Diabetes status and cognitive function in middle-aged and older adults in the Canadian longitudinal study on aging.

Objectives: Diabetes is recognized as a significant risk factor for cognitive impairment. However, this association has not been thoroughly examined using large-scale population-based datasets in the Canadian context. The objective of this study was to investigate the potential association between cognitive function and diabetes in a large population-based sample of middle-aged and older Canadians. Methods: We utilized baseline data from the Canadian Longitudinal Study on Aging (N=30,097) to test our hypotheses, using five indicators of cognitive function (animal fluency, Stroop interference, reaction time, immediate and delayed memory recall). We conducted multivariate multivariable linear regression and subsequently performed tests for moderation analysis with lifestyle factors and health status. Results: The analysis revealed that type 2 diabetes (T2DM) was associated with lower performance on most cognitive tasks, including those assessing executive function (b=0.60, 95% CI 0.31 to 0.90), reaction time (b=16.94, 95% CI 9.18 to 24.70), immediate memory recall (b=-0.10, 95% CI -0.18 to -0.02), and delayed memory recall (b=-0.12, 95% CI -0.21 to -0.02). However, no significant association was observed between other types of diabetes and cognitive performance. Moderation effects were largely null for T2DM, with the exception of alcohol intake for reaction time, and physical activity for animal fluency. Conclusions: The study showed that individuals with T2DM exhibit poor performance on tasks that assess executive function, reaction time, and memory. Therefore, optimizing cognitive health among individuals with T2DM should be a priority in primary care. Additionally, further studies should examine this association using longitudinal data.

Clinical efficacy of endovascular treatment approach in patients with carotid cavernous fistula: A systematic review and meta-analysis.

Background and objectives: Carotid-cavernous fistulas (CCFs) represent a group of rare, abnormal arteriovenous communications between the carotid arterial system and the cavernous sinuses (CS). CCFs often produce ophthalmologic symptoms related to increased CS pressures and retrograde venous drainage of the eye. Although endovascular occlusion remains the preferred treatment for symptomatic or high-risk CCFs, most of the data for these lesions is limited to small, single-center series. As such, we performed a systematic review and meta-analysis evaluating endovascular occlusions of CCFs to determine any differences in clinical outcomes based on presentation, fistula type, and treatment paradigm. Method: A retrospective review of all studies discussing the endovascular treatment of CCFs published through March 2023 was conducted using PubMed, Scopus, Web of Science, and Embase databases. A total of 36 studies were included in the meta-analysis. Data from the selected articles were extracted and analyzed using Stata software version 14. Results: 1494 patients were included. 55.08% were female and the mean age of the cohort was 48.10 years. A total number of 1516 fistulas underwent endovascular treatment, 48.05% of which were direct and 51.95% of which were indirect. 87.17% of CCFs were secondary to a known trauma while 10.18% were spontaneous. The most common presenting symptoms were 89% exophthalmos (95% CI: 78.0-100.0; I2 = 75.7%), 84% chemosis (95% CI: 79.0-88.0; I2 = 91.6%), 79% proptosis (95% CI: 72.0-86.0; I2 = 91.8%), 75.0% bruits (95% CI: 67.0-82.0; I2 = 90.7%), 56% diplopia (95% CI: 42.0-71.0; I2 = 92.3%), 49% cranial nerve palsy (95% CI: 32.0-66.0; I2 = 95.1%), 39% visual decline (95% CI: 32.0-45.0; I2 = 71.4%), 32% tinnitus (95% CI: 6.0-58.0; I2 = 96.7%), 29% elevated intraocular pain (95% CI: 22.0-36.0; I2 = 0.0%), 31% orbital or pre-orbital pain (95% CI: 14.0-48.0; I2 = 89.9%) and 24% headache (95% CI: 13.0-34.0; I2 = 74.98%). Coils, balloons, and stents were the three most used embolization methods respectively. Immediate complete occlusion of the fistula was seen in 68% of cases and complete remission was seen in 82%. Recurrence of CCF occurred in only 35% of the patients. Cranial nerve paralysis after treatment was observed in 7% of the cases. Conclusions: Exophthalmos, Chemosis, proptosis, bruits, cranial nerve palsy, diplopia, orbital and periorbital pain, tinnitus, elevated intraocular pressure, visual decline and headache are the most common clinical manifestations of CCFs. The majority of endovascular treatments involved coiling, balloons and onyx and a high percentage of CCF patients experienced complete remission with the improvement of their clinical symptoms.

Chronic early-life social isolation enhances spatial memory in male and female rats.

