White matter changes in healthy aging revealed by fixel-based analysis
Poster No:
1598
Submission Type:
Abstract Submission
Authors:
Feliberto de la Cruz1, Andy Schumann1, Katrin Rieger1, Daniel Güllmar1, Jürgen R. Reichenbach1, Karl- Jürgen Bär1
Institutions:
1Jena University Hospital, Jena, Germany
First Author:
Co-Author(s):
Introduction:
The healthy aging process is a multifaceted phenomenon involving numerous physiological, psychological, and neurobiological changes. With advancing age, individuals experience a series of white matter (WM) changes that contribute to alterations in cognitive processing, sensory perception, and motor function. However, most studies on WM changes in aging have mainly employed diffusion tensor imaging (DTI). While DTI performs well in regions characterized by a dominant fiber direction, its efficacy diminishes in regions with complex fiber geometry and various fiber populations. In contrast, a recently developed analytical framework known as fixel-based analysis (FBA) introduces a novel avenue for assessing WM characteristics. This methodology enables the statistical examination of quantitative measures in complex fiber geometry. Here, we aimed to characterize age-related WM changes across the entire brain using FBA. We complemented our study by exploring the relationship between potential risk factors contributing to WM alterations, such as pulse pressure, alcohol consumption, and frequency of physical activities and how these WM changes correlate with cognitive performance.
Methods:
We recruited 120 healthy volunteers, divided into 60 younger and 60 older adults. DWI parameters: TR/TE = 3318/87 ms, voxel size = 1.5x1.5x1.5 mm³, 96 axial slices, and a multiband acceleration factor = 4. Three diffusion-weighted shells: b = 800 s/mm² (16 volumes), b = 1600 s/mm² (32 volumes), and b = 2500 s/mm² (48 volumes), along with 8 non-diffusion-weighted volumes (b=0 s/mm²). Three fixel-based metrics were derived: fiber density (FD), fiber cross-section (FC) and a combined measure of FD and FC (FDC). All statistical analyses were conducted in the study-specific template space, controlled by total intracranial volume and gender.
Pulse pressure was computed as the difference between systolic and diastolic blood pressure. Participants completed a self-reported questionnaire and reported the frequency of physical activity and alcohol consumption per week, as well as the number of glasses of alcohol consumed per day. Cognitive performance was evaluated using the neuropsychological Trail Making Test (TMT-A/B).
Pulse pressure was computed as the difference between systolic and diastolic blood pressure. Participants completed a self-reported questionnaire and reported the frequency of physical activity and alcohol consumption per week, as well as the number of glasses of alcohol consumed per day. Cognitive performance was evaluated using the neuropsychological Trail Making Test (TMT-A/B).
Results:
The whole-brain FBA comparing younger and older adult participants revealed substantial WM changes at pFWE < 0.05 (Fig. 1A and B). These changes mainly encompassed reduced FD, FC and FDC in older participants. Specifically, reductions were evident across multiple fixels within the anterior thalamic radiation, corticospinal tract, body of the corpus callosum, forceps minor, fornix and middle cerebellar peduncle (Fig. 1A). Though to a lesser extent, the opposite contrast also identified a set of WM regions where FBA metrics were greater in older participants than their younger counterparts (Fig. 1B). These group differences were driven by greater FD and included fixels within the bilateral anterior thalamic radiation, superior portion of bilateral corticospinal tracts, and superior cerebellar peduncles.
We did not find any significant association between changes in FBA metrics in older participants and the examined risk factors. However, we observed significant associations between greater FBA metrics and cognitive performance in several major tracts, as depicted in Fig. 1C for the left corticospinal tract. Notably, the relationship between FBA and TMT was mainly influenced by the relationship between FD and TMT-A.
We did not find any significant association between changes in FBA metrics in older participants and the examined risk factors. However, we observed significant associations between greater FBA metrics and cognitive performance in several major tracts, as depicted in Fig. 1C for the left corticospinal tract. Notably, the relationship between FBA and TMT was mainly influenced by the relationship between FD and TMT-A.
Conclusions:
Our study provides additional insights into white matter alterations that occur with aging, utilizing a precise and interpretable approach known as fixel-based analysis. These findings highlight the complexity of age-related changes, involving both microstructural and macrostructural effects associated with variations in fiber density, cross-section, and FDC. This study demonstrates that fixel-based analysis could be valuable for exploring the white matter correlates of cognitive decline in older individuals.
Lifespan Development:
Aging 2
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis 1
Keywords:
Aging
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
1|2Indicates the priority used for review
Provide references using author date format
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Raffelt, D.A. (2017). Investigating white matter fibre density and morphology using fixel-based analysis. Neuroimage 144, 58–73.