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      Cortical Thickness in Dementia with Lewy Bodies and Alzheimer's Disease: A Comparison of Prodromal and Dementia Stages

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          Abstract

          Objectives

          To assess and compare cortical thickness (CTh) of patients with prodromal Dementia with Lewy bodies (pro-DLB), prodromal Alzheimer's disease (pro-AD), DLB dementia (DLB-d), AD dementia (AD-d) and normal ageing.

          Methods

          Study participants(28 pro-DLB, 27 pro-AD, 31 DLB-d, 54 AD-d and 33 elderly controls) underwent 3Tesla T1 3D MRI and detailed clinical and cognitive assessments. We used FreeSurfer analysis package to measure CTh and investigate patterns of cortical thinning across groups.

          Results

          Comparison of CTh between pro-DLB and pro-AD (p<0.05, FDR corrected) showed more right anterior insula thinning in pro-DLB, and more bilateral parietal lobe and left parahippocampal gyri thinning in pro-AD. Comparison of prodromal patients to healthy elderly controls showed the involvement of the same regions. In DLB-d (p<0.05, FDR corrected) cortical thinning was found predominantly in the right temporo-parietal junction, and insula, cingulate, orbitofrontal and lateral occipital cortices. In AD-d(p<0.05, FDR corrected),the most significant areas affected included the entorhinal cortices, parahippocampal gyri and parietal lobes. The comparison of AD-d and DLB-d demonstrated more CTh in AD-d in the left entorhinal cortex (p<0.05, FDR corrected).

          Conclusion

          Cortical thickness is a sensitive measure for characterising patterns of grey matter atrophy in early stages of DLB distinct from AD. Right anterior insula involvement may be a key region at the prodromal stage of DLB and needs further investigation.

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          Most cited references21

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          3D maps from multiple MRI illustrate changing atrophy patterns as subjects progress from mild cognitive impairment to Alzheimer's disease.

          Mild cognitive impairment (MCI), particularly the amnestic subtype (aMCI), is considered as a transitional stage between normal aging and a diagnosis of clinically probable Alzheimer's disease (AD). The aMCI construct is particularly useful as it provides an opportunity to assess a clinical stage which in most subjects represents prodromal AD. The aim of this study was to assess the progression of cerebral atrophy over multiple serial MRI during the period from aMCI to progression to AD. Thirty-three subjects were selected that fulfilled clinical criteria for aMCI and had three serial MRI scans: the first scan approximately 3 years before the diagnosis of AD, the second scan approximately 1 year before, and the third scan at the time of the diagnosis of AD. A group of 33 healthy controls were age and gender-matched to the study cohort. Voxel-based morphometry (VBM) was used to assess patterns of grey matter atrophy in the aMCI subjects at each time-point compared to the control group. Customized templates and prior probability maps were used to avoid normalization and segmentation bias. The pattern of grey matter loss in the aMCI subject scans that were 3 years before the diagnosis of AD was focused primarily on the medial temporal lobes, including the amygdala, anterior hippocampus and entorhinal cortex, with some additional involvement of the fusiform gyrus, compared to controls. The extent and magnitude of the cerebral atrophy further progressed by the time the subjects were 1 year before the diagnosis of AD. At this point atrophy in the temporal lobes spread to include the middle temporal gyrus, and extended into more posterior regions of the temporal lobe to include the entire extent of the hippocampus. The parietal lobe also started to become involved. By the time the subjects had progressed to a clinical diagnosis of AD the pattern of grey matter atrophy had become still more widespread with more severe involvement of the medial temporal lobes and the temporoparietal association cortices and, for the first time, substantial involvement of the frontal lobes. This pattern of progression fits well with the Braak and Braak neurofibrillary pathological staging scheme in AD. It suggests that the earliest changes occur in the anterior medial temporal lobe and fusiform gyrus, and that these changes occur at least 3 years before progression to the diagnosis of AD. These results also suggest that 3D patterns of grey matter atrophy may help to predict the time to the first diagnosis of AD in subjects with aMCI.
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            The cortical signature of prodromal AD: regional thinning predicts mild AD dementia.

