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).

Biomarkers.

Background: ALZ-801 (valiltramiprosate) is an oral inhibitor of amyloid oligomer formation in development as a disease-modifying AD treatment, including a fully enrolled APOLLOE4 Phase 3 trial in 325 APOE4/4 homozygotes. A Phase 2 study is evaluating ALZ-801 effects on plasma biomarkers, brain volumes and cognitive outcomes in APOE4 carriers. Plasma p-tau reduction over 104 weeks is primary endpoint.

Public Health.

Background: Some older adults succeed in maintaining excellent cognition despite high genetic risk for Alzheimer's disease (AD), reflecting cognitive resistance (CR) to potential neuropathologies. Although the etiological factors for CR are still unknown, some literature suggests that environmental/lifestyle risk factors may contribute to offset, or at least reduce, the effect of AD-related genes on cognitive decline and dementia risk. Yet, how modifiable lifestyle and health related risk factors may promote CR in genetically at-risk individuals remains to be elucidated.

Public Health.

Background: High-income countries (HICs) are over-represented in current global dementia incidence rates, skewing estimates. Variance in diagnostic methods between HICs and low- and middle-income countries (LMICs) is speculated to contribute to the regional differences in rates. Cohort Studies of Memory in an International Consortium (COSMIC) offers a unique opportunity to address these research inequalities by harmonising data from international studies, including representation from LMICs.

Public Health.

Background: To estimate the additive associations of cardiometabolic multimorbidity (CMM) and depression on long-term cognitive trajectory in multi-regional cohorts and validate the generalizability of the findings in varying clinical settings.

Method: Data harmonization was performed across 14 longitudinal cohort studies within the Cohort Studies of Memory in an International Consortium (COSMIC) group, spanning North America, South America, Europe, Africa, Asia, and Australia. Three external validation studies with distinct settings were employed to assess generalizability.

Public Health.

Background: Dementia is a major contributor to loss of autonomy in the elderly. Every year spent with dementia results in significant medical and societal costs. Understanding secular trends of life expectancy with and without dementia would enable us to better anticipate future needs.

Public Health.

Background: Higher Mediterranean- DASH for Neurodegenerative Delay (MIND) diet scores have previously been associated with larger total brain volume (TBV) in the Framingham Offspring Study (FOS) community-based cohort. We investigated cross-sectional relationships between the MIND diet and structural brain imaging volumes and white matter hyperintensity volume (WMHV) across six community-based cohorts.

Method: We analyzed data from 3130 dementia-, stroke- and other neurological disease free adults (aged 65 to 74) who participated in the Atherosclerosis Risk in Communities (ARIC) cohort, Cardiovascular Health Study (CHS), Three City (3C) cohort, FOS cohort, Rotterdam Study (RS) or the Study of Health in Pomerania (SHIP) cohort.

Public Health.

Background: Despite evidence that sex can modulate Alzheimer's disease (AD) risk, whether risk factors are similarly related to AD markers in women and men remains largely unexplored. We aimed to assess how a combination of potentially modifiable risk factors are associated with cognitive and pathological markers of AD in older women and men.

Method: We included 135 cognitively unimpaired older adults (≥65 years old, 83 women; Table 1) from the Age-Well trial (NCT02977819; baseline data) with multidomain assessments of modifiable risk factors, including cardiovascular (body mass index, systolic blood pressure, LDL cholesterol), lifestyle (complex mental activity throughout life, physical activity, diet), and psychological (quality of life, depressive and anxiety symptoms, rumination, worry).

Public Health.

Background: Smartphone-based assessments are a promising tool for early detection of cognitive decline in midlife. Previous research has shown such cognitive markers can be sensitive to a range of potentially modifiable dementia risk factors even in healthy adults. However, their sensitivity to genetic risk factors like APOE-ε4 is likely to differ by cognitive domain, with evidence of strong negative effects on wayfinding tasks but mixed for other domains.

Public Health.

Background: Diet is a primary source of exposure to chemicals in the general population. Dietary contaminants originate from food production (e.g.

Public Health.

Background: The prevalence of dementia in people aged 65 and over in the world is approximately 6-10%, two-thirds of these cases are due to Alzheimer disease The frequency of deaths from Alzheimer disease in Ukraine is 0.3 per 100,000 population, while in Great Britain this indicator is 112 per 100,000 people, USA - 82, France - 76, Germany - 51 [1, 2]. The purpose of the study was to estimate the prevalence of Alzheimer's disease in the Odesa region.

Public Health.

Chemicals are ubiquitous in modern life. More than 100,000 chemicals are currently used worldwide, and the production continues to increase. Measuring with accuracy all the components of the chemical exposome represents a tremendous challenge which has been only very partly met so far, and gaps in science remain multiple.

Public Health.

This critical overview aims to provide one of the most comprehensive synthesis of epidemiological and experimental evidence relating the chemical exposome to Alzheimer's Disease (AD). We have focused on chemical pollutants that mostly result from anthropic activities and involved in toxicology pathways, including pesticides, organic solvents, metals, combustion air pollutants, dioxins, flame retardants, fluorosurfactants, plastic components and food/cosmetic additives. In total, we have reviewed over 120 epidemiological studies examining the link between chemical exposures and the risk of AD or cognitive impairment in older adults, along with more than 250 experimental studies assessing the impact of chemical exposures on neurodegeneration-related pathways.

