Microbiome-derived indole-3-lactic acid reduces amyloidopathy through aryl-hydrocarbon receptor activation.

Alzheimer's disease (AD) pathogenesis has been associated with the gut microbiome and its metabolites, though the specific mechanisms have remained unclear. In our study, we used a multi-omics approach to identify specific microbial strains and metabolites that could potentially mitigate amyloidopathy in 5xFAD mice, a widely used model for AD research. Among the microbial strains tested, three showed promising results in reducing soluble amyloid-beta (Aβ) levels.

Moderation of Amyloid-β Deposition on the Effect of Cholinesterase Inhibitors on Cognition in Mild Cognitive Impairment.

Background: Clinical trial findings on cholinesterase inhibitors (ChEIs) for mild cognitive impairment (MCI) are inconclusive, offering limited support for their MCI treatment. Given that nearly half of amnestic MCI cases lack cerebral amyloid-β (Aβ) deposition, a hallmark of Alzheimer's disease; this Aβ heterogeneity may explain inconsistent results.

Objective: This study aimed to assess whether Aβ deposition moderates ChEI effects on amnestic MCI cognition.

Automated hepatic steatosis assessment on dual-energy CT-derived virtual non-contrast images through fully-automated 3D organ segmentation.

Purpose: To evaluate the efficacy of volumetric CT attenuation-based parameters obtained through automated 3D organ segmentation on virtual non-contrast (VNC) images from dual-energy CT (DECT) for assessing hepatic steatosis.

Materials And Methods: This retrospective study included living liver donor candidates having liver DECT and MRI-determined proton density fat fraction (PDFF) assessments. Employing a 3D deep learning algorithm, the liver and spleen were automatically segmented from VNC images (derived from contrast-enhanced DECT scans) and true non-contrast (TNC) images, respectively.

Implications of helplessness in depression: diagnosing mild cognitive impairment and analyzing its effects on cognitive decline in older adults.

Background: This study focuses on how elements of depression correlate with mild cognitive impairment (MCI) in older adults and the diagnostic efficacy of combining these components with the Mini-Mental State Examination (MMSE). The study also investigated the connection between individual depression components and overall cognitive function, as measured by the total score (TS) of the consortium to establish a registry for Alzheimer's disease (AD) assessment battery.

Methods: The study included 196 nondemented adults aged 65 to 90 years at a university hospital and community.

Utilizing fully-automated 3D organ segmentation for hepatic steatosis assessment with CT attenuation-based parameters.

Objectives: To investigate the clinical utility of fully-automated 3D organ segmentation in assessing hepatic steatosis on pre-contrast and post-contrast CT images using magnetic resonance spectroscopy (MRS)-proton density fat fraction (PDFF) as reference standard.

Materials And Methods: This retrospective study analyzed 362 adult potential living liver donors with abdominal CT scans and MRS-PDFF. Using a deep learning-based tool, mean volumetric CT attenuation of the liver and spleen were measured on pre-contrast (liver(L)_pre and spleen(S)_pre) and post-contrast (L_post and S_post) images.

Fully-automated multi-organ segmentation tool applicable to both non-contrast and post-contrast abdominal CT: deep learning algorithm developed using dual-energy CT images.

A novel 3D nnU-Net-based of algorithm was developed for fully-automated multi-organ segmentation in abdominal CT, applicable to both non-contrast and post-contrast images. The algorithm was trained using dual-energy CT (DECT)-obtained portal venous phase (PVP) and spatiotemporally-matched virtual non-contrast images, and tested using a single-energy (SE) CT dataset comprising PVP and true non-contrast (TNC) images. The algorithm showed robust accuracy in segmenting the liver, spleen, right kidney (RK), and left kidney (LK), with mean dice similarity coefficients (DSCs) exceeding 0.

Five dominant dimensions of brain aging are identified via deep learning: associations with clinical, lifestyle, and genetic measures.

Brain aging is a complex process influenced by various lifestyle, environmental, and genetic factors, as well as by age-related and often co-existing pathologies. MRI and, more recently, AI methods have been instrumental in understanding the neuroanatomical changes that occur during aging in large and diverse populations. However, the multiplicity and mutual overlap of both pathologic processes and affected brain regions make it difficult to precisely characterize the underlying neurodegenerative profile of an individual from an MRI scan.

Manganese level and cognitive decline in older adults with the APOE e4 allele: a preliminary study.

This study examined the relationship between serum manganese level and cognition, and the moderating effect of apolipoprotein E ε4 (APOE4) on this relationship. A total of 164 non-demented participants underwent clinical assessments including serum manganese level and cognition [episodic memory score (EMS), non-memory score (NMS) for executive function/attention/language/ visuospatial skill, and total score (TS)]. Serum manganese × APOE4 interaction had a significant effect on EMS and TS.

Association between physical activity and episodic memory and the moderating effects of the apolipoprotein E ε4 allele and age.

Background: An abundance of evidence indicates that physical activity may protect against Alzheimer's disease (AD) and related cognitive decline. However, little is known about the association between physical activity and AD-related cognitive decline according to age and the apolipoprotein E (APOE) ε4 allele (APOE4) as major risk factors. Therefore, we examined whether age and APOE4 status modulate the effects of physical activity on episodic memory as AD-related cognition in non-demented older adults.

