Multi-compartment diffusion magnetic resonance imaging models link tract-related characteristics with working memory performance in healthy older adults

Abstract

Multi-compartment diffusion MRI metrics [such as metrics from free water elimination diffusion tensor imaging (FWE-DTI) and neurite orientation dispersion and density imaging (NODDI)] may reflect more specific underlying white-matter tract characteristics than traditional, single-compartment metrics [i.e., metrics from Diffusion Tensor Imaging (DTI)]. However, it remains unclear if multi-compartment metrics are more closely associated with age and/or cognitive performance than single-compartment metrics. Here we compared the associations of single-compartment [Fractional Anisotropy (FA)] and multi-compartment diffusion MRI metrics [FWE-DTI metrics: Free Water Eliminated Fractional Anisotropy (FWE-FA) and Free Water (FW); NODDI metrics: Intracellular Volume Fraction (ICVF), Orientation Dispersion Index (ODI), and CSF-Fraction] with both age and working memory performance. A functional magnetic resonance imaging (fMRI) guided, white matter tractography approach was employed to compute diffusion metrics within a network of tracts connecting functional regions involved in working memory. Ninety-nine healthy older adults (aged 60–85) performed an in-scanner working memory task while fMRI was performed and also underwent multi-shell diffusion acquisition. The network of white matter tracts connecting functionally-activated regions was identified using probabilistic tractography. Diffusion metrics were extracted from skeletonized white matter tracts connecting fMRI activation peaks. Diffusion metrics derived from both single and multi-compartment models were associated with age (ps ≤ 0.011 for FA, FWE-FA, ICVF and ODI). However, only multi-compartment metrics, specifically FWE-FA (p = 0.045) and ICVF (p = 0.020), were associated with working memory performance. Our results suggest that while most current diffusion metrics are sensitive to age, several multi-compartment metrics (i.e., FWE-FA and ICVF) appear more sensitive to cognitive performance in healthy older adults.

Subtle white matter intensity changes on fluid-attenuated inversion recovery imaging in patients with ischaemic stroke

“… 28 , 29 From a clinical perspective, a growing body of evidence has shown that DTI-derived markers of free water are related to the progression of leukoaraiosis and cognitive performance. 30-32 Also, it has been shown that markers of blood–brain permeability are related to the long-term clinical outcome of patients with ischaemic stroke. 33 , 34 We believe that such blood–brain barrier leakage could possibly account for the subtle FLAIR signal intensity changes observed in our study, given that FLAIR signal hyperintensity presumably reflects tissue free-water accumulation.…”

Correlates of axonal content in healthy adult span: Age, sex, myelin, and metabolic health

“…The linear or quadratic negative correlations (in a region-dependent fashion) that are the strongest in frontal WM regions are consistent among studies involving middle-aged to older-adults (age ca. 45–80 years; [ [9] , [13] , [15] , [16] , [17] ]), as well as studies including the entire adult lifespan (ca. age 20–80; [ 8 , 10 , 12 , 18 , 19 ]).…”

“…The existing studies using NODDI reported mixed findings regarding age differences in axonal content estimated as ICVF. Some reported linear or quadratic declines, whereas others reported increases in ICVF, or no associations with age [ [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] ]. This may be because only few of these samples spanned the entire adulthood [ 8 , 10 , 12 , 18 , 19 ], which is necessary to capture quadratic or inverted U-shaped functions of ICVF with age.…”

A role for the fornix in temporal sequence memory

“…Only FWE‐DTI metrics were used in the subsequent analyses. For this reason, we refer to DTI metrics with the prefix FWE‐ (e.g., FWE‐FA) (Bauer et al, 2022).…”