El exceso de peso podría influir en el cociente intelectual de los niños pequeños

Impact of Early‐Life Weight Status on Cognitive Abilities in Children

Abstract

Objective

Whether obesity is associated with childhood cognition is unknown. Given the sensitivity of the developing brain to environmental factors, this study examined whether early‐life weight status was associated with children's cognition.

Methods

Using data from mother–child pairs enrolled in the Health Outcomes and Measures of the Environment (HOME) Study (2003–2006), children's early‐life weight status was assessed using weight‐for‐length/height standard deviation (SD) scores. A battery of neuropsychological tests was administered to assess cognition, executive function, and visual‐spatial abilities at ages 5 and 8 years. Using linear mixed models, associations between early‐life weight status and cognition were estimated.

Results

Among 233 children, 167 were lean (≤1 SD) and 48 were nonlean (>1 SD). After covariate adjustment, the results suggest that full‐scale intelligence quotient scores decreased with a 1‐unit increase in weight‐for‐height SD score (β = –1.4, 95% CI: –3.0 to 0.1). For individual component scores, with a 1‐unit increase in weight‐for‐height SD score, perceptual reasoning (β = –1.7, 95% CI: –3.3 to 0.0) and working memory (β: –2.4, CI: –4.4 to –0.4) scores decreased. Weight status was generally not associated with other cognition measures.

Conclusions

Within this cohort of typically developing children, early‐life weight status was inversely associated with children's perceptual reasoning and working memory scores and possibly with full‐scale intelligent quotient scores.

Asocian un antiguo fármaco para el embarazo con un mayor riesgo de TDAH generaciones más tarde

Association of Exposure to Diethylstilbestrol During Pregnancy With Multigenerational Neurodevelopmental Deficits

Key Points

Question  Is exposure to diethylstilbestrol during pregnancy associated with adverse multigenerational neurodevelopmental outcomes?

Findings  A cohort study of 47 450 women in the Nurses’ Health Study II found significantly elevated odds for attention-deficit/hyperactivity disorder in the grandchildren (third generation) of users of diethylstilbestrol, a potent endocrine disruptor.

Meaning  Exposure to endocrine disruptors during pregnancy may be associated with multigenerational neurodevelopmental deficits.

Abstract

Importance  Animal evidence suggests that endocrine disruptors affect germline cells and neurodevelopment. However, to date, the third-generation neurodevelopmental outcomes in humans have not been examined.

Objective  To explore the potential consequences of exposure to diethylstilbestrol or DES across generations—specifically, third-generation neurodevelopment.

Design, Setting, and Participants  This cohort study uses self-reported health information, such as exposure to diethylstilbestrol during pregnancy and attention-deficit/hyperactivity disorder (ADHD) diagnosis, from 47 540 participants enrolled in the ongoing Nurses’ Health Study II. The 3 generations analyzed in this study were the participants (F1 generation), their mothers (F0 generation), and their live-born children (F2 generation).

Main Outcomes and Measures  Participant- and mother-reported exposure to diethylstilbestrol during pregnancy and physician-diagnosed child ADHD.

Results  The total number of women included in this study was 47 540. Of the 47 540 F0 mothers, 861 (1.8%) used diethylstilbestrol and 46 679 (98.2%) did not while pregnant with the F1 participants. Use of diethylstylbestrol by F0 mothers was associated with an increased risk of ADHD among the F2 generation: 7.7% vs 5.2%, adjusted odds ratio (OR), 1.36 (95% CI, 1.10-1.67) and an OR of 1.63 (95% CI, 1.18-2.25) if diethylstilbestrol was taken during the first trimester of pregnancy. No effect modification was observed by the F2 children’s sex.

Conclusions and Relevance  This study provides evidence that diethylstilbestrol exposure is associated with multigenerational neurodevelopmental deficits. The doses and potency level of environmental endocrine disruptors to which humans are exposed are lower than those of diethylstilbestrol, but the prevalence of such exposure and the possibility of cumulative action are potentially high and thus warrant consideration.

Realidad virtual y demencia

Virtual reality and dementia

Introducción. La utilización de la tecnología de realidad virtual para el tratamiento de trastornos psicológicos se llevó a cabo por primera vez en 1994. Desde entonces, su uso ha despertado el interés de clínicos e investigadores y se ha convertido en una potencial herramienta destinada a la evaluación y neurorrehabilitación psicológicas. 

Objetivo. Revisar las diferentes investigaciones existentes para el tratamiento de las demencias en las que se ha utilizado realidad virtual, con la finalidad de evaluar su eficacia. 

