Multiclass classification of Alzheimer's disease prodromal stages using sequential feature embeddings and regularized multikernel support vector machine

•Introduces a novel framework for multiclass classification of Alzheimer's disease clinical stages using ensemble manifold regularization and regularized multikernel SVM.•Leverages multimodal data, integrating MRI and PET scans with genetic and cognitive scores, to enhance diagnostic precision.•The choice of biomarker(s) is as important as the classification framework for accurate diagnosis.•Introducing the minimum modality penalty parameter improves conventional multikernel SVM. The detection of patients in the cognitive normal (CN), mild cognitive impairment (MCI), and Alzheimer's disease (AD) stages of neurodegeneration is crucial for early treatment interventions. However, the heterogeneity of MCI data samples poses a challenge for CN vs. MCI vs. AD multiclass classification, as some samples are closer to AD while others are closer to CN in the feature space. Previous attempts to address this challenge produced inaccurate results, leading most frameworks to break the assessment into binary classification tasks such as AD vs. CN, AD vs. MCI, and CN vs. MCI. Other methods proposed sequential binary classifications such as CN vs. others and dividing others into AD vs. MCI. While those approaches may have yielded encouraging results, the sequential binary classification method makes interpretation and comparison with other frameworks challenging and subjective. Those frameworks exhibited varying accuracy scores for different binary tasks, making it unclear how to compare the model performance with other direct multiclass methods. Therefore, we introduce a classification framework comprising unsupervised ensemble manifold regularized sparse low-rank approximation and regularized multikernel support vector machine (SVM). This framework first extracts a joint feature embedding from MRI and PET neuroimaging features, which were then combined with the Apoe4, Adas11, MPACC digits, and Intracranial volume features using a regularized multikernel SVM. Using that framework, we achieved a state-of-the-art (SOTA) result in a CN vs. MCI vs. AD multiclass classification (mean accuracy: 84.87±6.09, F1 score: 84.83±6.12 vs 67.69). The methods generalize well to binary classification tasks, achieving SOTA results in all but the CN vs. MCI category, which was slightly lower than the best score by just 0.2%.