Effects of Oral ALZ-801/Valiltramiprosate on Plasma Biomarkers, Brain Hippocampal Volume, and Cognition: Results of 2-Year Single-Arm, Open-Label, Phase 2 Trial in APOE4 Carriers with Early Alzheimer's Disease.

Introduction: ALZ-801/valiltramiprosate is a small-molecule oral inhibitor of beta amyloid (Aβ) aggregation and oligomer formation being studied in a phase 2 trial in APOE4 carriers with early Alzheimer's disease (AD) to evaluate treatment effects on fluid and imaging biomarkers and cognitive assessments.

Methods: The single-arm, open-label phase 2 trial was designed to evaluate the effects of the ALZ-801 265 mg tablet taken twice daily (after 2 weeks once daily) on plasma fluid AD biomarkers, hippocampal volume (HV), and cognition over 104 weeks in APOE4 carriers. The study enrolled subjects aged 50-80 years, with early AD [Mini-Mental State Examination (MMSE) ≥ 22, Clinical Dementia Rating-Global (CDR-G) 0.

Mild behavioral impairment in early Alzheimer's disease and its association with APOE and BDNF risk genetic polymorphisms.

Background: Mild behavioral impairment (MBI) has been commonly reported in early Alzheimer's disease (AD) but rarely using biomarker-defined samples. It is also unclear whether genetic polymorphisms influence MBI in such individuals. We thus aimed to examine the association between the cognitive status of participants (amnestic mild cognitive impairment (aMCI-AD) vs cognitively normal (CN) older adults) and MBI severity.

Generation of the Human iPSC Line from Spontaneous Late-Onset Alzheimer's Disease Patient with ApoE3/3 Genotype and Sex-, Age-, and ApoE-Matched Healthy Control.

Human induced pluripotent stem cell (iPSC) lines were generated from peripheral blood mononuclear cells (PBMCs) isolated from a patient diagnosed with spontaneous late-onset Alzheimer's disease (AD) carrying ApoE3/3 gene and one age-, sex-, and ApoE-matched healthy control. Reprogramming was done using a commercially available Epi5 Reprogramming Kit containing OCT4, SOX2, KLF4, LIN28, and L-MYC as reprogramming factors. The pluripotency of the iPSC lines was verified by the expression of pluripotency markers and by their capacity to differentiate into all three embryonic germ layers in vitro.

Missorting of plasma miRNAs in aging and Alzheimer's disease.

The observation that aging is regulated by microRNAs (miRNA) and at the same time represents the greatest risk factor for Alzheimer's disease (AD), prompted us to examine the circulating miRNA network in AD beyond aging. We here show that plasma miRNAs in aging are downregulated and predicted to be preferentially targeted to the extracellular vesicle (EV) content. In AD, miRNAs are further downregulated, display altered proportions of motifs relevant to their loading into EVs and secretion propensity, and are forecast to be found exclusively in EVs.

Pathogenesis of Alzheimer's disease: Involvement of the choroid plexus.

The choroid plexus (ChP) produces and is bathed in the cerebrospinal fluid (CSF), which in aging and Alzheimer's disease (AD) shows extensive proteomic alterations including evidence of inflammation. Considering inflammation hampers functions of the involved tissues, the CSF abnormalities reported in these conditions are suggestive of ChP injury. Indeed, several studies document ChP damage in aging and AD, which nevertheless remains to be systematically characterized.

Effect of a Vegan Diet on Alzheimer's Disease.

There is evidence indicating that a vegan diet could be beneficial in the prevention of neurodegenerative disorders, including Alzheimer's disease (AD). The purpose of this review is to summarize the current knowledge on the positive and negative aspects of a vegan diet regarding the risk of AD. Regarding AD prevention, a vegan diet includes low levels of saturated fats and cholesterol, contributing to a healthy blood lipid profile.

Increased occurrence of Treponema spp. and double-species infections in patients with Alzheimer's disease.

Although the link between microbial infections and Alzheimer's disease (AD) has been demonstrated in multiple studies, the involvement of pathogens in the development of AD remains unclear. Here, we investigated the frequency of the 10 most commonly cited viral (HSV-1, EBV, HHV-6, HHV-7, and CMV) and bacterial (Chlamydia pneumoniae, Helicobacter pylori, Borrelia burgdorferi, Porphyromonas gingivalis, and Treponema spp.) pathogens in serum, cerebrospinal fluid (CSF) and brain tissues of AD patients.

