Gastrointestinal release site for delayed release and gelatin capsules in healthy dogs.

Gelatin capsules deliver their contents to the stomach, while delayed-release (DR) capsules are designed to allow delivery to the small intestine. This study evaluated the gastrointestinal release site of DR capsules in six healthy adult dogs compared to gelatin capsules. Both gelatin and DR capsules were filled with barium-impregnated polyethylene spheres (BIPS™), and following enteral administration, release site was assessed using abdominal radiographs at baseline, immediately after ingestion, 15 min post-ingestion, 30 min post-ingestion, and then every 30 min thereafter. The evaluated phases included fasted conditions (phase 1, n = 6), increased meal size (phase 2, n = 2), double encapsulation (phase 3, n = 2), and altered capsule size (phase 4, n = 1). The released site was the stomach in all phases for both capsule types. In phase 1, DR capsules had a significantly prolonged time (median 60 min, range 60-90) to release BIPS™ compared to gelatin capsules (15 min, range 15-30; p = .03). In phase 2 (full meal size), 3 (double encapsulation), and 4 (smaller capsule size) pilot studies, release time was prolonged but still occurred in the stomach. This is similar to the release site for gelatin capsules but differs from the release site for DR capsules in people. This has implications for pharmacologic outcomes for products that are affected by gastric physiology (e.g. fecal microbiota transplantation). Based on this pilot data, clinicians and researchers should not assume DR capsules will allow for intestinal delivery of contents in dogs. Future studies should be conducted on larger and varied populations of dogs.

Characterizing the emergence of amyloid and tau burden in Down syndrome.

INTRODUCTION: Almost all individuals with Down syndrome (DS) will develop neuropathological features of Alzheimer's disease (AD). Understanding AD biomarker trajectories is necessary for DS-specific clinical interventions and interpretation of drug-related changes in the disease trajectory. METHODS: A total of 177 adults with DS from the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) underwent positron emission tomography (PET) and MR imaging. Amyloid-beta (Aß) trajectories were modeled to provide individual-level estimates of Aß-positive (A+) chronicity, which were compared against longitudinal tau change. RESULTS: Elevated tau was observed in all NFT regions following A+ and longitudinal tau increased with respect to A+ chronicity. Tau increases in NFT regions I-III was observed 0-2.5 years following A+. Nearly all A+ individuals had tau increases in the medial temporal lobe. DISCUSSION: These findings highlight the rapid accumulation of amyloid and early onset of tau relative to amyloid in DS and provide a strategy for temporally characterizing AD neuropathology progression that is specific to the DS population and independent of chronological age. HIGHLIGHTS: Longitudinal amyloid trajectories reveal rapid Aß accumulation in Down syndrome NFT stage tau was strongly associated with A+ chronicity Early longitudinal tau increases were observed 2.5-5 years after reaching A.

Evaluation of Fecal Egg Count Tests for Effective Control of Equine Intestinal Strongyles.

The American Association of Equine Practitioners strongly advocates evidence-based intestinal strongyle control in horses. It recommends targeted treatment of all heavy egg shedders (>500 eggs per gram (EPG) of feces), while the low shedders (0-200 EPG) are left untreated. As 50-75% of adult horses in a herd are low shedders, preventing them from unnecessary anthelmintic exposure is critical for tackling resistance. There are various fecal egg count (FEC) techniques with many modifications and variations in use, but none is identified as a gold standard. The hypothesis of the study was that the diagnostic performance of 12 commonly used quantitation methodologies (three techniques with four variants) differs. In this regard, method comparison studies were performed using polystyrene beads as proxy for intestinal strongyle eggs. Mini-FLOTAC-based variants had the lowest coefficient of variation (CV%) in bead recovery, whereas McMaster variants had the highest. All four variants of Mini-FLOTAC and the NaNO3 1.33 specific gravity variant of modified Wisconsin followed a linear fit with R2 > 0.95. In contrast, the bead standard replicates for modified McMaster variants dispersed from the regression curve, causing a lower R2. The Mini-FLOTAC method seems less influenced by the choice of floatation solution and has better repeatability parameters and linearity for bead standard recovery. For FEC tests with high R2 (>0.95) but that underestimated the true bead count, a correction factor (CF) was determined to estimate the true count. Finally, the validity of CF was analyzed for 5 tests with R2 > 0.95 to accurately quantify intestinal strongyle eggs from 40 different horses. Overall, this study identified FEC methodologies with the highest diagnostic performance. The limitations in standardizing routine FEC tests are highlighted, and the importance of equalization of FEC results is emphasized for promoting uniformity in the implementation of parasite control guidelines.

