Associations between Vascular Function and Tau PET Are Associated with Global Cognition and Amyloid.

Tau pathology and vascular dysfunction are important contributors to Alzheimer's disease (AD), but vascular-tau associations and their effects on cognition are poorly understood. We investigated these associations in male and female humans by conducting voxelwise comparisons between cerebral blood flow (CBF) and tau positron emission tomography (PET) images in independent discovery [cognitively normal (CN), 19; mild cognitive impairment (MCI) risk, 43; MCI, 6] and replication (CN,73; MCI, 45; AD, 20) cohorts. In a subgroup, we assessed relationships between tau and soluble platelet-derived growth factor ß (sPDGFRß), a CSF marker of pericyte injury. We tested whether CBF/sPDGFRß-tau relationships differed based on Montreal Cognitive Assessment (MoCA) global cognition performance, or based on amyloid burden. Mediation analyses assessed relationships among CBF/sPDGFRß, tau, and cognition. Negative CBF-tau correlations were observed predominantly in temporal-parietal regions. In the replication cohort, early negative CBF-tau correlations increased in spatial extent and in strength of correlation with increased disease severity. Stronger CBF-tau and sPDGFRß-tau correlations were observed in participants with greater amyloid burden and lower MoCA scores. Importantly, when stratifying by amyloid status, stronger CBF-tau relationships in individuals with lower MoCA scores were driven by amyloid+ participants. Tau PET was a significant mediator CBF/sPDGFRß-MoCA relationships in numerous regions. Our results demonstrate vascular-tau associations across the AD spectrum and suggest that early vascular-tau associations are exacerbated in the presence of amyloid, consistent with a two-hit model of AD on cognition. Combination treatments targeting vascular health, as well as amyloid-ß and tau levels, may preserve cognitive function more effectively than single-target therapies.SIGNIFICANCE STATEMENT Emerging evidence demonstrates a role for vascular dysfunction as a significant contributor to Alzheimer's pathophysiology. However, associations between vascular dysfunction and tau pathology, and their effects on cognition remain poorly understood. Multimodal neuroimaging data from two independent cohorts were analyzed to provide novel in vivo evidence of associations between cerebral blood flow (CBF), an MRI measure of vascular health, and tau pathology using PET. CBF-tau associations were related to cognition and driven in part by amyloid burden. Soluble platelet-derived growth factor ß, an independent CSF vascular biomarker, confirmed vascular-tau associations in a subgroup analysis. These results suggest that combination treatments targeting vascular health, amyloid-ß, and tau levels may more effectively preserve cognitive function than single-target therapies.

L2C2: Last-level compressed-contents non-volatile cache and a procedure to forecast performance and lifetime.

Several emerging non-volatile (NV) memory technologies are rising as interesting alternatives to build the Last-Level Cache (LLC). Their advantages, compared to SRAM memory, are higher density and lower static power, but write operations wear out the bitcells to the point of eventually losing their storage capacity. In this context, this paper presents a novel LLC organization designed to extend the lifetime of the NV data array and a procedure to forecast in detail the capacity and performance of such an NV-LLC over its lifetime. From a methodological point of view, although different approaches are used in the literature to analyze the degradation of an NV-LLC, none of them allows to study in detail its temporal evolution. In this sense, this work proposes a forecasting procedure that combines detailed simulation and prediction, allowing an accurate analysis of the impact of different cache control policies and mechanisms (replacement, wear-leveling, compression, etc.) on the temporal evolution of the indices of interest, such as the effective capacity of the NV-LLC or the system IPC. We also introduce L2C2, a LLC design intended for implementation in NV memory technology that combines fault tolerance, compression, and internal write wear leveling for the first time. Compression is not used to store more blocks and increase the hit rate, but to reduce the write rate and increase the lifetime during which the cache supports near-peak performance. In addition, to support byte loss without performance drop, L2C2 inherently allows N redundant bytes to be added to each cache entry. Thus, L2C2+N, the endurance-scaled version of L2C2, allows balancing the cost of redundant capacity with the benefit of longer lifetime. For instance, as a use case, we have implemented the L2C2 cache with STT-RAM technology. It has affordable hardware overheads compared to that of a baseline NV-LLC without compression in terms of area, latency and energy consumption, and increases up to 6-37 times the time in which 50% of the effective capacity is degraded, depending on the variability in the manufacturing process. Compared to L2C2, L2C2+6 which adds 6 bytes of redundant capacity per entry, that means 9.1% of storage overhead, can increase up to 1.4-4.3 times the time in which the system gets its initial peak performance degraded.

Variability in objective sleep is associated with Alzheimer's pathology and cognition.

