Common Neuropsychiatric S ymptoms in Alzheimer's Disease, Mild Cognitive Impairment, and Subjective Memory Complaints: A Unified Framework.

The Alzheimer's disease (AD) continuum is a unique spectrum of cognitive impairment that typically involves the stages of subjective memory complaints (SMC), mild cognitive impairment (MCI), and AD dementia. Neuropsychiatric symptoms (NPS), such as apathy, anxiety, stress, and depression, are highly common throughout the AD continuum. However, there is a dearth of research on how these NPS vary across the AD continuum, especially SMC. There is also disagreement on the effects of specific NPS on each stage of the AD continuum due to their collinearity with other NPS, cognitive decline, and environmental factors (e.g., stress). In this article, we conduct a novel perspective review of the scientific literature to understand the presence of NPS across the AD continuum. Specifically, we review the effects of apathy, depression, anxiety, and stress in AD, MCI, and SMC. We then build on this knowledge by proposing two theories of NPS' occurrence across the AD continuum. Consequently, we highlight the current landscape, limitations (e.g., differing operationalization), and contentions surrounding the NPS literature. We also outline theories that could clear up contention and inspire future NPS research.

An Alzheimer's disease category progression sub-grouping analysis using manifold learning on ADNI.

Many current statistical and machine learning methods have been used to explore Alzheimer's disease (AD) and its associated patterns that contribute to the disease. However, there has been limited success in understanding the relationship between cognitive tests, biomarker data, and patient AD category progressions. In this work, we perform exploratory data analysis of AD health record data by analyzing various learned lower dimensional manifolds to separate early-stage AD categories further. Specifically, we used Spectral embedding, Multidimensional scaling, Isomap, t-Distributed Stochastic Neighbour Embedding, Uniform Manifold Approximation and Projection, and sparse denoising autoencoder based manifolds on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. We then determine the clustering potential of the learned embeddings and then determine if category sub-groupings or sub-categories can be found. We then used a Kruskal-sWallis H test to determine the statistical significance of the discovered AD subcategories. Our results show that the existing AD categories do exhibit sub-groupings, especially in mild cognitive impairment transitions in many of the tested manifolds, showing there may be a need for further subcategories to describe AD progression.

Functional magnetic resonance imaging, deep learning, and Alzheimer's disease: A systematic review.

Alzheimer's disease (AD) is currently diagnosed using a mixture of psychological tests and clinical observations. However, these diagnoses are not perfect, and additional diagnostic tools (e.g., MRI) can help improve our understanding of AD as well as our ability to detect the disease. Accordingly, a large amount of research has been invested into innovative diagnostic methods for AD. Functional MRI (fMRI) is a form of neuroimaging technology that has been used to diagnose AD; however, fMRI is incredibly noisy, complex, and thus lacks clinical use. Nonetheless, recent innovations in deep learning technology could enable the simplified and streamlined analysis of fMRI. Deep learning is a form of artificial intelligence that uses computer algorithms based on human neural networks to solve complex problems. For example, in fMRI research, deep learning models can automatically denoise images and classify AD by detecting patterns in participants' brain scans. In this systematic review, we investigate how fMRI (specifically resting-state fMRI) and deep learning methods are used to diagnose AD. In turn, we outline the common deep neural network, preprocessing, and classification methods used in the literature. We also discuss the accuracy, strengths, limitations, and future direction of fMRI deep learning methods. In turn, we aim to summarize the current field for new researchers, suggest specific areas for future research, and highlight the potential of fMRI to aid AD diagnoses.

Harnessing forgetfulness: can episodic-memory tests predict early Alzheimer's disease?

A rapid increase in the number of patients with Alzheimer's disease (AD) is expected over the next decades. Accordingly, there is a critical need for early-stage AD detection methods that can enable effective treatment strategies. In this study, we consider the ability of episodic-memory measures to predict mild cognitive impairment (MCI) to AD conversion and thus, detect early-stage AD. For our analysis, we studied 307 participants with MCI across four years using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Using a binary logistic regression, we compared episodic-memory tests to each other and to prominent neuroimaging methods in MCI converter (MCI participants who developed AD) and MCI non-converter groups (MCI participants who did not develop AD). We also combined variables to test the accuracy of mixed-predictor models. Our results indicated that the best predictors of MCI to AD conversion were the following: a combined episodic-memory and neuroimaging model in year one (59.8%), the Rey Auditory Verbal Learning Test in year two (71.7%), a mixed episodic-memory predictor model in year three (77.7%) and the Logical Memory Test in year four (77.2%) of ADNI. Overall, we found that individual episodic-memory measure and mixed models performed similarly when predicting MCI to AD conversion. Comparatively, individual neuroimaging measures predicted MCI conversion worse than chance. Accordingly, our results indicate that episodic-memory tests could be instrumental in detecting early-stage AD and enabling effective treatment.