Event Segmentation Enhances Older Adults' Reactive Cognitive Control Bias.

The present study examined the effect of event segmentation on cognitive control mode use in a sample of older adults (N = 30; Mage = 73, SDage = 4.75) using a modified AX-Continuous Performance Test (AX-CPT). This task included a perceptual event boundary between each cue and its forthcoming probe by means of a spatial shift across the left and right side of the display. Past research showed that young adults' existing proactive control bias could be enhanced in an event segmented AX-CPT relative to their performance on a standard AX-CPT. For older adults who adopt reactive control by default, the event boundary was expected to impede cue-reactivation during probe presentation, and thus further enhance their existing reactive control bias. To examine this, older adults were tested with a standard and an event segmented AX-CPT in two blocks, with error rates revealing a shift toward greater reactive control use in the event segmented relative to the standard AX-CPT. Findings supported our hypothesis that placing a spatial event boundary between each cue and forthcoming probe would further enhance older adults' reactive control bias. This study contributes to the sparse but growing literature on the effects of task-specific manipulations on cognitive control use. The results are discussed in light of the dual mechanisms of control framework and the event horizon model.

Multi-method investigation of factors influencing amyloid onset and impairment in three cohorts.

Alzheimer's disease biomarkers are becoming increasingly important for characterizing the longitudinal course of disease, predicting the timing of clinical and cognitive symptoms, and for recruitment and treatment monitoring in clinical trials. In this work, we develop and evaluate three methods for modelling the longitudinal course of amyloid accumulation in three cohorts using amyloid PET imaging. We then use these novel approaches to investigate factors that influence the timing of amyloid onset and the timing from amyloid onset to impairment onset in the Alzheimer's disease continuum. Data were acquired from the Alzheimer's Disease Neuroimaging Initiative (ADNI), the Baltimore Longitudinal Study of Aging (BLSA) and the Wisconsin Registry for Alzheimer's Prevention (WRAP). Amyloid PET was used to assess global amyloid burden. Three methods were evaluated for modelling amyloid accumulation using 10-fold cross-validation and holdout validation where applicable. Estimated amyloid onset age was compared across all three modelling methods and cohorts. Cox regression and accelerated failure time models were used to investigate whether sex, apolipoprotein E genotype and e4 carriage were associated with amyloid onset age in all cohorts. Cox regression was used to investigate whether apolipoprotein E (e4 carriage and e3e3, e3e4, e4e4 genotypes), sex or age of amyloid onset were associated with the time from amyloid onset to impairment onset (global clinical dementia rating ≥1) in a subset of 595 ADNI participants that were not impaired before amyloid onset. Model prediction and estimated amyloid onset age were similar across all three amyloid modelling methods. Sex and apolipoprotein E e4 carriage were not associated with PET-measured amyloid accumulation rates. Apolipoprotein E genotype and e4 carriage, but not sex, were associated with amyloid onset age such that e4 carriers became amyloid positive at an earlier age compared to non-carriers, and greater e4 dosage was associated with an earlier amyloid onset age. In the ADNI, e4 carriage, being female and a later amyloid onset age were all associated with a shorter time from amyloid onset to impairment onset. The risk of impairment onset due to age of amyloid onset was non-linear and accelerated for amyloid onset age >65. These findings demonstrate the feasibility of modelling longitudinal amyloid accumulation to enable individualized estimates of amyloid onset age from amyloid PET imaging. These estimates provide a more direct way to investigate the role of amyloid and other factors that influence the timing of clinical impairment in Alzheimer's disease.

Why do people share memories online? An examination of the motives and characteristics of social media users.

ABSTRACTSocial media has become one of the most powerful and ubiquitous means by which individuals curate and share their life stories with the world at large. Not surprisingly then, researchers have started to examine the reasons why individuals post personal memories on social media and said individuals' characteristics. Across two studies, we extended this line of research by further testing the Purposes of Online Memory Sharing Scale (POMSS) and its subscales: self, social, therapeutic and directive. Additionally, we examined which of these motives led college students (Study 1) and adults of a community sample (Study 2) to post personal memories on social media and whether said motives were associated with the individuals' psychological characteristics. Overall, the results revealed that emerging adults and older adults posted personal experiences on social media primarily for social reasons. We also found that extraversion, disclosure and social media usage predicted each of the motives for posting personal experiences on social media. In addition, individuals who were more lonely and who had lower self-esteem were more likely to post personal experiences on social media for therapeutic reasons. We discuss these results in terms of their implications towards understanding the mnemonic consequences associated with social media use.

