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Screening and predicting progression from high-risk mild cognitive impairment to Alzheimer's disease.

ABSTRACT: Individuals with mild cognitive impairment (MCI) are clinically heterogeneous, with different risks of progression to Alzheimer's disease. Regular follow-up and examination may be time-consuming and costly, especially for MRI and PET. Therefore, it is necessary to identify a more precise MRI population. In this study, a two-stage screening frame was proposed for evaluating the predictive utility of additional MRI measurements among high-risk MCI subjects. In the first stage, the K-means cluster was performed for trajectory-template based on two clinical assessments. In the second stage, high-risk individuals were filtered out and imputed into prognosis models with varying strategies. As a result, the ADAS-13 was more sensitive for filtering out high-risk individuals among patients with MCI. The optimal model included a change rate of clinical assessments and three neuroimaging measurements and was significantly associated with a net reclassification improvement (NRI) of 0.246 (95% CI 0.021, 0.848) and integrated discrimination improvement (IDI) of 0.090 (95% CI - 0.062, 0.170). The ADAS-13 longitudinal models had the best discrimination performance (Optimism-corrected concordance index = 0.830), as validated by the bootstrap method. Considering the limited medical and financial resources, our findings recommend follow-up MRI examination 1 year after identification for high-risk individuals, while regular clinical assessments for low-risk individuals.

SUBMITTER: Ge XY

PROVIDER: S-EPMC8413294 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionHeterogeneity in risk of conversion to Alzheimer's disease (AD) among individuals with mild cognitive impairment (MCI) is well known. Novel statistical methods that are based on partially ordered set (poset) models can be used to create models that provide detailed and accurate information about performance with specific cognitive functions. This approach allows for the study of direct links between specific cognitive functions and risk of conversion to AD from MCI. It also allows for further delineation of multi-domain amnestic MCI, in relation to specific non-amnestic cognitive deficits, and the modeling of a range of episodic memory functioning levels.MethodsFrom the Alzheimer's Disease Neuroimaging Initiative (ADNI) study, conversion at 24 months of 268 MCI subjects was analyzed. It was found that 101 of those subjects (37.7%) converted to AD within that time frame. Poset models were then used to classify cognitive performance for MCI subjects. Respective observed conversion rates to AD were calculated for various cognitive subgroups, and by APOE e4 allele status. These rates were then compared across subgroups.ResultsThe observed conversion rate for MCI subjects with a relatively lower functioning with a high level of episodic memory at baseline was 61.2%. In MCI subjects who additionally also had relatively lower perceptual motor speed functioning and at least one APOE e4 allele, the conversion rate was 84.2%. In contrast, the observed conversion rate was 9.8% for MCI subjects with a relatively higher episodic memory functioning level and no APOE e4 allele. Relatively lower functioning with cognitive flexibility and perceptual motor speed by itself also appears to be associated with higher conversion rates.ConclusionsAmong MCI subjects, specific baseline cognitive profiles that were derived through poset modeling methods, are clearly associated with differential rates of conversion to AD. More precise delineation of MCI by such cognitive functioning profiles, including notions such as multidomain amnestic MCI, can help in gaining further insight into how heterogeneity arises in outcomes. Poset-based modeling methods may be useful for providing more precise classification of cognitive subgroups among MCI for imaging and genetics studies, and for developing more efficient and focused cognitive test batteries.

Project description:Predicting progression of mild cognitive impairment (MCI) to Alzheimer's disease (AD) is clinically important. In this study, we propose a dual-model radiomic analysis with multivariate Cox proportional hazards regression models to investigate promising risk factors associated with MCI conversion to AD. T1 structural magnetic resonance imaging (MRI) and 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) data, from the AD Neuroimaging Initiative database, were collected from 131 patients with MCI who converted to AD within 3 years and 132 patients with MCI without conversion within 3 years. These subjects were randomly partition into 70% training dataset and 30% test dataset with multiple times. We fused MRI and PET images by wavelet method. In a subset of subjects, a group comparison was performed using a two-sample t-test to determine regions of interest (ROIs) associated with MCI conversion. 172 radiomic features from ROIs for each individual were established using a published radiomics tool. Finally, L1-penalized Cox model was constructed and Harrell's C index (C-index) was used to evaluate prediction accuracy of the model. To evaluate the efficacy of our proposed method, we used a same analysis framework to evaluate MRI and PET data separately. We constructed prognostic Cox models with: clinical data, MRI images, PET images, fused MRI/PET images, and clinical variables and fused MRI/PET images in combination. The experimental results showed that captured ROIs significantly associated with conversion to AD, such as gray matter atrophy in the bilateral hippocampus and hypometabolism in the temporoparietal cortex. Imaging model (MRI/PET/fused) provided significant enhancement in prediction of conversion compared to clinical models, especially the fused-modality Cox model. Moreover, the combination of fused-modality imaging and clinical variables resulted in the greatest accuracy of prediction. The average C-index for the clinical/MRI/PET/fused/combined model in the test dataset was 0.69, 0.73, 0.73 and 0.75, and 0.78, respectively. These results suggested that a combination of radiomic analysis and Cox model analyses could be used successfully in survival analysis and may be powerful tools for personalized precision medicine patients with potential to undergo conversion from MCI to AD.

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Screening and predicting progression from high-risk mild cognitive impairment to Alzheimer's disease.

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