Social adversity during childhood and adolescence can alter brain development in ways that may increase the likelihood of many prominent mental illnesses. To determine the underlying mechanisms, several animal models have been developed, such as Chronic Early-Life Social Isolation (CELSI), which sees rats isolated for several weeks after weaning. Although such a paradigm does cause many consistent changes in adult behaviour, one area where uncertainty exists concerns its effect upon hippocampal-dependent learning and memory. To help sort out how CELSI affects spatial learning and memory, male and female siblings from 15 Sprague-Dawley rat litters were stratified by sex and then randomly assigned to either group-housing (3 animals/cage), or social isolation (1 animal/cage) for 7 weeks. Spatial learning and memory were then tested over 5 days using the Morris water maze. Next, the animals were euthanised, and stress-sensitive biometrics, including serum corticosterone levels, were collected. Lastly, to determine whether CELSI affected neural cell density, the expression of key neuronal and glial proteins (such as PSD-95 and GFAP, respectively) was assessed in isolated hippocampal tissue using immunoblotting. Notably, both male and female rats that had experienced post-weaning social isolation displayed stronger spatial learning and memory abilities than their group-housed counterparts. As well, socially isolated male rats exhibited a clear increase in expression of PSD-95. However, housing condition did not seem to affect either stress-sensitive biometrics, or hippocampal GFAP expression. Our results support the possibility that CELSI may enhance some aspects of hippocampal-dependent behaviour in a fashion similar among male and female rats.

Immune defense in Drosophila melanogaster depends on diet, sex, and mating status.

Immune defense is a complex trait that affects and is affected by many other host factors, including sex, mating, and dietary environment. We used the agriculturally relevant fungal emtomopathogen, Beauveria bassiana, and the model host organism Drosophila melanogaster to examine how the impacts of sex, mating, and dietary environment on immunity are interrelated. We showed that the direction of sexual dimorphism in immune defense depends on mating status and mating frequency. We also showed that post-infection dimorphism in immune defense changes over time and is affected by dietary condition both before and after infection. Supplementing the diet with protein-rich yeast improved post-infection survival but more so when supplementation was done after infection instead of before. The multi-directional impacts among immune defense, sex, mating, and diet are clearly complex, and while our study shines light on some of these relationships, further study is warranted. Such studies have potential downstream applications in agriculture and medicine.

Bidirectional Associations Between Adiposity and Cognitive Function: A Prospective Analysis of the Canadian Longitudinal Study on Aging (CLSA).

BACKGROUND: Theoretical perspectives suggest that adiposity and cognitive function may be bidirectionally associated, but this has not been examined in a large-scale data set. The current investigation aims to fill this gap using a large, representative sample of middle-aged and older adults. METHODS: Using data from the Canadian Longitudinal Study on Aging (N = 25 854), the bidirectional hypothesis was examined with 3 indicators of cognitive function (ie, executive function, processing speed, and verbal fluency) and adiposity (ie, waist circumference [WC], body mass index [BMI], and total fat mass). We used multivariate multivariable regression and structural equation modeling to assess the prospective associations between adiposity and cognitive indicators. RESULTS: Analyses revealed that higher baseline WC was associated with higher Stroop interference at follow-up for both middle-aged (standardized estimate, ß = 0.08, 95% confidence interval [CI] 0.06, 0.10) and older adults (ß = 0.07, 95% CI 0.04, 0.09). Similarly, higher baseline Stroop interference was also associated with higher follow-up WC in middle-aged (ß = 0.08, 95% CI 0.06, 0.10) and older adults (ß = 0.03, 95% CI 0.01, 0.06). Effects involving semantic fluency and processing speed were less consistent. The earlier effects were similar to those observed using other adiposity indicators (eg, BMI and total fat mass) and were robust to adjustment for demographics and other cofounders, and when using latent variable modeling of the adiposity variable. CONCLUSION: Evidence for a bidirectional relationship between adiposity and cognitive function exists, though the associations are most reliable for executive function and primarily evident at midlife.

Cognitive Function Is Associated With Multiple Indices of Adiposity in the Canadian Longitudinal Study on Aging: A Cross-Sectional Analysis.

