Longitudinal Changes in Fiber Tract Integrity in Healthy Aging and Mild Cognitive Impairment: A DTI Follow-Up Study

Abstract

Cross-sectional studies using diffusion tensor imaging (DTI) suggest decline of the integrity of intracortically projecting fiber tracts with aging and in neurodegenerative diseases, such as Alzheimer's disease (AD). Longitudinal studies on the change of fiber tract integrity in normal and pathological aging are still rare. Here, we prospectively studied 11 healthy elderly subjects and 14 subjects with amnestic mild cognitive impairment (MCI), a clinical risk group for AD, using high-resolution DTI and MRI at baseline and after 13 to 16 months follow-up. Fractional anisotropy (FA), a DTI measure of fiber tract integrity, was compared across time points and groups using a repeated measures linear model and tract based spatial statistics. Additionally, we determined rates of grey matter and white matter atrophy using automated deformation based morphometry. Healthy elderly subjects showed decline of FA in intracortical projecting fiber tracts, such as corpus callosum, superior longitudinal fasciculus, uncinate fasciculus, inferior fronto-occipital fasciculus, and cingulate bundle (p < 0.05, corrected for multiple comparisons). MCI subjects showed significant FA decline predominantly in the anterior corpus callosum (p < 0.05, corrected for multiple comparisons). Grey and white matter atrophy involved prefrontal, parietal, and temporal lobe areas in controls and prefrontal, cingulate, and parietal lobe areas in MCI subjects and agreed with the pattern of fiber tract changes. Our findings indicate that DTI allows detection of microstructural changes in subcortical fiber tracts over time that are related to aging as well as to early stages of AD type neurodegeneration. The underlying mechanisms for these changes are unknown.

Individual Classification of Mild Cognitive Impairment Subtypes by Support Vector Machine Analysis of White Matter DTI

“…80 The more pronounced damage of inferior fronto-occipital and inferior longitudinal fasciculi in md-aMCI compared with sd-fMCI is in agreement with the retrogenesis hypothesis in AD that postulates an early involvement of late-myelinating pathways in the initial phases of the degenerative process. 29,31 The comparison between sd-fMCI and sd-aMCI yielded no significant group differences. There are 2 possible explanations for this result.…”

“…Most investigations included only 1 (not further specified) MCI group, [23][24][25] or only the sd-aMCI subtype, [26][27][28][29] or a mix of several subtypes, with the aim of discriminating stable versus progressive MCI. 30 Only 3 recent contributions compared DTI patterns in aMCI versus non-MCI.…”

“…Applying DTI analyses with voxelwise TBSS, 22 an increasing number of contributions described the damage of long interhemispheric and intrahemispheric white matter tracts with homogeneously oriented fibers (ie, genu or splenium of the corpus callosum, superior longitudinal fasciculus, cingulus) and, more rarely, in frontal, parietal, and temporal white matter in patients with MCI compared with healthy controls. [23][24][25][26][27][28][29][30][31] The biologic relevance of the description of MCI subtypes is still a challenging issue. In particular, it is unclear whether the neuropsychologic definition of these subtypes corresponds to distinct patterns of brain compromise.…”

Longitudinal change of small-vessel disease-related brain abnormalities

“…79 In a longitudinal study, in 62 CADASIL subjects the changes in mean diffusivity correlated with changes in the Rankin score, national institute of health stroke scale and structured interview for the diagnosis of dementia of the Alzheimer type, multiinfarct dementia and dementias of other aetiology within a 2-year observation period. 28 Diffusion tensor imaging was also used in early detection 80,81 and monitoring of disease progression from mild cognitive impairment to Alzheimer's disease. 82 Sample size calculation based on 2-year follow-up data in CADASIL patients showed that one would need 1,944 subjects per treatment arm to show a treatment effect of 20% with an 80% power when mean diffusivity is used as the trial outcome.…”

Transcallosal Connectivity Changes from Infancy to Late Adulthood: An Ex Vivo Diffusion Spectrum Imaging Study of Macaque Brains

“…A previous rsfMRI study has demonstrated that decreased interhemispheric functional connectivity in sensorimotor cortex, superior temporal gyrus, and superior parietal lobule was relevant to functional defects in autism patients (Anderson et al, 2011). A decline of anterior white matter integrity was also found in elderly people with cognitive impairment (Teipel et al, 2010). Such cognitive disorders could be associated with the abnormal transcallosal connectivity in the relevant cortical regions.…”