Six genetically linked mutations in the CD36 gene significantly delay the onset of Alzheimer's disease.

The risk of Alzheimer's disease (AD) has a strong genetic component, also in the case of late-onset AD (LOAD). Attempts to sequence whole genome in large populations of subjects have identified only a few mutations common to most of the patients with AD. Targeting smaller well-characterized groups of subjects where specific genetic variations in selected genes could be related to precisely defined psychological traits typical of dementia is needed to better understand the heritability of AD.

Emotional prosody recognition is impaired in Alzheimer's disease.

Background: The ability to understand emotions is often disturbed in patients with cognitive impairments. Right temporal lobe structures play a crucial role in emotional processing, especially the amygdala, temporal pole (TP), superior temporal sulcus (STS), and anterior cingulate (AC). Those regions are affected in early stages of Alzheimer´s disease (AD).

Progression from Subjective Cognitive Decline to Mild Cognitive Impairment or Dementia: The Role of Baseline Cognitive Performance.

Background: Older adults with subjective cognitive decline (SCD) are at an increased risk of progression to mild cognitive impairment (MCI) or dementia. However, few have examined the specific cognitive tests that are associated with progression.

Objective: This study examined performance on 18 neuropsychological tests among participants with SCD who later progressed to MCI or dementia.

Validation of the LUMIPULSE automated immunoassay for the measurement of core AD biomarkers in cerebrospinal fluid.

Objectives: The core cerebrospinal fluid (CSF) biomarkers; total tau (tTau), phospho-tau (pTau), amyloid β 1-42 (Aβ 1-42), and the Aβ 1-42/Aβ 1-40 ratio have transformed Alzheimer's disease (AD) research and are today increasingly used in clinical routine laboratories as diagnostic tools. Fully automated immunoassay instruments with ready-to-use assay kits and calibrators has simplified their analysis and improved reproducibility of measurements. We evaluated the analytical performance of the fully automated immunoassay instrument LUMIPULSE G (Fujirebio) for measurement of the four core AD CSF biomarkers and determined cutpoints for AD diagnosis.

Generation of three human iPSC lines from patients with a spontaneous late-onset Alzheimer's disease and three sex- and age-matched healthy controls.

Human induced pluripotent stem cell (iPSC) lines were generated from patients with spontaneous late-onset Alzheimer's disease (AD) and three healthy control individuals. Peripheral blood mononuclear cells were reprogrammed with Yamanaka factors (OSKM) using a commercially available Epi5 Reprogramming Kit. The pluripotency of iPSCs was confirmed by the expression of pluripotency factors and by their ability to differentiate to all three germ layers in vitro.

Biomarker counseling, disclosure of diagnosis and follow-up in patients with mild cognitive impairment: A European Alzheimer's disease consortium survey.

Objectives: Mild cognitive impairment (MCI) is associated with an increased risk of further cognitive decline, partly depending on demographics and biomarker status. The aim of the present study was to survey the clinical practices of physicians in terms of biomarker counseling, management, and follow-up in European expert centers diagnosing patients with MCI.

Methods: An online email survey was distributed to physicians affiliated with European Alzheimer's disease Consortium centers (Northern Europe: 10 centers; Eastern and Central Europe: 9 centers; and Southern Europe: 15 centers) with questions on attitudes toward biomarkers and biomarker counseling in MCI and dementia.

The Effect of Mindfulness-Based Stress Reduction (MBSR) on Depression, Cognition, and Immunity in Mild Cognitive Impairment: A Pilot Feasibility Study.

Background: Mindfulness-based programs have shown a promising effect on several health factors associated with increased risk of dementia and the conversion from mild cognitive impairment (MCI) to dementia such as depression, stress, cognitive decline, immune system and brain structural and functional changes. Studies on mindfulness in MCI subjects are sparse and frequently lack control intervention groups.

Objective: To determine the feasibility and the effect of mindfulness-based stress reduction (MBSR) practice on depression, cognition and immunity in MCI compared to cognitive training.

Czech Brain Aging Study (CBAS): prospective multicentre cohort study on risk and protective factors for dementia in the Czech Republic.