Neurofibrillary tau depositions emerge with subthreshold cerebral beta-amyloidosis in down syndrome.

INTRODUCTION: Adults with Down syndrome are genetically predisposed to develop Alzheimer's disease and accumulate beta-amyloid plaques (Aß) early in life. While Aß has been heavily studied in Down syndrome, its relationship with neurofibrillary tau is less understood. The aim of this study was to evaluate neurofibrillary tau deposition in individuals with Down syndrome with varying levels of Aß burden. METHODS: A total of 161 adults with Down syndrome (mean age = 39.2 (8.50) years) and 40 healthy, non-Down syndrome sibling controls (43.2 (12.6) years) underwent T1w-MRI, [C-11]PiB and [F-18]AV-1451 PET scans. PET images were converted to units of standardized uptake value ratios (SUVrs). Aß burden was calculated using the amyloid load metric (AßL); a measure of global Aß burden that improves quantification from SUVrs by suppressing the nonspecific binding signal component and computing the specific Aß signal from all Aß-carrying voxels from the image. Regional tau was assessed using control-standardized AV-1451 SUVr. Control-standardized SUVrs were compared across Down syndrome groups of Aß-negative (A-) (AßL < 13.3), subthreshold A+ (13.3 ≤ AßL < 20) and conventionally A+ (AßL ≥ 20) individuals. The subthreshold A + group was identified as having significantly higher Aß burden compared to the A- group, but not high enough to satisfy a conventional A + classification. RESULTS: A large-sized association that survived adjustment for chronological age, mental age (assessed using the Peabody Picture Vocabulary Test), and imaging site was observed between AßL and AV-1451 within each Braak region (p < .05). The A + group showed significantly higher AV-1451 retention across all Braak regions compared to the A- and subthreshold A + groups (p < .05). The subthreshold A + group showed significantly higher AV-1451 retention in Braak regions I-III compared to an age-matched sample from the A- group (p < .05). DISCUSSION: These results show that even the earliest detectable Aß accumulation in Down syndrome is accompanied by elevated tau in the early Braak stage regions. This early detection of tau can help characterize the tau accumulation phase during preclinical Alzheimer's disease progression in Down syndrome and suggests that there may be a relatively narrow window after Aß accumulation begins to prevent the downstream cascade of events that leads to Alzheimer's disease.

PET measurement of longitudinal amyloid load identifies the earliest stages of amyloid-beta accumulation during Alzheimer's disease progression in Down syndrome.

INTRODUCTION: Adults with Down syndrome (DS) are predisposed to Alzheimer's disease (AD) and reveal early amyloid beta (Aß) pathology in the brain. Positron emission tomography (PET) provides an in vivo measure of Aß throughout the AD continuum. Due to the high prevalence of AD in DS, there is need for longitudinal imaging studies of Aß to better characterize the natural history of Aß accumulation, which will aid in the staging of this population for clinical trials aimed at AD treatment and prevention. METHODS: Adults with DS (N = 79; Mean age (SD) = 42.7 (7.28) years) underwent longitudinal [C-11]Pittsburgh compound B (PiB) PET. Global Aß burden was quantified using the amyloid load metric (AßL). Modeled PiB images were generated from the longitudinal AßL data to visualize which regions are most susceptible to Aß accumulation in DS. AßL change was evaluated across Aß(-), Aß-converter, and Aß(+) groups to assess longitudinal Aß trajectories during different stages of AD-pathology progression. AßL change values were used to identify Aß-accumulators within the Aß(-) group prior to reaching the Aß(+) threshold (previously reported as 20 AßL) which would have resulted in an Aß-converter classification. With knowledge of trajectories of Aß(-) accumulators, a new cutoff of Aß(+) was derived to better identify subthreshold Aß accumulation in DS. Estimated sample sizes necessary to detect a 25% reduction in annual Aß change with 80% power (alpha 0.01) were determined for different groups of Aß-status. RESULTS: Modeled PiB images revealed the striatum, parietal cortex and precuneus as the regions with earliest detected Aß accumulation in DS. The Aß(-) group had a mean AßL change of 0.38 (0.58) AßL/year, while the Aß-converter and Aß(+) groups had change of 2.26 (0.66) and 3.16 (1.34) AßL/year, respectively. Within the Aß(-) group, Aß-accumulators showed no significant difference in AßL change values when compared to Aß-converter and Aß(+) groups. An Aß(+) cutoff for subthreshold Aß accumulation was derived as 13.3 AßL. The estimated sample size necessary to detect a 25% reduction in Aß was 79 for Aß(-) accumulators and 59 for the Aß-converter/Aß(+) group in DS. CONCLUSION: Longitudinal AßL changes were capable of distinguishing Aß accumulators from non-accumulators in DS. Longitudinal imaging allowed for identification of subthreshold Aß accumulation in DS during the earliest stages of AD-pathology progression. Detection of active Aß deposition evidenced by subthreshold accumulation with longitudinal imaging can identify DS individuals at risk for AD development at an earlier stage.