OBJECTIVE: Prior studies have suggested reciprocal relationships between cognitive function and adiposity, but this has not been investigated with population representative data sets. The purpose of this study was to examine the association between cognitive function and adiposity in a large population-based sample of middle-aged and older adults. It was hypothesized that better scores on tests of cognitive function would be associated with lower adiposity, and this association would be primarily mediated through life-style behavior and physical health status. METHODS: Using baseline data from the Canadian Longitudinal Study on Aging ( N = 30,097), we tested our hypotheses using three indicators of cognitive function (animal fluency, Stroop interference, and reaction time) and four indicators of adiposity (body mass index, total fat mass, waist circumference, and waist-hip ratio). Hierarchical multivariable linear regression modeling was conducted followed by tests for moderation by socioeconomic status and mediation through diet, physical activity, hypertension, and diabetes status. RESULTS: All measures of cognitive indicators were significantly associated with adiposity after adjusting for confounders. In general, superior performance on animal fluency, Stroop, and reaction time tasks were associated with lower adiposity by most metrics. Stroop interference was associated with lower adiposity across all metrics, including body mass index ( b = - 0.04, 95 % confidence interval [CI] = - 0.06 to - 0.01), total fat mass ( b = 19.35, 95 % CI = 8.57 to 30.12), waist circumference ( b = 33.83, 95 % CI = 10.08 to 57.58), and waist-hip ratio ( b = 0.13, 95 % CI = 0.01 to 0.24). These associations were more substantial for moderate- and high-income subpopulations. Mediation analyses suggested that the aforementioned effects were mediated through life-style behavior (e.g., diet and physical activity) and physical health conditions (e.g., diabetes and hypertension). CONCLUSIONS: Reliable associations exist between cognitive function and adiposity in middle-aged and older adults. The associations seem to be mediated through life-style behavior and physical health conditions.

The molecular architecture of Drosophila melanogaster defense against Beauveria bassiana explored through evolve and resequence and quantitative trait locus mapping.

Little is known about the genetic architecture of antifungal immunity in natural populations. Using two population genetic approaches, quantitative trait locus (QTL) mapping and evolve and resequence (E&R), we explored D. melanogaster immune defense against infection with the fungus Beauveria bassiana. The immune defense was highly variable both in the recombinant inbred lines from the Drosophila Synthetic Population Resource used for our QTL mapping and in the synthetic outbred populations used in our E&R study. Survivorship of infection improved dramatically over just 10 generations in the E&R study, and continued to increase for an additional nine generations, revealing a trade-off with uninfected longevity. Populations selected for increased defense against B. bassiana evolved cross resistance to a second, distinct B. bassiana strain but not to bacterial pathogens. The QTL mapping study revealed that sexual dimorphism in defense depends on host genotype, and the E&R study indicated that sexual dimorphism also depends on the specific pathogen to which the host is exposed. Both the QTL mapping and E&R experiments generated lists of potentially causal candidate genes, although these lists were nonoverlapping.

Skellam process with resetting: a neural spike train model.

This paper introduces the Skellam process with resetting. Resetting is a modification that accommodates the modeling of neural spike trains. We show this as a biologically plausible model, which codes the information content of neural spike trains with three, potentially, time-varying functions. We show that the interspike interval distribution under this model follows a mixture of gamma distributions, a flexible class covering a wide range of commonly used models. Through simulation studies and the analyses of connected retinal ganglion and lateral geniculate nucleus cells, we evaluate the performance of this model. Copyright © 2016 John Wiley & Sons, Ltd.

Multiscale analysis of neural spike trains.

This paper studies the multiscale analysis of neural spike trains, through both graphical and Poisson process approaches. We introduce the interspike interval plot, which simultaneously visualizes characteristics of neural spiking activity at different time scales. Using an inhomogeneous Poisson process framework, we discuss multiscale estimates of the intensity functions of spike trains. We also introduce the windowing effect for two multiscale methods. Using quasi-likelihood, we develop bootstrap confidence intervals for the multiscale intensity function. We provide a cross-validation scheme, to choose the tuning parameters, and study its unbiasedness. Studying the relationship between the spike rate and the stimulus signal, we observe that adjusting for the first spike latency is important in cross-validation. We show, through examples, that the correlation between spike trains and spike count variability can be multiscale phenomena. Furthermore, we address the modeling of the periodicity of the spike trains caused by a stimulus signal or by brain rhythms. Within the multiscale framework, we introduce intensity functions for spike trains with multiplicative and additive periodic components. Analyzing a dataset from the retinogeniculate synapse, we compare the fit of these models with the Bayesian adaptive regression splines method and discuss the limitations of the methodology. Computational efficiency, which is usually a challenge in the analysis of spike trains, is one of the highlights of these new models. In an example, we show that the reconstruction quality of a complex intensity function demonstrates the ability of the multiscale methodology to crack the neural code.