1 To extract patterns from neuroimaging data, various statistical methods and machine learning algorithms have been explored for the diagnosis of Alzheimer’s disease among older adults in both clinical and research applications; however, distinguishing between Alzheimer’s and healthy brain data has been challenging in older adults (age > 75) due to highly similar patterns of brain atrophy and image intensities. Recently, cutting-edge deep learning technologies have rapidly expanded into numerous fields, including medical image analysis. This paper outlines state-of-the-art deep learning-based pipelines employed to distinguish Alzheimer’s magnetic resonance imaging (MRI) and functional MRI (fMRI) from normal healthy control data for a given age group. Using these pipelines, which were executed on a GPU-based high-performance computing platform, the data were strictly and carefully preprocessed. Next, scale- and shift-invariant low- to high-level features were obtained from a high volume of training images using convolutional neural network (CNN) architecture. In this study, fMRI data were used for the first time in deep learning applications for the purposes of medical image analysis and Alzheimer’s disease prediction. These proposed and implemented pipelines, which demonstrate a significant improvement in classification output over other studies, resulted in high and reproducible accuracy rates of 99.9% and 98.84% for the fMRI and MRI pipelines, respectively. Additionally, for clinical purposes, subject-level classification was performed, resulting in an average accuracy rate of 94.32% and 97.88% for the fMRI and MRI pipelines, respectively. Finally, a decision making algorithm designed for the subject-level classification improved the rate to 97.77% for fMRI and 100% for MRI pipelines.

Advances in applied machine learning techniques for neuroimaging have encouraged scientists to implement models to diagnose brain disorders such as Alzheimer’s disease at early stages. Predicting the exact stage of Alzheimer’s disease is challenging; however, complex deep learning techniques can precisely manage this. While successful, these complex architectures are difficult to interrogate and computationally expensive. Therefore, using novel, simpler architectures with more efficient pattern extraction capabilities, such as transformers, is of interest to neuroscientists. This study introduced an optimized vision transformer architecture to predict the group membership by separating healthy adults, mild cognitive impairment, and Alzheimer’s brains within the same age group (>75 years) using resting-state functional (rs-fMRI) and structural magnetic resonance imaging (sMRI) data aggressively preprocessed by our pipeline. Our optimized architecture, known as OViTAD is currently the sole vision transformer-based end-to-end pipeline and outperformed the existing transformer models and most state-of-the-art solutions. Our model achieved F1-scores of $97\%\pm 0.0$ and $99.55\%\pm 0.39$ from the testing sets for the rs-fMRI and sMRI modalities in the triple-class prediction experiments. Furthermore, our model reached these performances using 30% fewer parameters than a vanilla transformer. Furthermore, the model was robust and repeatable, producing similar estimates across three runs with random data splits (we reported the averaged evaluation metrics). Finally, to challenge the model, we observed how it handled increasing noise levels by inserting varying numbers of healthy brains into the two dementia groups. Our findings suggest that optimized vision transformers are a promising and exciting new approach for neuroimaging applications, especially for Alzheimer’s disease prediction.

Mild cognitive impairment (MCI) represents the intermediate stage between normal cerebral aging and dementia associated with Alzheimer's disease (AD). Early diagnosis of MCI and AD through artificial intelligence has captured considerable scholarly interest; researchers hope to develop therapies capable of slowing or halting these processes. We developed a state-of-the-art deep learning algorithm based on an optimized convolutional neural network (CNN) topology called MCADNNet that simultaneously recognizes MCI, AD, and normally aging brains in adults over the age of 75 years, using structural and functional magnetic resonance imaging (fMRI) data. Following highly detailed preprocessing, four-dimensional (4D) fMRI and 3D MRI were decomposed to create 2D images using a lossless transformation, which enables maximum preservation of data details. The samples were shuffled and subject-level training and testing datasets were completely independent. The optimized MCADNNet was trained and extracted invariant and hierarchical features through convolutional layers followed by multi-classification in the last layer using a softmax layer. A decision-making algorithm was also designed to stabilize the outcome of the trained models. To measure the performance of classification, the accuracy rates for various pipelines were calculated before and after applying the decision-making algorithm. Accuracy rates of 99.77% ± 0.36% and 97.5% ± 1.16% were achieved for MRI and fMRI pipelines, respectively, after applying the decision-making algorithm. In conclusion, a cutting-edge and optimized topology called MCADNNet was designed and preceded a preprocessing pipeline; this was followed by a decision-making step that yielded the highest performance achieved for simultaneous classification of the three cohorts examined.

Human aging is characterized by reductions in the ability to remember associations between items, despite intact memory for single items. Older adults also show less selectivity in task-related brain activity, such that patterns of activation become less distinct across multiple experimental tasks. This reduced selectivity or dedifferentiation has been found for episodic memory, which is often reduced in older adults, but not for semantic memory, which is maintained with age. We used fMRI to investigate whether there is a specific reduction in selectivity of brain activity during associative encoding in older adults, but not during item encoding, and whether this reduction predicts associative memory performance. Healthy young and older adults were scanned while performing an incidental encoding task for pictures of objects and houses under item or associative instructions. An old/new recognition test was administered outside the scanner. We used agnostic canonical variates analysis and split-half resampling to detect whole-brain patterns of activation that predicted item versus associative encoding for stimuli that were later correctly recognized. Older adults had poorer memory for associations than did younger adults, whereas item memory was comparable across groups. Associative encoding trials, but not item encoding trials, were predicted less successfully in older compared with young adults, indicating less distinct patterns of associative-related activity in the older group. Importantly, higher probability of predicting associative encoding trials was related to better associative memory after accounting for age and performance on a battery of neuropsychological tests. These results provide evidence that neural distinctiveness at encoding supports associative memory and that a specific reduction of selectivity in neural recruitment underlies age differences in associative memory.

Over the past decade, machine learning techniques and in particular predictive modeling and pattern recognition in biomedical sciences, from drug delivery systems to medical imaging, have become one of the most important methods of assisting researchers in gaining a deeper understanding of issues in their entirety and solving complex medical problems. Deep learning is a powerful machine learning algorithm in classification that extracts low- to high-level features. In this paper, we employ a convolutional neural network to distinguish an Alzheimers brain from a normal, healthy brain. The importance of classifying this type of medical data lies in its potential to develop a predictive model or system in order to recognize the symptoms of Alzheimers disease when compared with normal subjects and to estimate the stages of the disease. Classification of clinical data for medical conditions such as Alzheimers disease has always been challenging, and the most problematic aspect has always been selecting the strongest discriminative features. Using the Convolutional Neural Network (CNN) and the famous architecture LeNet-5, we successfully classified functional MRI data of Alzheimers subjects from normal controls, where the accuracy of testing data reached 96.85%. This experiment suggests that the shift and scale invariant features extracted by CNN followed by deep learning classification represents the most powerful method of distinguishing clinical data from healthy data in fMRI. This approach also allows for expansion of the methodology to predict more complicated systems.