Securitization of a Drug Development Mega-Fund: The Time-Certain Research-Backed Obligation.

Without sufficient capital, the cost of engaging in sustainable clinical development of a drug or drug compound is exceedingly difficult. Fagnan, Fernandez, Lo, and Stein have proposed the securitization of a drug development "mega-fund" as a means of attracting capital from traditional long-term corporate bond investors to the clinical stage of drug development. Our contribution to this line of thinking is the modeling of the cash flows of such a biopharmaceutical mega-fund and their distributions over time to develop an innovative design of securities that control the timing risk of cash flows. This modeling offers a more efficient means of allocating the cash flows that the mega-fund consumes and generates, in an effort to lower the overall yields required to place the research-backed obligations. The new securities control the cash flow timing risk and the lower cost of funding ultimately means more funds are available to clinically test a treatment or cure. We obtain the cash flow profile of this new security, called 'the time-certain research-backed obligation', by isolating cash flows from two different time distribution of cash flow scenarios, so that investors will be assured of the time frame over which they will receive repayment of their investment. We have offered a security design that will lower the cost of funding the drug mega-fund. Success or failure of a drug is uncorrelated with the performance of the stock or bond markets, thus this asset class that is backed by a portfolio of drugs in the clinical stages of development should have little correlation with other asset markets, making them a valuable addition to diversified portfolios.

Amyloid duration is associated with preclinical cognitive decline and tau PET.

INTRODUCTION: This study applies a novel algorithm to longitudinal amyloid positron emission tomography (PET) imaging to identify age-heterogeneous amyloid trajectory groups, estimate the age and duration (chronicity) of amyloid positivity, and investigate chronicity in relation to cognitive decline and tau burden. METHODS: Cognitively unimpaired participants (n = 257) underwent one to four amyloid PET scans (Pittsburgh Compound B, PiB). Group-based trajectory modeling was applied to participants with longitudinal scans (n = 171) to identify and model amyloid trajectory groups, which were combined with Bayes theorem to estimate age and chronicity of amyloid positivity. Relationships between chronicity, cognition, clinical progression, and tau PET (MK-6240) were investigated using regression models. RESULTS: Chronicity explained more heterogeneity in amyloid burden than age and binary amyloid status. Chronicity was associated with faster cognitive decline, increased risk of abnormal cognition, and higher entorhinal tau. DISCUSSION: Amyloid chronicity provides unique information about cognitive decline and neurofibrillary tangle development and may be useful to investigate preclinical Alzheimer's disease.

Patterns of glucose hypometabolism in Down syndrome resemble sporadic Alzheimer's disease except for the putamen.

INTRODUCTION: Adults with Down syndrome (DS) are predisposed to Alzheimer's disease (AD) and the relationship between cognition and glucose metabolism in this population has yet to be evaluated. METHODS: Adults with DS (N = 90; mean age [standard deviation] = 38.0 [8.30] years) underwent [C-11]Pittsburgh compound B (PiB) and [F-18]fluorodeoxyglucose (FDG) positron emission tomography scans. Associations among amyloid beta (Aß), FDG, and measures of cognition were explored. Interregional FDG metabolic connectivity was assessed to compare cognitively stable DS and mild cognitive impairment/AD (MCI-DS/AD). RESULTS: Negative associations between Aß and FDG were evident in regions affected in sporadic AD. A positive association was observed in the putamen, which is the brain region showing the earliest increases in Aß deposition. Both Aß and FDG were associated with measures of cognition, and metabolic connectivity distinguished cases of MCI-DS/AD from cognitively stable DS. DISCUSSION: Associations among Aß, FDG, and cognition reveal that neurodegeneration in DS resembles sporadic AD with the exception of the putamen, highlighting the usefulness of FDG in monitoring neurodegeneration in DS.