Desarrollo. Se ha realizado una búsqueda de los últimos 10 años (2007-2017) en diferentes bases de datos (PubMed, PsycINFO y Dialnet), y también en Google Scholar. Las investigaciones encontradas son escasas y, por los resultados obtenidos, no puede decirse que sean concluyentes, si bien aportan ciertas evidencias que sugieren que la realidad virtual es un campo prometedor para la intervención en las personas con demencia. 

Conclusiones. La realidad virtual es un área en crecimiento y muy prometedora para la intervención psicológica en general, y para el tratamiento de la demencia en particular. Su acogida parece muy favorable entre las personas que padecen demencia. No obstante, es importante entender las nuevas tecnologías como una herramienta más que no sustituye al terapeuta. Asimismo, se advierte de la necesidad de más investigaciones rigurosas y sistemáticas que determinen la eficacia de este tipo de intervenciones.

Más de la mitad de los jóvenes tienen una relación de dependencia con los móviles

Information and Communications Technologies (ICT):Problematic use of Internet, video games, mobile phones,instant messaging and social networks using MULTICAGE-TIC

Resumen

El uso/abuso de las Tecnologías de la Información y la Comunicación (TIC) es un tema que suscita enorme interés en los últimos años. Está en discusión si debe recibir la consideración de conducta adictiva y si es un problema que afecte prioritariamente a adolescentes y jóvenes. El presente estudio pretende conocer los problemas que afectan a las personas de todas las edades en el control del uso de estas TICs y si están relacionados con problemas de salud mental, estrés y dificultades en el control superior del comportamiento. Se realiza una encuesta a través de redes sociales y correo electrónico, en el que se administra el cuestionario MULTICAGE-TIC, que explora problemas en el uso de Internet, teléfono móvil, videojuegos, mensajería instantánea y redes sociales. Adicionalmente se administra el Inventario de Síntomas Prefrontales, el Cuestionario de Salud General y la Escala de Estrés Percibido. Se obtiene una muestra de 1.276 sujetos de todas las edades y diferentes países de habla hispana. Los resultados apuntan a que alrededor del 50% de la muestra presenta importantes problemas en el uso de estas tecnologías, y que esos problemas se relacionan directamente con síntomas de mal funcionamiento prefrontal, estrés y problemas de salud mental, independientemente de la edad u otras variables. Estos resultados sugieren reconsiderar si se trata de una patología adictiva o si estamos ante un problema novedoso que requiere de explicaciones de índole ambiental, psicológica, sociológica y sociopolítica, debiendo reformular las acciones a emprender para reorientar la comprensión y el abordaje del problema.

Palabras clave

adicciones comportamentales; tecnologías de la información y la comunicación; estrés percibido; disfunción ejecutiva; salud mental

La depresión podría debilitar la memoria

Greater depressive symptoms, cognition, and markers of brain aging. Northern Manhattan Study

Abstract

Objective We examined whether greater depressive symptoms were associated with domain-specific cognitive performance, change in cognition, and MRI markers of brain atrophy and subclinical cerebrovascular disease in a diverse sample of older adults from the Northern Manhattan Study.

Methods Data were analyzed from the Northern Manhattan Study, a prospective cohort study of mostly Caribbean Hispanic, stroke-free, older adults. A total of 1,111 participants had baseline measures of depressive symptoms, measured as the Center of Epidemiological Studies–Depression Scale, MRI markers, and cognitive function. A Center of Epidemiological Studies–Depression score ≥16 was considered indicative of greater depressive symptoms. Multivariable linear and logistic regression models were used to examine the associations of interest.

Results At baseline, 22% of participants had greater depressive symptoms. Greater depressive symptoms were significantly associated with worse baseline episodic memory in models adjusted for sociodemographic, vascular risk factor, behavioral, and antidepressive medication variables (β [95% confidence interval] = −0.21 [−0.33 to −0.10], p = 0.0003). Greater depressive symptoms were also associated with smaller cerebral parenchymal fraction (β [95% confidence interval] = −0.56 [−1.05 to −0.07], p = 0.02) and increased odds of subclinical brain infarcts (odds ratio [95% confidence interval] = 1.55 [1.00–2.42], p = 0.05), after adjustment for sociodemographic, behavioral, and vascular risk factor variables. Greater depressive symptoms were not significantly associated with white matter hyperintensity volume, hippocampal volume, or change in cognition over an average of 5 years. Results were unchanged when stabilized inverse probability weights were applied to address selective attrition during the study period.

Conclusions In this sample of mostly Caribbean Hispanic, stroke-free, older adults, greater depressive symptoms were associated with worse episodic memory, smaller cerebral volume, and silent infarcts.

