Diffusion Tensor Imaging of the Posterior Cingulate is a Useful Biomarker of Mild Cognitive Impairment

doi:10.1097/JGP.0b013e3181a76e0b

The American Journal of Geriatric Psychiatry

Volume 17, Issue 7, July 2009, Pages 602-613

https://doi.org/10.1097/JGP.0b013e3181a76e0b Get rights and content

Objectives:

Mild cognitive impairment (MCI) is recognized as a predementia state, but its definition is inconsistent and only 20%–30% develop dementia after 2 years. Biomarkers may help identify individuals at greatest risk of progressive decline. The authors examine a novel neuroimaging technique, diffusion tensor imaging (DTI) as a potential biomarker of MCI.

Design:

Cross-sectional prospective study.

Setting:

Subjects were recruited randomly using the electoral roll from two electorates in East Sydney, Australia.

Participants:

A community-dwelling sample (N = 249) and age 70–90 years.

Measurements:

Screening to exclude dementia, comprehensive neuropsychiatric assessment, cognitive test battery, structural magnetic resonance imaging and DTI to obtain measures of fractional anisotropy (FA) and mean diffusivity (MD). MCI was diagnosed by standard criteria.

Results:

After controlling for age, sex, and years of education, the amnestic MCI (aMCI) group demonstrated microstructural pathology in the parahippocampal white matter, frontal white matter, splenium of corpus callosum, and posterior cingulate region. The nonamnestic MCI (naMCI) group demonstrated microstructural pathology in the frontal white matter, internal capsule, occipital white matter, and the posterior cingulate region. A binary logistic regression model showed that DTI of the left posterior cingulate was significant in identifying persons with aMCI to an accuracy of 85.1%. Receiver operating characteristics curve analysis yielded a sensitivity of 80% and specificity of 60.3% in distinguishing aMCI from naMCI and the normal comparison group.

Conclusion:

DTI of the posterior cingulate region discriminates MCI from cognitively normal individuals with accuracy and has the potential to be used as a biomarker of MCI, in particular aMCI.

Section snippets

Participants

The study sample is part of the larger Memory and Ageing Study, which comprises community-dwelling individuals aged 70–90 years recruited using the electoral roll from two electorates in East Sydney, Australia. Potential subjects were approached by mail after random assignment from the roll, and those who responded positively were screened for eligibility. Participants with insufficient English language competency to complete the assessment, history of neurological (e.g., diagnosed dementia,

Sample

We studied the initial 284 participants of the Memory and Ageing Study. Of these, 20 neither meet the MCI diagnostic criteria nor could be classified as normal, and 15 had missing neuropsychological test data, which would not allow an accurate classification. Of the remaining 249 participants, 153 were classified as cognitively NC subjects and 96 as having MCI. Within the MCI group, there were 55 participants with a diagnosis of aMCI and 41 participants with a diagnosis of naMCI. The three

CONCLUSION

The aims of our study were to use DTI to examine microstructural abnormality in MCI and its subtypes and to evaluate its utility as a diagnostic tool in the predementia work-up. We found that microstructural abnormalities occurring in aMCI tend to occur in the regions receiving efferent outputs from the entorhinal-hippocampal system and in naMCI tend to occur in more diverse regions. We also observed fair overall diagnostic utility of DTI measures of the posterior cingulate region in aMCI.