Amyloid and tau imaging biomarkers explain cognitive decline from late middle-age.

This study investigated differences in retrospective cognitive trajectories between amyloid and tau PET biomarker stratified groups in initially cognitively unimpaired participants sampled from the Wisconsin Registry for Alzheimer's Prevention. One hundred and sixty-seven initially unimpaired individuals (baseline age 59 ± 6 years; 115 females) were stratified by elevated amyloid-ß and tau status based on 11C-Pittsburgh compound B (PiB) and 18F-MK-6240 PET imaging. Mixed effects models were used to determine if longitudinal cognitive trajectories based on a composite of cognitive tests including memory and executive function differed between biomarker groups. Secondary analyses investigated group differences for a variety of cross-sectional health and cognitive tests, and associations between 18F-MK-6240, 11C-PiB, and age. A significant group × age interaction was observed with post hoc comparisons indicating that the group with both elevated amyloid and tau pathophysiology were declining approximately three times faster in retrospective cognition compared to those with just one or no elevated biomarkers. This result was robust against various thresholds and medial temporal lobe regions defining elevated tau. Participants were relatively healthy and mostly did not differ between biomarker groups in health factors at the beginning or end of study, or most cognitive measures at study entry. Analyses investigating association between age, MK-6240 and PiB indicated weak associations between age and 18F-MK-6240 in tangle-associated regions, which were negligible after adjusting for 11C-PiB. Strong associations, particularly in entorhinal cortex, hippocampus and amygdala, were observed between 18F-MK-6240 and global 11C-PiB in regions associated with Braak neurofibrillary tangle stages I-VI. These results suggest that the combination of pathological amyloid and tau is detrimental to cognitive decline in preclinical Alzheimer's disease during late middle-age. Within the Alzheimer's disease continuum, middle-age health factors likely do not greatly influence preclinical cognitive decline. Future studies in a larger preclinical sample are needed to determine if and to what extent individual contributions of amyloid and tau affect cognitive decline. 18F-MK-6240 shows promise as a sensitive biomarker for detecting neurofibrillary tangles in preclinical Alzheimer's disease.

Editors' Introduction: Remembering With Others: Conversational Dynamics and Mnemonic Outcomes.

Remembering the past through conversations with others is a uniquely human endeavor. Conversational remembering consists of specific dynamics and can lead to mnemonic outcomes. While conversational dynamics refer to the interactive processes (e.g., the roles speakers and listeners may undertake during the conversation) shaping collaborative remembering, conversational outcomes are about the mnemonic and functional consequences (e.g., forging social bonds) of those processes. Thus, the aim of the present article is to introduce the reader to key concepts and paradigms that have been rigorously developed to empirically investigate the dynamics and outcomes of conversational remembering in cognitive research. The collected review and empirical articles gathered in this topic provide the state-of-the-art in the field.

The Mnemonic Consequences of Jurors' Selective Retrieval During Deliberation.

The jury is a defining component of the American criminal justice system, and the courts largely assume that the collaborative nature of jury deliberations will enhance jurors' memory for important trial information. However, research suggests that this kind of collaboration, although sometimes improving memory, can also lead to incomplete and inaccurate "collective" memories. The present research examines whether jury deliberations, where individuals collaboratively recall and discuss trial evidence to render unanimous verdicts, might shape jurors' memories through the robust phenomena of Within-Individual and Socially Shared Retrieval-Induced Forgetting (WI-RIF and SS-RIF, respectively). The results revealed no WI-RIF or SS-RIF. However, we did find evidence in the direction of Within-Individual and Socially-shared Retrieval Induced Facilitation (WI-RIFA and SS-RIFA, respectively) in speakers' and listeners' narrative and open-ended recall of evidentiary details. The present results are discussed in terms of whether jurors' goals during deliberation and the deliberation structure (e.g., six or more discussants) protect against forgetting, or whether possible methodological issues (e.g., the vast amount of information presented) eliminated WI-RIF and SS-RIF and, in turn, make drawing conclusions surrounding the mnemonic impact of jury deliberation difficult. Regardless, the present results suggest jury deliberations are quite limited in terms of how much evidence is actually discussed compared to the total of what could be discussed, and our methodology provides an ecologically valid baseline for future research to better understand the mnemonic consequences associated with jury deliberations and, in turn, jury decision making.

