Using the Schmahmann Syndrome Scale to Assess Cognitive Impairment in Young Adults with Metabolic Syndrome: a Hypothesis-Generating Report.

The posterior cerebellum is the most significantly compromised brain structure in individuals with metabolic syndrome (MetS) (Hum Brain Mapp 40(12):3575-3588, 2019). In light of this, we hypothesized that cognitive decline reported in patients with MetS is likely related to posterior cerebellar atrophy. In this study, we performed a post hoc analyses using T1-weighted magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) in the form of voxel-wise tract-based spatial statistics (TBSS), biometric, and psychometric data from young participants with (n = 52, aged 18-35 years) and without MetS (n = 52, aged 18-35 years). To test the predictive value of components of the Schmahmann syndrome scale (SSS), also known as the cerebellar cognitive affective syndrome scale, we used structural equation modeling to adapt available psychometric scores in our participant sample to the SSS and compare them to the composite score of all psychometric data available. Our key findings point to a statistically significant correlation between TBSS fractional anisotropy (FA) values from DTI and adapted SSS psychometric scores in individuals with MetS (r2 = .139, 95% CI = 0.009, .345). This suggests that the SSS could be applied to assess cognitive and likely neuroanatomical effects associated with MetS. We strongly suggest that future work aimed at investigating the neurocognitive effects of MetS and related comorbidities (i.e., dyslipidemia, diabetes, obesity) would benefit from implementing and further exploring the validity of the SSS in this patient population.

A neural signature of metabolic syndrome.

That metabolic syndrome (MetS) is associated with age-related cognitive decline is well established. The neurobiological changes underlying these cognitive deficits, however, are not well understood. The goal of this study was to determine whether MetS is associated with regional differences in gray-matter volume (GMV) using a cross-sectional, between-group contrast design in a large, ethnically homogenous sample. T1-weighted MRIs were sampled from the genetics of brain structure (GOBS) data archive for 208 Mexican-American participants: 104 participants met or exceeded standard criteria for MetS and 104 participants were age- and sex-matched metabolically healthy controls. Participants ranged in age from 18 to 74 years (37.3 ± 13.2 years, 56.7% female). Images were analyzed in a whole-brain, voxel-wise manner using voxel-based morphometry (VBM). Three contrast analyses were performed, a whole sample analysis of all 208 participants, and two post hoc half-sample analyses split by age along the median (35.5 years). Significant associations between MetS and decreased GMV were observed in multiple, spatially discrete brain regions including the posterior cerebellum, brainstem, orbitofrontal cortex, bilateral caudate nuclei, right parahippocampus, right amygdala, right insula, lingual gyrus, and right superior temporal gyrus. Age, as shown in the post hoc analyses, was demonstrated to be a significant covariate. A further functional interpretation of the structures exhibiting lower GMV in MetS reflected a significant involvement in reward perception, emotional valence, and reasoning. Additional studies are needed to characterize the influence of MetS's individual clinical components on brain structure and to explore the bidirectional association between GMV and MetS.

A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment.

Nicotinamide riboside (NR) increases blood levels of NAD+, a cofactor central to energy metabolism, and improves brain function in some rodent models of neurodegeneration. We conducted a placebo-controlled randomized pilot study with the primary objective of determining safety of NR in older adults with mild cognitive impairment (MCI). Twenty subjects with MCI were randomized to receive placebo or NR using dose escalation to achieve, and maintain, a final dose of 1 g/day over a 10-week study duration. The primary outcome was post-treatment change from baseline measures of cognition (Montreal Cognitive Assessment, MoCA). Predefined secondary outcomes included post-treatment changes in cerebral blood flow (CBF); blood NAD+ levels; and additional neurocognitive, psychometric, and physical performance tests. DNA methylation was assessed in peripheral blood mononuclear cells (PBMCs) as an exploratory outcome. The target NR dose was safely achieved as evidenced by a 2.6-fold increase in blood NAD+ in the NR group (p < 0.001, 95% CI [17.77, 43.49]) with no between-group difference in adverse event reporting. MoCA and other neurocognitive and psychometric metrics remained stable throughout the study. NR reduced CBF in the default mode network (DMN) with greatest differences observed in the left inferior parietal lobe (IPL) (DMN p = 0.013, µ = 0.92, 95% CI [0.23, 1.62]; left IPL p = 0.009, µ = 1.66, 95% CI [0.5, 2.82]). Walking speed in the placebo group significantly improved across the study duration suggestive of a practice effect but did not change in the NR group (p = 0.0402 and p = 0.4698, respectively). Other secondary outcome measures remained stable. Global methylation analyses indicated a modest NR-associated increase in DNA methylation and concomitant reduction in epigenetic age as measured by PhenoAge and GrimAge epigenetic clock analyses. In summary, NR significantly increased blood NAD+ concentrations in older adults with MCI. NR was well tolerated and did not alter cognition. While CBF was reduced by NR treatment, statistical significance would not have withstood multiple comparisons correction. A larger trial of longer duration is needed to determine the potential of NR as a strategy to improve cognition and alter CBF in older adults with MCI. ClinicalTrials.gov NCT02942888.

