Utility of perfusion PET measures to assess neuronal injury in Alzheimer's disease

Introduction: 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is commonly used to estimate neuronal injury in Alzheimer's disease (AD). Here, we evaluate the utility of dynamic PET measures of perfusion using 11C-Pittsburgh compound B (PiB) to estimate neuronal injury in comparison to FDG PET. Methods: FDG, early frames of PiB images, and relative PiB delivery rate constants (PiB-R1) were obtained from 110 participants from the Dominantly Inherited Alzheimer Network. Voxelwise, regional cross-sectional, and longitudinal analyses were done to evaluate the correlation between images and estimate the relationship of the imaging biomarkers with estimated time to disease progression based on family history. Results: Metabolism and perfusion images were spatially correlated. Regional PiB-R1 values and FDG, but not early frames of PiB images, significantly decreased in the mutation carriers with estimated year to onset and with increasing dementia severity. Discussion: Hypometabolism estimated by PiB-R1 may provide a measure of brain perfusion without increasing radiation exposure

Sexual arousal: the correspondence of eyes and genitals.

Men's, more than women's, sexual responses may include a coordination of several physiological indices in order to build their sexual arousal to relevant targets. Here, for the first time, genital arousal and pupil dilation to sexual stimuli were simultaneously assessed. These measures corresponded more strongly with each other, subjective sexual arousal, and self-reported sexual orientation in men than women. Bisexual arousal is more prevalent in women than men. We therefore predicted that if bisexual-identified men show bisexual arousal, the correspondence of their arousal indices would be more female-typical, thus weaker, than for other men. Homosexual women show more male-typical arousal than other women; hence, their correspondence of arousal indices should be stronger than for other women. Findings, albeit weak in effect, supported these predictions. Thus, if sex-specific patterns are reversed within one sex, they might affect more than one aspect of sexual arousal. Because pupillary responses reflected sexual orientation similar to genital responses, they offer a less invasive alternative for the measurement of sexual arousal

Measurement of diets that are healthy, environmentally sustainable, affordable, and equitable: A scoping review of metrics, findings, and research gaps

IntroductionResearch on the impacts of dietary patterns on human and planetary health is a rapidly growing field. A wide range of metrics, datasets, and analytical techniques has been used to explore the role of dietary choices/constraints in driving greenhouse gas (GHG) emissions, environmental degradation, health and disease outcomes, and the affordability of food baskets. Many argue that each domain is important, but few have tackled all simultaneously in analyzing diet-outcome relationships.MethodsThis paper reviews studies published between January 2015 and December 2021 (inclusive) that examined dietary patterns in relation to at least two of the following four thematic pillars: (i) planetary health, including, climate change, environmental quality, and natural resource impacts, (ii) human health and disease, (iii) economic outcomes, including diet cost/affordability, and (iv) social outcomes, e.g., wages, working conditions, and culturally relevant diets. We systematically screened 2,425 publications by title and abstract and included data from 42 eligible publications in this review.ResultsMost dietary patterns used were statistically estimated or simulated rather than observed. A rising number of studies consider the cost/affordability of dietary scenarios in relation to optimized environmental and health outcomes. However, only six publications incorporate social sustainability outcomes, which represents an under-explored dimension of food system concerns.DiscussionThis review suggests a need for (i) transparency and clarity in datasets used and analytical methods; (ii) explicit integration of indicators and metrics linking social and economic issues to the commonly assessed diet-climate-planetary ecology relationships; (iii) inclusion of data and researchers from low- and middle-income countries; (iv) inclusion of processed food products to reflect the reality of consumer choices globally; and (v) attention to the implications of findings for policymakers. Better understanding is urgently needed on dietary impacts on all relevant human and planetary domains simultaneously

Accurate detection of spontaneous seizures using a generalized linear model with external validation

Objective Seizure detection is a major facet of electroencephalography (EEG) analysis in neurocritical care, epilepsy diagnosis and management, and the instantiation of novel therapies such as closed-loop stimulation or optogenetic control of seizures. It is also of increased importance in high-throughput, robust, and reproducible pre-clinical research. However, seizure detectors are not widely relied upon in either clinical or research settings due to limited validation. In this study, we create a high-performance seizure-detection approach, validated in multiple data sets, with the intention that such a system could be available to users for multiple purposes. Methods We introduce a generalized linear model trained on 141 EEG signal features for classification of seizures in continuous EEG for two data sets. In the first (Focal Epilepsy) data set consisting of 16 rats with focal epilepsy, we collected 1012 spontaneous seizures over 3 months of 24/7 recording. We trained a generalized linear model on the 141 features representing 20 feature classes, including univariate and multivariate, linear and nonlinear, time, and frequency domains. We tested performance on multiple hold-out test data sets. We then used the trained model in a second (Multifocal Epilepsy) data set consisting of 96 rats with 2883 spontaneous multifocal seizures. Results From the Focal Epilepsy data set, we built a pooled classifier with an Area Under the Receiver Operating Characteristic (AUROC) of 0.995 and leave-one-out classifiers with an AUROC of 0.962. We validated our method within the independently constructed Multifocal Epilepsy data set, resulting in a pooled AUROC of 0.963. We separately validated a model trained exclusively on the Focal Epilepsy data set and tested on the held-out Multifocal Epilepsy data set with an AUROC of 0.890. Latency to detection was under 5 seconds for over 80% of seizures and under 12 seconds for over 99% of seizures. Significance This method achieves the highest performance published for seizure detection on multiple independent data sets. This method of seizure detection can be applied to automated EEG analysis pipelines as well as closed loop interventional approaches, and can be especially useful in the setting of research using animals in which there is an increased need for standardization and high-throughput analysis of large number of seizures