Purpose: Identification of demographic, physical/physiological, lifestyle and genetic factors contributing to the onset of dementia, specifically Alzheimer disease (AD), and implementation of novel methods for early diagnosis are important to alleviate prevalence of dementia globally. The Czech Brain Aging Study (CBAS) is the first large, prospective study to address these issues in Central/Eastern Europe by enrolling non-demented adults aged 55+ years, collecting a variety of personal and biological measures and tracking cognitive function over time.

Participants: The CBAS recruitment was initiated in 2011 from memory clinics at Brno and Prague University Hospitals, and by the end of 2018, the study included 1228 participants.

Differences in Subjective Cognitive Complaints Between Non-Demented Older Adults from a Memory Clinic and the Community.

Background: Subjective cognitive complaints (SCCs) may represent an early cognitive marker of Alzheimer's disease (AD). There is a need to identify specific SCCs associated with an increased likelihood of underlying AD.

Objective: Using the Questionnaire of Cognitive Complaints (QPC), we evaluated the pattern of SCCs in a clinical sample of non-demented older adults in comparison to cognitively healthy community-dwelling volunteers (HV).

Subjective Spatial Navigation Complaints - A Frequent Symptom Reported by Patients with Subjective Cognitive Decline, Mild Cognitive Impairment and Alzheimer's Disease.

Background: Great effort has been put into developing simple and feasible tools capable to detect Alzheimer's disease (AD) in its early clinical stage. Spatial navigation impairment occurs very early in AD and is detectable even in the stage of mild cognitive impairment (MCI).

Objective: The aim was to describe the frequency of self-reported spatial navigation complaints in patients with subjective cognitive decline (SCD), amnestic and non-amnestic MCI (aMCI, naMCI) and AD dementia and to assess whether a simple questionnaire based on these complaints may be used to detect early AD.

Psychological Benefits of Nonpharmacological Methods Aimed for Improving Balance in Parkinson's Disease: A Systematic Review.

Parkinson's disease (PD) is a serious condition with a major negative impact on patient's physical and mental health. Postural instability is one of the cardinal difficulties reported by patients to deal with. Neuroanatomical, animal, and clinical studies on nonparkinsonian and parkinsonian subjects suggest an important correlation between the presence of balance dysfunction and multiple mood disorders, such as anxiety, depression, and apathy.

Famous landmark identification in amnestic mild cognitive impairment and Alzheimer's disease.

Background: Identification of famous landmarks (FLI), famous faces (FFI) and recognition of facial emotions (FER) is affected early in the course of Alzheimer's disease (AD). FFI, FER and FLI may represent domain specific tasks relying on activation of distinct regions of the medial temporal lobe, which are affected successively during the course of AD. However, the data on FFI and FER in MCI are controversial and FLI domain remains almost unexplored.

APOE and spatial navigation in amnestic MCI: results from a computer-based test.

Objective: We investigated the association between APOE ε4 status and spatial navigation in patients with amnestic mild cognitive impairment (aMCI) and assessed the role of hippocampal volume in this association.

Method: Participants were 74 patients with clinically confirmed aMCI (33 APOE ε4 noncarriers, 26 heterozygous, and 15 homozygous ε4 carriers). Body-centered (egocentric) and world-centered (allocentric) spatial navigation in a computerized human analogue of the Morris Water Maze was assessed.

Neuropsychological correlates of hippocampal atrophy in memory testing in nondemented older adults.

Background And Objective: Cognitive deficits in older adults attributable to Alzheimer's disease (AD) pathology are featured early on by hippocampal impairment. Among tests used to evaluate memory, verbal memory tests with controlled encoding and cued recall are believed to be specific for hippocampal impairment. The objective of this study was to assess the relation between left and right hippocampal volumes and several frequently used memory tests.

Effect of meditation on cognitive functions in context of aging and neurodegenerative diseases.

Effect of different meditation practices on various aspects of mental and physical health is receiving growing attention. The present paper reviews evidence on the effects of several mediation practices on cognitive functions in the context of aging and neurodegenerative diseases. The effect of meditation in this area is still poorly explored.

Spatial navigation in young versus older adults.

Older age is associated with changes in the brain, including the medial temporal lobe, which may result in mild spatial navigation deficits, especially in allocentric navigation. The aim of the study was to characterize the profile of real-space allocentric (world-centered, hippocampus-dependent) and egocentric (body-centered, parietal lobe dependent) navigation and learning in young vs. older adults, and to assess a possible influence of gender.