and voxel-based MTR-symptom mapping (VMTRSM) to assess the macrostructural and microstructural determinants of gait velocity in aging. We chose those 230 non-disabled participants of the ASPS-Fam who were over or equal to 60 years old. Gait velocity was calculated at normal pace. Every participant underwent 3T MRI including Magnetization Transfer Imaging (MTI). VLSM and VMTRSM were carried out to correlate white matter hyperintensity (WMH) location and Magnetization Transfer Ratio (MTR) of each voxel with gait velocity. All analyses were adjusted for possible confounders. To account for multiple comparisons, a Family-Wise Error (FWE) corrected p-value <0.05 was considered statistically significant. VLSM did not find any significant clusters where WMH were associated with slower gait. In the VMTRSM analysis, MTR in several voxels was significantly associated with gait velocity. Most significant voxels were located in the forceps minor. Region of interest (ROI) analysis revealed a significant association between forceps minor MTR and gait velocity (ß=0.160; 95%CI 0.025-0.295; p=0.02), independent of demographics, brain volume and vascular risk factors. Analysis of covariance (ANCOVA) demonstrated that the association between quartiles of MTR within the forceps minor and gait velocity was dose-dependent (p for linear trend =0.016). Our studies provide new evidence for the importance of microstructural brain tissue changes in cognition and gait disturbances at older age. Further research is needed to understand the basis of these associations at the tissue level, and to determine the role of MTR in predicting cognitive decline, dementia and gait impairment.

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