Impaired macroscopic CSF flow by sevoflurane in humans - both during and after anesthesia.

Background: According to the model of the glymphatic system, the directed flow of cerebrospinal fluid (CSF) is a driver of waste clearance from the brain. In sleep, glymphatic transport is enhanced, but it is unclear how it is affected by anesthesia. Animal research indicates partially opposing effects of distinct anesthetics but corresponding results in humans are lacking.

Biomarkers.

Background: Speech abnormalities are increasingly recognized as a manifestation of cognitive deficits in Alzheimer's disease (AD) and its preclinical and prodromal stages. Here, we investigated whether MRI measures of brain atrophy, specifically in the basal forebrain and cortical language areas, can predict cognitive decline and speech difficulties in older adults within the AD spectrum.

Method: The ongoing Prospect-AD study aims to develop an algorithm to automatically identify speech biomarkers in individuals with early signs of AD.

Biomarkers.

Background: Subjective cognitive decline (SCD), in the absence of objective cognitive impairment, may be the first symptomatic manifestation of Alzheimer's disease (AD). Previous studies have suggested that its combination with amyloid-positivity (Aβ+) may represent stage 2 AD, and is associated with a higher risk of future cognitive decline. Here, we aim to (1) confirm this using the plasma Aβ42/40 ratio, and (2) test whether the addition of plasma phospho-tau181 (ptau, a marker of Aβ and tau pathology) could help refine the prediction of future cognitive decline in SCD patients.

Biomarkers.

Background: Differences in task-fMRI activation have recently been found to be related to neuropathological hallmarks of AD. However, the evolution of fMRI-based activation throughout AD disease progression and its relationship with other biomarkers remains elusive. Applying a disease progression model (DPM) to a multicentric cohort with up to four annual task-fMRI visits, we hope to provide a deeper insight into these relationships.

Biomarkers.

Background: Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer's disease (AD) patients, are prevalent and clinically meaningful in this group of older adults.

Method: To uncover atrophy subtypes, we applied the Subtype and Stage Inference (SuStaIn) algorithm to structural MRI data from 813 participants (mean ± SD age = 70.

Biomarkers.

Background: For over three decades, the concomitance of cortical neurodegeneration and white matter hyperintensities (WMH) has sparked discussion about their coupled temporal dynamics (Garnier-Crussard et al. 2023). Longitudinal evidence supporting this hypothesis remains nonetheless scarce (Ter Telgte et al.

Biomarkers.

Background: Perivascular spaces (PVS) can become large enough to be visible in magnetic resonance imaging (MRI). The exact aetiology of PVS enlargement in humans remains, however, elusive and under continuous debate [1-5]. Here, we tracked PVS volumes longitudinally over three years in 525 individuals along AD syndromal cognitive stages, namely cognitively unimpaired (CU), mild cognitive impairment (MCI), and Alzheimer's disease (AD), to pinpoint conditions related to PVS enlargement.

Biomarkers.

Background: Analysis of neuroimaging data based on convolutional neural networks (CNNs) can improve detection of clinically relevant characteristics of patients with Alzheimer's disease (AD). Previously, our group developed a CNN-based approach for detecting AD via magnetic resonance imaging (MRI) scans and for identifying features that are relevant to the decision of the network. In the current study, we aimed to evaluate the potential utility of applying this approach to MRI scans to assist in the identification of individuals at high risk for amyloid positivity to aid in the selection of study samples and case finding for treatment.

Developing Topics.

Background: Inadequate glymphatic clearance through perivascular spaces (PVS) is hypothesized to contribute to the formation of white matter hyperintensities (WMH). However, longitudinal evidence for such a mechanistic link in aging remains limited. Using multivariate modelling, we investigated the interrelationship between PVS and WMH over time to elucidate potential cascades of early cerebrovascular alterations and tested whether AD-biomarkers and inflammatory markers associated with vascular disease can explain individual variability in their occurrence and progression.

Alzheimer's Imaging Consortium.

Background: Differences in task-fMRI activation have recently been found to be related to neuropathological hallmarks of AD. However, the evolution of fMRI-based activation throughout AD disease progression and its relationship with other biomarkers remains elusive. Applying a disease progression model (DPM) to a multicentric cohort with up to four annual task-fMRI visits, we hope to provide a deeper insight into these relationships.

Alzheimer's Imaging Consortium.

Background: Analysis of neuroimaging data based on convolutional neural networks (CNNs) can improve detection of clinically relevant characteristics of patients with Alzheimer's disease (AD). Previously, our group developed a CNN-based approach for detecting AD via magnetic resonance imaging (MRI) scans and for identifying features that are relevant to the decision of the network. In the current study, we aimed to evaluate the potential utility of applying this approach to MRI scans to assist in the identification of individuals at high risk for amyloid positivity to aid in the selection of study samples and case finding for treatment.

Alzheimer's Imaging Consortium.

Background: Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer's disease (AD) patients, are prevalent and clinically meaningful in this group of older adults.

Method: To uncover atrophy subtypes, we applied the Subtype and Stage Inference (SuStaIn) algorithm to structural MRI data from 813 participants (mean ± SD age = 70.

Dementia Care Research and Psychosocial Factors.

Background: Environmental factors account for a considerable percentage of dementia cases. Studies in animal models have shown that environmental enrichment (EE; i.e.

Environmental enrichment is associated with favorable memory-related functional brain activity patterns in older adults.

