Developing Topics.

Background: DNA methylation is an epigenetic change characterized by the addition of methyl groups to DNA, typically in the cytosine- phosphate-guanine (CpG) nucleotide base pairings. Given that DNA methylation alterations are shown to be associated with Alzheimer's Disease (AD) pathology in autopsied brains, blood-based DNA methylation changes are increasingly being studied as a potential peripheral biomarker for AD. However, the role of blood-based DNA methylation changes as a marker of cognitive impairment in AD remains unclear.

Genetic susceptibility of diffuse large B-cell lymphoma: a meta genome-wide association study in Asian population.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy and the most common form of non-Hodgkin lymphoma (NHL) that occurs worldwide. To discover risk factors and pathogenesis of DLBCL, we performed the largest GWAS of DLBCL to date in samples of East Asian ancestry, consisting of 2,888 patients with DLBCL and 12,458 controls. The meta-analysis identified three novel loci, rs2233434 on 6p21.

Modeling the progression of neuropsychiatric symptoms in Alzheimer's disease with PET-based Braak staging.

In Alzheimer's disease (AD), neuropsychiatric symptoms (NPS) correlate with tau deposition in the brain. Here, we investigated the association of PET-based Braak stages with NPS and assessed whether they predict annual changes in NPS. We evaluated 231 individuals in the aging and AD continuum.

Hippocampal volume maximally modulates the relationship between subsyndromal symptomatic depression and cognitive impairment in non-demented older adults.

Background: Subsyndromal symptomatic depression (SSD) is associated with an elevated risk of cognitive impairment in non-demented older adults. Given that hippocampal and middle temporal gyrus atrophy have been shown to cause SSD, our study aimed to investigate the effect of hippocampal volume on the association between SSD and cognitive impairment.

Methods: 338 non-demented older adults from the ADNI (Alzheimer's Disease Neuroimaging Initiative) cohort who underwent cognitive assessments, questionnaires on depressive symptoms and MRI brain were studied.

Predicting the severity of mood and neuropsychiatric symptoms from digital biomarkers using wearable physiological data and deep learning.

Neuropsychiatric symptoms (NPS) and mood disorders are common in individuals with mild cognitive impairment (MCI) and increase the risk of progression to dementia. Wearable devices collecting physiological and behavioral data can help in remote, passive, and continuous monitoring of moods and NPS, overcoming limitations and inconveniences of current assessment methods. In this longitudinal study, we examined the predictive ability of digital biomarkers based on sensor data from a wrist-worn wearable to determine the severity of NPS and mood disorders on a daily basis in older adults with predominant MCI.

Visual Cognitive Assessment Test: Utility of the brief cognitive battery for early screening of cognitive impairment in Chongqing, China.

Objectives: Early detection of cognitive impairment is essential for timely intervention. Currently, most widely used cognitive screening tests are influenced by language and cultural differences; therefore, there is a need for the development of a language-neutral, visual-based cognitive assessment tool. The Visual Cognitive Assessment Test (VCAT), a 30-point test that assesses memory, executive function, visuospatial function, attention, and language, has demonstrated its utility in a multilingual population.

Predicting functional decline in aging and Alzheimer's disease with PET-based Braak staging.

The progression of PET-based Braak stages correlates with cognitive deterioration in aging and Alzheimer's disease. Here, we investigate the association between PET-based Braak stages and functional impairment and assess whether PET-based Braak staging predicts a longitudinal decline in the performance of activities of daily living. In this cohort study, we evaluated cognitively unimpaired individuals and individuals with mild cognitive impairment or Alzheimer's disease dementia.

Modelling the Distribution of Cognitive Outcomes for Early-Stage Neurocognitive Disorders: A Model Comparison Approach.

: Cognitive assessments for patients with neurocognitive disorders are mostly measured by the Montreal Cognitive Assessment (MoCA) and Visual Cognitive Assessment Test (VCAT) as screening tools. These cognitive scores are usually left-skewed and the results of the association analysis might not be robust. This study aims to study the distribution of the cognitive outcomes and to discuss potential solutions.

