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Single-subject grey matter graphs in Alzheimer's disease.

ABSTRACT: Coordinated patterns of cortical morphology have been described as structural graphs and previous research has demonstrated that properties of such graphs are altered in Alzheimer's disease (AD). However, it remains unknown how these alterations are related to cognitive deficits in individuals, as such graphs are restricted to group-level analysis. In the present study we investigated this question in single-subject grey matter networks. This new method extracts large-scale structural graphs where nodes represent small cortical regions that are connected by edges when they show statistical similarity. Using this method, unweighted and undirected networks were extracted from T1 weighted structural magnetic resonance imaging scans of 38 AD patients (19 female, average age 72±4 years) and 38 controls (19 females, average age 72±4 years). Group comparisons of standard graph properties were performed after correcting for grey matter volumetric measurements and were correlated to scores of general cognitive functioning. AD networks were characterised by a more random topology as indicated by a decreased small world coefficient (p?=?3.53×10(-5)), decreased normalized clustering coefficient (p?=?7.25×10(-6)) and decreased normalized path length (p?=?1.91×10(-7)). Reduced normalized path length explained significantly (p?=?0.004) more variance in measurements of general cognitive decline (32%) in comparison to volumetric measurements (9%). Altered path length of the parahippocampal gyrus, hippocampus, fusiform gyrus and precuneus showed the strongest relationship with cognitive decline. The present results suggest that single-subject grey matter graphs provide a concise quantification of cortical structure that has clinical value, which might be of particular importance for disease prognosis. These findings contribute to a better understanding of structural alterations and cognitive dysfunction in AD.

SUBMITTER: Tijms BM

PROVIDER: S-EPMC3594199 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Single-subject grey matter graphs in Alzheimer's disease.

Tijms Betty M BM Möller Christiane C Vrenken Hugo H Wink Alle Meije AM de Haan Willem W van der Flier Wiesje M WM Stam Cornelis J CJ Scheltens Philip P Barkhof Frederik F

PloS one 20130311 3

Coordinated patterns of cortical morphology have been described as structural graphs and previous research has demonstrated that properties of such graphs are altered in Alzheimer's disease (AD). However, it remains unknown how these alterations are related to cognitive deficits in individuals, as such graphs are restricted to group-level analysis. In the present study we investigated this question in single-subject grey matter networks. This new method extracts large-scale structural graphs whe ...[more]

PMID: 23536835

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Project description:Structural grey matter covariance networks provide an individual quantification of morphological patterns in the brain. The network integrity is disrupted in sporadic Alzheimer's disease, and network properties show associations with the level of amyloid pathology and cognitive decline. Therefore, these network properties might be disease progression markers. However, it remains unclear when and how grey matter network integrity changes with disease progression. We investigated these questions in autosomal dominant Alzheimer's disease mutation carriers, whose conserved age at dementia onset allows individual staging based upon their estimated years to symptom onset. From the Dominantly Inherited Alzheimer Network observational cohort, we selected T1-weighted MRI scans from 269 mutation carriers and 170 non-carriers (mean age 38 ± 15 years, mean estimated years to symptom onset -9 ± 11), of whom 237 had longitudinal scans with a mean follow-up of 3.0 years. Single-subject grey matter networks were extracted, and we calculated for each individual the network properties which describe the network topology, including the size, clustering, path length and small worldness. We determined at which time point mutation carriers and non-carriers diverged for global and regional grey matter network metrics, both cross-sectionally and for rate of change over time. Based on cross-sectional data, the earliest difference was observed in normalized path length, which was decreased for mutation carriers in the precuneus area at 13 years and on a global level 12 years before estimated symptom onset. Based on longitudinal data, we found the earliest difference between groups on a global level 6 years before symptom onset, with a greater rate of decline of network size for mutation carriers. We further compared grey matter network small worldness with established biomarkers for Alzheimer disease (i.e. amyloid accumulation, cortical thickness, brain metabolism and cognitive function). We found that greater amyloid accumulation at baseline was associated with faster decline of small worldness over time, and decline in grey matter network measures over time was accompanied by decline in brain metabolism, cortical thinning and cognitive decline. In summary, network measures decline in autosomal dominant Alzheimer's disease, which is alike sporadic Alzheimer's disease, and the properties show decline over time prior to estimated symptom onset. These data suggest that single-subject networks properties obtained from structural MRI scans form an additional non-invasive tool for understanding the substrate of cognitive decline and measuring progression from preclinical to severe clinical stages of Alzheimer's disease.

