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White matter hyperintensity (WMH) volume is a neuroimaging marker of lesion load related to small vessel disease that has been associated with cognitive aging and Alzheimer’s disease (AD) risk.
Method:
The present study sought to examine whether regional WMH volume mediates the relationship between APOE ε4 status, a strong genetic risk factor for AD, and cognition and if this association is moderated by age group differences within a sample of 187 healthy older adults (APOE ε4 status [carrier/non-carrier] = 56/131).
Results:
After we controlled for sex, education, and vascular risk factors, ANCOVA analyses revealed significant age group by APOE ε4 status interactions for right parietal and left temporal WMH volumes. Within the young-old group (50-69 years), ε4 carriers had greater right parietal and left temporal WMH volumes than non-carriers. However, in the old-old group (70-89 years), right parietal and left temporal WMH volumes were comparable across APOE ε4 groups. Further, within ε4 non-carriers, old-old adults had greater right parietal and left temporal WMH volumes than young-old adults, but there were no significant differences across age groups in ε4 carriers. Follow-up moderated mediation analyses revealed that, in the young-old, but not the old-old group, there were significant indirect effects of ε4 status on memory and executive functions through left temporal WMH volume.
Conclusions:
These findings suggest that, among healthy young-old adults, increased left temporal WMH volume, in the context of the ε4 allele, may represent an early marker of cognitive aging with the potential to lead to greater risk for AD.
We study a class of ordinary differential equations with a non-Lipschitz point singularity that admits non-unique solutions through this point. As a selection criterion, we introduce stochastic regularizations depending on a parameter $\nu $: the regularized dynamics is globally defined for each $\nu> 0$, and the original singular system is recovered in the limit of vanishing $\nu $. We prove that this limit yields a unique statistical solution independent of regularization when the deterministic system possesses a chaotic attractor having a physical measure with the convergence to equilibrium property. In this case, solutions become spontaneously stochastic after passing through the singularity: they are selected randomly with an intrinsic probability distribution.
Identifying the correlates of mental health resilience (MHR)—defined as the discrepancy between one’s reported current mental health and one’s predicted mental health based on their physical performance—may lead to strategies to alleviate the burden of poor mental health in aging adults. Socioeconomic factors, such as income and education, may promote MHR via modifiable factors, such as physical activity and social networks.
Design:
A cross-sectional study was conducted. Multivariable generalized additive models characterized the associations between socioeconomic and modifiable factors with MHR.
Setting:
Data were taken from the population-based Canadian Longitudinal Study on Aging (CLSA), which collected data at various data collection sites across Canada.
Participants:
Approximately 31,000 women and men between the ages of 45 and 85 years from the comprehensive cohort of the CLSA.
Measurements:
Depressive symptoms were assessed by the Center for Epidemiological Studies Depression Scale. Physical performance was measured objectively using a composite of grip strength, sit-to-stand, and balance performance. Socioeconomic and modifiable factors were measured by self-report questionnaires.
Results:
Household income, and to a lesser extent, education were associated with greater MHR. Individuals reporting more physical activity and larger social networks had greater MHR. Physical activity accounted for 6% (95% CI: 4 to 11%) and social network accounted for 16% (95% CI: 11 to 23%) of the association between household income and MHR.
Conclusions:
The burden of poor mental health in aging adults may be alleviated through targeted interventions involving physical activity and social connectedness for individuals with lower socioeconomic resources.
Data from neurocognitive assessments may not be accurate in the context of factors impacting validity, such as disengagement, unmotivated responding, or intentional underperformance. Performance validity tests (PVTs) were developed to address these phenomena and assess underperformance on neurocognitive tests. However, PVTs can be burdensome, rely on cutoff scores that reduce information, do not examine potential variations in task engagement across a battery, and are typically not well-suited to acquisition of large cognitive datasets. Here we describe the development of novel performance validity measures that could address some of these limitations by leveraging psychometric concepts using data embedded within the Penn Computerized Neurocognitive Battery (PennCNB).
