Biomarkers.

Background: The posterior-medial network is crucial for episodic memory. However, the medial temporal lobe (MTL) and posteromedial cortex (PMC) regions are vulnerable to aging and early Alzheimer's disease (AD). Both processes might elicit distinct early functional connectivity (FC) changes which could be detrimental or protective/ compensatory regarding cognition.

Biomarkers.

Background: While some memory decline in old age is "normal", there are some older individuals with maintained high cognitive performance. Using a multimodal approach including neuroimaging, fitness, genetic and questionnaire data (Figure 1A), we aimed to identify factors that are related to successful cognitive aging and whether these differ between sexes.

Method: We analyzed 165 cognitively normal older adults age ≥ 60 years from an ongoing study (SFB1436) (age=71±8years, 43% female).

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: Alzheimer disease (AD) plasma biomarkers change in the preclinical stage of AD. However, the robustness of the discrimination performance of these biomarkers, as well as their association with longitudinal primary pathology (amyloid and tau) changes, is less understood. We aimed to determine the ability of baseline and longitudinal plasma amyloid-β (Aβ)42/40, p-tau181, GFAP and NfL to detect primary pathology in CU individuals at risk of AD.

Biomarkers.

Background: The human brain integrity relies on the synergistic interplay between neural activity and supporting vascular and metabolic processes throughout life. This relationship, ruled by allostatic mechanisms, regulates brain architecture and activity. White matter hyperintensities (WMH) serve as indicators of the vascular impact on brain structure.

Biomarkers.

Background: To date, all computerised perivascular spaces (PVS) quantification methods require case-wise, imaging modality, or study-specific parameter adjustments, and suffer from generalisability problems in clinical settings, and misdetection of other cerebral small vessel disease (CSVD) markers. We propose a deep learning-based PVS detection method to overcome these issues. We compare our proposal on magnetic resonance imaging data of CSVD participants against the performance of the Frangi filter.

Biomarkers.

Background: Recent technological advancements have revolutionized our approach to healthcare, enabling us to harness the potential of smartphones and wearables to collect data that can be used to characterize Alzheimer's disease (AD) heterogeneity and to develop digital biomarkers. Our focus is to create comprehensive cross-domain digital datasets and establish an infrastructure that allows for seamless data sharing. Central to accelerating the potential of digital biomarkers for more accurate and early detection is privacy-protecting data access, which when combined with deep molecular phenotyping, will enhance our understanding of the biological mechanisms underlying clinical expression.

Biomarkers.

Background: Dementia with Lewy bodies (DLB) is a an α-synucleinopathy characterized by dementia and a combination of parkinsonism, visual hallucinations, fluctuating cognition or REM sleep behaviour disorder. Specific biomarkers for DLB are lacking. DLB-related pattern (DLBRP) is a metabolic network imaging biomarker which expression can be quantified on a single patient basis.

Biomarkers.

Background: Alzheimer's Disease (AD) is often accompanied by neuroinflammation, which manifests prior to significant cognitive decline. Reactive astrocytosis is a hallmark of such inflammation, potentially serving as an early biomarker for AD pathology. Our study employs [18F]fluorodeprenyl-D2 ([18F]F-DED) positron emission tomography (PET) imaging to in vivo quantify astrocytosis comparing AD with healthy controls and examines its assocciation with cognitive deterioration in AD.

Biomarkers.

Background: In Alzheimer's disease (AD), cortical tau aggregation is a strong predictor of cortical brain atrophy as shown by MRI and PET studies, particularly driving the degeneration of neuronal somata in the grey matter. However, tau's physiological role is to stabilize microtubules within axons in the brain's white matter (WM) pathways. Therefore, tau's white-to-grey-matter translocation and aggregation in neurofibrillary tangles close to neuronal somata may induce WM degeneration through destabilization of axonal microtubule integrity.

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: Cavum Septum Pellucidum [CSP] is commonly observed on neuroimaging in individuals exposed to repetitive head impacts [RHI] and in post-mortem examination in Chronic Traumatic Encephalopathy [CTE]. A CSP is proposed as a potential biomarker for CTE, yet prevalence across neurodegenerative diseases and its clinical implications are largely unknown. We assessed CSP prevalence and clinical associations in RHI-exposed individuals in comparison to veterans with a history of traumatic brain injury [TBI], individuals with a neurodegenerative disease (i.

Biomarkers.

Background: Different patterns of atrophy exist in the dementia stage of AD. However, little is known about the heterogeneity of atrophy patterns and the mechanisms that drive subsequent propagation of the disease in the preclinical stages.

Method: From the AMYPAD-PNHS cohort, we included a total of 1323 non-demented individuals, including 1094 amyloid-negative, and 229 amyloid-positive participants (Table 1).

