Multi-population Genome-Wide Association Study Identifies Multiple Novel Loci Associated with Asymptomatic Intracranial Large Artery Stenosis.

Introduction: Intracranial large artery stenosis (ILAS) is one of the most common causes of stroke worldwide and is associated with the risk for future vascular events. Asymptomatic ILAS is a frequent finding on neuroimaging and shares many risk factors with atherosclerotic vascular disease. Whether asymptomatic ILAS is driven by genetic variants is not well-understood.

Healthy Lifestyle Mitigates the Adverse Association of Particulate Matter with Cognitive Function: A 10-year Longitudinal Analysis of Older Adults in China.

Background: Both air pollution and lifestyle are associated with cognitive function, with air pollution being detrimental and positive lifestyles being beneficial. The extent to which a favorable lifestyle can mitigate the harmful effects of air pollution on cognitive function in later life warrants further investigation.

Methods: 7,651 individuals aged 65 years and above from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) were followed up between 2008 and 2018.

Signature White Matter Hyperintensity Locations Associated With Vascular Risk Factors Derived From 15 653 Individuals.

Background: White matter hyperintensities (WMHs) of presumed vascular origin are common in the elderly and are associated with vascular risk factors. There is evidence that vascular risk factors, in particular hypertension, are associated with WMH in particular locations of the white matter. However, it remains unclear whether this is true for all risk factors and whether signature WMH locations differ between risk factors.

Synergistic effect between cortical cerebral microinfarcts and brain atrophy on cognitive decline.

Cortical cerebral microinfarcts are associated with brain atrophy in cross-sectional studies, while further investigation using longitudinal datasets is warranted. Moreover, little is known about their combined impact on cognition. This study aims to establish the association between cortical cerebral microinfarcts and brain volume loss over time and to explore whether they synergistically contribute to cognitive decline.

Facilitators and barriers for use of digital technology in chronic disease management.

Despite increased screening efforts and accessibility of healthcare services, the prevalence of chronic disease is on the rise in Singapore. Digital technology has become a valuable tool to aid management of chronic diseases. However, its utilisation remains challenging among older Singaporeans.

Effect of metabolic syndrome severity on cerebral haemodynamics and cognition in community-based cohort.

Background And Aims: Metabolic syndrome (METS) increases the risk of cognitive decline, but its impact on cerebral haemodynamics remains unclear. This study investigated relationships between continuous metabolic syndrome severity score (cMETS), cerebral haemodynamics, and cognition.

Methods: In this cross-sectional study from the Epidemiology of Dementia in Singapore (EDIS) cohort, participants underwent neuropsychological assessments and arterial spin labelling MRI to evaluate cerebral haemodynamics, cognitive function, and composite metabolic syndrome severity (cMETS).

Role of Brain Age Gap as a Mediator in the Relationship Between Cognitive Impairment Risk Factors and Cognition.

Background And Objectives: Cerebrovascular disease (CeVD) and cognitive impairment risk factors contribute to cognitive decline, but the role of brain age gap (BAG) in mediating this relationship remains unclear, especially in Southeast Asian populations. This study investigated the influence of cognitive impairment risk factors on cognition and examined how BAG mediates this relationship, particularly in individuals with varying CeVD burden.

Methods: This cross-sectional study analyzed Singaporean community and memory clinic participants.

Rate of brain aging associates with future executive function in Asian children and older adults.

Brain age has emerged as a powerful tool to understand neuroanatomical aging and its link to health outcomes like cognition. However, there remains a lack of studies investigating the rate of brain aging and its relationship to cognition. Furthermore, most brain age models are trained and tested on cross-sectional data from primarily Caucasian, adult participants.

Multi-population Genome-Wide Association Study Identifies Multiple Novel Loci associated with Asymptomatic Intracranial Large Artery Stenosis.

Background: Intracranial large artery stenosis (ILAS) is one of the most common causes of stroke worldwide and is associated with the risk for future vascular events. Asymptomatic ILAS is a frequent finding on neuroimaging and shares many risk factors with atherosclerotic vascular disease. Whether asymptomatic ILAS is driven by genetic variants is not well-understood.

WMH-DualTasker: A Weakly Supervised Deep Learning Model for Automated White Matter Hyperintensities Segmentation and Visual Rating Prediction.

White matter hyperintensities (WMH) are neuroimaging markers linked to an elevated risk of cognitive decline. WMH severity is typically assessed via visual rating scales and through volumetric segmentation. While visual rating scales are commonly used in clinical practice, they offer limited descriptive power.