Safety and efficacy of the automated suture system in valvular heart surgery: a multicenter, prospective registry.

Background: In the last years, the Cor-Knot device has been increasingly used in heart valve surgery. Our aim was to investigate the incidence of valvular complications in patients who underwent valvular surgery using the Cor-Knot device in multicentric cohorts at one-year follow-up.

Methods: Three hundred and sixty-eight patient underwent heart valve repair or replacement surgery using automated titanium suture fasteners in four cardiothoracic surgery departments between September 2018 and January 2020.

Biomarkers.

Background: The identification of biomarkers for Alzheimer's disease (AD) remains a significant challenge, particularly for the clinical severity of the disease. Recent studies have shown that plasma brain-derived-tau (BD-Tau) could be a promising biomarker for the identification of AD-type neurodegeneration. This study aimed to investigate the potential of BD-Tau in differentiating various clinical stages of AD, ranging from cognitively unimpaired AD to severe dementia AD.

Biomarkers.

Background: The Amyloid Imaging to Prevent Alzheimer's Disease (AMYPAD) Prognostic & Natural History Study (PNHS) is a prospective longitudinal PET cohort of over 1,500 non-demented individuals from 10 parent cohorts across Europe. We provide an overview of ongoing efforts to curate and integrate magnetic resonance imaging (MRI) multimodal images across sites and to extract biologically meaningful information (i.e.

Biomarkers.

Background: Less adequate cardiorespiratory fitness (CRF) is associated with several aspects of Alzheimer's disease (AD) pathology, including neuroinflammation, neurodegeneration and synaptic dysfunction, all of which are known contributors to the clinical outcome - progressive cognitive decline [1]. AD-associated biomolecular changes also seem to be attenuated in carriers of the functionally advantageous variant of the KLOTHO gene (KL-VS) [2]. While KL-VS and CRF both appear to mitigate aspects of AD pathology, they have been exclusively studied in isolation.

Biomarkers.

Background: Microbiota is modulated by normal aging, but also by Alzheimer's disease (AD) risk factors as poor diet or alteration of sleep patterns. Patients with AD exhibit a dysbiosis characterized by changes in the relative proportions of specific bacterial phyla. Eventually, fecal microbiota transplants (FMT) can improve cognitive deficits and reduce amyloid-ß deposition, at least in mouse models of AD.

Biomarkers.

Background: Recent developments in physiological and digital biomarkers provide an opportunity to shift the first diagnostic steps to the home-setting, thus allowing earlier detection and treatment of Alzheimer's disease (AD). Blood-based, magnetic resonance imaging, electrophysiological, digital and microbiome biomarkers have shown great promise and call for an evaluation of their accuracy, feasibility and safety in primary care and the community. The aim of PREDICTOM is to develop and test the accuracy of an artificial intelligence (AI) driven screening platform for the prediction and early detection of AD and to extend the clinical pathway to home-based screening using established and novel biomarkers.

Biomarkers.

Background: Posterior cortical atrophy (PCA) is often considered the most common atypical Alzheimer's disease phenotype, being characterized by progressive loss of visual and other posterior cortical functions. Early reading and other visuoperceptual difficulties prompt PCA patients presenting to eye clinics and receiving ocular misdiagnoses. Patients also report altered perception of body position- for example, difficulty locating ones' arm during dressing.

Biomarkers.

Background: Detection and quantification of White Matter Hyperintensities (WMH) are clinically important across multiple CNS disorders and neurodegenerative dementias. However, the prohibitively labor-intensive nature of manual segmentation limits widespread clinical application. Accurate automated methods for segmenting WMH are needed to overcome this unmet clinical need.

Biomarkers.

Background: The quantification of neurofilament light chain (NfL) in blood and cerebrospinal fluid (CSF) has proved useful in many contexts, for the diagnosis and prognosis of various neurological disorders. There is, however, a diversity of practices between centers, essentially linked to the context of use (COU), analytical methods, consideration of comorbidities, determination of cut-points or use of interpretation scales. Finally, for the same biochemical profile, the interpretation and reporting of results may differ from one center to another, raising the question of test commutability.

Biomarkers.

Background: Glial fibrillary acidic protein (GFAP) is a marker of cerebral astrogliosis and occasionally elevated in patients with dementia. GFAP in cerebrospinal fluid (CSF), is routinely requested in referrals to neurochemistry laboratories; however, its ability to differentiate dementias and diagnostic capability is unclear. Our aim was to elucidate this, using two large datasets.

Biomarkers.

Background: Increasing evidence supports the notion that vascular dysfunction contributes to the evolution of Alzheimer's disease (AD). Cerebral pulsatility index (PI) is reportedly higher in AD and MCI compared to age matched controls and has been associated with greater beta-amyloid (Aß) burden. Higher cardiorespiratory fitness (CRF) positively affects vascular function and is associated with lower PI in several large cerebral vessels.