Methods:
We first developed these validity measures using simulations of invalid response patterns with parameters drawn from real data. Next, we examined their application in two large, independent samples: 1) children and adolescents from the Philadelphia Neurodevelopmental Cohort (n = 9498); and 2) adult servicemembers from the Marine Resiliency Study-II (n = 1444).
Results:
Our performance validity metrics detected patterns of invalid responding in simulated data, even at subtle levels. Furthermore, a combination of these metrics significantly predicted previously established validity rules for these tests in both developmental and adult datasets. Moreover, most clinical diagnostic groups did not show reduced validity estimates.
Conclusions:
These results provide proof-of-concept evidence for multivariate, data-driven performance validity metrics. These metrics offer a novel method for determining the performance validity for individual neurocognitive tests that is scalable, applicable across different tests, less burdensome, and dimensional. However, more research is needed into their application.
Understanding deviations from typical brain development is a promising approach to comprehend pathophysiology in childhood and adolescence. We investigated if cerebellar volumes different than expected for age and sex could predict psychopathology, executive functions and academic achievement.
Methods
Children and adolescents aged 6–17 years from the Brazilian High-Risk Cohort Study for Mental Conditions had their cerebellar volume estimated using Multiple Automatically Generated Templates from T1-weighted images at baseline (n = 677) and at 3-year follow-up (n = 447). Outcomes were assessed using the Child Behavior Checklist and standardized measures of executive functions and school achievement. Models of typically developing cerebellum were based on a subsample not exposed to risk factors and without mental-health conditions (n = 216). Deviations from this model were constructed for the remaining individuals (n = 461) and standardized variation from age and sex trajectory model was used to predict outcomes in cross-sectional, longitudinal and mediation analyses.
Results
Cerebellar volumes higher than expected for age and sex were associated with lower externalizing specific factor and higher executive functions. In a longitudinal analysis, deviations from typical development at baseline predicted inhibitory control at follow-up, and cerebellar deviation changes from baseline to follow-up predicted changes in reading and writing abilities. The association between deviations in cerebellar volume and academic achievement was mediated by inhibitory control.
Conclusions
Deviations in the cerebellar typical development are associated with outcomes in youth that have long-lasting consequences. This study highlights both the potential of typical developing models and the important role of the cerebellum in mental health, cognition and education.
Fructose (C6H12O6) is acutely obesogenic and is a risk factor for hypertension, cardiovascular disease, and nonalcoholic fatty liver disease. However, the possible long-lasting effects of early-life fructose consumption have not been studied. We tested for effects of early-life fructose and/or wheel access (voluntary exercise) in a line of selectively bred High Runner (HR) mice and a non-selected Control (C) line. Exposures began at weaning and continued for 3 weeks to sexual maturity, followed by a 23-week "washout" period (equivalent to ∼17 human years). Fructose increased total caloric intake, body mass, and body fat during juvenile exposure, but had no effect on juvenile wheel running and no important lasting effects on adult physical activity or body weight/composition. Interestingly, adult maximal aerobic capacity (VO2max) was reduced in mice that had early-life fructose and wheel access. Consistent with previous studies, early-life exercise promoted adult wheel running. In a 3-way interaction, C mice that had early-life fructose and no wheel access gained body mass in response to 2 weeks of adult wheel access, while all other groups lost mass. Overall, we found some long-lasting positive effects of early-life exercise, but minimal effects of early-life fructose, regardless of the mouse line.
Accurate and easy to use methods for dietary Na intake estimation in population level are lacking. We aimed at (i) estimating the mean Na intake in the group level using a variety of dietary methods (DM) and urinary methods (UM) and correlating them with 24-h urine collection (24UCol) and (ii) improving the accuracy of the existing DM.
Design:
The most common DM (three 24-h dietary recalls (24DR) and FFQ) and UM (24UCol and spot urine collection using common equations) were applied. To improve the existing: (i) 24DR, discretionary Na was quantified using salt-related questions or adding extra 15 % in total Na intake and (ii) FFQ, food items rich in Na and salt-related questions were added in the standard questionnaire (NaFFQ).
