Preclinical Alzheimer's Disease: Implications for Refinement of the Concept.

Increasing interest in clinical trials and clinical research settings to identify Alzheimer's disease (AD) in the earliest stages of the disease has led to the concept of preclinical AD. Individuals with preclinical AD have AD pathology without clinical symptoms yet. Accumulating evidence has shown that biomarkers can identify preclinical AD and that preclinical AD is associated with a poor clinical outcome.

Plants for Sustainable Improvement of Indoor Air Quality.

Indoor pollution poses a serious threat to human health. Plants represent a sustainable but underexploited solution to enhance indoor air quality. However, the current selection of plants suitable for indoors fails to consider the physiological processes and mechanisms involved in phytoremediation.

Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins.

Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.

European Prevention of Alzheimer's Dementia Registry: Recruitment and prescreening approach for a longitudinal cohort and prevention trials.

Introduction: It is a challenge to find participants for Alzheimer's disease (AD) prevention trials within a short period of time. The European Prevention of Alzheimer's Dementia Registry (EPAD) aims to facilitate recruitment by preselecting subjects from ongoing cohort studies. This article introduces this novel approach.

Gray Matter Network Disruptions and Regional Amyloid Beta in Cognitively Normal Adults.

The accumulation of amyloid plaques is one of the earliest pathological changes in Alzheimer's disease (AD) and may occur 20 years before the onset of symptoms. Examining associations between amyloid pathology and other early brain changes is critical for understanding the pathophysiological underpinnings of AD. Alterations in gray matter networks might already start at early preclinical stages of AD.

White matter hyperintensities and vascular risk factors in monozygotic twins.

Cerebral white matter hyperintensities (WMHs) have been associated with vascular risk factors, both of which are under genetic influence. We examined in a monozygotic twin sample whether the association between vascular risk and WMHs is influenced by overlapping genetic factors. We included 195 cognitively normal monozygotic twins (age = 70 ± 7 years), including 94 complete pairs.

Using the GOCE star trackers for validating the calibration of its accelerometers.

A method for validating the calibration parameters of the six accelerometers on board the Gravity field and steady-state Ocean Circulation Explorer (GOCE) from star tracker observations that was originally tested by an end-to-end simulation, has been updated and applied to real data from GOCE. It is shown that the method provides estimates of scale factors for all three axes of the six GOCE accelerometers that are consistent at a level significantly better than 0.01 compared to the a priori calibrated value of 1.

MICROSCOPE Mission: First Results of a Space Test of the Equivalence Principle.

According to the weak equivalence principle, all bodies should fall at the same rate in a gravitational field. The MICROSCOPE satellite, launched in April 2016, aims to test its validity at the 10^{-15} precision level, by measuring the force required to maintain two test masses (of titanium and platinum alloys) exactly in the same orbit. A nonvanishing result would correspond to a violation of the equivalence principle, or to the discovery of a new long-range force.

Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline.

Background: Cerebrovascular disease (CVD) and amyloid-β (Aβ) often coexist, but their influence on neurodegeneration and cognition in predementia stages remains unclear. We investigated the association between CVD and Aβ on neurodegenerative markers and cognition in patients without dementia.

Methods: We included 271 memory clinic patients with subjective or objective cognitive deficits but without dementia from the BioBank Alzheimer Center Limburg cohort (n = 99) and the LeARN (n = 50) and DESCRIPA (n = 122) multicenter studies.

Unbiased Approach to Counteract Upward Drift in Cerebrospinal Fluid Amyloid-β 1-42 Analysis Results.

Background: Low cerebrospinal fluid (CSF) amyloid-β 1-42 (Aβ 1-42) concentrations indicate amyloid plaque accumulation in the brain, a pathological hallmark of Alzheimer disease (AD). Innotest assay values of Aβ 1-42 have gradually increased over the past 2 decades, which might lead to misclassification of AD when a single cutpoint for abnormality is used. We propose an unbiased approach to statistically correct for drift.

The effect of diagnostic criteria on outcome measures in preclinical and prodromal Alzheimer's disease: Implications for trial design.

Introduction: We investigated the influence of different inclusion criteria for preclinical and prodromal Alzheimer's disease (AD) on changes in biomarkers and cognitive markers and on trial sample size estimates.

Methods: We selected 522 cognitively normal subjects and 872 subjects with mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative study. Compared inclusion criteria were (1) preclinical or prodromal AD (amyloid marker abnormal); (2) preclinical or prodromal AD stage-1 (amyloid marker abnormal, injury marker normal); and (3) preclinical or prodromal AD stage-2 (amyloid and injury markers abnormal).

