Predicting conversion from mild cognitive impairment to Alzheimer's disease: a multimodal approach

Successively predicting whether mild cognitive impairment patients will progress to Alzheimer's disease is of significant clinical relevance. This ability may provide information that can be leveraged by emerging intervention approaches and thus mitigate some of the negative effects of the disease. Neuroimaging biomarkers have gained some attention in recent years and may be useful in predicting the conversion of mild cognitive impairment to Alzheimer's disease. We implemented a novel multi-modal approach that allowed us to evaluate the potential of different imaging modalities, both alone and in different degrees of combinations, in predicting the conversion to Alzheimer's disease of mild cognitive impairment patients. We applied this approach to the imaging data from the Alzheimer's Disease Neuroimaging Initiative that is a multi-modal imaging dataset comprised of MRI, Fluorodeoxyglucose PET, Florbetapir PET and diffusion tensor imaging. We included a total of 480 mild cognitive impairment patients that were split into two groups: converted and stable. Imaging data were segmented into atlas-based regions of interest, from which relevant features were extracted for the different imaging modalities and used to construct machine-learning models to classify mild cognitive impairment patients into converted or stable, using each of the different imaging modalities independently. The models were then combined, using a simple weight fusion ensemble strategy, to evaluate the complementarity of different imaging modalities and their contribution to the prediction accuracy of the models. The single-modality findings revealed that the model, utilizing features extracted from Florbetapir PET, demonstrated the highest performance with a balanced accuracy of 83.51%. Concerning multi-modality models, not all combinations enhanced mild cognitive impairment conversion prediction. Notably, the combination of MRI with Fluorodeoxyglucose PET emerged as the most promising, exhibiting an overall improvement in predictive capabilities, achieving a balanced accuracy of 78.43%. This indicates synergy and complementarity between the two imaging modalities in predicting mild cognitive impairment conversion. These findings suggest that beta-amyloid accumulation provides robust predictive capabilities, while the combination of multiple imaging modalities has the potential to surpass certain single-modality approaches. Exploring modality-specific biomarkers, we identified the brainstem as a sensitive biomarker for both MRI and Fluorodeoxyglucose PET modalities, implicating its involvement in early Alzheimer's pathology. Notably, the corpus callosum and adjacent cortical regions emerged as potential biomarkers, warranting further study into their role in the early stages of Alzheimer's disease. Agostinho et al. predict conversion to Alzheimer's in mild cognitive impairment patients. AV45-PET excels as a single modality (83.51%). Combining structural MRI with fluorodeoxyglucose (FDG-PET) yields some promise, showing synergy in terms of improved accuracy (78.43%). These findings underscore the predictive value of beta-amyloid markers and reveal modality-specific biomarkers (e.g. brainstem and corpus callosum), urging deeper exploration in early Alzheimer's pathology. Graphical Abstract