Setting:
National and Kapodistrian University of Athens, Greece.
Mean 24 h Na excretion (24UNa) was 2810 ± 1304 mg/d. Spot urine methods overestimated the 24UNa (bias range: −1781 to −492 mg) and were moderately correlated to 24UCol (r = 0·469–0·596, P ≤ 0·01). DM underestimated the 24UNa (bias range: 877 to 1212 mg) and were weakly correlated with 24UCol. The improved DM underestimated the 24UNa (bias range: 877 to 923 mg). The NaFFQ presented the smallest bias (−290 ± 1336 mg) and the strongest correlation with 24UCol (r = 0·497, P ≤ 0·01), but wide limits of agreement in Bland–Altman plots (−2909 mg; 2329 mg), like all the other methods did.
Conclusions:
The existing methods exhibit poor accuracy. Further improvement of the newly developed NaFFQ could be promising for more accurate estimation of mean dietary Na intake in epidemiological studies. Additional validation studies are needed.
We construct smooth, non-symmetric plasma equilibria which possess closed, nested flux surfaces and solve the magnetohydrostatic (steady three-dimensional incompressible Euler) equations with a small force. The solutions are also ‘nearly’ quasisymmetric. The primary idea is, given a desired quasisymmetry direction $\xi$, to change the smooth structure on space so that the vector field $\xi$ is Killing for the new metric and construct $\xi$–symmetric solutions of the magnetohydrostatic equations on that background by solving a generalized Grad–Shafranov equation. If $\xi$ is close to a symmetry of Euclidean space, then these are solutions on flat space up to a small forcing.
Impairment in reciprocal social behavior (RSB), an essential component of early social competence, clinically defines autism spectrum disorder (ASD). However, the behavioral and genetic architecture of RSB in toddlerhood, when ASD first emerges, has not been fully characterized. We analyzed data from a quantitative video-referenced rating of RSB (vrRSB) in two toddler samples: a community-based volunteer research registry (n = 1,563) and an ethnically diverse, longitudinal twin sample ascertained from two state birth registries (n = 714). Variation in RSB was continuously distributed, temporally stable, significantly associated with ASD risk at age 18 months, and only modestly explained by sociodemographic and medical factors (r2 = 9.4%). Five latent RSB factors were identified and corresponded to aspects of social communication or restricted repetitive behaviors, the two core ASD symptom domains. Quantitative genetic analyses indicated substantial heritability for all factors at age 24 months (h2 ≥ .61). Genetic influences strongly overlapped across all factors, with a social motivation factor showing evidence of newly-emerging genetic influences between the ages of 18 and 24 months. RSB constitutes a heritable, trait-like competency whose factorial and genetic structure is generalized across diverse populations, demonstrating its role as an early, enduring dimension of inherited variation in human social behavior. Substantially overlapping RSB domains, measurable when core ASD features arise and consolidate, may serve as markers of specific pathways to autism and anchors to inform determinants of autism's heterogeneity.
Waters, Ruiz, and Roisman (2017) recently published evidence based on the Minnesota Longitudinal Study of Risk and Adaptation (MLSRA) that sensitive caregiving during childhood is associated with higher levels of secure base script knowledge during the Adult Attachment Interview (AAIsbs). At present, however, little is known about the role of variation in atypical caregiving, including abuse and/or neglect, in explaining individual differences in AAIsbs. This study revisited data from the MLSRA (N = 157) to examine the association between experiencing abuse and/or neglect in the first 17.5 years of life and secure base script knowledge measured at ages 19 and 26 years. Several aspects of abuse and/or neglect experiences were assessed, including perpetrator identity, timing, and type. Regressions revealed that childhood abuse and/or neglect was robustly associated with lower AAIsbs scores in young adulthood, above and beyond previously documented associations with maternal sensitivity and demographic covariates. Follow-up analyses provided evidence that the predictive significance of abuse for secure base script knowledge was specific to perpetration by parental figures, rather than non-caregivers. Exploratory analyses indicated that abuse and/or neglect: (a) in middle childhood and adolescence (but not infancy and early childhood) and (b) physical abuse (but not sexual abuse or neglect) were uniquely associated with lower AAIsbs scores.
