Biomarkers.

Background: Alzheimer's disease (AD) is a complex disorder with a strong genetic component, yet many genetic risk factors remain unknown. Integrating genome-wide association studies (GWAS) and high-throughput proteomic platforms is a useful strategy to evaluate protein quantitative trait loci (pQTLs) and to detect candidate genes and pathways involved in AD. Due to the novelty of these techniques, the identification of reliable protein measures through a comprehensive quality control is mandatory.

Biomarkers.

Background: Increasing evidence supports the use of plasma biomarkers of amyloid, tau, neurodegeneration and neuroinflammation for diagnosis of dementia. However, their performance for positive and differential diagnosis of dementia with Lewy bodies (DLB) in clinical settings is still uncertain.

Method: We conducted a retrospective biomarker study in two tertiary memory centers, Paris Lariboisière and CM2RR Strasbourg, France, enrolling patients with DLB (n=104), Alzheimer's disease (AD, n=76) and neurological controls (NC, n=27).

Biomarkers.

Background: Brain MRI segmentation is required for quantitative PET analysis, in order to derive regional uptake and calculate uptake ratio relative to reference regions. FreeSurfer has been a popular method but is being supplanted by faster and more robust AI-driven methods. The objective of this work is to confirm that the use of Clario's novel AI segmentation method, whose impact was assessed towards various MRI endpoints, is also valid in the context of PET quantification.

Biomarkers.

Background: Education has been associated with reserve mechanisms and lower dementia risk, but the literature shows inconsistent results on the association between education and brain outcomes across the lifespan. Considering that both dementia risk and education are likely to differ between sexes, our study aims at understanding the association between education and brain outcomes across the lifespan and whether it differs by sex.

Method: In 207 healthy individuals (110women) aged 19-84 years old (47.

Biomarkers.

Background: Sleep disturbances have been identified as a risk factor for developing dementia. The hypothalamus is involved in sleep regulation and may be affected early by neurodegeneration. Our aim was to investigate the relationship between subjective sleep and hypothalamic structure in adults at higher risk of developing dementia.

Biomarkers.

White matter hyperintensities (WMH) are highly prevalent in aging and Alzheimer's disease (AD) and typically attributed to vascular damage and cerebral small vessel disease. Yet, several lines of evidence from the literature emphasize the heterogeneity in the mechanisms leading to WMH, notably in AD, suggesting that WMH may be partly attributable to AD. Thus, firstly, neuropathological studies demonstrate heterogeneity in WMH histology, with indications of a link between tau pathology, Wallerian degeneration, and WMH severity.

A phase I clinical trial of intrahepatic artery delivery of TG6002 in combination with oral 5-fluorocytosine in patients with liver-dominant metastatic colorectal cancer.

Background: Effective treatment for patients with metastatic cancer is limited, particularly for colorectal cancer patients with metastatic liver lesions (mCRC), where accessibility to numerous tumours is essential for favourable clinical outcomes. Oncolytic viruses (OVs) selectively replicate in cancer cells; however, direct targeting of inaccessible lesions is limited when using conventional intravenous or intratumoural administration routes.

Methods: We conducted a multi-centre, dose-escalation, phase I study of vaccinia virus, TG6002, via intrahepatic artery (IHA) delivery in combination with the oral pro-drug 5-fluorocytosine to fifteen mCRC patients.

Biomarkers.

Background: Neuropsychiatric symptoms (NPS), including depression and circadian rhythm disruptions, are early non-cognitive markers along the Alzheimer's Disease (AD) continuum. These pathological states are thought to resemble AD pathogenesis, both of which are characterized by a marked decline in adult hippocampal neurogenesis.

Method: 96 elderly participants divided into three groups based on the global depression scale, neuropsychiatric inventory, clinical dementia rating, and mini-mental status examination.

Biomarkers.

Background: Patterns of regional atrophy and hypometabolism have been observed in dementia with Lewy bodies (DLB). However, determinants of regional vulnerability to structural and functional neurodegeneration remain largely unexplored. First, we investigated the association between regional gene expression and grey matter volumes in probable DLB patients.

Biomarkers.

Background: Tau-PET imaging allows in-vivo detection of neurofibrillary tangles. One tau-PET tracer (i.e.

Biomarkers.

Background: Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a neurodegenerative disease that is often comorbid with Alzheimer's disease (AD) and for which there are no reliable specific chemical or PET biomarkers available. Recent progress in disease-modifying treatments for AD elevates the need for reliable in vivo detection of LATE and other comorbid neurodegenerative diseases. The promise of postmortem and antemortem MRI studies in LATE is that they will lead to the discovery of patterns of neurodegeneration associated with TDP-43 pathology that could be reliably detected in vivo and used as a biomarker of LATE.

Optimal Word Reading Rate as Evidenced by Frequency-tagging Electrophysiology.

Fast periodic visual stimulation (FPVS) coupled with EEG has been used for a decade to measure word-selective neural responses in (a)typical adults and developmental readers. Here, we used this FPVS-EEG approach to evaluate suitable and optimal stimulation frequency rates for prelexical and lexical word-selective responses and relate these rates to typical reading speed and interindividual variability in reading performance. EEG was recorded in 41 healthy adults who viewed words inserted periodically (1 Hz) at four different stimulation frequency rates (4 Hz, 6 Hz, 10 Hz, and 20 Hz).

