Biology subjects

Goerss, D.

Publications and source records attributed to Goerss, D..

6 recordsLinked to original sources

bioRxiv2025

Disrupted Forward Connectivity in Parieto-temporal Network Impairs Memory Performance in Alzheimer's Disease

Alzheimers disease (AD) is characterised by the accumulation of beta-amyloid (A{beta}) and tau proteins, leading to neurodegeneration and cognitive decline. While A{beta} and tau are known to disrupt synaptic function, the mechanisms linking these molecular pathologies to network-level dysfunction and memory impairment remain poorly understood. Here we investigated the effects of A{beta} and tau pathology (CSF A{beta}42/40 ratio and tau phosphorylated at position 181, p-tau-181, respectively) on effective connectivity (EC) related to memory encoding, which may constitute a link between synaptic pathology and cognitive outcomes. Functional magnetic resonance imaging (fMRI) during visual memory encoding was acquired from participants of the multicentric DZNE Longitudinal Cognitive Impairment and Dementia Study (DELCODE), including 203 cognitively normal older participants (CN) as well as individuals with subjective cognitive decline (SCD; N = 204), mild cognitive impairment (MCI; N = 65), and early dementia due to AD (DAT; N = 21). EC was assessed by applying Dynamic causal modelling (DCM) to the fMRI data, using brain regions previously implicated in memory-encoding: the parahippocampal place area (PPA), the hippocampus (HC) and the precuneus (PCU). Disruptions in forward connectivity from the PPA to the HC and PCU were associated with both memory impairment and indices of AD pathology. Specifically, reduced excitatory EC from the PPA to the HC was associated with higher p-tau-181 levels and correlated with poorer memory performance. Diminished inhibitory EC from the PPA to the PCU was driven by both tau and amyloid pathology and was likewise linked to memory decline. Our findings suggest that disrupted forward connectivity within the temporo-parietal memory network constitutes a candidate mechanism mediating the relationship between molecular pathology and cognitive dysfunction.

neuroscience↗

bioRxiv2024

SMAS: Structural MRI-Based AD Score using Bayesian VAE

This study introduces the Structural MRI-based Alzheimers Disease Score (SMAS), a novel index intended to quantify Alzheimers Disease (AD)-related morphometric patterns using a deep learning Bayesian-supervised Variational Autoencoder (Bayesian-SVAE). SMAS index was constructed using baseline structural MRI data from the DELCODE study and evaluated longitudinally in two independent cohorts: DEL-CODE (n=415) and ADNI (n=190). Our findings indicate that SMAS has strong associations with cognitive performance (DELCODE: r=-0.83; ADNI: r=-0.62), age (DEL-CODE: r=0.50; ADNI: r=0.28), hippocampal volume (DEL-CODE: r=-0.44; ADNI: r=-0.66), and total grey matter volume (DELCODE: r=-0.42; ADNI: r=-0.47), suggesting its potential as a biomarker for AD-related brain atrophy. Moreover, our longitudinal studies suggest that SMAS may be useful for early identification and tracking of AD. The model demonstrated significant predictive accuracy in distinguishing cognitively healthy individuals from those with AD (DELCODE: AUC=0.971 at baseline, 0.833 at 36 months; ADNI: AUC=0.817 at baseline, improving to 0.903 at 24 months). Notably, over a 36-month period, SMAS index outperformed existing measures such as SPARE-AD and hippocampal volume. Relevance map analysis revealed significant morphological changes in key AD-related brain regions--including the hippocampus, posterior cingulate cortex, precuneus, and lateral parietal cortex--highlighting that SMAS is a sensitive and interpretable biomarker of brain atrophy, suitable for early AD detection and longitudinal monitoring of disease progression.

neuroscience↗

bioRxiv2024

Dysfunction of the episodic memory network in the Alzheimer's disease cascade

Alzheimers disease (AD) is a major cause of dementia and cognitive decline. Here we assessed how episodic memory circuit dysfunction, a hallmark of AD, is related to the longitudinal cascade of AD biomarkers, neurodegeneration and cognition using data from the DZNE Longitudinal Cognitive Impairment and Dementia study. This data set is unique by including over 1000 longitudinal functional magnetic resonance imaging (fMRI) measurements during episodic memory encoding. We leveraged a disease progression model (DPM) to obtain AD progression scores. Voxel-wise analyses revealed widespread loss of deactivation (hyperactivation) and activation (hypoactivation) with increasing disease stage. Hyperactivation trajectories were nonlinear and visually preceded trajectories of cognition. Overall, hyperactivation was independently associated with co-occurrence of amyloid- and tau-positivity and neurodegeneration, suggesting synaptic dysfunction and neurodegeneration as two independent drives of cognitive decline. Our results therefore provide evidence for a critical time window in which pharmacological treatments targeting the synapse may improve cognition.