The Pedagogy of Pedagogues for Sexual Education in Riobamba, Ecuador: A Pilot Approach to Training Sexual Education Facilitators in a Latin American and Spanish Language Setting.

Educational efforts to reduce global rates of adolescent pregnancy vary widely with a significant deficiency found in the domain of sex education facilitator training. In this study, we sought to establish a pilot approach to comprehensive sex education facilitator training as applied in Riobamba, Ecuador. The approach was aligned with UNESCO recommendations for training facilitators using an adapted version of the U.S.-based Big Decisions curriculum. Four internationally recruited bilingual instructors led a six-day (27-hour) intensive training-of-facilitators programme with twenty trainees using the Big Decisions sex education curriculum. Quantitative and qualitative analyses were conducted using various approaches: anonymised and pre/post-self-assessments, daily feedback surveys of self and instructors, and facilitation practice evaluations. Responses to anonymised surveys indicated improved self-perceived confidence in teaching each curriculum section. More objective pre- and post-teach-back evaluations showed improved ability to teach randomly assigned lessons as assessed by trainers. The pedagogy of facilitator training in comprehensive sex education seeks to combine evidence-informed and culturally appropriate approaches to training facilitators under unique local conditions using adapted assessment tools. This project revealed important culturally relevant insights that would be beneficial to the future training of comprehensive sex education facilitators working within culturally conservative communities, and Latin America in particular.

Metabolic syndrome predictors of brain gray matter volume in an age-stratified community sample of 776 Mexican- American adults: Results from the genetics of brain structure image archive.

Introduction: This project aimed to investigate the association between biometric components of metabolic syndrome (MetS) with gray matter volume (GMV) obtained with magnetic resonance imaging (MRI) from a large cohort of community-based adults (n = 776) subdivided by age and sex and employing brain regions of interest defined previously as the "Neural Signature of MetS" (NS-MetS). Methods: Lipid profiles, biometrics, and regional brain GMV were obtained from the Genetics of Brain Structure (GOBS) image archive. Participants underwent T1-weighted MR imaging. MetS components (waist circumference, fasting plasma glucose, triglycerides, HDL cholesterol, and blood pressure) were defined using the National Cholesterol Education Program Adult Treatment Panel III. Subjects were grouped by age: early adult (18-25 years), young adult (26-45 years), and middle-aged adult (46-65 years). Linear regression modeling was used to investigate associations between MetS components and GMV in five brain regions comprising the NS-MetS: cerebellum, brainstem, orbitofrontal cortex, right insular/limbic cluster and caudate. Results: In both men and women of each age group, waist circumference was the single component most strongly correlated with decreased GMV across all NS-MetS regions. The brain region most strongly correlated to all MetS components was the posterior cerebellum. Conclusion: The posterior cerebellum emerged as the region most significantly associated with MetS individual components, as the only region to show decreased GMV in young adults, and the region with the greatest variance between men and women. We propose that future studies investigating neurological effects of MetS and its comorbidities-namely diabetes and obesity-should consider the NS-MetS and the differential effects of age and sex.

Creutzfeldt-Jakob Disease: In-hospital demographics report of national data in the United States from 2016 and review of a rapidly-progressive case.