Smooth solutions of the incompressible Euler equations are characterized by the property that circulation around material loops is conserved. This is the Kelvin theorem. Likewise, smooth solutions of Navier–Stokes are characterized by a generalized Kelvin's theorem, introduced by Constantin–Iyer (2008). In this note, we introduce a class of stochastic fluid equations, whose smooth solutions are characterized by natural extensions of the Kelvin theorems of their deterministic counterparts, which hold along certain noisy flows. These equations are called the stochastic Euler–Poincaré and stochastic Navier–Stokes–Poincaré equations respectively. The stochastic Euler–Poincaré equations were previously derived from a stochastic variational principle by Holm (2015), which we briefly review. Solutions of these equations do not obey pathwise energy conservation/dissipation in general. In contrast, we also discuss a class of stochastic fluid models, solutions of which possess energy theorems but do not, in general, preserve circulation theorems.
Robust and persistent links between early-life adversities and later-life mental distress have previously been observed. Individual and social resources are associated with greater mental health and resilience. This study aimed to test these resources as moderators and mediators of the association between childhood psychosocial adversity and later-life mental distress.
Methods:
Participant data came from the Medical Research Council National Survey of Health and Development, a nationally-representative birth cohort study. The General Health Questionnaire-28 (GHQ-28) captured mental distress at ages 53, 60–64, and 68–69. An eight-item cumulative psychosocial adversity score was created (0, 1, 2, ≥3 adversities). Individual (i.e., education, occupational status, physical activity) and social (i.e., social support, neighborhood cohesion) resources were examined as mediators and moderators of CPA and GHQ-28 in longitudinal multilevel models.
Findings:
Greater adversity was associated with an average GHQ-28 score increase of 0.017, per unit adversity (β = 0·017, p < 0·001, 95% CI 0·011, 0·022). Lower mental distress was associated with higher levels of physical activity, occupational status, education, social support, and neighborhood cohesion. There was no evidence that resources moderated the relationship between GHQ-28 and adversity. All resources, save for physical activity and occupational status, partly mediated this relationship.
Conclusions:
Individual and social resources were associated with lower mental distress. They did not modify, but partly mediated the association between childhood adversity and adult mental distress. Social support was the most important mediator, suggesting that interventions to promote greater social support may offset psychosocial adversities experienced in childhood to foster better mental health in older adults.
Depression treatment is hampered by low efficacy of antidepressant medications and concerns about alternative modalities. Animal studies of treatment with low-level (0.5 Watt or less) near infrared (NIR) light from diodes has shown some benefit in models of traumatic brain injury (TBI) with evidence of reduced lesion size, increased neurotrophin production, synaptogenesis, fewer apoptotic cells, and improved neurological function. Two small case series have demonstrated transient clinical improvement with low-level NIR treatment given on a daily basis over several weeks. We have previously shown marked and persistent clinical improvement in a case series of patients with chronic mild-to-moderate (m-MTBI) after treatmentwith NIR at a power of 9 Watts or greater. We also have published a review of the potential for application of NIR for the treatment of depression. The current study explores NIR efficacy in a proof-of-concept study as a treatment for depression.
Methods
Thirty-nine sequential patients treated for TBI between March 2013 and May 2017 provided depression self-assessment data and/or were administered the Hamilton Depression Rating Scale. Each completed the Quick Inventory of Depression Symptomatology-Self Reports (QIDS) before and after treatment. Patients received transcranial multi-Watt near-infrared light treatment (NILT) using near-infrared lasers (810/980 nm at 8-15 Watts) applied to forehead and temporal regions bilaterally for 9-12 minutes to each area.