Biomarkers.

Background: Alzheimer's disease (AD) and related dementias can have long preclinical phases; thus, midlife intervention and prevention methods could prove efficacious. Multiple health-related lifestyle factors have been associated with risk for AD. However, research on lifestyle factors has focused on clinical outcomes such as cognitive decline, mild cognitive impairment and/or AD dementia; their associations with potential early changes in cerebrospinal fluid (CSF) biomarkers are less understood.

A weight of evidence review on the mode of action, adversity, and the human relevance of xylene's observed thyroid effects in rats.

Xylene substances have wide industrial and consumer uses and are currently undergoing dossier and substance evaluation under Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) for further toxicological testing including consideration of an additional neurotoxicological testing cohort to an extended one-generation reproduction toxicity (EOGRT) study. New repeated dose study data on xylenes identify the thyroid as a potential target tissue, and therefore a weight of evidence review is provided to investigate whether or not xylene-mediated changes on the hypothalamus-pituitary-thyroid (HPT) axis are secondary to liver enzymatic induction and are of a magnitude that is relevant for neurological human health concerns. Multiple published studies confirm xylene-mediated increases in liver weight, hepatocellular hypertrophy, and liver enzymatic induction the oral or inhalation routes, including an increase in uridine 5'-diphospho-glucuronosyltransferase (UDP-GT) activity, the key step in thyroid hormone metabolism in rodents.

Use and limitations of clinical data in the identification and classification of low molecular weight chemicals (LMWCs) as respiratory sensitizers: recommendations for improvement.

While progress has been made in recent years, there are still no suitable and accepted , or models that can be used to accurately predict whether a chemical substance has the intrinsic property to cause immune-mediated chemical respiratory allergy, typically manifested as allergic asthma or allergic rhinitis which represents a severe health hazard. Regulatory authorities have relied primarily on clinical evidence (case reports, clinical databases, worker exposure studies) to classify substances as respiratory sensitizers, but this evidence can lack a proven immunological mechanism which is necessary to identify substances which can cause life-long sensitization and clinically relevant allergic symptoms in the respiratory tract in an exposed population (such respiratory allergens may be considered as "true" sensitizers, in analogy to the definition of skin sensitization, and in contrast to respiratory irritants). In light of this, the European Center for Ecotoxicology and Toxicology of Chemicals convened a Task Force to evaluate the types of clinical methods and data sources and the implications of relying on such data for regulatory decision making from a scientific perspective.

Biomarkers.

Background: Fluid biomarkers provide a convenient way to predict AD pathophysiology. However, few studies have focused on determining associations with tau neurofibrillary tangle pathology in the early preclinical AD continuum, relevant to prevention strategies.

Methods: Ninety-nine cognitively unimpaired individuals from the ALFA+ cohort with valid F-RO-948 and F-flutemetamol PET, T1-weighted MRI, cognition, CSF, and plasma biomarkers were included.

Biomarkers.

Background: Training studies report beneficial effects of physical (PP) on cognitive performance (COG) in older adults, but are often accompanied by potentially biased parameters, conclusions, and lack of directionality. To address these issues, we used a dynamic Bayesian approach to analyse the dynamic session-to-session change and coupling of PP and COG over time.

Methods: We used two studies (N = 17 each): Study 1 contained 24-weeks (72 sessions) of training of older adults with suspected Alzheimer's disease (AD).

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: Familial Alzheimer's disease research necessitates innovative methodologies to disentangle the intricate relationships between genetic factors and neuroimaging measures. Traditional frequentist approaches, often hampered by small sample sizes in this population and challenges in incorporating prior knowledge transparently, may limit the robustness of findings.

Methods: We analyzed neuroimaging data of preclinical PSNE1 single mutation carriers, utilizing the software JASP to test effects of carrier status on measures of basal forebrain functional connectivity using both frequentist and Bayesian approach.

Biomarkers.

Background: Digital health research on Alzheimer's disease (AD) points to automated speech and language analysis (ASLA) as a globally scalable approach for diagnosis and monitoring. However, most studies target uninterpretable features in Anglophone samples, casting doubts on the approach's clinical utility and cross-linguistic validity. The present study was designed to tackle both issues.

Biomarkers.

Background: White matter lesions (WMLs) are common with aging and are prevalent in AD, but the underlying physiology as well as associations with conventional vascular risk factors are not yet fully understood. In this study, we investigated the relationship between vascular risk factors and microvascular physiology (i.e.

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: Synaptic loss is identified as a strong correlate of cognitive impairment in Alzheimer's disease (AD). Pathological tau can induce direct toxicity to synapse and spread trans-synaptically across connected neurons. Recent neuroimaging evidence revealed that tau pathology propagates along interconnected brain regions throughout macroscale brain networks.