Neural markers of reduced arousal and consciousness in mild cognitive impairment.

OBJECTIVES: People with Alzheimer's Disease (AD) experience changes in their level and content of consciousness, but there is little research on biomarkers of consciousness in pre-clinical AD and Mild Cognitive Impairment (MCI). This study investigated whether levels of consciousness are decreased in people with MCI. METHODS: A multi-site site magnetoencephalography (MEG) dataset, BIOFIND, comprising 83 people with MCI and 83 age matched controls, was analysed. Arousal (and drowsiness) was assessed by computing the theta-alpha ratio (TAR). The Lempel-Ziv algorithm (LZ) was used to quantify the information content of brain activity, with higher LZ values indicating greater complexity and potentially a higher level of consciousness. RESULTS: LZ was lower in the MCI group versus controls, indicating a reduced level of consciousness in MCI. TAR was higher in the MCI group versus controls, indicating a reduced level of arousal (i.e. increased drowsiness) in MCI. LZ was also found to be correlated with mini-mental state examination (MMSE) scores, suggesting an association between cognitive impairment and level of consciousness in people with MCI. CONCLUSIONS: A decline in consciousness and arousal can be seen in MCI. As cognitive impairment worsens, measured by MMSE scores, levels of consciousness and arousal decrease. These findings highlight how monitoring consciousness using biomarkers could help understand and manage impairments found at the preclinical stages of AD. Further research is needed to explore markers of consciousness between people who progress from MCI to dementia and those who do not, and in people with moderate and severe AD, to promote person-centred care.

Multimodal subtypes identified in Alzheimer's Disease Neuroimaging Initiative participants by missing-data-enabled subtype and stage inference.

Alzheimer's disease is a highly heterogeneous disease in which different biomarkers are dynamic over different windows of the decades-long pathophysiological processes, and potentially have distinct involvement in different subgroups. Subtype and Stage Inference is an unsupervised learning algorithm that disentangles the phenotypic heterogeneity and temporal progression of disease biomarkers, providing disease insight and quantitative estimates of individual subtype and stage. However, a key limitation of Subtype and Stage Inference is that it requires a complete set of biomarkers for each subject, reducing the number of datapoints available for model fitting and limiting applications of Subtype and Stage Inference to modalities that are widely collected, e.g. volumetric biomarkers derived from structural MRI. In this study, we adapted the Subtype and Stage Inference algorithm to handle missing data, enabling the application of Subtype and Stage Inference to multimodal data (magnetic resonance imaging, positron emission tomography, cerebrospinal fluid and cognitive tests) from 789 participants in the Alzheimer's Disease Neuroimaging Initiative. Missing-data Subtype and Stage Inference identified five subtypes having distinct progression patterns, which we describe by the earliest unique abnormality as 'Typical AD with Early Tau', 'Typical AD with Late Tau', 'Cortical', 'Cognitive' and 'Subcortical'. These new multimodal subtypes were differentially associated with age, years of education, Apolipoprotein E (APOE4) status, white matter hyperintensity burden and the rate of conversion from mild cognitive impairment to Alzheimer's disease, with the 'Cognitive' subtype showing the fastest clinical progression, and the 'Subcortical' subtype the slowest. Overall, we demonstrate that missing-data Subtype and Stage Inference reveals a finer landscape of Alzheimer's disease subtypes, each of which are associated with different risk factors. Missing-data Subtype and Stage Inference has broad utility, enabling the prediction of progression in a much wider set of individuals, rather than being restricted to those with complete data.

Imaging biomarkers in neurodegeneration: current and future practices.

There is an increasing role for biological markers (biomarkers) in the understanding and diagnosis of neurodegenerative disorders. The application of imaging biomarkers specifically for the in vivo investigation of neurodegenerative disorders has increased substantially over the past decades and continues to provide further benefits both to the diagnosis and understanding of these diseases. This review forms part of a series of articles which stem from the University College London/University of Gothenburg course "Biomarkers in neurodegenerative diseases". In this review, we focus on neuroimaging, specifically positron emission tomography (PET) and magnetic resonance imaging (MRI), giving an overview of the current established practices clinically and in research as well as new techniques being developed. We will also discuss the use of machine learning (ML) techniques within these fields to provide additional insights to early diagnosis and multimodal analysis.

Systematic Review on Resting-State EEG for Alzheimer's Disease Diagnosis and Progression Assessment.

Alzheimer's disease (AD) is a neurodegenerative disorder that accounts for nearly 70% of the more than 46 million dementia cases estimated worldwide. Although there is no cure for AD, early diagnosis and an accurate characterization of the disease progression can improve the quality of life of AD patients and their caregivers. Currently, AD diagnosis is carried out using standardized mental status examinations, which are commonly assisted by expensive neuroimaging scans and invasive laboratory tests, thus rendering the diagnosis time consuming and costly. Notwithstanding, over the last decade, electroencephalography (EEG) has emerged as a noninvasive alternative technique for the study of AD, competing with more expensive neuroimaging tools, such as MRI and PET. This paper reports on the results of a systematic review on the utilization of resting-state EEG signals for AD diagnosis and progression assessment. Recent journal articles obtained from four major bibliographic databases were analyzed. A total of 112 journal articles published from January 2010 to February 2018 were meticulously reviewed, and relevant aspects of these papers were compared across articles to provide a general overview of the research on this noninvasive AD diagnosis technique. Finally, recommendations for future studies with resting-state EEG were presented to improve and facilitate the knowledge transfer among research groups.