Dataset Information

Prognostic classification of mild cognitive impairment and Alzheimer's disease: MRI independent component analysis.

ABSTRACT: Identifying predictors of mild cognitive impairment (MCI) and Alzheimer's disease (AD) can lead to more accurate diagnosis and facilitate clinical trial participation. We identified 320 participants (93 cognitively normal or CN, 162 MCI, 65 AD) with baseline magnetic resonance imaging (MRI) data, cerebrospinal fluid biomarkers, and cognition data in the Alzheimer's Disease Neuroimaging Initiative database. We used independent component analysis (ICA) on structural MR images to derive 30 matter covariance patterns (ICs) across all participants. These ICs were used in iterative and stepwise discriminant classifier analyses to predict diagnostic classification at 24 months for CN vs. MCI, CN vs. AD, MCI vs. AD, and stable MCI (MCI-S) vs. MCI progression to AD (MCI-P). Models were cross-validated with a "leave-10-out" procedure. For CN vs. MCI, 84.7% accuracy was achieved based on cognitive performance measures, ICs, p-tau(181p), and ApoE ?4 status. For CN vs. AD, 94.8% accuracy was achieved based on cognitive performance measures, ICs, and p-tau(181p). For MCI vs. AD and MCI-S vs. MCI-P, models achieved 83.1% and 80.3% accuracy, respectively, based on cognitive performance measures, ICs, and p-tau(181p). ICA-derived MRI biomarkers achieve excellent diagnostic accuracy for MCI conversion, which is little improved by CSF biomarkers and ApoE ?4 status.

SUBMITTER: Willette AA

PROVIDER: S-EPMC4586157 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Prognostic classification of mild cognitive impairment and Alzheimer's disease: MRI independent component analysis.

Willette Auriel A AA Calhoun Vince D VD Egan Josephine M JM Kapogiannis Dimitrios D

Psychiatry research 20140817 2

Identifying predictors of mild cognitive impairment (MCI) and Alzheimer's disease (AD) can lead to more accurate diagnosis and facilitate clinical trial participation. We identified 320 participants (93 cognitively normal or CN, 162 MCI, 65 AD) with baseline magnetic resonance imaging (MRI) data, cerebrospinal fluid biomarkers, and cognition data in the Alzheimer's Disease Neuroimaging Initiative database. We used independent component analysis (ICA) on structural MR images to derive 30 matter c ...[more]

PMID: 25194437

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Project description:Effective and accurate diagnosis of Alzheimer's disease (AD), as well as its prodromal stage (i.e., mild cognitive impairment (MCI)), has attracted more and more attention recently. So far, multiple biomarkers have been shown to be sensitive to the diagnosis of AD and MCI, i.e., structural MR imaging (MRI) for brain atrophy measurement, functional imaging (e.g., FDG-PET) for hypometabolism quantification, and cerebrospinal fluid (CSF) for quantification of specific proteins. However, most existing research focuses on only a single modality of biomarkers for diagnosis of AD and MCI, although recent studies have shown that different biomarkers may provide complementary information for the diagnosis of AD and MCI. In this paper, we propose to combine three modalities of biomarkers, i.e., MRI, FDG-PET, and CSF biomarkers, to discriminate between AD (or MCI) and healthy controls, using a kernel combination method. Specifically, ADNI baseline MRI, FDG-PET, and CSF data from 51AD patients, 99 MCI patients (including 43 MCI converters who had converted to AD within 18 months and 56 MCI non-converters who had not converted to AD within 18 months), and 52 healthy controls are used for development and validation of our proposed multimodal classification method. In particular, for each MR or FDG-PET image, 93 volumetric features are extracted from the 93 regions of interest (ROIs), automatically labeled by an atlas warping algorithm. For CSF biomarkers, their original values are directly used as features. Then, a linear support vector machine (SVM) is adopted to evaluate the classification accuracy, using a 10-fold cross-validation. As a result, for classifying AD from healthy controls, we achieve a classification accuracy of 93.2% (with a sensitivity of 93% and a specificity of 93.3%) when combining all three modalities of biomarkers, and only 86.5% when using even the best individual modality of biomarkers. Similarly, for classifying MCI from healthy controls, we achieve a classification accuracy of 76.4% (with a sensitivity of 81.8% and a specificity of 66%) for our combined method, and only 72% even using the best individual modality of biomarkers. Further analysis on MCI sensitivity of our combined method indicates that 91.5% of MCI converters and 73.4% of MCI non-converters are correctly classified. Moreover, we also evaluate the classification performance when employing a feature selection method to select the most discriminative MR and FDG-PET features. Again, our combined method shows considerably better performance, compared to the case of using an individual modality of biomarkers.