The

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Differential and subtype-specific neuroimaging abnormalities in amnestic and nonamnestic mild cognitive impairment: A systematic review and meta-analysis
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Citation Excerpt :
The forest plots of these meta-analyses can be found in Supplementary Figure 3. Ten DTI studies evaluated microscopic white matter integrity in terms of fractional anisotropy (k = 10), mean diffusivity (k = 7), and other diffusivity metrics (Chua et al., 2009; Delano-Wood et al., 2012; Gyebnár et al., 2018; O'Dwyer et al., 2011; Rowley et al., 2013; Thillainadesan et al., 2012; Wai et al., 2014; Wang et al., 2021; Zhuang et al., 2010, 2012). All ten studies (100%) and eight studies (80%) detected lower fractional anisotropy values or higher (mean) diffusivity values across white matter tracts in aMCI and naMCI compared with NC, respectively.
While mild cognitive impairment (MCI) has been classified into amnestic MCI (aMCI) and nonamnestic MCI (naMCI), the neuropathological bases of these two subtypes remain elusive. Here, we performed a systematic review and meta-analysis to determine the subtype specificity of neuroimaging abnormalities in MCI and to identify neural features that may differ between aMCI and naMCI. We synthesized 50 studies that used common neuroimaging modalities, including magnetic resonance imaging and positron emission tomography, to compare brain atrophy, white matter abnormalities, cortical thinning, cerebral hypometabolism, amyloid/tau deposition, or other features among aMCI, naMCI, and normal cognition. Compared with normal cognition, aMCI shows diverse neuroimaging abnormalities of large effect sizes. In contrast, naMCI exhibits restricted abnormalities of small effect sizes. Some features, including medial temporal lobe atrophy and white matter abnormalities, are shared by the two MCI subtypes. Overall, brain abnormalities are worse, if not similar, in aMCI than in naMCI. The only neuroimaging abnormality specific to aMCI is increased amyloid burden; no feature specific to naMCI was found. Taken together, our findings have elucidated the neuropathological changes that occur in aMCI and naMCI. Clarifying the neuroimaging profiles of aMCI and naMCI can improve the early identification, differentiation, and intervention of prodromal dementia.
White matter integrity is associated with gait impairment and falls in mild cognitive impairment. Results from the gait and brain study
2019, NeuroImage: Clinical
Mild Cognitive Impairment (MCI) is an intermediate state between normal cognition and dementia that is associated with twice the risk of falls. It is unknown whether white matter integrity (WMI) is associated with increased risk of falls in MCI. The purpose of this study was to evaluate if early changes in WMI were associated with gait impairment and falls.
Forty-three participants with MCI from the Gait and Brain Study underwent standardized assessment of cognition, gait performance under single and dual-task conditions (walking while talking), and WMI using 3 Tesla diffusion tensor imaging (DTI). Macro-structural imaging characteristics (white and grey matter morphology) as well as microstructural WMI parameters were examined for associations with falls and gait performance. Significantly associated WM tracts were then used to test the interplay between WMI and history of falls, after adjusting for other important covariates.
Multiple WM tracts (corpus callosum, forceps minor, and the left inferior fronto-occipital fasciculus) were significantly associated with history of falls and lower dual-task gait performance. A multivariable regression model showed that fall history was associated with the radial diffusivity in the forceps minor, even after adjusting for education, sex, BMI, MMSE scores, comorbidities, gait velocity and WMH volume as covariates.
Multiple WM tracts that are known to be involved in executive and visuospatial functions were preferentially affected in MCI individuals with history of falls. Our preliminary findings support the notion that WMI in key brain regions may increase risk of falls in older adults with MCI.
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The diagnostic value of cerebrospinal fluid (CSF) biomarkers is well established in Alzheimer's disease, but our current knowledge about how abnormal CSF levels affect cerebral integrity, at local and network levels, is incomplete in asymptomatic older adults. Here, we have collected CSF samples and performed structural magnetic resonance imaging scans in cognitively normal elderly as part of a cross-sectional multicenter study (SIGNAL project). To identify group differences in cortical thickness, white matter volume, and properties of structural networks, participants were split into controls (N = 20), positive amyloid-β (Aβ_1–42 ⁺) (N = 19), and positive phosphorylated tau (N = 18). The Aβ_1–42 ⁺ group exhibited thickening of middle temporal regions, while positive phosphorylated tau individuals showed thinning in the superior parietal and orbitofrontal cortices. Subjects with abnormal CSF biomarkers further showed regional white matter atrophy and more segregated cortical networks, the Aβ_1–42 ⁺ group showing heightened isolation of cingulate and temporal cortices. Collectively, these findings highlight the relevance of combining structural brain imaging and connectomics for in vivo tracking of Alzheimer's disease lesions in asymptomatic stages.
White matter microstructural abnormalities in amnestic mild cognitive impairment: A meta-analysis of whole-brain and ROI-based studies
2017, Neuroscience and Biobehavioral Reviews
Studies that examined white matter (WM) alterations in amnestic mild cognitive impairment (aMCI) abound. This timely meta-analysis aims to synthesize the results of these studies. Seventy-seven studies (total N_aMCI = 1844) were included. Fourteen region-of-interest-based (ROI-based) (k ≥ 8; N_aMCI ≥ 284 per ROI) and two activation likelihood estimation (ALE) meta-analyses (fractional anisotropy [FA]: k = 15; N_aMCI = 463; mean diffusivity [MD]: k = 8; N_aMCI = 193) were carried out. Among the many significant ROI-related findings, reliable FA and MD alterations in the fornix, uncinate fasciculus, and parahippocampal cingulum were observed in aMCI. Larger effects were observed in MD relative to FA. The ALE meta-analysis revealed a significant FA decrease among aMCI subjects in the posterior corona radiata. These results provide robust evidence of the presence of WM abnormalities in aMCI. Our findings also highlight the importance of carrying out both ROI-based and whole-brain-based research to obtain a complete picture of WM microstructural alterations associated with the condition..
Age-related differences in the topological efficiency of the brain structural connectome in amnestic mild cognitive impairment
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Amnestic mild cognitive impairment (aMCI) is accompanied by the accelerated cognitive decline and rapid brain degeneration with aging. However, the age-related alterations of the topological organization of the brain connectome in aMCI patients remained largely unknown. In this study, we constructed the brain structural connectome in 51 aMCI patients and 51 healthy controls by diffusion magnetic resonance imaging and deterministic tractography. The different age-related alteration patterns of the global and regional network metrics between aMCI patients and healthy controls were assessed by a linear regression model. Compared with healthy controls, significantly decreased global and local network efficiency in aMCI patients were found. When correlating network efficiency with age, we observed a significant decline in network efficiency with aging in the aMCI patients, while not in the healthy controls. The age-related decreases of nodal efficiency in aMCI patients were mainly distributed in the key regions of the default-mode network, such as precuneus, anterior cingulate gyrus, and parahippocampal gyrus. In addition, age-related decreases in the connection strength of the edges between peripheral nodes were observed in aMCI patients. Moreover, the decreased regional efficiency of the parahippocampal gyrus was correlated with impaired memory performances in patients. The present study suggests an age-related disruption of the topological organization of the brain structural connectome in aMCI patients, which may provide evidence for different neural mechanisms underlying aging in aMCI and may serve as a potential imaging marker for the early diagnosis of Alzheimer's disease.
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Pattern of diffusion tensor MRI (DTI) alterations were investigated in pathologically-staged Alzheimer's disease (AD) patients (n = 46). Patients with antemortem DTI studies and a range of AD pathology at autopsy were included. Patients with a high neurofibrillary tangle (NFT) stage (Braak IV–VI) had significantly elevated mean diffusivity (MD) in the crus of fornix and ventral cingulum tracts, precuneus, and entorhinal white matter on voxel-based analysis after adjusting for age and time from MRI to death (p < 0.001). Higher MD and lower fractional anisotropy in the ventral cingulum tract, entorhinal, and precuneus white matter was associated with higher Braak NFT stage and clinical disease severity. There were no MD and fractional anisotropy differences among the low (none and sparse) and high (moderate and frequent) β-amyloid neuritic plaque groups. The NFT pathology of AD is associated with DTI alterations involving the medial temporal limbic connections and medial parietal white matter. This pattern of diffusion abnormalities is also associated with clinical disease severity.

