Longitudinal blood biomarker trajectories in preclinical Alzheimer's disease.

INTRODUCTION: Plasma biomarkers are altered years prior to Alzheimer's disease (AD) clinical onset. METHODS: We measured longitudinal changes in plasma amyloid-beta (Aß)42/40 ratio, pTau181, pTau231, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) in a cohort of older adults at risk of AD (n = 373 total, n = 229 with Aß and tau positron emission tomography [PET] scans) considering genetic and demographic factors as possible modifiers of these markers' progression. RESULTS: Aß42/40 ratio concentrations decreased, while NfL and GFAP values increased over the 4-year follow-up. Apolipoprotein E (APOE) ε4 carriers showed faster increase in plasma pTau181 than non-carriers. Older individuals showed a faster increase in plasma NfL, and females showed a faster increase in plasma GFAP values. In the PET subsample, individuals both Aß-PET and tau-PET positive showed faster plasma pTau181 and GFAP increase compared to PET-negative individuals. DISCUSSION: Plasma markers can track biological change over time, with plasma pTau181 and GFAP markers showing longitudinal change in individuals with preclinical AD. HIGHLIGHTS: Longitudinal increase of plasma pTau181 and glial fibrillary acidic protein (GFAP) can be measured in the preclinical phase of AD. Apolipoprotein E Îµ4 carriers experience faster increase in plasma pTau181 over time than non-carriers. Female sex showed accelerated increase in plasma GFAP over time compared to males. Aß42/40 and pTau231 values are already abnormal at baseline in individuals with both amyloid and tau PET burden.

Alignments between cortical neurochemical systems, proteinopathy and neurophysiological alterations along the Alzheimer's disease continuum.

Two neuropathological hallmarks of Alzheimer's disease (AD) are the accumulation of amyloid-ß (Aß) proteins and alterations in cortical neurophysiological signaling. Despite parallel research indicating disruption of multiple neurotransmitter systems in AD, it has been unclear whether these two phenomena are related to the neurochemical organization of the cortex. We leveraged task-free magnetoencephalography and positron emission tomography, with a cortical atlas of 19 neurotransmitters to study the alignment and interactions between alterations of neurophysiological signaling, Aß deposition, and the neurochemical gradients of the human cortex. In patients with amnestic mild cognitive impairment (N = 18) and probable AD (N = 20), we found that changes in rhythmic, but not arrhythmic, cortical neurophysiological signaling relative to healthy controls (N = 20) are topographically aligned with cholinergic, serotonergic, and dopaminergic neurochemical systems. These neuro-physio-chemical alignments are related to the severity of cognitive and behavioral impairments. We also found that cortical Aß plaques are preferentially deposited along neurochemical boundaries, and mediate how beta-band rhythmic cortical activity maps align with muscarinic acetylcholine receptors. Finally, we show in an independent dataset that many of these alignments manifest in the asymptomatic stages of cortical Aß accumulation (N = 33; N = 71 healthy controls), particularly the Aß-neurochemical alignments (57.1%) and neuro-physio-chemical alignments in the alpha frequency band (62.5%). Overall, the present study demonstrates that the expression of pathology in pre-clinical and clinical AD aligns topographically with the cortical distribution of chemical neuromodulator systems, scaling with clinical severity and with implications for potential pharmacotherapeutic pathways.

Simultaneous and independent electroencephalography and magnetic resonance imaging: A multimodal neuroimaging dataset.