Project description:The identification of prognostic markers in early multiple sclerosis (MS) is challenging and requires reliable measures that robustly predict future disease trajectories. Ideally, such measures should make inferences at the individual level to inform clinical decisions. This study investigated the prognostic value of longitudinal structural networks to predict 5-year Expanded Disability Status Scale (EDSS) progression in patients with relapsing-remitting MS (RRMS). We hypothesized that network measures, derived from MRI, outperform conventional MRI measurements at identifying patients at risk of developing disability progression. This longitudinal, multicentre study within the Magnetic Resonance Imaging in MS (MAGNIMS) network included 406 patients with RRMS (mean age = 35.7 ± 9.1 years) followed up for 5 years (mean follow-up = 5.0 ± 0.6 years). EDSS was determined to track disability accumulation. A group of 153 healthy subjects (mean age = 35.0 ± 10.1 years) with longitudinal MRI served as controls. All subjects underwent MRI at baseline and again 1 year after baseline. Grey matter atrophy over 1 year and white matter lesion load were determined. A single-subject brain network was reconstructed from T1-weighted scans based on grey matter atrophy measures derived from a statistical parameter mapping-based segmentation pipeline. Key topological measures, including network degree, global efficiency and transitivity, were calculated at single-subject level to quantify network properties related to EDSS progression. Areas under receiver operator characteristic (ROC) curves were constructed for grey matter atrophy and white matter lesion load, and the network measures and comparisons between ROC curves were conducted. The applied network analyses differentiated patients with RRMS who experience EDSS progression over 5 years through lower values for network degree [H(2) = 30.0, P < 0.001] and global efficiency [H(2) = 31.3, P < 0.001] from healthy controls but also from patients without progression. For transitivity, the comparisons showed no difference between the groups [H(2) = 1.5, P = 0.474]. Most notably, changes in network degree and global efficiency were detected independent of disease activity in the first year. The described network reorganization in patients experiencing EDSS progression was evident in the absence of grey matter atrophy. Network degree and global efficiency measurements demonstrated superiority of network measures in the ROC analyses over grey matter atrophy and white matter lesion load in predicting EDSS worsening (all P-values < 0.05). Our findings provide evidence that grey matter network reorganization over 1 year discloses relevant information about subsequent clinical worsening in RRMS. Early grey matter restructuring towards lower network efficiency predicts disability accumulation and outperforms conventional MRI predictors.

Project description:BackgroundChanges in grey matter covariance networks have been reported in preclinical and clinical stages of Alzheimer's disease (AD) and have been associated with amyloid-β (Aβ) deposition and cognitive decline. However, the role of tau pathology on grey matter networks remains unclear. Based on previously reported associations between tau pathology, synaptic density and brain structural measures, tau-related connectivity changes across different stages of AD might be expected. We aimed to assess the relationship between tau aggregation and grey matter network alterations across the AD continuum.MethodsWe included 533 individuals (178 Aβ-negative cognitively unimpaired (CU) subjects, 105 Aβ-positive CU subjects, 122 Aβ-positive patients with mild cognitive impairment, and 128 patients with AD dementia) from the BioFINDER-2 study. Single-subject grey matter networks were extracted from T1-weighted images and graph theory properties including degree, clustering coefficient, path length, and small world topology were calculated. Associations between tau positron emission tomography (PET) values and global and regional network measures were examined using linear regression models adjusted for age, sex, and total intracranial volume. Finally, we tested whether the association of tau pathology with cognitive performance was mediated by grey matter network disruptions.ResultsAcross the whole sample, we found that higher tau load in the temporal meta-ROI was associated with significant changes in degree, clustering, path length, and small world values (all p < 0.001), indicative of a less optimal network organisation. Already in CU Aβ-positive individuals associations between tau burden and lower clustering and path length were observed, whereas in advanced disease stages elevated tau pathology was progressively associated with more brain network abnormalities. Moreover, the association between higher tau load and lower cognitive performance was only partly mediated (9.3 to 9.5%) through small world topology.ConclusionsOur data suggest a close relationship between grey matter network disruptions and tau pathology in individuals with abnormal amyloid. This might reflect a reduced communication between neighbouring brain areas and an altered ability to integrate information from distributed brain regions with tau pathology, indicative of a more random network topology across different AD stages.

Project description:Biomarkers are needed to monitor disease progression in Alzheimer's disease. Grey matter network measures have such potential, as they are related to amyloid aggregation in cognitively unimpaired individuals and to future cognitive decline in predementia Alzheimer's disease. Here, we investigated how grey matter network measures evolve over time within individuals across the entire Alzheimer's disease cognitive continuum and whether such changes relate to concurrent decline in cognition. We included 190 cognitively unimpaired, amyloid normal (controls) and 523 individuals with abnormal amyloid across the cognitive continuum (preclinical, prodromal, Alzheimer's disease dementia) from the Alzheimer's Disease Neuroimaging Initiative and calculated single-subject grey matter network measures (median of five networks per individual over 2 years). We fitted linear mixed models to investigate how network measures changed over time and whether such changes were associated with concurrent changes in memory, language, attention/executive functioning and on the Mini-Mental State Examination. We further assessed whether associations were modified by baseline disease stage. We found that both cognitive functioning and network measures declined over time, with steeper rates of decline in more advanced disease stages. In all cognitive stages, decline in network measures was associated with concurrent decline on the Mini-Mental State Examination, with stronger effects for individuals closer to Alzheimer's disease dementia. Decline in network measures was associated with concurrent cognitive decline in different cognitive domains depending on disease stage: In controls, decline in networks was associated with decline in memory and language functioning; preclinical Alzheimer's disease showed associations of decline in networks with memory and attention/executive functioning; prodromal Alzheimer's disease showed associations of decline in networks with cognitive decline in all domains; Alzheimer's disease dementia showed associations of decline in networks with attention/executive functioning. Decline in grey matter network measures over time accelerated for more advanced disease stages and was related to concurrent cognitive decline across the entire Alzheimer's disease cognitive continuum. These associations were disease stage dependent for the different cognitive domains, which reflected the respective cognitive stage. Our findings therefore suggest that grey matter measures are helpful to track disease progression in Alzheimer's disease.

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Single-subject grey matter graphs in Alzheimer's disease.

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Single-subject grey matter graphs in Alzheimer's disease.

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