Imaging neurodegeneration in Down syndrome: brain templates for amyloid burden and tissue segmentation.

The focus of Alzheimer's disease (AD) neuroimaging research has shifted towards an investigation of the earliest stages of AD pathogenesis, which manifests in every young adult with Down syndrome (DS; trisomy 21) resulting from a deterministic genetic predisposition to amyloid precursor protein overproduction. Due to morphological differences in brain structure in the DS population, special consideration must be given to processing pipelines and the use of normative atlases developed for the non-DS population. Further, the use of typical MRI to MRI template spatial normalization is less desirable in this cohort due to a greater presence of motion artefacts in MRI images. The diffuse nature of PiB uptake and comparatively lower spatial resolution of the PET image permits the purposing of this modality as a template for spatial normalization, which can substantially improve the robustness of this procedure in the cases of MRI images with motion. The aim of this work was to establish standardized methods for spatial normalization and tissue type segmentation using DS specific templates in order to perform voxel-wise analyses. A total of 72 adults with DS underwent [11C]PiB PET to assess brain amyloid burden and volumetric MRI imaging. A DS specific PiB template for spatial normalization and a set of DS specific prior probability templates were created with two-pass methods. With implementation of this DS specific PiB template, no participants were excluded due to poor spatial normalization, thus maximizing the sample size for PiB analyses in standardized space. In addition, difference images between prior probability templates created from the general population and the DS population reflected known morphological differences, particularly in the frontal cortex. In conclusion, DS specific templates that account for unique challenges improve spatial normalization and tissue type segmentation, and provide a framework for reliable voxel-wise analysis of AD biomarkers in this atypical population.

In Vivo Characterization and Quantification of Neurofibrillary Tau PET Radioligand 18F-MK-6240 in Humans from Alzheimer Disease Dementia to Young Controls.

Tau PET imaging has potential for elucidating changes in the deposition of neuropathological tau aggregates that are occurring during the progression of Alzheimer disease (AD). This work investigates in vivo kinetics, quantification strategies, and imaging characteristics of a novel tau PET radioligand 18F-MK-6240 in humans. Methods: Fifty-one individuals ranging from cognitively normal young controls to persons with dementia underwent T1-weighted MRI as well as 11C-PiB and 18F-MK-6240 PET imaging. PET data were coregistered to the MRI, and time-activity curves were extracted from regions of interest to assess 18F-MK-6240 kinetics. The pons and inferior cerebellum were investigated as potential reference regions. Reference tissue methods (Logan graphical analysis [LGA] and multilinear reference tissue method [MRTM2]) were investigated for quantification of 18F-MK-6240 distribution volume ratios (DVRs) in a subset of 19 participants. Stability of DVR methods was evaluated using truncated scan durations. SUV ratio (SUVR) estimates were compared with DVR estimates to determine the optimal timing window for SUVR analysis. Parametric SUVR images were used to identify regions of potential off-target binding and to compare binding patterns with neurofibrillary tau staging established in neuropathology literature. Results: SUVs in the pons and the inferior cerebellum indicated consistent clearance across all 51 subjects. LGA and MRTM2 DVR estimates were similar, with LGA slightly underestimating DVR compared with MRTM2. DVR estimates remained stable when truncating the scan duration to 60 min. SUVR determined 70-90 min after injection of 18F-MK-6240 indicated linearity near unity when compared with DVR estimates and minimized potential spill-in from uptake outside the brain. 18F-MK-6240 binding patterns in target regions were consistent with neuropathological neurofibrillary tau staging. Off-target binding regions included the ethmoid sinus, clivus, meninges, substantia nigra, but not the basal ganglia or choroid plexus. Conclusion:18F-MK-6240 is a promising PET radioligand for in vivo imaging of neurofibrillary tau aggregates in AD with minimal off-target binding in the human brain.

From Conversations to Digital Communication: The Mnemonic Consequences of Consuming and Producing Information via Social Media.