Comparing cortical signatures of atrophy between late-onset and autosomal dominant Alzheimer disease

Defining a signature of cortical regions of interest preferentially affected by Alzheimer disease (AD) pathology may offer improved sensitivity to early AD compared to hippocampal volume or mesial temporal lobe alone. Since late-onset Alzheimer disease (LOAD) participants tend to have age-related comorbidities, the younger-onset age in autosomal dominant AD (ADAD) may provide a more idealized model of cortical thinning in AD. To test this, the goals of this study were to compare the degree of overlap between the ADAD and LOAD cortical thinning maps and to evaluate the ability of the ADAD cortical signature regions to predict early pathological changes in cognitively normal individuals. We defined and analyzed the LOAD cortical maps of cortical thickness in 588 participants from the Knight Alzheimer Disease Research Center (Knight ADRC) and the ADAD cortical maps in 269 participants from the Dominantly Inherited Alzheimer Network (DIAN) observational study. Both cohorts were divided into three groups: cognitively normal controls (nADRC = 381; nDIAN = 145), preclinical (nADRC = 153; nDIAN = 76), and cognitively impaired (nADRC = 54; nDIAN = 48). Both cohorts underwent clinical assessments, 3T MRI, and amyloid PET imaging with either 11C-Pittsburgh compound B or 18F-florbetapir. To generate cortical signature maps of cortical thickness, we performed a vertex-wise analysis between the cognitively normal controls and impaired groups within each cohort using six increasingly conservative statistical thresholds to determine significance. The optimal cortical map among the six statistical thresholds was determined from a receiver operating characteristic analysis testing the performance of each map in discriminating between the cognitively normal controls and preclinical groups. We then performed within-cohort and cross-cohort (e.g. ADAD maps evaluated in the Knight ADRC cohort) analyses to examine the sensitivity of the optimal cortical signature maps to the amyloid levels using only the cognitively normal individuals (cognitively normal controls and preclinical groups) in comparison to hippocampal volume. We found the optimal cortical signature maps were sensitive to early increases in amyloid for the asymptomatic individuals within their respective cohorts and were significant beyond the inclusion of hippocampus volume, but the cortical signature maps performed poorly when analyzing across cohorts. These results suggest the cortical signature maps are a useful MRI biomarker of early AD-related neurodegeneration in preclinical individuals and the pattern of decline differs between LOAD and ADAD.Fil: Dincer, Aylin. Washington University in St. Louis; Estados UnidosFil: Gordon, Brian A.. Washington University in St. Louis; Estados UnidosFil: Hari-Raj, Amrita. Ohio State University; Estados UnidosFil: Keefe, Sarah J.. Washington University in St. Louis; Estados UnidosFil: Flores, Shaney. Washington University in St. Louis; Estados UnidosFil: McKay, Nicole S.. Washington University in St. Louis; Estados UnidosFil: Paulick, Angela M.. Washington University in St. Louis; Estados UnidosFil: Shady Lewis, Kristine E.. University of Kentucky; Estados UnidosFil: Feldman, Rebecca L.. Washington University in St. Louis; Estados UnidosFil: Hornbeck, Russ C.. Washington University in St. Louis; Estados UnidosFil: Allegri, Ricardo Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Ances, Beau M.. Washington University in St. Louis; Estados UnidosFil: Berman, Sarah B.. University of Pittsburgh; Estados UnidosFil: Brickman, Adam M.. Columbia University; Estados UnidosFil: Brooks, William S.. Neuroscience Research Australia; Australia. University of New South Wales; AustraliaFil: Cash, David M.. UCL Queen Square Institute of Neurology; Reino UnidoFil: Chhatwal, Jasmeer P.. Harvard Medical School; Estados UnidosFil: Farlow, Martin R.. Indiana University; Estados UnidosFil: Fougère, Christian la. German Center for Neurodegenerative Diseases; Alemania. University Hospital of Tübingen; AlemaniaFil: Fox, Nick C.. UCL Queen Square Institute of Neurology; Reino UnidoFil: Fulham, Michael J.. Royal Prince Alfred Hospital; Australia. University of Sydney; AustraliaFil: Jack, Clifford R.. Mayo Clinic; Estados UnidosFil: Joseph-Mathurin, Nelly. Washington University in St. Louis; Estados UnidosFil: Karch, Celeste M.. Washington University in St. Louis; Estados UnidosFil: Lee, Athene. University Brown; Estados UnidosFil: Levin, Johannes. German Center for Neurodegenerative Diseases; Alemania. Ludwig Maximilians Universitat; Alemania. Munich Cluster for Systems Neurology; AlemaniaFil: Masters, Colin L.. University of Melbourne; AustraliaFil: McDade, Eric M.. Washington University in St. Louis; Estados UnidosFil: Oh, Hwamee. University Brown; Estados UnidosFil: Perrin, Richard J.. Washington University in St. Louis; Estados Unido