Cyclic Peptides to Improve Delivery and Exon Skipping of Antisense Oligonucleotides in a Mouse Model for Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a severe, progressive muscle wasting disorder caused by reading frame disrupting mutations in the DMD gene. Exon skipping is a therapeutic approach for DMD. It employs antisense oligonucleotides (AONs) to restore the disrupted open reading frame, allowing the production of shorter, but partly functional dystrophin protein as seen in less severely affected Becker muscular dystrophy patients.

24-month intervention with a specific multinutrient in people with prodromal Alzheimer's disease (LipiDiDiet): a randomised, double-blind, controlled trial.

Background: Nutrition is an important modifiable risk factor in Alzheimer's disease. Previous trials of the multinutrient Fortasyn Connect showed benefits in mild Alzheimer's disease dementia. LipiDiDiet investigated the effects of Fortasyn Connect on cognition and related measures in prodromal Alzheimer's disease.

Cost-Utility of Using Alzheimer's Disease Biomarkers in Cerebrospinal Fluid to Predict Progression from Mild Cognitive Impairment to Dementia.

Background: Diagnostic research criteria for Alzheimer's disease support the use of biomarkers in the cerebrospinal fluid (CSF) to improve the accuracy of the prognosis regarding progression to dementia for people with mild cognitive impairment (MCI).

Objective: The aim of this study was to estimate the potential incremental cost-effectiveness ratio of adding CSF biomarker testing to the standard diagnostic workup to determine the prognosis for patients with MCI.

Methods: In an early technology assessment, a mathematical simulation model was built, using available evidence on added prognostic value as well as expert opinion to estimate the incremental costs and quality-adjusted life years (QALYs) of 20,000 virtual MCI patients with (intervention strategy) and without (control strategy) relying on CSF, from a health-care sector perspective and with a 5-year time horizon.

Fast, Efficient and Low E-Factor One-Pot Palladium-Catalyzed Cross-Coupling of (Hetero)Arenes.

The homocoupling of aryl halides and the heterocoupling of aryl halides with either aryl bromides or arenes bearing an ortho-lithiation directing group are presented. The use of a Pd catalyst, in combination with t-BuLi, allows for the rapid and efficient formation of a wide range of polyaromatic compounds in a one pot procedure bypassing the need for the separate preformation of an organometallic coupling partner. These polyaromatic structures are obtained in high yields, in 10 min at room temperature, with minimal waste generation (E-factors as low as 1.

Association Between Later Life Lifestyle Factors and Alzheimer's Disease Biomarkers in Non-Demented Individuals: A Longitudinal Descriptive Cohort Study.

Background: Lifestyle factors have been associated with the risk of dementia, but the association with Alzheimer's disease (AD) remains unclear.

Objective: To examine the association between later life lifestyle factors and AD biomarkers (i.e.

Relation of Odor Identification with Alzheimer's Disease Markers in Cerebrospinal Fluid and Cognition.

Background: Impaired olfactory function is an early characteristic of Alzheimer's disease (AD), but it remains unclear if odor identification also relates to early markers of AD in cerebrospinal fluid (CSF).

Objective: To investigate the association between odor identification and amyloid-β 1-42 (Aβ42) and total tau (t-tau) concentrations in CSF. In addition, to examine the relation between odor identification and cognitive function at baseline and at follow-up, and whether these associations are moderated by CSF Aβ42 and t-tau and apolipoprotein E (APOE) genotype.

Memory Correlates of Alzheimer's Disease Cerebrospinal Fluid Markers: A Longitudinal Cohort Study.

Background: Performance on episodic, semantic, and working memory tests is impaired in Alzheimer's disease (AD)-type dementia, but it is unclear which type of memory test is most strongly associated with early AD biomarkers in cerebrospinal fluid (CSF), and most useful for monitoring disease progression.

Objective: To examine the association between amyloid-β 1-42 (Aβ42) and tau in CSF with performance on different memory domains at baseline, and how these CSF markers are related with memory decline.

Methods: We included 263 individuals with normal cognition, mild cognitive impairment, AD-type dementia, and non-AD dementia from the European EDAR study.

Amyloid-independent atrophy patterns predict time to progression to dementia in mild cognitive impairment.

Background: Amyloid pathology in subjects with mild cognitive impairment (MCI) is an important risk factor for progression to dementia due to Alzheimer's disease. Predicting the onset of dementia is challenging even in the presence of amyloid, as time to progression varies considerably among patients and depends on the onset of neurodegeneration. Survival analysis can account for variability in time to event, but has not often been applied to MRI measurements beyond singular predefined brain regions such as the hippocampus.