Both sleep duration and sleep efficiency have been associated with risk of Alzheimer's disease, suggesting that interventions to promote optimal sleep may be a way to reduce Alzheimer's disease risk. However, studies often focus on average sleep measures, usually from self-report questionnaires, ignoring the role of intra-individual variability in sleep across nights quantified from objective sleep measures. The current cross-sectional study sought to investigate the role of intra-individual variability in accelerometer-based objective sleep duration and sleep efficiency in relation to in vivo Alzheimer's disease pathology (ß-amyloid and tau) using positron emission tomography imaging and cognition (working memory, inhibitory control, verbal memory, visual memory and global cognition). To examine these relationships, we evaluated 52 older adults (age = 66.4 ± 6.89, 67% female, 27% apolipoprotein E4 carriers) with objective early mild cognitive impairment. Modifying effects of apolipoprotein E4 status were also explored. Less intra-individual variability in sleep duration was associated with lower ß-amyloid burden, higher global cognition and better inhibitory control, with a trend for lower tau burden. Less intra-individual variability in sleep efficiency was associated with lower ß-amyloid burden, higher global cognition and better inhibitory control, but not with tau burden. Longer sleep duration was associated with better visual memory and inhibitory control. Apolipoprotein E4 status significantly modified the association between intra-individual variability in sleep efficiency and ß-amyloid burden, such that less sleep efficiency variability was associated with lower ß-amyloid burden in apolipoprotein E4 carriers only. There was a significant interaction between sleep duration and apolipoprotein E4 status, suggesting that longer sleep duration is more strongly associated with lower ß-amyloid burden in apolipoprotein E4 carriers relative to non-carriers. These results provide evidence that lower intra-individual variability in both sleep duration and sleep efficiency and longer mean sleep duration are associated with lower levels of ß-amyloid pathology and better cognition. The relationships between sleep duration and intra-individual variability in sleep efficiency with ß-amyloid burden differ by apolipoprotein E4 status, indicating that longer sleep duration and more consistent sleep efficiency may be protective against ß-amyloid burden in apolipoprotein E4 carriers. Longitudinal and causal studies are needed to better understand these relationships. Future work should investigate factors contributing to intra-individual variability in sleep duration and sleep efficiency in order to inform intervention studies.

Mediating influences of negative affect and risk perception on the relationship between sensation seeking and adolescent cigarette smoking.

INTRODUCTION: A substantial number of adolescents are current and regular cigarette smokers, and there is a need to better understand factors that contribute to smoking behavior during these years. Sensation seeking (SS) is one factor that has consistently been associated with smoking, but less is known about mechanisms that may explain this relationship. METHODS: The present study tested the hypothesis that high school students high in SS would report heavier cigarette smoking and that this relationship would be mediated by negative affect and by perceptions about the risks of smoking. Students (n = 1,688) participated in an annual survey of substance use and related attitudes and characteristics. RESULTS: As expected, higher SS was associated with greater levels of past 30-day (odds ratio [OR] = 1.46, p = .004) and lifetime (OR = 1.37, p = .004) smoking, particularly for males. Multiple mediation models indicated that effect of SS on both 30-day (combined indirect effect z = 5.38, p < .001) and lifetime (z = 6.14, p < .001) smoking was mediated by both negative affect and risk perception. CONCLUSIONS: These findings suggest a need for increasing the sensation value of anti-tobacco messages to increase their efficacy for high SS youth. High SS youth may also benefit from prevention efforts designed to teach healthy ways of coping with negative affect.

An open trial evaluating an attention bias modification program for overweight adults who binge eat.

BACKGROUND AND OBJECTIVES: Binge eating is prevalent and is associated with significant psychiatric and medical comorbidities. To date, the most effective psychological treatments for individuals who binge eat are not effective for all patients and they do not result in significant weight loss. Dual process theories suggest that implicit factors, such as attention bias, may influence behavior, even when the behavior is in opposition to long-term goals. Attention bias modification programs have been tested in other areas of psychopathology, and could be utilized to improve outcomes for people who binge eat. Thus, the aim of this open trial was to conduct a preliminary evaluation of an attention bias modification program (ABM-Food) designed to train attention away from food cues. METHODS: Adults who binge eat and were overweight or obese enrolled in an 8-week ABM-Food program, which consisted of one session in the lab each week and two training sessions at home. Nine participants completed the ABM-Food training program and the post-treatment assessment, and 8 completed the 3-month post-treatment assessment. RESULTS: Results showed that the ABM-Food program is a feasible and acceptable treatment for adults who binge eat. Initial effectiveness data showed decreases in weight, eating disorder symptoms, binge eating, loss of control and responsivity to food in the environment, as well as changes in attention bias. The majority of these effects remained at the 3-month follow-up time point. LIMITATIONS: This study is limited by the single-group open label trial, and the small sample size. CONCLUSIONS: This open trial provides initial evidence for the feasibility, acceptability and effectiveness of ABM-Food for individuals who binge eat and are overweight or obese.

Adolescent satisfaction with brief motivational enhancement for alcohol abuse.

Although many investigations point to the importance of treatment satisfaction and working alliance as predictors of treatment engagement and outcome, few studies have closely examined these issues among adolescents. This study investigates satisfaction among a nonclinical adolescent sample participating in a school-based alcohol-prevention program. Adolescents self-selected to one of three formats: individual, group, and website. Three hundred nineteen satisfaction measures completed at the time of each participant's final session were used for analyses. Hierarchical regression analyses examined predictors of consumer satisfaction. In general, greater participation in the program was significantly related to satisfaction. Students who participated in the group and individual formats reported greater satisfaction than students who participated in the website format. Current alcohol users were less satisfied with the session focusing on how experimental use can lead to problem use; lifetime abstainers were more satisfied with the session focusing on stress and coping. These analyses have implications for informing future adolescent school-based interventions for alcohol problems.

Body image and size perceptions of Mexican American women.

Purpose was to examine in Mexican American women the influences of age, weight, socioeconomic status and acculturation level on body image, perceptions of attractive and acceptable female shapes, and tolerance for overweight and obesity. Participants were 276 Mexican American women. Age, body mass index, socioeconomic status, and acculturation level were measured. The Figure Rating Scale was used to assess body image, preferences for body size, and perceptions of underweight to obese and acceptable body sizes. Significant effects for acculturation level and current weight were found. Women who were more Anglo oriented showed greater preference for thinner figures. As compared to normal weight women, obese women chose larger figures as ideal, realistic, attractive, and thinnest acceptable. Findings point to the impact of acculturation and obesity on body image and size perceptions. Health professionals working with Mexican Americans should consider each individual's current weight and level of acculturation.