The successful development of amyloid-based biomarkers and tests for Alzheimer's disease (AD) represents an important milestone in AD diagnosis. However, two major limitations remain. Amyloid-based diagnostic biomarkers and tests provide limited information about the disease process and they are unable to identify individuals with the disease before significant amyloid-beta accumulation in the brain develops. The objective in this study is to develop a method to identify potential blood-based non-amyloid biomarkers for early AD detection. The use of blood is attractive because it is accessible and relatively inexpensive. Our method is mainly based on machine learning (ML) techniques (support vector machines in particular) because of their ability to create multivariable models by learning patterns from complex data. Using novel feature selection and evaluation modalities we identified 5 novel panels of non-amyloid proteins with the potential to serve as biomarkers of early AD. In particular, we found that the combination of A2M, ApoE, BNP, Eot3, RAGE and SGOT may be a key biomarker profile of early disease. Disease detection models based on the identified panels achieved sensitivity (SN) > 80%, specificity (SP) > 70%, and area under receiver operating curve (AUC) of at least 0.80 at prodromal stage (with higher performance at later stages) of the disease. Existing ML models performed poorly in comparison at this stage of the disease suggesting that the underlying protein panels may not be suitable for early disease detection. Our results demonstrate the feasibility of early detection of AD using non-amyloid based biomarkers.

Alzheimer’s disease (AD) is a progressive disorder that affects cognitive brain functions and starts many years before its clinical manifestations. A biomarker that provides a quantitative measure of changes in the brain due to AD in the early stages would be useful for early diagnosis of AD, but this would involve dealing with large numbers of people because up to 50% of dementia sufferers do not receive formal diagnosis. Thus, there is a need for accurate, low‐cost, and easy to use biomarkers that could be used to detect AD in its early stages. Potentially, electroencephalogram (EEG) based biomarkers can play a vital role in early diagnosis of AD as they can fulfill these needs. This is a cross‐sectional study that aims to demonstrate the usefulness of EEG complexity measures in early AD diagnosis. We have focused on the three complexity methods which have shown the greatest promise in the detection of AD, Tsallis entropy (TsEn), Higuchi Fractal Dimension (HFD), and Lempel‐Ziv complexity (LZC) methods. Unlike previous approaches, in this study, the complexity measures are derived from EEG frequency bands (instead of the entire EEG) as EEG activities have significant association with AD and this has led to enhanced performance. The results show that AD patients have significantly lower TsEn, HFD, and LZC values for specific EEG frequency bands and for specific EEG channels and that this information can be used to detect AD with a sensitivity and specificity of more than 90%.

Biomarkers to detect Alzheimer’s disease (AD) would enable patients to gain access to appropriate services and may facilitate the development of new therapies. Given the large numbers of people affected by AD, there is a need for a low-cost, easy to use method to detect AD patients. Potentially, the electroencephalogram (EEG) can play a valuable role in this, but at present no single EEG biomarker is robust enough for use in practice. This study aims to provide a methodological framework for the development of robust EEG biomarkers to detect AD with a clinically acceptable performance by exploiting the combined strengths of key biomarkers. A large number of existing and novel EEG biomarkers associated with slowing of EEG, reduction in EEG complexity and decrease in EEG connectivity were investigated. Support vector machine and linear discriminate analysis methods were used to find the best combination of the EEG biomarkers to detect AD with significant performance. A total of 325,567 EEG biomarkers were investigated, and a panel of six biomarkers was identified and used to create a diagnostic model with high performance (≥85% for sensitivity and 100% for specificity).

As the limitations of heart-rate based intrapartum monitoring have become apparent, there is renewed interest in analysis of the fetal electrocardiographic waveform as obtained from a fetal scalp electrode. A high quality ECG signal is necessary for waveform analysis. This study examined the suitability of five commonly available scalp electrodes for collecting this signal by examining their physical and electrical characteristics, together with a randomised clinical trial in which the ECG trace quality was assessed in 50 patients. The frequency response of Copeland electrodes was such that they attenuate the ECG signal more than the baseline noise. Difficulties were experienced in obtaining optimum attachment and the long, semi-rigid design increased movement artefact resulting in significantly poorer quality ECG signals. Whilst the Hewlett-Packard double spiral electrode had a near ideal frequency response, certain design features made it difficult to apply and remain secure so the clinical signals were of intermediate quality. The Corometrics and Cetro single spirals had the most stable attachment to the scalp and a near ideal frequency response, so produced significantly better signal quality in the clinical trial. Currently, single spiral electrodes are the most suitable for electrocardiographic data collection.

Stroke remains a leading cause of morbidity and mortality. Despite this, current risk stratification tools such as CHA₂DS₂-VASc and QRISK3 are of limited accuracy, particularly in those without a diagnosis of atrial-fibrillation. Hence, there is a need for more accurate stroke risk prediction models. Machine-learning (ML) may provide a solution to this by leveraging existing routine hospital databases to build accurate stroke risk prediction models and identify novel risk factors for stroke. In this systematic review we appraise current research using ML to predict stroke risk from routine hospital data. Based on these findings we then highlight common methodological limitations and recommendations for future research. In this review we identify 49 original research (38 in the general population and 11 in AF specific populations) articles from the PUBMED database from January-2013 to December-2024 using ML and routine hospital data to predict the risk of stroke. ML models were able to accurately predict stroke risk in both AF specific and general populations, with AUCs ranging from 0.64 to 0.99. Where tested, ML also consistently outperformed traditional risk stratification tool, such as CHA₂DS₂-VASc. ML also appeared useful in identifying several novel risk factors from electrocardiogram, laboratory test and echocardiography data. However, the quality of datasets were often limited, there was a high suspicion of overfitting and models often lacked calibration, external validation and explainability analysis. Whilst ML has shown great potential in stroke prediction and identifying novel risk factors for stroke, improvements in study methodology is required prior to integration of ML into routine healthcare. Future research should adhere to the EQUATOR guidance on prediction models and encourage interdisciplinary collaboration between computer scientists and clinicians. Further prospective RCTs are also required to validate models in the clinical setting and the identify barriers of integrating ML into routine healthcare.

This study examines a novel methodology for continuous fetal heart rate variability (FHRV) assessment in a non-stationary intrapartum fetal heart rate (FHR). The specific aim was to investigate simple statistics, dimension estimates and entropy estimates as methods to discriminate situations of low FHRV related to non-reassuring fetal status or as a consequence of sedatives given to the mother. Using a t-test it is found that the dimension of the zero set and sample entropy reveal a difference in mean distribution of significance >99%. Thus it may prove possible to build a discriminating system based on either one or a combination of these techniques