            We previously used exploratory analyses across the entire cortex to determine that mild Alzheimer disease (AD) is reliably associated with a cortical signature of thinning in specific limbic and association regions. Here we investigated whether the cortical signature of AD-related thinning is present in individuals with questionable AD dementia (QAD) and whether a greater degree of regional cortical thinning predicts mild AD dementia. Participants included 49 older adults with mild impairment consistent with mild cognitive impairment (Clinical Dementia Rating [CDR] = 0.5) at the time of structural MRI scanning. Cortical thickness was measured in nine regions of interest (ROIs) identified previously from a comparison of patients with mild AD and controls. Longitudinal clinical follow-up revealed that 20 participants converted to mild AD dementia (progressors) while 29 remained stable (nonprogressors) approximately 2.5 years after scanning. At baseline, QAD participants showed a milder degree of cortical thinning than typically seen in mild AD, and CDR Sum-of-Boxes correlated with thickness in temporal and parietal ROIs. Compared to nonprogressors, progressors showed temporal and parietal thinning. Using receiver operating characteristic curves, the thickness of an aggregate measure of these regions predicted progression to mild AD with 83% sensitivity and 65% specificity. Thinning in specific cortical areas known to be affected by Alzheimer disease (AD) is detectable in individuals with questionable AD dementia (QAD) and predicts conversion to mild AD dementia. This method could be useful for identifying individuals at relatively high risk for imminent progression from QAD to mild AD dementia, which may be of value in clinical trials.
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              The Clinician Assessment of Fluctuation and the One Day Fluctuation Assessment Scale. Two methods to assess fluctuating confusion in dementia.

              The identification of fluctuating confusion is central to improving the differential diagnosis of the common dementias. To determine the value of two rating scales to measure fluctuating confusion. The agreement between the clinician-rated scale and the scale completed by a non-clinician was determined. Correlations between the two scales were calculated; variability in attention was calculated on a computerised cognitive assessment and variability in delta rhythm on an electroencephalogram (EEG). The Clinician Assessment of Fluctuation and the computerised cognitive assessment were completed for 155 patients (61 Alzheimer's disease, 37 dementia with Lewy bodies, 22 vascular dementia, 35 elderly controls). A subgroup (n = 40) received a further evaluation using the One Day Fluctuation Assessment Scale and an EEG. The two scales correlated significantly with each other, and with the neuropsychological and electrophysiological measures of fluctuation. Both scales are useful instruments for the clinical assessment of fluctuation in dementia.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                10 June 2015
                2015
                : 10
                : 6
                : e0127396
                Affiliations
                [1 ]University Hospital of Strasbourg, Neuropsychology Unit, Neurology Service, Strasbourg, France
                [2 ]University of Strasbourg and CNRS, ICube laboratory UMR 7357 and FMTS (Fédération de MédecineTranslationnelle de Strasbourg), team IMIS/Neurocrypto, Strasbourg, France
                [3 ]University Hospital of Strasbourg, CMRR (Memory Resources and Research Centre), Strasbourg, France
                [4 ]Institute of Neuroscience, Campus for Aging and Vitality, Newcastle University, Newcastle upon Tyne, United Kingdom
                [5 ]University Hospital of Strasbourg, Hôpital de jour de gériatrie, Geriatry Service, Strasbourg, France
                [6 ]Department of Psychiatry, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom
                [7 ]University Hospital of Strasbourg, Neuroradiology Service, Strasbourg, France
                Beijing Normal University,Beijing, CHINA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: F. Blanc SJC IM JT. Performed the experiments: F. Blanc SJC. Analyzed the data: F. Blanc SJC JT. Contributed reagents/materials/analysis tools: F. Bing SJC NP XdP BJ CD CP PA AT JL CMH JTO BC JPA. Wrote the paper: F. Blanc SJC JT. Inclusion and examination of patients: F. Blanc NP XdP CD PA CP AT CMH JTO BC IM JT. Quality control of the data: BJ JL F. Bing F. Blanc JA CP. Revising critically for important intellectual content: F. Bing IM SJC NP AT JT.

                Article
                PONE-D-14-54828
                10.1371/journal.pone.0127396
                4489516
                26061655
                7b05a243-e965-4565-8b22-11fd08825e40
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 18 December 2014
                : 15 April 2015
                Page count
                Figures: 4, Tables: 2, Pages: 18
                Funding
                This study was funded by Appel à Projet Interne (API) of the University Hospital of Strasbourg, Alsace Alzheimer 67, Fondation Université de Strasbourg and famille Jean Amrhein, and Projet Hospitalier de Recherche Clinique (PHRC) inter-régional (IDRCB 2012-A00992-41). The work was also supported by the following: the Newcastle Healthcare Charity (BH0070250); Academy of Medical Sciences, Wellcome Trust Starter Grants scheme for Clinical Lecturers (BH090112 to J-P.T.); Wellcome Intermediate Clinical Fellowship (BH083281 to J-P.T.); National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre in Ageing and Chronic Disease and Biomedical Research Unit in Lewy Body Dementia based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University; NIHR Dementia Biomedical Research Unit at Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.
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