Results
For 36 of the 39 patients, after 16.82 + 6.26 treatments, QIDS scores indicated a robust response (decrease of QIDS total score by > 50%). For 32 of 39 patients post-treatment QIDS scores indicated a remission from depression (decrease of QIDS total score < 5). Overall, the QIDS score fell from 14.10 + 3.39 to 3.44 + 3.39 SD (p=6.29 X 10-19). With 12 or fewer treatments, QIDS score dropped from 14.83 + 2.55 to 4.17 + 3.93. Patients receiving 13 or more treatments showed a change in QIDS score from 13.67 + 3.64 to 3.11 + 3.14. Those (N=15) who received the entire treatment course within 8 weeks or less (5.33 + 1.72 weeks) showed a change in QIDS score from 13.86 + 3.14 to 4.5 + 3.94. Suicidal ideation resolved in all, but two patients. The non-responsive patients are described in detail. Patients remained in remission for up to 55 months after a single course of treatment.
Conclusion
This is the first report of high-powered NILT showing efficacy for depression. Patients saw benefit often within 4 treatments and some had resolution of depressive symptoms in as little as 4 weeks. These data raise an intriguing possibility – that NILT may be a safe, effective, and rapid treatment for depression. A double-blind, placebo controlled trial is warranted to verify these proof-of-concept data.
Depression treatment is hampered by low efficacy of antidepressant medications and concerns about alternative modalities. Animal studies of treatment with low-level (0.5 Watt or less) near infrared (NIR) light from diodes has shown some benefit in models of traumatic brain injury (TBI) with evidence of reduced lesion size, increased neurotrophin production, synaptogenesis, fewer apoptotic cells, and improved neurological function. Two small case series have demonstrated transient clinical improvement with low-level NIR treatment given on a daily basis over several weeks. We have previously shown marked and persistent clinical improvement in a case series of patients with chronic mild-to-moderate (m-MTBI) after treatmentwith NIR at a power of 9 Watts or greater. We also have published a review of the potential for application of NIR for the treatment of depression. The current study explores NIR efficacy in a proof-of-concept study as a treatment for depression.
Methods
Thirty-nine sequential patients treated for TBI between March 2013 and May 2017 provided depression self-assessment data and/or were administered the Hamilton Depression Rating Scale. Each completed the Quick Inventory of Depression Symptomatology-Self Reports (QIDS) before and after treatment. Patients received transcranial multi-Watt near-infrared light treatment (NILT) using near-infrared lasers (810/980 nm at 8-15 Watts) applied to forehead and temporal regions bilaterally for 9-12 minutes to each area.
Results
For 36 of the 39 patients, after 16.82 + 6.26 treatments, QIDS scores indicated a robust response (decrease of QIDS total score by > 50%). For 32 of 39 patients post-treatment QIDS scores indicated a remission from depression (decrease of QIDS total score < 5). Overall, the QIDS score fell from 14.10 + 3.39 to 3.44 + 3.39 SD (p=6.29 X 10-19). With 12 or fewer treatments, QIDS score dropped from 14.83 + 2.55 to 4.17 + 3.93. Patients receiving 13 or more treatments showed a change in QIDS score from 13.67 + 3.64 to 3.11 + 3.14. Those (N=15) who received the entire treatment course within 8 weeks or less (5.33 + 1.72 weeks) showed a change in QIDS score from 13.86 + 3.14 to 4.5 + 3.94. Suicidal ideation resolved in all, but two patients. The non-responsive patients are described in detail. Patients remained in remission for up to 55 months after a single course of treatment.
Conclusion
This is the first report of high-powered NILT showing efficacy for depression. Patients saw benefit often within 4 treatments and some had resolution of depressive symptoms in as little as 4 weeks. These data raise an intriguing possibility – that NILT may be a safe, effective, and rapid treatment for depression. A double-blind, placebo controlled trial is warranted to verify these proof-of-concept data.
Traumatic stressors during childhood and adolescence are associated with psychopathology, mostly studied in the context of post-traumatic stress disorder (PTSD) and depression. We investigated broader associations of traumatic stress exposure with psychopathology and cognition in a youth community sample.
