Blood-based biomarkers for Alzheimer's disease and related dementias: Keys to success and things to consider

During the last two decades, considerable progress has been made in the field of fluid and imaging biomarkers for neurodegenerative dementias. As a result, the most recent research and clinical guidelines (the National Institute on Aging and Alzheimer's Association, International Working Group 2, National Institute for Health and Care Excellence) incorporate cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers in the diagnostic criteria of dementia and mild cognitive impairment due to Alzheimer's disease (AD) [[1], [2], [3]]. However, as both CSF and amyloid PET examinations require expert knowledge and are of limited availability outside specialized memory clinics, there is no doubt that blood tests would be much easier to implement in clinical medicine and as screening tools when recruiting patients for clinical trials

Cognitive impairment and decline in cognitively normal older adults with high amyloid-β: A meta-analysis

AbstractIntroductionThis meta-analysis aimed to characterize the nature and magnitude of amyloid (Aβ)-related cognitive impairment and decline in cognitively normal (CN) older individuals.MethodMEDLINE Ovid was searched from 2012 to June 2016 for studies reporting relationships between cerebrospinal fluid or positron emission tomography (PET) Aβ levels and cognitive impairment (cross-sectional) and decline (longitudinal) in CN older adults. Neuropsychological data were classified into domains of episodic memory, executive function, working memory, processing speed, visuospatial function, semantic memory, and global cognition. Type of Aβ measure, how Aβ burden was analyzed, inclusion of control variables, and clinical criteria used to exclude participants, were considered as moderators. Random-effects models were used for analyses with effect sizes expressed as Cohen's d.ResultsA total of 38 studies met inclusion criteria contributing 30 cross-sectional (N = 5005) and 14 longitudinal (N = 2584) samples. Aβ-related cognitive impairment was observed for global cognition (d = 0.32), visuospatial function (d = 0.25), processing speed (d = 0.18), episodic memory, and executive function (both d's = 0.15), with decline observed for global cognition (d = 0.30), semantic memory (d = 0.28), visuospatial function (d = 0.25), and episodic memory (d = 0.24). Aβ-related impairment was moderated by age, amyloid measure, type of analysis, and inclusion of control variables and decline moderated by amyloid measure, type of analysis, inclusion of control variables, and exclusion criteria used.DiscussionCN older adults with high Aβ show a small general cognitive impairment and small to moderate decline in episodic memory, visuospatial function, semantic memory, and global cognition

Brain amyloid in preclinical Alzheimer\u27s disease is associated with increased driving risk

INTRODUCTION: Postmortem studies suggest that fibrillar brain amyloid places people at higher risk for hazardous driving in the preclinical stage of Alzheimer's disease (AD). METHODS: We administered driving questionnaires to 104 older drivers (19 AD, 24 mild cognitive impairment, and 61 cognitive normal) who had a recent (18)F-florbetapir positron emission tomography scan. We examined associations of amyloid standardized uptake value ratios with driving behaviors: traffic violations or accidents in the past 3 years. RESULTS: The frequency of violations or accidents was curvilinear with respect to standardized uptake value ratios, peaking around a value of 1.1 (model r(2) = 0.10, P = .002); moreover, this relationship was evident for the cognitively normal participants. DISCUSSION: We found that driving risk is strongly related to accumulating amyloid on positron emission tomography, and that this trend is evident in the preclinical stage of AD. Brain amyloid burden may in part explain the increased crash risk reported in older adults

Observation of a translational energy threshold for a highly exoergic ion‐molecule reaction

This is the publisher's version, also available electronically from http://scitation.aip.org/content/aip/journal/jcp/60/9/10.1063/1.1681592

An Expanded Modern Coexistence Theory for Empirical Applications

Understanding long‐term coexistence of numerous competing species is a longstanding challenge in ecology. Progress requires determining which processes and species differences are most important for coexistence when multiple processes operate and species differ in many ways. Modern coexistence theory (MCT), formalized by Chesson, holds out the promise of doing that, but empirical applications remain scarce. We argue that MCT\u27s mathematical complexity and subtlety have obscured the simplicity and power of its underlying ideas and hindered applications. We present a general computational approach that extends our previous solution for the storage effect to all of standard MCT\u27s spatial and temporal coexistence mechanisms, and also process‐defined mechanisms amenable to direct study such as resource partitioning, indirect competition, and life history trade‐offs. The main components are a method to partition population growth rates into contributions from different mechanisms and their interactions, and numerical calculations in which some mechanisms are removed and others retained. We illustrate how our approach handles features that have not been analyzed in the standard framework through several case studies: competing diatom species under fluctuating temperature, plant–soil feedbacks in grasslands, facilitation in a beach grass community, and niche differences with independent effects on recruitment, survival and growth in sagebrush steppe