Pattern and degree of individual brain atrophy predicts dementia onset in dominantly inherited Alzheimer\u27s disease

Introduction: Asymptomatic and mildly symptomatic dominantly inherited Alzheimer\u27s disease mutation carriers (DIAD-MC) are ideal candidates for preventative treatment trials aimed at delaying or preventing dementia onset. Brain atrophy is an early feature of DIAD-MC and could help predict risk for dementia during trial enrollment. Methods: We created a dementia risk score by entering standardized gray-matter volumes from 231 DIAD-MC into a logistic regression to classify participants with and without dementia. The score\u27s predictive utility was assessed using Cox models and receiver operating curves on a separate group of 65 DIAD-MC followed longitudinally. Results: Our risk score separated asymptomatic versus demented DIAD-MC with 96.4% (standard error = 0.02) and predicted conversion to dementia at next visit (hazard ratio = 1.32, 95% confidence interval [CI: 1.15, 1.49]) and within 2 years (area under the curve = 90.3%, 95% CI [82.3%-98.2%]) and improved prediction beyond established methods based on familial age of onset. Discussion: Individualized risk scores based on brain atrophy could be useful for establishing enrollment criteria and stratifying DIAD-MC participants for prevention trials

Male bisexual arousal: A matter of curiosity?

Conflicting evidence exists regarding whether bisexual-identified men are sexually aroused to both men and women. We hypothesized that a distinct characteristic, level of curiosity about sexually diverse acts, distinguishes bisexual-identified men with and without bisexual arousal. Study 1 assessed men's (n = 277) sexual arousal via pupil dilation to male and female sexual stimuli. Bisexual men were, on average, higher in their sexual curiosity than other men. Despite this general difference, only bisexual-identified men with elevated sexual curiosity showed bisexual arousal. Those lower in curiosity had responses resembling those of homosexual men. Study 2 assessed men's (n = 72) sexual arousal via genital responses and replicated findings of Study 1. Study 3 provided information on the validity on our measure of sexual curiosity by relating it to general curiosity and sexual sensation seeking (n = 83). Based on their sexual arousal and personality, at least two groups of men identify as bisexual

Gay, Mostly Gay, or Bisexual Leaning Gay? An Exploratory Study Distinguishing Gay Sexual Orientations Among Young Men

This exploratory study assessed physiological, behavioral, and self-report measures of sexual and romantic indicators of sexual orientation identities among young men (mean age = 21.9 years) with predominant same-sex sexual and romantic interests: those who described themselves as bisexual leaning gay (n = 11), mostly gay (n = 17), and gay (n = 47). Although they were not significantly distinguishable based on physiological (pupil dilation) responses to nude stimuli, on behavioral and self-report measures a descending linear trend toward the less preferred sex (female) was significant regarding sexual attraction, fantasy, genital contact, infatuation, romantic relationship, sex appeal, and gazing time to the porn stimuli. Results supported a continuum of sexuality with distinct subgroups only for the self-report measure of sexual attraction. The other behavioral and self-report measures followed the same trend but did not significantly differ between the bisexual leaning gay and mostly gay groups, likely the result of small sample size. Results suggest that romantic indicators are as good as sexual measures in assessing sexual orientation and that a succession of logically following groups from bisexual leaning gay, mostly gay, to gay. Whether these three groups are discrete or overlapping needs further research

Trapping \u3ci\u3ePhyllophaga \u3c/i\u3espp. (Coleoptera: Scarabaeidae: Melolonthinae) in the United States and Canada using sex attractants.

The sex pheromone of the scarab beetle, Phyllophaga anxia, is a blend of the methyl esters of two amino acids, L-valine and L-isoleucine. A field trapping study was conducted, deploying different blends of the two compounds at 59 locations in the United States and Canada. More than 57,000 males of 61 Phyllophaga species (Coleoptera: Scarabaeidae: Melolonthinae) were captured and identified. Three major findings included: (1) widespread use of the two compounds [of the 147 Phyllophaga (sensu stricto) species found in the United States and Canada, males of nearly 40% were captured]; (2) in most species intraspecific male response to the pheromone blends was stable between years and over geography; and (3) an unusual pheromone polymorphism was described from P. anxia. Populations at some locations were captured with L-valine methyl ester alone, whereas populations at other locations were captured with L-isoleucine methyl ester alone. At additional locations, the L-valine methyl ester-responding populations and the L-isoleucine methyl ester-responding populations were both present, producing a bimodal capture curve. In southeastern Massachusetts and in Rhode Island, in the United States, P. anxia males were captured with blends of L-valine methyl ester and L-isoleucine methyl ester