Quantification of alterations in diffusion measures of white matter integrity associated with healthy aging

Abstract

1819 This study aimed to evaluate the linear association of age with diffusion tensor imaging (DTI) 20 measures of white matter such as fractional anisotropy (FA), mean diffusivity (MD), axial 21 diffusivity (AD) and radial diffusivity (RD). We assessed patterns of overlap between linear 22 correlations of age with FA with RD, MD and AD to characterize the process of white matter 23 degeneration observed with ageing. 79 healthy adults aged between 18 and 75 took part in the 24 study. The DTI data were based on 61 directions acquired with a b-value of 2000. There was a 25 statistically significant negative linear correlation of age with FA and AD and a positive linear 26 correlation with RD and MD, and AD. The forceps minor tract showed largest percentage of voxels 27 with an association of age with FA, RD and AD, and the anterior thalamic radiation with MD. We 28 found 5 main patterns of overlap: FA alone (15.95%); FA and RD (31.90%); FA and AD (12.99%); 29 FA, RD and AD (27.37%); FA RD, and MD (6.94%). Patterns of overlap between diffusion measures 30 may reflect underlying biological changes with healthy ageing such as loss of myelination, axonal 31 damage, as well as mild microstructural and chronic white matter impairments. This study may 32 provide information about causes of degeneration in specific regions of the brain, and how this 33 may affect healthy brain functioning in older adults. 3 34 Introduction 35 36Diffusion tensor imaging (DTI) is a neuroimaging technique, which allows for non-invasive, 37 in vivo, investigation of white matter [1][2][3]. DTI measures are based on random motion of water 38 molecules, where within the brain diffusion of water is less restricted, or more isotropic, in areas 39 of grey matter and CSF, and more restricted, or more anisotropic, in areas of white matter. When 40 white matter structural architecture deteriorates, water molecules within white matter tissue 41 become more isotropic, making DTI a useful tool for assessing atrophy [4][5][6][7][8][9]. 43The diffusion tensor is a 3x3 covariance matrix used to model diffusion within a voxel, in 44 which there are 3 positive eigenvalues (λ1, λ2, λ3) and 3 orthogonal eigenvectors (ε1, ε2, ε3). The 45 eigenvalues of the tensor give the diffusivity in the direction of each eigenvector. Together they 46 describe diffusion probability using an ellipsoid, where the axes of the ellipsoid are aligned with 47 the eigenvectors, and the major eigenvector (λ1) represents the principal diffusion direction. 49Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial 50 diffusivity (AD) are the four main diffusion-based measurements of white matter structural 51 architecture. FA measures the amount of diffusion asymmetry within a voxel, where a value of 0 52 is isotropic and is represented by a spherical ellipsoid with equal eigenvalues, and a value of 1 is 53 anisotropic and is represented by an elongated ellipsoid with unequal eigenvalues. FA has been 54 associated with the microstructural integrity of white m...

Gradient Patterns of Age-Related Diffusivity Changes in Cerebral White Matter

“…One recent study also tried to group the findings in DTI metrics across the brain white matter tracts. The FA–RD pattern was observed only in the posterior thalamic radiation in our study sample, while in the study of Molloy et al, it was the most observed pattern, detected in more than 30% of the brain tracts ( 10 ). The FA–RD–AD pattern in this study was observed in almost 30% of the brain ( 10 ).…”

“…DTI fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) measures can give insight into diffusivity changes in the brain which can be driven both by physiological brain aging and pathological processes (degeneration, inflammation, neoplastic and other diseases). Most published DTI studies on the aging brain have relied on the FA, which has been shown to decrease throughout the white matter of the brain during the aging process ( 10 – 12 ). Age-related increases in MD and RD have also been consistently observed ( 13 ).…”

“…Age-related increases in MD and RD have also been consistently observed ( 13 ). However, findings regarding AD have been inconsistent, with both increases and decreases observed in different settings ( 10 , 13 ). The studies comprehensively exploring all four DTI metrics mainly explored pathological processes in the brain (neurodegenerative and genetic disorders) ( 14 , 15 ).…”

Age-related differences in decision-making process in the context of healthy aging

“…White matter tracts, which consist mainly of axons, were also reported to be influenced by aging process [23][24]. With DTI it was shown, that white matter tracts tend to lose integrity with increasing age, so that defining deficits in cognitive functions [25].…”

Differential Effects of Serum Lipoprotein-Associated Phospholipase A2 on Periventricular and Deep Subcortical White Matter Hyperintensity in Brain

“…It depends on the sequence parameters and the severity of pathological changes (3). To date, WMH shows a high prevalence in the aged population (4)(5)(6), which affects stroke outcome (7)(8)(9), cognitive impairment (10,11), and several neurological symptoms (12,13). Therefore, it is necessary to screen the risk factors associated with the pathogenesis of WMH.…”