Background: In humans, environmental enrichment (EE), as measured by the engagement in a variety of leisure activities, has been associated with larger hippocampal structure and better memory function. The present cross-sectional study assessed whether EE during early life (13-30 years) and midlife (30-65 years) is associated with better preserved memory-related brain activity patterns in older age.

Methods: In total, 372 cognitively unimpaired older adults (aged ≥60 years old) of the DZNE-Longitudinal Study on Cognitive Impairment and Dementia (DELCODE; DRKS00007966) were investigated.

Sex-associated differences in incentive salience and drinking behaviour in a rodent model of alcohol relapse.

The ability of environmental cues to trigger alcohol-seeking behaviours is thought to facilitate problematic alcohol use. Individuals' tendency to attribute incentive salience to cues may increase the risk of addiction. We sought to study the relationship between incentive salience and alcohol addiction using non-preferring rats to model the heterogeneity of human alcohol consumption, investigating both males and females.

40 Hz Visual Stimulation During Sleep Evokes Neuronal Gamma Activity in NREM and REM Stages.

Study Objectives: Visual stimulation at 40 Hz is being tested as a non-invasive approach against dementias such as Alzheimer's disease. Applying it during sleep could increase convenience, duration, and efficacy of stimulation. Here, we tested the feasibility of 40 Hz visual stimulation during sleep in a proof-of-concept study.

Artificial intelligence-based rapid brain volumetry substantially improves differential diagnosis in dementia.

Introduction: This study evaluates the clinical value of a deep learning-based artificial intelligence (AI) system that performs rapid brain volumetry with automatic lobe segmentation and age- and sex-adjusted percentile comparisons.

Methods: Fifty-five patients-17 with Alzheimer's disease (AD), 18 with frontotemporal dementia (FTD), and 20 healthy controls-underwent cranial magnetic resonance imaging scans. Two board-certified neuroradiologists (BCNR), two board-certified radiologists (BCR), and three radiology residents (RR) assessed the scans twice: first without AI support and then with AI assistance.

Blood-based quantification of Aβ oligomers indicates impaired clearance from brain in ApoE ε4 positive subjects.

Background: Quantification of Amyloid beta (Aβ) oligomers in plasma enables early diagnosis of Alzheimer's Disease (AD) and improves our understanding of underlying pathologies. However, quantification necessitates an extremely sensitive and selective technology because of very low Aβ oligomer concentrations and possible interference from matrix components.

Methods: In this report, we developed and validated a surface-based fluorescence distribution analysis (sFIDA) assay for quantification of Aβ oligomers in plasma.

Claustrum volumes are lower in schizophrenia and mediate patients' attentional deficits.

Background: While the last decade of extensive research revealed the prominent role of the claustrum for mammalian forebrain organization, i.e., widely distributed claustral-cortical circuits coordinate basic cognitive functions such as attention, it is poorly understood whether the claustrum is relevant for schizophrenia and related cognitive symptoms.

Illumina SBS Sequencing and DNBSEQ Perform Similarly for Single-Cell Transcriptomics.

Background/objectives: High-throughput single-cell RNA sequencing (scRNA-seq) workflows produce libraries that demand extensive sequencing. However, standard next-generation sequencing (NGS) methods remain expensive, contributing to the high running costs of single-cell experiments and often negatively affecting the sample numbers and statistical strength of such projects. In recent years, a plethora of new sequencing technologies have become available to researchers through several manufacturers, often providing lower-cost alternatives to standard NGS.

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 test this hypothesis in the continuum from cognitively normal to at-risk stages for Alzheimer's Disease (AD) to AD dementia using longitudinal data from 490 participants of the DELCODE multicentric observational study. Brain function is measured using task fMRI of visual memory encoding.

Perivascular space enlargement accelerates in ageing and Alzheimer's disease pathology: evidence from a three-year longitudinal multicentre study.

Background: Perivascular space (PVS) enlargement in ageing and Alzheimer's disease (AD) and the drivers of such a structural change in humans require longitudinal investigation. Elucidating the effects of demographic factors, hypertension, cerebrovascular dysfunction, and AD pathology on PVS dynamics could inform the role of PVS in brain health function as well as the complex pathophysiology of AD.

Methods: We studied PVS in centrum semiovale (CSO) and basal ganglia (BG) computationally over three to four annual visits in 503 participants (255 females; mean = 70.

Longitudinal evidence for a mutually reinforcing relationship between white matter hyperintensities and cortical thickness in cognitively unimpaired older adults.

Background: For over three decades, the concomitance of cortical neurodegeneration and white matter hyperintensities (WMH) has sparked discussions about their coupled temporal dynamics. Longitudinal studies supporting this hypothesis nonetheless remain scarce.

Methods: We applied global and regional bivariate latent growth curve modelling to determine the extent to which WMH and cortical thickness were interrelated over a four-year period.

Mapping the glial transcriptome in Huntington's disease using snRNAseq: selective disruption of glial signatures across brain regions.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease with a fatal outcome. There is accumulating evidence of a prominent role of glia in the pathology of HD, and we investigated this by conducting single nuclear RNA sequencing (snRNAseq) of human post mortem brain in four differentially affected regions; caudate nucleus, frontal cortex, hippocampus and cerebellum. Across 127,205 nuclei from donors with HD and age/sex matched controls, we found heterogeneity of glia which is altered in HD.