Mild Behavioral Impairment and Cerebrovascular Profiles Are Associated with Early Cognitive Impairment in a Community-Based Southeast Asian Cohort.

Background: Mild behavioral impairment (MBI) is one of the earliest observable changes when a person experiences cognitive decline and could be an early manifestation of underlying Alzheimer's disease neuropathology. Limited attention has been given to investigating the clinical applicability of behavioral biomarkers for detection of prodromal dementia.

Objective: This study compared the prevalence of self-reported MBI and vascular risk factors in Southeast Asian adults to identify early indicators of cognitive impairment and dementia.

Predicting cognitive scores from wearable-based digital physiological features using machine learning: data from a clinical trial in mild cognitive impairment.

Background: Continuous assessment and remote monitoring of cognitive function in individuals with mild cognitive impairment (MCI) enables tracking therapeutic effects and modifying treatment to achieve better clinical outcomes. While standardized neuropsychological tests are inconvenient for this purpose, wearable sensor technology collecting physiological and behavioral data looks promising to provide proxy measures of cognitive function. The objective of this study was to evaluate the predictive ability of digital physiological features, based on sensor data from wrist-worn wearables, in determining neuropsychological test scores in individuals with MCI.

Clinical characteristics of pathological confirmed prodromal dementia with Lewy bodies.

Introduction: Misdiagnosis rate of Dementia with Lewy Bodies (DLB) remains high despite being second most common cause of neurodegenerative dementia. To date, understanding of clinical profile of pathologically confirmed prodromal DLB remains limited. The main objective of this study was to describe and compare it with pathologically confirmed Alzheimer's disease (AD).

The Use of Tau PET to Stage Alzheimer Disease According to the Braak Staging Framework.

Amyloid-β plaques and neurofibrillary tangles (NFTs) are the 2 histopathologic hallmarks of Alzheimer disease (AD). On the basis of the pattern of NFT distribution in the brain, Braak and Braak proposed a histopathologic staging system for AD. Braak staging provides a compelling framework for staging and monitoring of NFT progression in vivo using PET imaging.

APOE4 carrier status determines association between white matter disease and grey matter atrophy in early-stage dementia.

Background: White matter hyperintensities, a neuroimaging marker of small-vessel cerebrovascular disease and apolipoprotein ε4 (APOE4) allele, are important dementia risk factors. However, APOE4 as a key effect modifier in the relationship between white matter hyperintensities and grey matter volume needs further exploration.

Methods: One hundred ninety-two early-stage dementia (including mild cognitive impairment and mild dementia) and 259 cognitively unimpaired participants from a neurocognitive research cohort with neuroimaging data, APOE genotyping, and neuropsychological assessments were studied.

Corrigendum: Topology of diffusion changes in corpus callosum in Alzheimer's disease: An exploratory case-control study.

[This corrects the article DOI: 10.3389/fneur.2022.

C9orf72 expansions are the most common cause of genetic frontotemporal dementia in a Southeast Asian cohort.

Objective: Frontotemporal dementia (FTD) encompasses a spectrum of neurodegenerative disorders, including behavioural variant FTD (bvFTD), semantic variant primary progressive aphasia (svPPA) and non-fluent variant PPA (nfvPPA). While a strong genetic component is implicated in FTD, genetic FTD in Asia is less frequently reported. We aimed to investigate the frequency of Southeast Asian FTD patients harbouring known genetic FTD variants.

Topology of diffusion changes in corpus callosum in Alzheimer's disease: An exploratory case-control study.

Aim: This study aims to assess the integrity of white matter in various segments of the corpus callosum in Alzheimer's disease (AD) by using metrics derived from diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI) and white matter tract integrity model (WMTI) and compare these findings to healthy controls (HC).

Methods: The study was approved by the institutional ethics board. 12 AD patients and 12 HC formed the study population.