Serum Adiponectin and In Vivo Brain Amyloid Deposition in Cognitively Normal Older Adults: A Cohort Study.

High blood adiponectin has been associated with Alzheimer's disease (AD) dementia and related cognitive decline. We aimed to investigate the association between serum adiponectin level and in vivo AD pathologies. Cross-sectional and longitudinal study designs for the data of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease, an ongoing prospective cohort study that began in 2014.

Low Ankle-Brachial Index Relates to Alzheimer-Signature Cerebral Glucose Metabolism in Cognitively Impaired Older Adults.

Background: Ankle-brachial index (ABI), an indicator of atherosclerosis or arterial stiffness, has been associated with Alzheimer's disease (AD) dementia and related cognitive impairment. Nevertheless, only limited information is available regarding its contribution to brain alterations leading to cognitive decline in late-life.

Objective: We aimed to investigate the relationship of ABI with in vivo AD pathologies and cerebrovascular injury in cognitively impaired older adults.

Implantable device actuated by manual button clicks for noninvasive self-drug administration.

Self-injectable therapy has several advantages in the treatment of metabolic disorders. However, frequent injections with needles impair patient compliance and medication adherence. Therefore, we develop a fully implantable device capable of on-demand administration of self-injection drugs via noninvasive manual button clicks on the outer skin.

Synergistic interaction of high blood pressure and cerebral beta-amyloid on tau pathology.

Background: Hypertension has been associated with Alzheimer's disease (AD) dementia as well as vascular dementia. However, the underlying neuropathological changes that link hypertension to AD remain poorly understood. In our study, we examined the relationships of a history of hypertension and high current blood pressure (BP) with in vivo AD pathologies including β-amyloid (Aβ) and tau and also investigated whether a history of hypertension and current BP respectively affect the association between Aβ and tau deposition.

Enlarged perivascular spaces are associated with decreased brain tau deposition.

Aims: The aim of this study was to investigate the associations of enlarged perivascular spaces (EPVS) in the basal ganglia (BG) and centrum semiovale (CSO) with beta-amyloid (Aβ) and tau deposition in older adults with a diverse cognitive spectrum.

Methods: A total of 163 (68 cognitively normal and 95 cognitively impaired) older participants underwent [ C] Pittsburgh compound B and [ F] AV-1451 PET, and MRI. EPVS in the BG and CSO and other small vessel disease markers, such as white matter hyperintensities, lacunes, and deep and lobar microbleeds, were assessed.

Gut microbiome alterations in preclinical Alzheimer's disease.

Background: Although some human studies have reported gut microbiome changes in individuals with Alzheimer's disease (AD) dementia or mild cognitive impairment (MCI), gut microbiome alterations in preclinical AD, i.e., cerebral amyloidosis without cognitive impairment, is largely unknown.

Association of low meal frequency with decreased Alzheimer's pathology.

Little is known about the association between meal frequency and Alzheimer's disease (AD) in humans. We tested the hypothesis that low meal frequency (LMF) is associated with reduced AD pathology in human brain, and additionally investigated the mediation of serum ghrelin, a hunger-related hormone, for the association. A total of 411 non-demented older adults were systematically interviewed to identify their dietary patterns including meal frequency and underwent multi-modal neuroimaging for cerebral beta-amyloid (Aβ) and tau deposition, glucose metabolism, and cerebrovascular injury.

HLA-A*24:02 increase the risk of allopurinol-induced drug reaction with eosinophilia and systemic symptoms in HLA-B*58:01 carriers in a Korean population; a multicenter cross-sectional case-control study.

Background: HLA-B*58:01 is a well-known risk factor for allopurinol-induced severe cutaneous adverse reactions (SCARs). However, only a minority of HLA-B*58:01 carriers suffer SCARs after taking allopurinol. The aim of this study was to investigate subsidiary genetic markers that could identify those at further increased risk of developing allopurinol-induced drug reaction with eosinophilia and systemic symptoms (DRESS) in subjects with HLA-B*58:01.

Reducing severe cutaneous adverse and type B adverse drug reactions using pre-stored human leukocyte antigen genotypes.

Background: Several type B adverse drug reactions (ADRs), especially severe cutaneous adverse reactions (SCARs), are associated with particular human leukocyte antigen (HLA) genotypes. However, pre-stored HLA information obtained from other clinical workups has not been used to prevent ADRs. We aimed to simulate the preemptive use of pre-stored HLA information in electronic medical records to evaluate whether this information can prevent ADRs.

Late-Life Physical Activities Moderate the Relationship of Amyloid-β Pathology with Neurodegeneration in Individuals Without Dementia.

Background: Physical activities (PA) have been suggested to reduce the risk of Alzheimer's disease (AD) dementia. However, information on the neuropathological links underlying the relationship is limited.

Objective: We investigated the role of midlife and late-life PA with in vivo AD neuropathologies in old adults without dementia.

Serum zinc levels and in vivo beta-amyloid deposition in the human brain.

Background: Despite the known associations between zinc levels and Alzheimer's disease (AD) dementia and related cognitive impairment, the underlying neuropathological links remain poorly understood. We tested the hypothesis that serum zinc level is associated with cerebral beta-amyloid protein (Aβ) deposition. Additionally, we explored associations between serum zinc levels and other AD pathologies [i.