Left Atrial Myocardial Mechanics: Association With Cognitive Dysfunction, Cerebrovascular Disease, and Circulating Biomarkers.

Background: The relationship of left atrial (LA) strain with cognition in the absence of atrial fibrillation is poorly understood. We investigated the association of LA strain with cognitive impairment and its pathogenetic subtype (vascular [VCI] or neurodegenerative) and underlying mechanisms via associations with circulating and neuroimaging markers of cerebrovascular disease.

Methods And Results: LA strain (reservoir, conduit [LAScd], contractile) was determined using speckle-tracking echocardiography in a prospective memory clinic cohort with brain magnetic resonance imaging, neuropsychological assessments, and circulating biomarker measurements.

The effect of hippocampal subfield volumes on cognitive decline and incident dementia in a memory clinic cohort.

BackgroundThe hippocampus plays a central role in cognition and hippocampal atrophy is a key hallmark of Alzheimer's disease. Evidence has suggested associations between hippocampal subfield volumes and specific cognitive domains and dementia risk. However, to our knowledge, no study has examined the role of hippocampal subfield volumes in cognitive decline across different domains over time.

Current status and future directions for the diagnosis and management of mild cognitive impairment in Southeast Asia: A SEACURE consensus paper.

Global aging populations are facing increased prevalence of mild cognitive impairment (MCI) - the preclinical stage of dementia characterized by single/multi-domain neurocognitive decline that does not impair an individual's normal daily functioning. Asian populations are at increased risk of developing MCI and dementia, and many cases go undetected in Southeast Asia (SEA), resulting in increased burden on patients, caregivers and national healthcare systems. There is an urgent need for efficient and scalable diagnostic and management strategies across SEA.

Comorbid cerebrovascular and neurodegenerative burden in mild behavioural impairment and their impact on clinical trajectory.

Aim: Mild behavioural impairment (MBI) is a neurobehavioral prodrome to dementia with multiple phenotypic characteristics. To investigate the complex neurobiological substrate underlying MBI, we evaluated its association with a composite magnetic resonance imaging (MRI)-based measure of concomitant cerebrovascular disease (CeVD) and neurodegeneration; and the interaction effects of MBI and MRI scores on cognitive and clinical trajectory.

Methods: 253 dementia-free participants (mean age = 71.

Longitudinal associations of carotid artery stiffness with progression of cerebrovascular disease, incident dementia and cognitive decline in older adults.

Background: Carotid artery stiffness is associated with cerebrovascular disease (CeVD) and cognitive impairment, but evidence for its longitudinal effects on progression of CeVD and cognitive decline are limited.

Objectives: To evaluate the longitudinal associations of carotid artery stiffness with CeVD progression, incident dementia, and cognitive decline.

Design: Longitudinal analyses from a memory-clinic cohort with a follow-up of 2 years.

Plasma NfL, P-tau181, and P-tau181/Aβ42 Ratio in Predicting Mild Behavioral Impairment in Dementia-Free Multiethnic Asian Older Adults With Mixed Pathology in a 5-Year Clinical Cohort.

The underlying mechanisms of mild behavioral impairment (MBI), a marker for cognitive impairment and dementia, have remained unclear especially in a multiethnic Asian population. The study aimed to examine whether baseline Alzheimer disease biomarkers, including plasma neurofilament light (NfL) chain, phosphorylated tau-181 (p-tau181), and the p-tau181-to-amyloid-β42 (p-tau181/Aβ42) ratio, could predict MBI incidence in dementia-free Asian older adults. Participants were recruited from the community and memory clinics from August 2010 to April 2022.

A deep-learning retinal aging biomarker for cognitive decline and incident dementia.

Introduction: The utility of retinal photography-derived aging biomarkers for predicting cognitive decline remains under-explored.

Methods: A memory-clinic cohort in Singapore was followed-up for 5 years. RetiPhenoAge, a retinal aging biomarker, was derived from retinal photographs using deep-learning.

Plasma proteomics for cognitive decline and dementia-A Southeast Asian cohort study.

Introduction: The prognostic utility of plasma proteomics for cognitive decline and dementia in a Southeast Asian population characterized by high cerebrovascular disease (CeVD) burden is underexplored.

Methods: We examined this in a Singaporean memory clinic cohort of 528 subjects (n = 300, CeVD; n = 167, incident cognitive decline) followed-up for 4 years.