Project description:The purpose of this study was to use serial imaging to gain insight into the sequence of pathologic events in Alzheimer's disease, and the clinical features associated with this sequence. We measured change in amyloid deposition over time using serial (11)C Pittsburgh compound B (PIB) positron emission tomography and progression of neurodegeneration using serial structural magnetic resonance imaging. We studied 21 healthy cognitively normal subjects, 32 with amnestic mild cognitive impairment and 8 with Alzheimer's disease. Subjects were drawn from two sources--ongoing longitudinal registries at Mayo Clinic, and the Alzheimer's disease Neuroimaging Initiative (ADNI). All subjects underwent clinical assessments, MRI and PIB studies at two time points, approximately one year apart. PIB retention was quantified in global cortical to cerebellar ratio units and brain atrophy in units of cm(3) by measuring ventricular expansion. The annual change in global PIB retention did not differ by clinical group (P = 0.90), and although small (median 0.042 ratio units/year overall) was greater than zero among all subjects (P < 0.001). Ventricular expansion rates differed by clinical group (P < 0.001) and increased in the following order: cognitively normal (1.3 cm(3)/year) < amnestic mild cognitive impairment (2.5 cm(3)/year) < Alzheimer's disease (7.7 cm(3)/year). Among all subjects there was no correlation between PIB change and concurrent change on CDR-SB (r = -0.01, P = 0.97) but some evidence of a weak correlation with MMSE (r =-0.22, P = 0.09). In contrast, greater rates of ventricular expansion were clearly correlated with worsening concurrent change on CDR-SB (r = 0.42, P < 0.01) and MMSE (r =-0.52, P < 0.01). Our data are consistent with a model of typical late onset Alzheimer's disease that has two main features: (i) dissociation between the rate of amyloid deposition and the rate of neurodegeneration late in life, with amyloid deposition proceeding at a constant slow rate while neurodegeneration accelerates and (ii) clinical symptoms are coupled to neurodegeneration not amyloid deposition. Significant plaque deposition occurs prior to clinical decline. The presence of brain amyloidosis alone is not sufficient to produce cognitive decline, rather, the neurodegenerative component of Alzheimer's disease pathology is the direct substrate of cognitive impairment and the rate of cognitive decline is driven by the rate of neurodegeneration. Neurodegeneration (atrophy on MRI) both precedes and parallels cognitive decline. This model implies a complimentary role for MRI and PIB imaging in Alzheimer's disease, with each reflecting one of the major pathologies, amyloid dysmetabolism and neurodegeneration.

Project description:BackgroundIndividuals with mild cognitive impairment (MCI) have a substantially increased risk of developing dementia due to Alzheimer's disease (AD). In this study, we developed a multivariate prognostic model for predicting MCI-to-dementia progression at the individual patient level.MethodsUsing baseline data from 259 MCI patients and a probabilistic, kernel-based pattern classification approach, we trained a classifier to distinguish between patients who progressed to AD-type dementia (n = 139) and those who did not (n = 120) during a three-year follow-up period. More than 750 variables across four data sources were considered as potential predictors of progression. These data sources included risk factors, cognitive and functional assessments, structural magnetic resonance imaging (MRI) data, and plasma proteomic data. Predictive utility was assessed using a rigorous cross-validation framework.ResultsCognitive and functional markers were most predictive of progression, while plasma proteomic markers had limited predictive utility. The best performing model incorporated a combination of cognitive/functional markers and morphometric MRI measures and predicted progression with 80% accuracy (83% sensitivity, 76% specificity, AUC = 0.87). Predictors of progression included scores on the Alzheimer's Disease Assessment Scale, Rey Auditory Verbal Learning Test, and Functional Activities Questionnaire, as well as volume/cortical thickness of three brain regions (left hippocampus, middle temporal gyrus, and inferior parietal cortex). Calibration analysis revealed that the model is capable of generating probabilistic predictions that reliably reflect the actual risk of progression. Finally, we found that the predictive accuracy of the model varied with patient demographic, genetic, and clinical characteristics and could be further improved by taking into account the confidence of the predictions.ConclusionsWe developed an accurate prognostic model for predicting MCI-to-dementia progression over a three-year period. The model utilizes widely available, cost-effective, non-invasive markers and can be used to improve patient selection in clinical trials and identify high-risk MCI patients for early treatment.

Project description:Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) are closely associated with Tau proteins accumulation. In this study, we aimed to implement radiomics analysis to discover high-order features from pathological biomarker and improve the classification accuracy based on Tau PET images. Two cross-racial independent cohorts from the ADNI database (121 AD patients, 197 MCI patients and 211 normal control (NC) subjects) and Huashan hospital (44 AD patients, 33 MCI patients and 36 NC subjects) were enrolled. The radiomics features of Tau PET imaging of AD related brain regions were computed for classification using a support vector machine (SVM) model. The radiomics model was trained and validated in the ADNI cohort and tested in the Huashan hospital cohort. The standard uptake value ratio (SUVR) and clinical scores model were also performed to compared with radiomics analysis. Additionally, we explored the possibility of using Tau PET radiomics features as a good biomarker to make binary identification of Tau-negative MCI versus Tau-positive MCI or apolipoprotein E (ApoE) ε4 carrier versus ApoE ε4 non-carrier. We found that the radiomics model demonstrated best classification performance in differentiating AD/MCI patients and NC in comparison to SUVR and clinical scores models, with an accuracy of 84.8 ± 4.5%, 73.1 ± 3.6% in the ANDI cohort. Moreover, the radiomics model also demonstrated greater performance in diagnosing AD than other methods in the Huashan hospital cohort, with an accuracy of 81.9 ± 6.1%. In addition, the radiomics model also showed the satisfactory classification performance in the MCI-tau subgroup experiment (72.3 ± 3.5%, 71.9 ± 3.6% and 63.7 ± 5.9%) and in the MCI-ApoE subgroup experiment (73.5 ± 4.3%, 70.1 ± 3.9% and 62.5 ± 5.4%). In conclusion, our study showed that based on Tau PET radiomics analysis has the potential to guide and facilitate clinical diagnosis, further providing evidence for identifying the risk factors in MCI patients.

Dataset Information

Prognostic classification of mild cognitive impairment and Alzheimer's disease: MRI independent component analysis.

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Prognostic classification of mild cognitive impairment and Alzheimer's disease: MRI independent component analysis.

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