Basic Science and Pathogenesis.

Background: The X-chromosome remains largely unexplored in Alzheimer's disease (AD). We performed the first, stratified X-wide association study (XWAS) of AD to chart the role of X-chromosome genetic variation in AD sexual dimorphism and heterogeneity of APOE*4-related AD risk.

Method: The study overview is shown in Figure 1A.

Quantifying the evolutionary dynamics of structure and content in closely-related E. coli genomes.

Bacterial genomes primarily diversify via gain, loss, and rearrangement of genetic material in their flexible accessory genome. Yet the dynamics of accessory genome evolution are very poorly understood, in contrast to the core genome where diversification is readily described by mutations and homologous recombination. Here, we tackle this problem for the case of very closely related genomes.

Clinical predictors of disease severity in oral lichen planus.

Background: The limited understanding of factors influencing the disease progression of oral lichen planus (OLP) poses challenges in delivering effective and personalised treatment for this condition, known to increase the risk of oral cancer and adversely impact patient quality of life.

Objective: This study aimed to systematically identify clinical predictors of disease severity in OLP patients.

Methods: This cross-sectional and single-site prospective study was conducted between December 2021 and February 2024 in the Departments of Oral Medicine and Oral & Maxillofacial Surgery, Aberdeen Royal Infirmary.

Clinical Manifestations.

Background: Dementia-related biomarkers can detect pathology years before clinical diagnostic criteria are met. Understanding the relationship between biomarkers and early cognitive changes is crucial as disease-modifying therapies may have maximum benefits when delivered early. We aimed to demonstrate the utility of remote computerised cognitive tests in a large cohort of cognitively normal older individuals, comparing these to standard in-person assessments and investigating their associations with biomarkers.

Clinical Manifestations.

Background: Subjective Cognitive Decline (SCD) may represent the initial symptom of Alzheimer's disease (AD), but SCD may be absent and/or unrelated to actual cognitive decline. Objective Subtle Cognitive Decline (obj-SCD) can be identified through longitudinal standardized neuropsychological tests in individuals not yet meeting criteria for Mild Cognitive Impairment (MCI). We argue that the relationship between SCD and obj-SCD might help to inform clinical and research criteria in pre-MCI stages.

Basic Science and Pathogenesis.

Background: A recent study with large samples of electronic health records (EHRs) suggested Shingles vaccination may reduce dementia risk. Although further investigation is needed to pinpoint the underlying mechanism, such observation adds to the evidence for a connection between peripheral and central nervous system immunity. Since microglia is the major cell type implicated in AD genetics, here, we set out to probe the shared biology between microglia in human brain and macrophages in peripheral system, through the common genes that express in both cell types.

Clinical Manifestations.

Background: To investigate the associations between courses of depression, the application of depression treatment, and the risk of incident dementia.

Method: In this prospective cohort study, 354,313 participants aged 50 to 70 years were recruited from the UK Biobank between 2006 and 2010, and were followed-up until 2020, with a total of 4,212,929 person-years. We initially studied the effect of depression on dementia incidence across four subgroups characterized by courses of depressive symptoms.

Clinical Manifestations.

Background: Objective Subtle Cognitive Decline (obj-SCD) can be identified through standardized neuropsychological tests and may precede the development of Mild Cognitive Impairment (MCI). Nevertheless, current clinical and research criteria lack a standardized protocol for identifying obj-SCD. This study introduces cutting-edge sensitive methods to characterize obj-SCD, defined through Alzheimer's disease (AD) biomarker-based longitudinal cognitive performance in episodic memory.

Clinical Manifestations.

Background: Epidemiological evidence regarding the association between cataract onset age and risk of incident dementia remains unexplored. To examine whether age at cataract diagnosis is associated with risk of incident dementia and its subtypes.

Methods: This prospective, population-based cohort study utilized data from the UK Biobank that collected baseline information between 2006 and 2010.

Clinical Manifestations.

Background: Dementia is associated with a range of non-cognitive features that can occur during the prodromal phase. Improved recognition of non-cognitive presentations of dementia could reduce inequalities in dementia diagnosis, particularly if sociocultural factors influence rates of help-seeking for cognitive symptoms. We aimed to investigate presentations to primary care in the years before dementia diagnosis in a deprived and ethnically diverse population with universal access to health care.

Clinical Manifestations.

Background: Frontotemporal degeneration (FTD) is a complex, heterogeneous group of fatal adult-onset disorders which lead to progressive dysfunction in behavior, motor symptoms, language, and/or cognition. While advances in research are cause for optimism, trials are hindered by the availability of participants. As FTD clinical trials typically require co-participation of a study partner, care partner perspectives on research are critical to understanding how to support recruitment and retention.

Clinical Manifestations.

Background: Speech and language impairments are associated with cognitive decline in neurodegenerative dementias, particularly Alzheimer's Disease (AD), where subtle speech changes may precede clinical dementia onset. As clinical trials prioritize early identification for disease-modifying treatments, digital biomarkers for timely screening become imperative. Digital speech-based biomarkers can be employed for screening populations at the earliest AD stages.

Basic Science and Pathogenesis.

Background: For large genomic studies of middle-aged individuals, the prevalence of Alzheimer's disease (AD) is extremely low, making it difficult to conduct genomic analysis of the condition. To enable genome-wide association studies of AD in such datasets, an approach called Genome-wide association by proxy (GWAX) uses family history of disease as a proxy for disease status. Borrowing from the machine learning (ML) literature, we treat the development of proxy phenotypes as a pseudo-labelling task, where an ideal proxy label accurately predicts the lifetime risk of AD.

