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Detection of Alzheimer's Disease using cortical diffusion tensor imaging.

ABSTRACT: The aim of this research was to test a novel in-vivo brain MRI analysis method that could be used in clinical cohorts to investigate cortical architecture changes in patients with Alzheimer's Disease (AD). Three cohorts of patients with probable AD and healthy volunteers were used to assess the results of the method. The first group was used as the "Discovery" cohort, the second as the "Test" cohort and the last "ATN" (Amyloid, Tau, Neurodegeneration) cohort was used to test the method in an ADNI 3 cohort, comparing to amyloid and Tau PET. The method can detect altered quality of cortical grey matter in AD patients, providing an additional tool to assess AD, distinguishing between these and healthy controls with an accuracy range between good and excellent. These new measurements could be used within the "ATN" framework as an index of cortical microstructure quality and a marker of Neurodegeneration. Further development may aid diagnosis, patient selection, and quantification of the "Neurodegeneration" component in response to therapies in clinical trials.

SUBMITTER: Torso M

PROVIDER: S-EPMC7856641 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Detection of Alzheimer's Disease using cortical diffusion tensor imaging.

Torso Mario M Bozzali Marco M Zamboni Giovanna G Jenkinson Mark M Chance Steven A SA

Human brain mapping 20201111 4

The aim of this research was to test a novel in-vivo brain MRI analysis method that could be used in clinical cohorts to investigate cortical architecture changes in patients with Alzheimer's Disease (AD). Three cohorts of patients with probable AD and healthy volunteers were used to assess the results of the method. The first group was used as the "Discovery" cohort, the second as the "Test" cohort and the last "ATN" (Amyloid, Tau, Neurodegeneration) cohort was used to test the method in an ADN ...[more]

PMID: 33174658

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Project description:BackgroundAlthough diffusion tensor imaging has been a major research focus for Alzheimer's disease in recent years, it remains unclear whether it has sufficient stability to have biomarker potential. To date, frequently inconsistent results have been reported, though lack of standardisation in acquisition and analysis make such discrepancies difficult to interpret. There is also, at present, little knowledge of how the biometric properties of diffusion tensor imaging might evolve in the course of Alzheimer's disease.MethodsThe biomarker question was addressed in this study by adopting a standardised protocol both for the whole brain (tract-based spatial statistics), and for a region of interest: the midline corpus callosum. In order to study the evolution of tensor changes, cross-sectional data from very mild (N?=?21) and mild (N?=?22) Alzheimer's disease patients were examined as well as a longitudinal cohort (N?=?16) that had been rescanned at 12 months.Findings and significanceThe results revealed that increased axial and mean diffusivity are the first abnormalities to occur and that the first region to develop such significant differences was mesial parietal/splenial white matter; these metrics, however, remained relatively static with advancing disease indicating they are suitable as 'state-specific' markers. In contrast, increased radial diffusivity, and therefore decreased fractional anisotropy-though less detectable early-became increasingly abnormal with disease progression, and, in the splenium of the corpus callosum, correlated significantly with dementia severity; these metrics therefore appear 'stage-specific' and would be ideal for monitoring disease progression. In addition, the cross-sectional and longitudinal analyses showed that the progressive abnormalities in radial diffusivity and fractional anisotropy always occurred in areas that had first shown an increase in axial and mean diffusivity. Given that the former two metrics correlate with dementia severity, but the latter two did not, it would appear that increased axial diffusivity represents an upstream event that precedes neuronal loss.

Project description:ObjectiveTo describe and compare diffusion tensor imaging (DTI) parameters between patients with subcortical ischemic vascular disease (SIVD) and Alzheimer's disease (AD) diagnosed using structuralized neuropsychiatric assessments, and investigate potential neuronal substrates related to cognitive performance.MethodsThirty-five patients with SIVD, 40 patients with AD, and 33 cognitively normal control (NC) subjects matched by age and education level were consecutively recruited and underwent cognitive function assessments and DTI examinations. Comparisons among these three subgroups with regards to cognitive performance and DTI parameters including fractional anisotropy (FA) and mean diffusivity (MD) values were performed. Partial correlation analysis after controlling for age and education was used to evaluate associations between cognitive performance and DTI parameters.ResultsWith regards to cognitive performance, the patients with SIVD had lower total scores in frontal assessment battery (FAB) compared to those with AD (p < 0.05) in the context of comparable Mini-Mental Status Examination and Cognitive Abilities Screening Instrument scores. With regards to DTI parameters, there were more regions of significant differences in FA among these three subgroups compared with MD. Compared with NC group, the patients with SIVD had significant global reductions in FA (p < 0.001 ~ 0.05), while significant reductions in FA among the patients with AD were regionally confined within the left superior longitudinal fasciculus, genu and splenium of the corpus callosum, and bilateral forceps major, and the anterior thalamic radiation, uncinate fasciculus, and cingulum of the left side (p < 0.01 ~ 0.05). Analysis of FA values within the left forceps major, left anterior thalamic radiation, and genu of the corpus callosum revealed a 71.8% overall correct classification (p < 0.001) with sensitivity of 69.4%, specificity of 73.8%, positive predictive value of 69.4%, and negative predictive value of 73.8% in discriminating patients with SIVD from those with AD. In combined analysis of the patients with SIVD and AD (n = 75), the total FAB score was positively correlated with FA within the bilateral forceps minor, genu of the corpus callosum, left forceps major, left uncinate fasciculus, and right inferior longitudinal fasciculus (p = 0.001 ~ 0.038), and inversely correlated with MD within the right superior longitudinal fasciculus, genu and body of the corpus callosum, bilateral forceps minor, right uncinate fasciculus, and right inferior longitudinal fasciculus (p = 0.003 ~ 0.040).ConclusionsOur findings suggest the effectiveness of DTI measurements in distinguishing patients with early-stage AD from those with SIVD, with discernible changes in spatial distribution and magnitude of significance of the DTI parameters. Strategic FA assessments provided the most robust discriminative power to differentiate SIVD from AD, and FAB may serve as an additional cognitive marker. We also identified the neuronal substrates responsible for FAB performance.

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Detection of Alzheimer's Disease using cortical diffusion tensor imaging.

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Detection of Alzheimer's Disease using cortical diffusion tensor imaging.

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