Effectiveness of regional DTI measures in distinguishing Alzheimer's disease, MCI, and normal aging

Nir, Talia M.; Jahanshad, Neda; Villalon‐Reina, Julio E.; Toga, Arthur W.; Jack, Clifford R.; Weiner, Michael W.; Thompson, Paul M.

doi:10.1016/j.nicl.2013.07.006

Cited by 296 publications

(324 citation statements)

References 108 publications

(59 reference statements)

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“…It was not clear whether the increased axial diffusivity that we observed in GW veterans with predicted GB/GF exposure relative to unexposed veterans was associated with neurodegeneration or white matter reorganization because increased axial diffusivity has been linked with both (e.g., amyotrophic lateral sclerosis (Metwalli et al, 2010), Alzheimer's disease (Bosch et al, 2010;Nir et al, 2013;Shu et al, 2011), animal models of Parkinson disease (Hikishima et al, 2015), white matter reorganization due to axonal recovery or even regrowth (Sidaros et al, 2008;Voss et al, 2006)). For this reason, we conducted post hoc analyses to examine the association between DTI measures and neurobehavioral performance.…”

Section: Va Author Manuscriptmentioning

confidence: 93%

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Effects of low-level sarin and cyclosarin exposure on white matter integrity in Gulf War Veterans

Chao

Buckley

2015

NeuroToxicology

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Background-We previously found evidence of reduced gray and white matter volume in Gulf War (GW) veterans with predicted low-level exposure to sarin (GB) and cyclosarin (GF). Because loss of white matter tissue integrity has been linked to both gray and white matter atrophy, the current study sought to test the hypothesis that GW veterans with predicted GB/GF exposure have evidence of disrupted white matter microstructural integrity.Methods-Measures of fractional anisotropy and directional (i.e., axial and radial) diffusivity were assessed from the 4 T diffusion tensor images (DTI) of 59 GW veterans with predicted GB/GF exposure and 59 "matched" unexposed GW veterans (mean age: 48 ± 7 years). The DTI data were analyzed using regions of interest (ROI) analyses that accounted for age, sex, total brain gray and white matter volume, trauma exposure, posttraumatic stress disorder, current major depression, and chronic multisymptom illness status.Results-There were no significant group differences in fractional anisotropy or radial diffusivity. However, there was increased axial diffusivity in GW veterans with predicted GB/GF exposure compared to matched, unexposed veterans throughout the brain, including the temporal stem, corona radiata, superior and inferior (hippocampal) cingulum, inferior and superior frontooccipital fasciculus, internal and external capsule, and superficial cortical white matter blades. Post hoc analysis revealed significant correlations between higher fractional anisotropy and lower radial diffusivity with better neurobehavioral performance in unexposed GW veterans. In contrast, only Conflict of interestThe authors declare that there are no conflicts of interest. Transparency documentThe Transparency document associated with this article can be found in the online version. U.S. Department of Veterans Affairs VA Author ManuscriptVA Author Manuscript VA Author Manuscript increased axial diffusivity in posterior limb of the internal capsule was associated with better psychomotor function in GW veterans with predicted GB/GF exposure.Conclusions-The finding that increased axial diffusivity in a region of the brain that contains descending corticospinal fibers was associated with better psychomotor function and the lack of significant neurobehavioral deficits in veterans with predicted GB/GF exposure hint at the possibility that the widespread increases in axial diffusivity that we observed in GW veterans with predicted GB/GF exposure relative to unexposed controls may reflect white matter reorganization after brain injury (i.e., exposure to GB/GF).

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Section: Va Author Manuscriptmentioning

confidence: 93%

“…VA Author Manuscript VA Author Manuscript Nir et al, 2013;Sullivan et al, 2010). This was our rationale for examining other DTI parameters in GW veterans with and without predicted GB/GF exposure in the present study.…”

Section: Va Author Manuscriptmentioning

confidence: 99%

Effects of low-level sarin and cyclosarin exposure on white matter integrity in Gulf War Veterans

Chao

Buckley

2015

NeuroToxicology

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“…Some of these studies also demonstrated strong correlation with widely-used clinical measures [20,23,24].…”

Section: Introductionmentioning

confidence: 83%

“…Prior DTI studies in sporadic AD have reported lower FA and increased MD, RD, and/or AxD, throughout WM, mainly in the corpus callosum, fornix, cingulum, superior longitudinal fasciculus, and inferior longitudinal fasciculus [19][20][21][22]. Some of these studies also demonstrated strong correlation with widely-used clinical measures [20,23,24].…”

Section: Introductionmentioning

confidence: 91%

White Matter Abnormalities Track Disease Progression in PSEN1 Autosomal Dominant Alzheimer’s Disease