Clinical Manifestations.

Background: People with dementia frequently develop behavioural and psychological symptoms, sometimes necessitating care in specialist dementia mental health wards. There has been little research on their life expectancy following admission or need for palliative care. The work presented here explores the mortality of these patients and whether this can be predicted at their time of admission to the ward.

Clinical Manifestations.

Background: Previous findings evaluating longitudinal cognition in relation to the MeDi diet are inconsistent, and few studies have examined it in relation to the presence/absence of subjective cognitive decline (SCD). Our current aims are to test whether adherence to the MeDi diet is associated with the risk of clinical progression, future cognitive decline, and atrophy over time in Alzheimer's disease (AD)-sensitive regions in cognitively unimpaired (CU) older adults with or without SCD.

Methods: This longitudinal study includes 171 controls and 228 SCD patients recruited from memory clinics in the DELCODE study.

Clinical Manifestations.

Background: Smell dysfunction has been one of coronavirus disease 2019 (Covid-19) symptoms. Identification of those with these symptoms are important as olfactory impairment in general has been studied to have increased mortality, poor quality of life, increased incidence of depression and risk for dementia. Smell dysfunction related to Covid-19 in older adults and its impact is lesser studied.

Clinical Manifestations.

Background: Cognitive assessments are essential for detecting and monitoring cognitive changes in neurological populations. Compared to standard pen-and-paper tests, online cognitive tasks offer a more accessible, scalable, repeatable and cost-effective approach to assessment. Cognitron is an online cognitive assessment platform with previously demonstrated validity and reliability (1).

Clinical Manifestations.

Background: The identification of cognitively unimpaired individuals at risk of short-term cognitive decline is a critical task for Alzheimer´s disease (AD) research. Cognitively normal individuals with amyloid and/or tau pathology have a high risk for short-term cognitive decline. However, not all of these individuals show clinical progression.

Clinical Manifestations.

Background: Accelerated long-term forgetting (ALF) is a form of episodic memory impairment where information is retained normally over 30-60 minutes but lost at an accelerated rate over subsequent days to weeks, and is a very early - perhaps the earliest - cognitive change in both autosomal dominant and sporadic Alzheimer's disease (AD). However, the neuroanatomical changes underlying ALF in AD have remained elusive. We explored associations between ALF and focal cortical thickness in presymptomatic autosomal dominant AD (ADAD).

Clinical characterisation and outcomes of human clade IIb mpox virus disease - a European multicentre observational cohort study (MOSAIC).

Background: The global mpox outbreak which started in May 2022 was caused by a novel clade IIb variant of the mpox virus (MPXV). It differed from the traditional Western and Central Africa disease in transmission patterns and clinical presentation.

Methods: To address the need for detailed clinical and virologic data, we conducted an observational cohort study (MOSAIC) during May 2022-July 2023 in individuals with confirmed MPXV infection enrolled in six European Countries.

Sex-related differences in heart failure patients: physiological mechanisms of cardiovascular ageing and evidence-based sex-specific medical therapies.

This review aims to describe the sex differences in heart failure (HF) patients, with a particular emphasis on the effect of cardiovascular ageing. Additionally, it takes into consideration the sex-related variation in cardiovascular health and physiology and the role ageing plays in HF and its implications in drug therapy. The pharmacokinetics and pharmacodynamics of the common HF medications, classified according to the established sub-types, are summarised with respect to sex-specific documented findings.

Large-Scale Plasma Proteomics Improves Prediction of Peripheral Artery Disease in Individuals With Type 2 Diabetes: A Prospective Cohort Study.

Objective: Peripheral artery disease (PAD) is a significant complication of type 2 diabetes (T2D), yet the association between plasma proteomics and PAD in people with T2D remains unclear. We aimed to explore the relationship between plasma proteomics and PAD in individuals with T2D, and assess whether proteomics could refine PAD risk prediction.

Research Design And Methods: This cohort study included 1,859 individuals with T2D from the UK Biobank.

Omega-3 fatty acids and sleep: recent advances in understanding effects and mechanisms.

Purpose Of Review: Sleep disturbance and low dietary intake of omega-3 fatty acids are common in modern society. Previous research shows that omega-3 fatty acids play an integral role in the regulation of sleep processes, but efficacy data in adults have been equivocal to date. This review examines recent studies highlighting the effects of omega-3 fatty acids on sleep quality and circadian processes.

Global, regional, and national burden of primary liver cancer attributable to metabolic risks: an analysis of the Global Burden of Disease Study 1990-2021.

Background: The global burden of metabolic diseases is increasing, but estimates of their impact on primary liver cancer are uncertain. We aimed to assess the global burden of primary liver cancer attributable to metabolic risk factors, including high body mass index (BMI) and high fasting plasma glucose (FPG) levels, between 1990 and 2021.

Methods: The total number and age-standardized rates of deaths and disability-adjusted life years (DALYs) from primary liver cancer attributable to each metabolic risk factor were extracted from the Global Burden of Disease Study 1990-2021.

Fiber Vector Light-Field-Based Tip-Enhanced Raman Spectroscopy.

Tip-enhanced Raman spectroscopy (TERS) has been extensively employed to investigate the light-matter interaction at the nanoscale. However, the current TERS strategies lack the ability to excite the low-background inhomogeneous electromagnetic field with significant enhancement of electric field, electric field gradient, and optomagnetic field, simultaneously. To overcome this, we developed a fiber vector light-field-based TERS strategy aimed at exploring the multipole Raman scattering processes of molecules.