Results: Of 1441 plasma proteins surveyed, a 12-protein signature significantly predicted cognitive decline (q-value < .

Association of arterial structure and function with incident cardiovascular diseases and cognitive decline.

Introduction: We examined the associations of carotid intima-media thickness (CIMT), arterial stiffness index (ASI), and pulse pressure (PP) with cerebrovascular disease, cognitive function and decline, and incident cardiovascular diseases (CVD) and dementia in the UK Biobank cohort.

Methods: The study consisted of 42,711 participants (mean age 64.2 years) with brain magnetic resonance imaging (MRI), vascular assessments, and cognitive testing.

A point-based cognitive impairment scoring system for southeast Asian adults.

Background: Cognitive impairment is a growing concern in Southeast Asian populations, where the burden of cerebrovascular disease (CeVD) is high. Currently, there is no point-based scoring system for identifying cognitive impairment in these populations.

Objective: To develop and validate a simple point-based Cognitive Impairment Scoring System (CISS) for identifying individuals with cognitive impairment no dementia (CIND) and concomitant CeVD in Southeast Asian populations.

Cross-Sectional Association Between Left Ventricular Geometric Patterns, Cortical Cerebral Microinfarcts, and Cognition.

Background: Left ventricular (LV) geometric patterns are associated with cognitive impairment and cerebral small vessel disease. As a novel magnetic resonance imaging marker of cerebral small vessel disease and a risk factor for cognitive dysfunction, cortical cerebral microinfarcts (CMIs) have been associated with heart disease through mechanisms including cardioembolism and cerebral hypoperfusion. Further investigation is required to determine whether cortical CMIs could arise from hemodynamic changes related to LV geometry, thus elucidating the connection between LV geometry and cognitive function.

Low serum serotonin is associated with functional decline, mild behavioural impairment and brain atrophy in dementia-free subjects.

Brain serotonin dysregulation is associated with dementia and neuropsychiatric symptomology. However, the prognostic utility of circulating serotonin levels in detecting features of prodromal dementia including functional decline, cognitive impairment, mild behavioural impairment and brain atrophy remains unclear. In this prospective study of memory clinic subjects followed-up for ≤5 years, dementia-free subjects, classified as having no cognitive impairment or cognitive impairment, no dementia at baseline, underwent annual neuropsychological assessments including Montreal Cognitive Assessment, Global Cognition scores and Clinical Dementia Rating Scale Global Scores (where a ≥ 0.

Associations between potential risk factors and blood-brain barrier water permeability in middle-aged and older adults.

Blood-brain barrier (BBB) dysfunction is suggested to be a potential mediator between vascular risk factors and cognitive impairment, leading to vascular cognitive impairment. To investigate the relationships between age, sex, and vascular risk factors and BBB water permeability as well as their relationship with cognition. To measure BBB permeability, a novel arterial spin labelling MRI technique (ME-ASL) was applied to derive the time of exchange (Tex), arterial time transit (ATT), and cerebral blood flow (CBF).

Utilizing deep learning to predict Alzheimer's disease and mild cognitive impairment with optical coherence tomography.

Introduction: Diagnostic performance of optical coherence tomography (OCT) to detect Alzheimer's disease (AD) and mild cognitive impairment (MCI) remains limited. We aimed to develop a deep-learning algorithm using OCT to detect AD and MCI.

Methods: We performed a cross-sectional study involving 228 Asian participants (173 cases/55 controls) for model development and testing on 68 Asian (52 cases/16 controls) and 85 White (39 cases/46 controls) participants.

Clinical utility of plasma p-tau217 in identifying abnormal brain amyloid burden in an Asian cohort with high prevalence of concomitant cerebrovascular disease.

Introduction: Using an Asian cohort with high prevalence of concomitant cerebrovascular disease (CeVD), we evaluated the performance of a plasma immunoassay for tau phosphorylated at threonine 217 (p-tau217) in detecting amyloid beta positivity (Aβ+) on positron emission tomography and cognitive decline, based on a three-range reference, which stratified patients into low-, intermediate-, and high-risk groups for Aβ+.

Methods: Brain amyloid status (Aβ- [n = 142] vs Aβ+ [n = 73]) on amyloid PET scans was assessed along with the plasma ALZpath p-tau217 assay to derive three-range reference points for PET Aβ+ based on 90% sensitivity (lower threshold) and 90% specificity (upper threshold).

Results: Plasma p-tau217 (area under the curve [AUC] = 0.