Methods
The Philadelphia Neurodevelopmental Cohort (N = 9498) is an investigation of clinical and neurobehavioral phenotypes in a diverse (56% Caucasian, 33% African American, 11% other) US youth community population (aged 8–21). Participants were ascertained through children's hospital pediatric (not psychiatric) healthcare network in 2009–2011. Structured psychiatric evaluation included screening for lifetime exposure to traumatic stressors, and a neurocognitive battery was administered.
Results
Exposure rate to traumatic stressful events was high (none, N = 5204; one, N = 2182; two, N = 1092; three or more, N = 830). Higher stress load was associated with increased psychopathology across all clinical domains evaluated: mood/anxiety (standardized β = .378); psychosis spectrum (β = .360); externalizing behaviors (β = .311); and fear (β = .256) (controlling for covariates, all p < 0.001). Associations remained significant controlling for lifetime PTSD and depression. Exposure to high-stress load was robustly associated with suicidal ideation and cannabis use (odds ratio compared with non-exposed 5.3 and 3.2, respectively, both p < 0.001). Among youths who experienced traumatic stress (N = 4104), history of assaultive trauma was associated with greater psychopathology and, in males, vulnerability to psychosis and externalizing symptoms. Stress load was negatively associated with performance on executive functioning, complex reasoning, and social cognition.
Conclusions
Traumatic stress exposure in community non-psychiatric help-seeking youth is substantial, and is associated with more severe psychopathology and neurocognitive deficits across domains, beyond PTSD and depression.
A Lagrangian fluctuation–dissipation relation has been derived in a previous work to describe the dissipation rate of advected scalars, both passive and active, in wall-bounded flows. We apply this relation here to develop a Lagrangian description of thermal dissipation in turbulent Rayleigh–Bénard convection in a right-cylindrical cell of arbitrary cross-section, with either imposed temperature difference or imposed heat flux at the top and bottom walls. We obtain an exact relation between the steady-state thermal dissipation rate and the time $\unicode[STIX]{x1D70F}_{mix}$ for passive tracer particles released at the top or bottom wall to mix to their final uniform value near those walls. We show that an ‘ultimate regime’ with the Nusselt number scaling predicted by Spiegel (Annu. Rev. Astron., vol. 9, 1971, p. 323) or, with a log correction, by Kraichnan (Phys. Fluids, vol. 5 (11), 1962, pp. 1374–1389) will occur at high Rayleigh numbers, unless this near-wall mixing time is asymptotically much longer than the free-fall time $\unicode[STIX]{x1D70F}_{free}$. Precisely, we show that $\unicode[STIX]{x1D70F}_{mix}/\unicode[STIX]{x1D70F}_{free}=(RaPr)^{1/2}/Nu,$ with $Ra$ the Rayleigh number, $Pr$ the Prandtl number, and $Nu$ the Nusselt number. We suggest a new criterion for an ultimate regime in terms of transition to turbulence of a thermal ‘mixing zone’, which is much wider than the standard thermal boundary layer. Kraichnan–Spiegel scaling may, however, not hold if the intensity and volume of thermal plumes decrease sufficiently rapidly with increasing Rayleigh number. To help resolve this issue, we suggest a program to measure the near-wall mixing time $\unicode[STIX]{x1D70F}_{mix}$, which is precisely defined in the paper and which we argue is accessible both by laboratory experiment and by numerical simulation.
As the population ages, interest is increasing in studying aging well. However, more refined means of examining predictors of biopsychosocial conceptualizations of successful aging (SA) are required. Existing evidence of the relationship between early-life education and later-life SA is unclear. The Successful Aging Index (SAI) was mapped onto the Cognitive Function and Aging Study (CFAS), a longitudinal population-based cohort (n = 1,141). SAI scores were examined using growth mixture modelling (GMM) to identify SA trajectories. Unadjusted and adjusted (age, sex, occupational status) ordinal logistic regressions were conducted to examine the association between trajectory membership and education level. GMM identified a three-class model, capturing high, moderate, and low functioning trajectories. Adjusted ordinal logistic regression models indicated that individuals in higher SAI classes were significantly more likely to have higher educational attainment than individuals in the lower SAI classes. These results provide evidence of a life course link between education and SA.