A study of the longitudinal changes in multiple cerebrospinal fluid and volumetric magnetic resonance imaging biomarkers on converter and non-converter Alzheimer's disease subjects with consideration for their amyloid beta status.

INTRODUCTION: This study aims to determine whether newly introduced biomarkers Visinin-like protein-1 (VILIP-1), chitinase-3-like protein 1 (YKL-40), synaptosomal-associated protein 25 (SNAP-25), and neurogranin (NG) in cerebrospinal fluid are useful in evaluating the asymptomatic and early symptomatic stages of Alzheimer's disease (AD). It further aims to shed new insight into the differences between stable subjects and those who progress to AD by associating cerebrospinal fluid (CSF) biomarkers and specific magnetic resonance imaging (MRI) regions with disease progression, more deeply exploring how such biomarkers relate to AD pathology. METHODS: We examined baseline and longitudinal changes over a 7-year span and the longitudinal interactions between CSF and MRI biomarkers for subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We stratified all CSF (140) and MRI (525) cohort participants into five diagnostic groups (including converters) further dichotomized by CSF amyloid beta (Aß) status. Linear mixed models were used to compare within-person rates of change across diagnostic groups and to evaluate the association of CSF biomarkers as predictors of magnetic resonance imaging (MRI) biomarkers. CSF biomarkers and disease-prone MRI regions are assessed for CSF proteins levels and brain structural changes. RESULTS: VILIP-1 and SNAP-25 displayed within-person increments in early symptomatic, amyloid-positive groups. CSF amyloid-positive (Aß+) subjects showed elevated baseline levels of total tau (tTau), phospho-tau181 (pTau), VILIP-1, and NG. YKL-40, SNAP-25, and NG are positively intercorrelated. Aß+ subjects showed negative MRI biomarker changes. YKL-40, tTau, pTau, and VILIP-1 are longitudinally associated with MRI biomarkers atrophy. DISCUSSION: Converters (CNc, MCIc) highlight the evolution of biomarkers during the disease progression. Results show that underlying amyloid pathology is associated with accelerated cognitive impairment. CSF levels of Aß42, pTau, tTau, VILIP-1, and SNAP-25 show utility to discriminate between mild cognitive impairment (MCI) converter and control subjects (CN). Higher levels of YKL-40 in the Aß+ group were longitudinally associated with declines in temporal pole and entorhinal thickness. Increased levels of tTau, pTau, and VILIP-1 in the Aß+ groups were longitudinally associated with declines in hippocampal volume. These CSF biomarkers should be used in assessing the characterization of the AD progression.

Real-time frequency-independent single-Lead and single-beat myocardial infarction detection.

This study proposes a novel real-time frequency-independent myocardial infarction detector for Lead II electrocardiograms. The underlying Deep-LSTM network is trained using the PTB-XL database, the largest to date publicly available electrocardiography dataset, and is tested over the same and the older PTB database. By testing the model over distinct datasets, collected under different conditions and from different patients, a more realistic measure of the performance can be gauged from the deployed system. The detector is trained over 3589 myocardial infarction (MI) patients and 7115 healthy controls (HC) while it is evaluated on 1076 MIs and 1840 HCs. The proposed algorithm, achieved an accuracy of 77.12%, recall/sensitivity of 75.85%, and a specificity of 83.02% over the entire PTB database; 85.07%, 81.54%, 87.31% over the PTB-XL validation set (fold 9), and 84.17%, 78.37%, 87.55% over the PTB-XL test set (fold 10). The model also achieves stable performance metrics over the frequency range of 202 Hz to 2.8 kHz. The processing time is dependent on the sampling frequency, ranging from 130 ms at 202 Hz to 1.8 s at 2.8 kHz. Such outcome is within the time required for real-time processing (less than 300 ms for fast heartbeats), between 202 Hz and 500 Hz making the algorithm practically real-time. Therefore, the proposed MI detector could be readily deployed onto existing wearable and/or portable devices and test instruments; potentially having significant societal and clinical impact in the lives of patients at risk for myocardial infarction.

Greater Regional Cortical Thickness is Associated with Selective Vulnerability to Atrophy in Alzheimer's Disease, Independent of Amyloid Load and APOE Genotype.

BACKGROUND: Regional cortical thickness (rCTh) among cognitively normal (CN) adults (rCThCN) varies greatly between brain regions, as does the vulnerability to neurodegeneration. OBJECTIVE: The goal of this study was to: 1) rank order rCThCN for various brain regions, and 2) explore their vulnerability to neurodegeneration in Alzheimer's disease (AD) within these brain regions. METHODS: The relationship between rCTh among the CN group (rCThCN) and the percent difference in CTh (% CThDiff) in each region between the CN group and AD patients was examined. Pearson correlation analysis was performed accounting for amyloid-ß (Aß) protein and APOE genotype using 210 age, gender, and APOE matched CN (n = 105, age range: 56-90) and AD (n = 105, age range: 56-90) ADNI participants. RESULTS: Strong positive correlations were observed between rCThCN and % CThDiff accounting for Aß deposition and APOE status. Regions, such as the entorhinal cortex, which had the greatest CTh in the CN state, were also the regions which had the greatest % CThDiff. CONCLUSIONS: Regions with the greatest CTh at the CN stage are found to aggregate in disease prone regions of AD, namely in the medial temporal lobe, including the temporal pole, ERC, parahippocampal gyrus, fusiform and the middle and inferior temporal gyrus. Although rCTh has been found to vary considerably across the different regions of the brain, our results indicate that regions with the greatest CTh at the CN stage are actually regions which have been found to be most vulnerable to neurodegeneration in AD.