Chemical accelerator studies of reaction dynamics: Ar^+ + CH4 → ArH^+ + CH3

This is the publisher's version, also available electronically from http://scitation.aip.org/content/aip/journal/jcp/62/7/10.1063/1.430836.Chemical accelerator studies on isotopic variants of the reaction Ar+ + CH4 → ArH+ + CH3 are reported. Velocity and angular distributions of the ionic product as a function of initial translational energy have been measured over the energy range 0.39–25 eV center-of-mass (c.m.). The asymmetry of the product distribution with respect to the center of mass indicates that the reaction is predominantly direct over the energy range studied. The dynamics of the reaction are approximated by the spectator stripping model: The reaction exothermicity appears as product internal energy and product excitation increases with collision energy at the rate predicted by this model. The internal degrees of freedom of the neutral product have little effect on reactiondynamics, and product excitation appears to reside principally in the ionic product. Deviations from the spectator stripping model suggest the existence of a basin in the potential energy hypersurface for this reaction; the ArCH4 + complex which may be formed at low collision energies, however, preferentially decomposes via reaction channels other than that resulting in ArH+ formation

OCTA reveals remodeling of the peripheral capillary free zones in normal aging

The retinal neurovascular unit consists of blood vessel endothelial cells, pericytes, neurons, astrocytes, and Müller cells that form the inner retinal blood barrier. A peripheral capillary free zone (pCFZ) represents the distance that oxygen and nutrients must diffuse to reach the neural retina, and serves as a metric of retinal tissue oxygenation. The pCFZs are formed based on oxygen saturation in the retinal arterioles and venules. Because retinal arterioles contain a larger concentration of oxygenated blood than venules, there is a reduced need for capillaries to exist closely to arterioles compared to venules. Therefore, in a healthy individual, larger periarteriole CFZs are expected compared to perivenule CFZs. With normal aging, there is atrophy of the inner retinal neurons, and consequently reduced extraction of oxygen and nutrients from the retinal vessels (i.e., increased oxygen saturation). Therefore, we hypothesized that the peripheral CFZ will remodel with normal aging. Using Optical Coherence Tomography Angiography, we showed that the pCFZs do remodel in normal aging with large (perivenule: η2p = 0.56) and moderate (periarteriole: η2p = 0.12) effect sizes, opening the possibility that such changes may be further increased by neurodegenerative diseases that adversely impact the health of the retinal neural cell layers

Observation of a stripping threshold for the reaction N2 ^++CH4→N2H^++CH3

This is the publisher's version, also available electronically from http://scitation.aip.org/content/aip/journal/jcp/64/9/10.1063/1.432690Chemical accelerator studies on isotopic variants of the reaction N2 ++CH4→N2H++CH3 are reported. Reaction cross sections, as well as velocity and angular distributions of the ionic products have been measured as a function of initial translational energy over the energy range 0.65–35 eV (center of mass). The results are similar to those recently reported for the reaction of Ar+ with CH4. The excitation function maximizes at about 5 eV (c.m.) and decreases at lower collision energies, appearing to possess a threshold at 0.1 eV. At the higher energies there is a large isotope effect favoring abstraction of H over D. The product velocity vector distribution is strongly peaked forward of the center of mass, indicating that the reaction is predominantly direct over the energy range studied. The spectator stripping model, although providing a reasonable first approximation to the reaction dynamics, overestimates the product translational energy by approximately 0.1 eV. This behavior is presumed to be caused by a basin in the potential energy hypersurface for this reaction. If, however, an N2CH4 + complex is formed at low collision energies, it appears to decompose via reaction channels other than that resulting in N2H+ formation

Direct and mediated effects of a social-emotional and character development program on adolescent substance use

Mitigating and preventing substance use among adolescents requires approaches that address the multitude of factors that influence this behavior. Such approaches must be tested, not only for evidence of empirical effectiveness, but also to determine the mechanisms by which they are successful. The aims of the present study were twofold: 1) To determine the effectiveness of a school-based social-emotional and character development (SECD) program, Positive Action (PA), in reducing substance use (SU) among a sample of U.S. youth living in a low-income, urban environment, and 2) to test one mechanism by which the program achieves its success. We used longitudinal mediation analysis to test the hypotheses that: 1) students attending PA intervention schools engage in significantly less SU than students attending control schools, 2) students attending PA intervention schools show significantly better change in SECD than students attending control schools, and 3) the effect of the PA intervention on SU is mediated by the change in SECD. Analyses revealed program effects on both SECD and SU, a relationship between SECD and SU, and the effects of PA on SU were completely mediated by changes in SECD. Future research directions and implications for schoolbased social-emotional and character development efforts and substance use prevention are addressed.peer-reviewe