neuroscience↗

bioRxiv2024

Fully Automated MRI-based Analysis of the Locus Coeruleus in Aging and Alzheimer's Disease Dementia using ELSI-Net

INTRODUCTIONThe Locus Coeruleus (LC) is linked to the development and pathophysiology of neurodegenerative diseases such as Alzheimers Disease (AD). Magnetic Resonance Imaging based LC features have shown potential to assess LC integrity in vivo. METHODSWe present a Deep Learning based LC segmentation and feature extraction method: ELSI-Net and apply it to healthy aging and AD dementia datasets. Agreement to expert raters and previously published LC atlases were assessed. We aimed to reproduce previously reported differences in LC integrity in aging and AD dementia and correlate extracted features to cerebrospinal fluid (CSF) biomarkers of AD pathology. RESULTSELSI-Net demonstrated high agreement to expert raters and published atlases. Previously reported group differences in LC integrity were detected and correlations to CSF biomarkers were found. DISCUSSIONAlthough we found excellent performance, further evaluations on more diverse datasets from clinical cohorts are required for a conclusive assessment of ELSI-Nets general applicability. HighlightsO_LIthorough evaluation of a fully automatic LC segmentation method termed ELSI-Net in aging and AD dementia C_LIO_LIELSI-Net outperforms previous work and shows high agreement with manual ratings and previously published LC atlases C_LIO_LIELSI-Net replicates previously shown LC group differences in aging and AD C_LIO_LIELSI-Nets LC volume correlates with CSF biomarkers of AD pathology C_LI RESEARCH IN CONTEXTO_LISystematic Review: The authors reviewed the literature using traditional sources (e.g. Pubmed, Google Scholar). Although there are several publications introducing semi-automatic methods for LC segmentation, the application of Deep Learning methods is underexplored. To the best of our knowledge, this is the first paper using a Deep Learning based approach for automated LC segmentation in AD dementia. C_LIO_LIInterpretation: Our work introduces and evaluates an improved automatic, Deep Learning based LC segmentation and analysis approach. The results suggest a very high potential for practical applicability, e.g. in large-scale clinical studies for neurodegenerative diseases. C_LIO_LIFuture Directions: ELSI-Net can be used to assess LC integrity on large- or small-scale studies in Alzheimers Disease dementia. To ensure robust performance, ELSI-Net should be further evaluated in larger, more diverse datasets comprising varying LC MRI protocols and clinical populations. C_LI

bioinformatics↗

bioRxiv2023

Cognitive Reserve Against Alzheimer's Pathology Is Linked to Brain Activity During Memory Formation

The cognitive reserve (CR) hypothesis posits that individuals can differ in how their brain function is disrupted by pathology associated with aging and neurodegeneration. Here, we tested this hypothesis in the Alzheimers disease continuum using longitudinal data from 490 participants of the DELCODE multicentric observational study. Brain function was measured using task fMRI of visual memory encoding. Using a multivariate moderation analysis we identified a CR-related activity pattern underlying successful memory encoding that moderated the detrimental effect of AD pathological load on cognitive performance. CR was mainly represented by a more pronounced expression of the task-active network encompassing the default mode network (DMN), anterior cingulate cortex (ACC) and inferior temporal regions including the fusiform gyrus. We devised personalized fMRI-based CR scores that moderated the impact of AD pathology on cognitive performance and were positively associated with years of education. Furthermore, higher CR scores were associated with slower cognitive decline over time. Our findings suggest maintenance of core cognitive circuits including the DMN and ACC as the primary mechanism of CR. Individual brain activity levels of these areas during memory encoding have prognostic value for future cognitive decline.

neuroscience↗

bioRxiv2023

Fornix fractional anisotropy mediates the association between Mediterranean diet adherence and memory four years later in older adults without dementia

Here, we investigated whether fractional anisotropy (FA) of hippocampus-relevant white-matter tracts mediates the association between baseline Mediterranean diet adherence (MeDiAd) and verbal episodic memory over four years. Participants were healthy older adults with and without subjective cognitive decline and patients with amnestic mild cognitive impairment from the DELCODE cohort study (n = 376; age: 71.47 {+/-} 6.09 years; 48.7% female). MeDiAd and diffusion data were obtained at baseline. Verbal episodic memory was assessed at baseline and four yearly follow-ups. The associations between baseline MeDiAd and white matter, and verbal episodic memorys mean and rate of change over four years were tested with latent growth curve modeling. Baseline MeDiAd was associated with verbal episodic memory four years later (95% confidence interval, CI [0.01, 0.32]) but not with its rate of change over this period. Baseline Fornix FA mediated - and, thus, explained - that association (95% CI [0.002, 0.09]). Fornix FA may be an appropriate response biomarker of Mediterranean diet interventions on verbal memory in older adults.

neuroscience↗