Social media has become one of the most powerful and ubiquitous means by which individuals curate, share, and communicate information with their friends, family, and the world at large. Indeed, 90% of the American adolescents are active social media users, as well as 65% of American adults (Perrin, 2015; see also Duggan & Brenner, 2013). Despite this, psychologists are only beginning to understand the mnemonic consequences associated with social media use. In this article, we will distill this nascent literature by focusing on two primary factors: the type of information (personal vs. public) and the role (producer vs. consumer) individuals play when engaging with social media. In particular, we will highlight research examining induced forgetting for personal information as well as false memories and truthiness for public information. We will end by providing some tentative conclusions and a discussion of areas in need of additional research that will provide a more holistic understanding of the mnemonic consequences associated with social media use.

Fluctuating confidence: the dynamic consequences of true/false affirmatives and denials on how a listener appraises their personal past.

The present study examined the mnemonic consequences of true/false denials and affirmatives on how a listener appraises their personal past. To this end, participants (listeners) rated the extent to which they were confident certain events occurred during their childhood. They rated these events both before and after a confederate (speaker) denied or affirmed the occurrence of four different childhood events each, for a total of eight "rehearsed" events. For each set (denials and affirmatives) of events, half were true and half were false. In turn, this created four types of events (two each): true denials, true affirmatives, false denials, and false affirmatives. Additionally, half of the participants were told that the speaker was provided independent information about the veracity of the event's occurrence ("expert" condition). Overall, listeners were less confident in the occurrence of false denial events, but more so when they believed the speaker to be more knowledgeable of the listeners memories, more confident in false affirmative events and, counter intuitively, more confident in the occurrence of true denial events. These results underscore the importance of a nuanced approach to the mnemonic consequences of true and false denials and affirmations in the course of social interactions.

Alzheimer-Like Pattern of Hypometabolism Emerges with Elevated Amyloid-ß Burden in Down Syndrome.

BACKGROUND: The Down syndrome (DS) population is genetically predisposed to amyloid-ß protein precursor overproduction and Alzheimer's disease (AD). OBJECTIVE: The temporal ordering and spatial association between amyloid-ß, glucose metabolism, and gray matter (GM) volume in the DS population can provide insight into those associations in the more common sporadic AD. METHODS: Twenty-four adults (13 male, 11 female; 39±7 years) with DS underwent [11C]PiB, [18F]FDG, and volumetric MRI scans. Voxel-wise associations between PiB SUVR, FDG SUVR, and GM volume were investigated, with and without individual adjustments for variables of interest. RESULTS: Positive associations of PiB and age were widespread throughout the neocortex and striatum. Negative associations of FDG and age (frontal, parietal, and temporal cortex) and of GM volume and age (frontal and insular cortex) were observed. PiB and FDG were negatively associated in parietal cortex, after adjustment for GM volume. CONCLUSIONS: In adults with DS, early amyloid-ß accumulation in the striatum is divergent from sporadic AD; however, despite the early striatal amyloid-ß, glucose hypometabolism was confined to the typical AD-associated regions, which occurs similarly in autosomal dominant AD. Importantly, the glucose hypometabolism was not explained solely by increased partial volume effect due to GM volume reductions.

Human biodistribution and dosimetry of [18F]nifene, an α4ß2* nicotinic acetylcholine receptor PET tracer.

INTRODUCTION: The α4ß2* nicotinic acetylcholine receptor (nAChR) system is implicated in many neuropsychiatric pathologies. [18F]Nifene is a positron emission tomography (PET) ligand that has shown promise for in vivo imaging of the α4ß2* nAChR system in preclinical models and humans. This work establishes the radiation burden associated with [18F]nifene PET scans in humans. METHODS: Four human subjects (2M, 2F) underwent whole-body PET/CT scans to determine the human biodistribution of [18F]nifene. Source organs were identified and time-activity-curves (TACs) were extracted from the PET time-series. Dose estimates were calculated for each subject using OLINDA/EXM v1.1. RESULTS: [18F]Nifene was well tolerated by all subjects with no adverse events reported. The mean whole-body effective dose was 28.4±3.8 mSv/MBq without bladder voiding, and 22.6±1.9 mSv/MBq with hourly micturition. The urinary bladder radiation dose limited the maximum injected dose for a single scan to 278 MBq without urinary bladder voiding, and 519 MBq with hourly voiding. CONCLUSIONS: [18F]Nifene is a safe PET radioligand for imaging the α4ß2* nAChR system in humans. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: This works presents human internal dosimetry for [18F]nifene in humans for the first time. These results facilitate safe development of future [18F]nifene studies to image the α4ß2* nAChR system in humans.