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This work was supported by a Program grant of the National Health & Medical Research Council of Australia ID number 350833.

The funding body had no involvement in the design, conduct, and reporting of this study.

The authors declare no conflict of interest.

The study was approved by the Human Research Ethics Committees of the University of New South Wales and the South Eastern Sydney, Australia, Area Health Service Human Research Ethics Committee. All subjects provided informed written consent.

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Regular Research ArticlesDiffusion Tensor Imaging of the Posterior Cingulate is a Useful Biomarker of Mild Cognitive Impairment

Objectives:

Design:

Setting:

Participants:

Measurements:

Results:

Conclusion:

Section snippets

Participants

Sample

CONCLUSION

Lancet

Lancet Neurol

Alzheimer's Dement

Neuropsychologia

Med Image Anal

J Magn Reson B

Neurobiol Aging

Magn Reson Imaging

Lancet

J Psych Res

Mild cognitive impairment as a diagnostic entity

J Intern Med

Mild cognitive impairment: a nosological entity?

Curr Opin Neurol

Diffusion-tensor MRI: theory, experimental design and data analysis—a technical review

NMR Biomed

Diffusion tensor imaging in mild cognitive impairment and Alzheimer's disease: a review

Curr Opin Neurol

Potential role of diffusion tensor MRI in the differential diagnosis of mild cognitive impairment and Alzheimer's disease

AJR Am J Roentgenol

WAIS-III/WMS-III Technical Manual Update

L'examen clinique en psychologie

Der Benton Test

Boston Naming Test

Manual for the Wechsler Adult Intelligence Scale-Revised

Wechsler Adult Intelligence Scale

Regular Research Articles
Diffusion Tensor Imaging of the Posterior Cingulate is a Useful Biomarker of Mild Cognitive Impairment