Amyloid-Tau-Neurodegeneration Profiles and Longitudinal Cognition in Sporadic Young-Onset Dementia.

We examined amyloid-tau-neurodegeneration biomarker effects on cognition in a Southeast-Asian cohort of 84 sporadic young-onset dementia (YOD; age-at-onset <65 years) patients. They were stratified into A+N+, A- N+, and A- N- profiles via cerebrospinal fluid amyloid-β1-42 (A), phosphorylated-tau (T), MRI medial temporal atrophy (neurodegeneration- N), and confluent white matter hyperintensities cerebrovascular disease (CVD). A, T, and CVD effects on longitudinal Mini-Mental State Examination (MMSE) were evaluated.

Stage-dependent differential influence of metabolic and structural networks on memory across Alzheimer's disease continuum.

Background: Large-scale neuronal network breakdown underlies memory impairment in Alzheimer's disease (AD). However, the differential trajectories of the relationships between network organisation and memory across pathology and cognitive stages in AD remain elusive. We determined whether and how the influences of individual-level structural and metabolic covariance network integrity on memory varied with amyloid pathology across clinical stages without assuming a constant relationship.

Alzheimer's Disease Blood Biomarkers Associated With Neuroinflammation as Therapeutic Targets for Early Personalized Intervention.

The definitive diagnosis of Alzheimer's Disease (AD) without the need for neuropathological confirmation remains a challenge in AD research today, despite efforts to uncover the molecular and biological underpinnings of the disease process. Furthermore, the potential for therapeutic intervention is limited upon the onset of symptoms, providing motivation for studying and treating the AD precursor mild cognitive impairment (MCI), the prodromal stage of AD instead. Applying machine learning classification to transcriptomic data of MCI, AD, and cognitively normal (CN) control patients, we identified differentially expressed genes that serve as biomarkers for the characterization and classification of subjects into MCI or AD groups.

[C]Martinostat PET analysis reveals reduced HDAC I availability in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by the brain accumulation of amyloid-β and tau proteins. A growing body of literature suggests that epigenetic dysregulations play a role in the interplay of hallmark proteinopathies with neurodegeneration and cognitive impairment. Here, we aim to characterize an epigenetic dysregulation associated with the brain deposition of amyloid-β and tau proteins.

Correlation Between Plasma Oligomeric Amyloid-β and Performance on the Language Neutral Visual Cognitive Assessment Test in a Southeast Asian Population.

Oligomeric amyloid-β (OAβ), an upstream driver of Alzheimer's disease (AD) neuropathology, correlates with poor cognitive performance and brain volume reduction. Its effect on cognitive performance measured by the language neutral Visual Cognitive Assessment Test (VCAT) remains to be evaluated. We studied the correlation of plasma OAβ with VCAT scores and grey matter volume (GMV) in a Southeast Asian cohort with mild cognitive impairment.

Upregulated Blood miR-150-5p in Alzheimer's Disease Dementia Is Associated with Cognition, Cerebrospinal Fluid Amyloid-β, and Cerebral Atrophy.

Background: There is an urgent need for noninvasive, cost-effective biomarkers for Alzheimer's disease (AD), such as blood-based biomarkers. They will not only support the clinical diagnosis of dementia but also allow for timely pharmacological and nonpharmacological interventions and evaluations.

Objective: To identify and validate a novel blood-based microRNA biomarker for dementia of the Alzheimer's type (DAT).

APOE4 and Confluent White Matter Hyperintensities Have a Synergistic Effect on Episodic Memory Impairment in Prodromal Dementia.

Background: White matter hyperintensities (WMH) are a known risk factor for cognitive decline. While the ɛ4 allele of apolipoprotein E gene (APOE4) is another risk factor for cognitive decline, it remains unclear how APOE4 affects the relationship between WMH and cognitive decline, specifically in the prodromal stage of dementia.

Objective: To determine how APOE4 moderates the relationship between WMH and cognition in prodromal dementia.