Biomarkers.

Background: Locus coeruleus (LC) imaging using neuromelanin-sensitive (NM) MRI sequences is a promising biomarker for detecting early Alzheimer's Disease (AD). Although automatic approaches have been developed to estimate LC integrity by measuring its intensity, these techniques most often rely on a single template built in a standardized space and/or depend on a number of voxels to be accounted that is defined a priori. Thus, these algorithms make it impossible to perform direct volumetric analyses and do not properly account for inter-individual anatomical variability.

Biomarkers.

Background: Increased stress, a proposed risk factor for Alzheimer's disease (AD), is associated with increased brain and cognitive vulnerabilities in older populations, which may be different in women and men.

Objective: To examine cross-sectional associations between circulating stress hormones (epinephrine, norepinephrine, cortisol, dehydroepiandrosterone sulfate (DHEAS), and DHEAS/cortisol ratio) and multimodal measures of brain health and cognition sensitive to AD.

Method: 132 cognitively unimpaired older participants without clinical depression (age = 74.

Biomarkers.

Background: Tau pathology and neurodegeneration in the medial temporal lobe (MTL) are highly associated in Alzheimer's Disease (AD). However, the spatial pattern of neurodegeneration, contribution of individual tau inclusion types, and influence of MTL co-pathologies (i.e.

Biomarkers.

Background: The immune complement system is key to the elimination of redundant neural connections in the brain through a process called synaptic pruning. In neurodegenerative diseases such as Alzheimer's disease (AD), this system may result in excessive synapse loss, leading to brain atrophy and cognitive impairment. While increased cerebrospinal fluid (CSF) levels of complement proteins have been observed in patients with AD dementia, no studies have yet investigated the role of complement in the pre-symptomatic phase of AD, nor throughout its progression.

Biomarkers.

Background: Typical Alzheimer's disease (AD) and Limbic-predominant Age-related TDP-43 Encephalopathy (LATE) are two neurodegenerative diseases that present with a similar initial amnestic clinical phenotype but have distinct proteinopathies. AD is characterised by ß-amyloid plaques and intraneuronal neurofibrillary tangles, while LATE is characterised by abnormal neuronal TDP-43 protein. With reference to the prion-like hypothesis regarding the propagation of proteinopathies, investigating white matter fibre bundle alterations could provide new insights into the propagation pathways of specific proteinopathies.

Biomarkers.

Background: Cerebral small vessel disease (cSVD) is a leading cause of stroke and dementia. Its underlying mechanisms remain elusive and specific mechanism-based drugs are lacking.

Method: We integrated more than 2,800 CSF and 4,600 plasma pQTL, derived from the largest proteomic studies so far (SOMAscan 7k and 4k; in up to 35,559 individuals), and the two most prevalent MRI-markers of cSVD (MRI-cSVD, white matter hyperintensities and perivascular spaces burden; in up to 48,454 individuals) in a Mendelian Randomization (MR) framework to identify causal and druggable targets for cSVD.

Biomarkers.

Background: It is estimated that up to 80% of people with Alzheimer's disease (AD) may have some form of anosognosia. Anosognosia also constitutes a major source of stress for caregivers as it delays diagnosis and affects compliance with treatment. Here, we aimed to explore whether and how early anosognosia and caregiver burden could independently serve as indicators for identifying patients at risk of converting to AD.

Short-term exposure to PM pollution in Iran and related burden diseases.

The objective of this study was to estimate the health effects attributed to PM exposure in southwest of Iran. In order to estimate HA-CVD, HA-RD, LC-M, I-As in children, RAD, and WDL, the exposure-response function method was used. The annual mean of PM regularly exceeded 5.

Biomarkers.

Background: Cerebrovascular reactivity (CVR) is implicated in the progression of dementia, though the underlying mechanisms is not understood. This study examines the relationships between CVR and brain structure and cognitive decline, moderated by mid-life dementia risk.

Method: 163 participants from the Whitehall-II cohort underwent neuropsychological testing and MRI, including T1-weighted, FLAIR, and DTI sequences, at two phases (Phase-I: mean age=68.

Biomarkers.

Background: Individuals with Down Syndrome (DS) almost invariably develop Alzheimer's Disease (AD), but detecting early clinical changes is challenging due to comorbid intellectual disability, highlighting the importance of non-invasive biomarkers. Neuroimaging of the medial temporal lobe (MTL), a key site of tau pathology, shows promise as an early AD biomarker. Here, we aimed to characterise volumetric patterns of the MTL in DS across the AD clinical continuum, and define associations with AD cerebrospinal fluid (CSF) biomarkers.

Biomarkers.

Background: Recently, the development of ultra-sensitive immunoassays has allowed for the detection, in blood, of proteins related to the pathophysiology of Alzheimer's disease (AD), with phosphorylated tau (p-tau) being the most promising. However, current methods are often limited by their ability to measure one analyte, lacking the potential for discovery and inclusion of additional biomarkers with supplemental value. In this pilot study, we explored proteomic changes using the novel NUcleic acid Linked Immuno-Sandwich Assay (NULISA™) platform, focusing on patients with mild cognitive impairment (MCI).