Sánchez‐Valle

Monté

Sala‐Llonch

et al. 2016

JAD

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Abstract. PSEN1 mutations are the most frequent cause of autosomal dominant Alzheimer's disease (ADAD), and show nearly full penetrance. There is presently increasing interest in the study of biomarkers that track disease progression in order to test therapeutic interventions in ADAD. We used white mater (WM) volumetric characteristics and diffusion tensor imaging (DTI) metrics to investigate correlations with the normalized time to expected symptoms onset (relative age ratio) and group differences in a cohort of 36 subjects from PSEN1 ADAD families: 22 mutation carriers, 10 symptomatic (SMC) and 12 asymptomatic (AMC), and 14 non-carriers (NC). Subjects underwent a 3T MRI. WM morphometric data and DTI metrics were analyzed. We found that PSEN1 MC showed significant negative correlation between fractional anisotropy (FA) and the relative age ratio in the genus and body of corpus callosum and corona radiate (p < 0.05 Family-wise error correction (FWE) at cluster level) and positive correlation with mean diffusivity (MD), axial diffusivity (AxD), and radial diffusivity (RD) in the splenium of corpus callosum. SMC presented WM volume loss, reduced FA and increased MD, AxD, and RD in the anterior and posterior corona radiate, corpus callosum (p < 0.05 FWE) compared with NC. No significant differences were observed between AMC and NC in WM volume or DTI measures. These findings suggest that the integrity of the WM deteriorates linearly in PSEN1 ADAD from the early phases of the disease; thus DTI metrics might be useful to monitor the disease progression. However, the lack of significant alterations at the preclinical stages suggests that these indexes might not be good candidates for early markers of the disease.

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“…A more sensitive to microscope WM changes technique is diffusion tension imaging (DTI). Nir et al (2013) showed widespread diffusivity disruptions associated with neuropsychological and cognitive deficits in specific tracts that passed through the temporal lobe and posterior brain regions in AD and MCI patients 10 . Despite MRI is widely used for AD, the accuracy of MRI as biomarker of early AD generally reaches an accuracy of 80% 11 , what encourages the search of better biomarkers and more accurate diagnostic tools.…”

Section: Challenges In the Discovery Of Potential Biomarkers In Alzhementioning

confidence: 95%

New perspectives in the search for reliable biomarkers in Alzheimer disease

2015

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-Background and Objectives:The search for accurate biomarkers in Alzheimer Disease (AD), on of the most devastating neurodegenerative diseases, remains essential to enable an early prognosis and diagnosis of the disease and to provide more efficient therapeutic strategies.A wide variety of potential biomarkers are has been identified by neuroimaging techniques and by the analysis of fluid samples, such as cerebrospinal fluid (CSF) or blood. Recently, a growing number of studies are focused on the discovery of reliable bloodbased biomarkers in blood, especially in the prodromal stage of AD, which can predict the conversion of asymptomatic cases to AD demented cases.In this review, the latest challenges in the search for accurate biomarkers of AD is revised, in particular, an update in blood-based biomarkers is described in depth.Conclusions: Finally, the close link among AD and other neurodegenerative diseases is discussed, mainly based on the last discovered mutation, the chromosome 9 open reading frame 72, C9ORF72. Challenges in the discovery of potential biomarkers in Alzheimer DiseaseTo date there are no effective therapies to preserve normal brain function in potential future Alzheimer's disease (AD) patients. The absence of reliable biomarkers to identify cognitive normal individuals that will become early-stage AD patients support this fact. Therefore, this overlap between demented and non-demented population has limited the diagnostic accuracy of the current known biomarkers for AD. Due to the fact that neurological processes that finally result in dementia are assumed to be actively long before the first symptoms appear, the availability of diagnostic biomarkers could make a preclinical diagnostic testing and an early treatment of AD possible.A great variety of biomarkers of AD has been described using different approaches (Table 1). As Figure 1 shows, different strategies can be studied along AD progression for a better understanding of the disease and to enable an accurate identification of potential AD biomarkers. Currently, the most studied methods to identify markers of mild cognitive impairment (MCI) and AD are neuroimaging and molecular techniques based on cerebrospinal fluid (CSF). A systematic search on PubMed and Scopus databases was performed to find the most relevant studies and review papers. The key words used for this purpose were: "Alzheimer's disease", "Mild Cognitive Impairment", "biomarkers", "blood", "neuroimaging" and "neurodegenerative diseases" in various combinations. The articles selected were published in English from 2004 to 2015.Neuroimaging is a non-invasive technique which monitors brain regions and allows the subsequent identification and quantification of diagnostic and candidate biomarkers of dementia progression 1 . Magnetic resonance imaging (MRI) is the most widely used neuroimaging technique to investigate brain changes and neurodegeneration. Several longitudinal studies using MRI have been conducted with positive results 2,3 . After followup assessments, th...

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Effectiveness of regional DTI measures in distinguishing Alzheimer's disease, MCI, and normal aging

Cited by 296 publications

References 108 publications

Effects of low-level sarin and cyclosarin exposure on white matter integrity in Gulf War Veterans

Effects of low-level sarin and cyclosarin exposure on white matter integrity in Gulf War Veterans

White Matter Abnormalities Track Disease Progression in PSEN1 Autosomal Dominant Alzheimer’s Disease

New perspectives in the search for reliable biomarkers in Alzheimer disease

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