We introduce an open access, multimodal neuroimaging dataset comprising simultaneously and independently collected Electroencephalography (EEG) and Magnetic Resonance Imaging (MRI) data from twenty healthy, young male individuals (mean age = 26 years; SD = 3.8 years). The dataset adheres to the BIDS standard specification and is structured into two components: 1) EEG data recorded outside the Magnetic Resonance (MR) environment, inside the MR scanner without image collection and during simultaneous functional MRI acquisition (EEG-fMRI) and 2) Functional MRI data acquired with and without simultaneous EEG recording and structural MRI data obtained with and without the participants wearing the EEG cap. EEG data were recorded with an MR-compatible EEG recording system (GES 400 MR, Electrical Geodesics Inc.) using a 32-channel sponge-based EEG cap (Geodesic Sensor Net). Eyes-closed resting-state EEG data were recorded for two minutes in both the outside and inside scanner conditions and for ten minutes during simultaneous EEG-fMRI. Eyes-open resting-state EEG data were recorded for two minutes under each condition. Participants also performed an eyes opening-eyes closure block-design task outside the scanner (two minutes) and during simultaneous EEG-fMRI (four minutes). The EEG data recorded outside the scanner provides a reference signal devoid of MR-related artifacts. The data collected inside the scanner without image acquisition captures the contribution of the ballistocardiographic (BCG) without the gradient artifact, making it suitable for testing and validating BCG artifact correction methods. The EEG-fMRI data is affected by both the gradient and BCG artifacts. Brain images were acquired using a 3T GE MR750-Discovery MR scanner equipped with a 32-channel head coil. Whole-brain functional images were obtained using a GRE-EPI T2* weighted sequence (TR = 2000 ms, TE = 40 ms, 35 interleaved axial slices with 4 mm isometric voxels). Structural images were acquired using an SPGR sequence (TR = 8.1 ms, TE = 3.2 ms, flip angle = 12°, 176 sagittal slices with 1 mm isometric voxels). This stands as one of the largest open access EEG-fMRI datasets available, which allows researchers to: 1) Assess the impact of gradient and BCG artifacts on EEG data, 2) Evaluate the effectiveness of novel artifact removal techniques to minimize artifact contribution and preserve EEG signal integrity, 3) Conduct hardware/setup comparison studies, 4) Evaluate the quality of structural and functional MRI data obtained with this particular EEG system, and 5) Implement and validate multimodal integrative analysis approaches on simultaneous EEG-fMRI data.

Preservation of EEG spectral power features during simultaneous EEG-fMRI.

Introduction: Electroencephalographic (EEG) data quality is severely compromised when recorded inside the magnetic resonance (MR) environment. Here we characterized the impact of the ballistocardiographic (BCG) artifact on resting-state EEG spectral properties and compared the effectiveness of seven common BCG correction methods to preserve EEG spectral features. We also assessed if these methods retained posterior alpha power reactivity to an eyes closure-opening (EC-EO) task and compared the results from EEG-informed fMRI analysis using different BCG correction approaches. Method: Electroencephalographic data from 20 healthy young adults were recorded outside the MR environment and during simultaneous fMRI acquisition. The gradient artifact was effectively removed from EEG-fMRI acquisitions using Average Artifact Subtraction (AAS). The BCG artifact was corrected with seven methods: AAS, Optimal Basis Set (OBS), Independent Component Analysis (ICA), OBS followed by ICA, AAS followed by ICA, PROJIC-AAS and PROJIC-OBS. EEG signal preservation was assessed by comparing the spectral power of traditional frequency bands from the corrected rs-EEG-fMRI data with the data recorded outside the scanner. We then assessed the preservation of posterior alpha functional reactivity by computing the ratio between the EC and EO conditions during the EC-EO task. EEG-informed fMRI analysis of the EC-EO task was performed using alpha power-derived BOLD signal predictors obtained from the EEG signals corrected with different methods. Results: The BCG artifact caused significant distortions (increased absolute power, altered relative power) across all frequency bands. Artifact residuals/signal losses were present after applying all correction methods. The EEG reactivity to the EC-EO task was better preserved with ICA-based correction approaches, particularly when using ICA feature extraction to isolate alpha power fluctuations, which allowed to accurately predict hemodynamic signal fluctuations during the EEG-informed fMRI analysis. Discussion: Current software solutions for the BCG artifact problem offer limited efficiency to preserve the EEG spectral power properties using this particular EEG setup. The state-of-the-art approaches tested here can be further refined and should be combined with hardware implementations to better preserve EEG signal properties during simultaneous EEG-fMRI. Existing and novel BCG artifact correction methods should be validated by evaluating signal preservation of both ERPs and spontaneous EEG spectral power.