BACKGROUND: This report highlights a rapidly progressive case of Creutzfeldt-Jakob Disease (CJD) whose time from symptom onset to death spanned less than two months. We also explore the most recently available in-patient demographics data for discharges with CJD in the United States. METHODS: We reviewed a CJD case and systematically analyzed a retrospective cohort of CJD discharges using the Healthcare Cost and Utilization Project (HCUP) to evaluate the existing national data on the status of CJD demographics and dispositions in the United States in 2016. RESULTS: An estimated total of 710 hospital discharges with a diagnosis of CJD were seen across the United States in 2016. According to HCUP, the average age of patients was 66.15 ±â€¯11.54 years with 48.6 % female. Average time to intubation from admission to hospital was 4.71 ±â€¯7.32 days with a rate of intubation of 6.34 %. The mean hospital cost was $19,901.25 ± $18,743.48. The rate of in-hospital mortality was 8.45 %. No significant geographical differences were noted (p = 0.49). No significant differences were seen among incidence in specific ethnic groups (p = 0.33) or income quartiles (p = 0.90). CONCLUSIONS: Our data shows that the incidence of CJD in 2016 appears to be equally distributed among individuals in the United States by demographic categories. Additionally, our case-study from 2019 illustrates an important example for diagnosing a rapidly-progressing case of CJD.

The hippocampal network model: A transdiagnostic metaconnectomic approach.

Purpose: The hippocampus plays a central role in cognitive and affective processes and is commonly implicated in neurodegenerative diseases. Our study aimed to identify and describe a hippocampal network model (HNM) using trans-diagnostic MRI data from the BrainMap® database. We used meta-analysis to test the network degeneration hypothesis (NDH) (Seeley et al., 2009) by identifying structural and functional covariance in this hippocampal network. Methods: To generate our network model, we used BrainMap's VBM database to perform a region-to-whole-brain (RtWB) meta-analysis of 269 VBM experiments from 165 published studies across a range of 38 psychiatric and neurological diseases reporting hippocampal gray matter density alterations. This step identified 11 significant gray matter foci, or nodes. We subsequently used meta-analytic connectivity modeling (MACM) to define edges of structural covariance between nodes from VBM data as well as functional covariance using the functional task-activation database, also from BrainMap. Finally, we applied a correlation analysis using Pearson's r to assess the similarities and differences between the structural and functional covariance models. Key findings: Our hippocampal RtWB meta-analysis reported consistent and significant structural covariance in 11 key regions. The subsequent structural and functional MACMs showed a strong correlation between HNM nodes with a significant structural-functional covariance correlation of r = .377 (p = .000049). Significance: This novel method of studying network covariance using VBM and functional meta-analytic techniques allows for the identification of generalizable patterns of functional and structural abnormalities pertaining to the hippocampus. In accordance with the NDH, this framework could have major implications in studying and predicting spatial disease patterns using network-based assays.

Long-term hormonal promotion overcomes genetic resistance to mammary cancer.

It is well known that ovarian steroids estradiol and progesterone play a vital role in the development of mammary cancer. Here, using the genetically highly resistant Copenhagen rats we demonstrate that sustained exogenous treatment with estradiol and progesterone overcomes genetic resistance to mammary cancer. It has been demonstrated that Copenhagen rats develop preneoplastic lesions upon exposure to carcinogens. However, these preneoplastic lesions fail to progress to ductal carcinomas in situ or overt mammary carcinomas. The preneoplastic lesions eventually decrease in number and are absent by 60 days post-carcinogen treatment. In the present study, we exposed 7-week-old female Copenhagen rats to N-methyl-N-nitrosourea (MNU; 50mg/kg BW). Immediately after MNU treatment the rats were divided into the following groups: (1) control; (2) 30 mg estradiol 17ß; (3) 30 mg progesterone; and (4) 30 mg estradiol 17ß plus 30 mg progesterone. All hormone treatments were administered via individual silastic pellets for a period of 9 months post-carcinogen treatment. The control animals displayed a low incidence of mammary cancer (10%). Hormone treatments produced significantly higher incidences of mammary cancer, with estradiol at 50%, progesterone at 65% and estradiol plus progesterone at 90%. Hormone treatment sustained the growth of the lesions induced by MNU by increasing expression of Areg, Bcl-2, Ccnd-1 and Vegf genes, while decreasing expression of Bad, Bax, Casp 3, 8, 9 and p53 genes. Furthermore, hormone treatment increased CCND-1 and PARP proteins levels. The data clearly demonstrates that hormonal environment supports mammary cancer progression by increasing cell proliferation, and angiogenesis while inhibiting apoptosis.