Los menores prematuros muestran características diferenciales para el cribado de trastornos del espectro autista

Autism spectrum disorder and prematurity: towards a prospective screening program

INTRODUCTION:

The prevalence of autism spectrum disorders (ASD) reported in current studies in risk groups such as preterm or low birth weight infants is higher than in the normal population. This fact has led to the increase in recent years of screening studies that investigate possible risk factors for ASD in preterm newborns and their developmental trajectory.

AIM:

To present the results of the main screening studies of preterm newborns in order to propose screening recommendations for this population at risk.

DEVELOPMENT:

The results of the studies presented suggest the possibility that the trajectory of socio-communicative and behavioral development of preterm infants differed from what was expected if their birth had occurred at term. This supports the fact that screening programs are carried out based on developmental surveillance and that it is advisable to use screening tools adapted to this population at risk.

CONCLUSION:

Premature children are a risk group that shows differential characteristics for the screening of ASD.

Descubierto un mecanismo fundamental para reparar los nervios periféricos dañados

Class IIa histone deacetylases link cAMP signaling to the myelin transcriptional program of Schwann cells

Abstract

Schwann cells respond to cyclic adenosine monophosphate (cAMP) halting proliferation and expressing myelin proteins. Here we show that cAMP signaling induces the nuclear shuttling of the class IIa histone deacetylase (HDAC)–4 in these cells, where it binds to the promoter and blocks the expression of c-Jun, a negative regulator of myelination. To do it, HDAC4 does not interfere with the transcriptional activity of MEF2. Instead, by interacting with NCoR1, it recruits HDAC3 and deacetylates histone 3 in the promoter of c-Jun, blocking gene expression. Importantly, this is enough to up-regulate Krox20 and start Schwann cell differentiation program–inducing myelin gene expression. Using conditional knockout mice, we also show that HDAC4 together with HDAC5 redundantly contribute to activate the myelin transcriptional program and the development of myelin sheath in vivo. We propose a model in which cAMP signaling shuttles class IIa HDACs into the nucleus of Schwann cells to regulate the initial steps of myelination in the peripheral nervous system.

Vinculan cambios en la corteza somatosensorial con el síndrome de piernas inquietas

Involvement of the central somatosensory system in restless legs syndrome. A neuroimaging study.

Abstract

Objective To investigate morphologic changes in the somatosensory cortex and the thickness of the corpus callosum subdivisions that provide interhemispheric connections between the 2 somatosensory cortical areas.

Methods Twenty-eight patients with severe restless legs syndrome (RLS) symptoms and 51 age-matched healthy controls were examined with high-resolution MRI at 3.0 tesla. The vertex-wise analysis in conjunction with a novel cortical surface classification method was performed to assess the cortical thickness across the whole-brain structures. In addition, the thickness of the midbody of the corpus callosum that links postcentral gyri in the 2 hemispheres was measured.

Results We demonstrated that a morphologic change occurred in the brain somatosensory system in patients with RLS compared to controls. Patients with RLS exhibited a 7.5% decrease in average cortical thickness in the bilateral postcentral gyrus (p < 0.0001). Accordingly, there was a substantial decrease in the corpus callosum posterior midbody (p < 0.008) wherein the callosal fibers are connected to the postcentral gyrus, suggesting altered white matter properties in the somatosensory pathway.

Conclusion Our results provide in vivo evidence of morphologic changes in the primary somatosensory system, which could be responsible for the sensory functional symptoms of RLS. These results provide a better understanding of the pathophysiology underlying the RLS sensory symptoms and could lead to a potential imaging marker for RLS.

La música podría calmar la agitación en pacientes con enfermedad de Alzheimer

Increasedfunctional connectivity after listening to favored music in adults withalzheimer dementia

Background: Personalized music programs have been proposed as an adjunct therapy for patients with Alzheimer disease related dementia, and multicenter trials have now demonstrated improvements in agitation, anxiety, and behavioral symptoms. Underlying neurophysiological mechanisms for these effects remain unclear. Methods: We examined 17 individuals with a clinical diagnosis of Alzheimer disease related dementia using functional MRI following a training period in a personalized music listening program. Results: We find that participants listening to preferred music show specific activation of the supplementary motor area, a region that has been associated with memory for familiar music that is typically spared in early Alzheimer disease. We also find widespread increases in functional connectivity in corticocortical and corticocerebellar networks following presentation of preferred musical stimuli, suggesting a transient effect on brain function. Conclusions: Findings support a mechanism whereby attentional network activation in the brain’s salience network may lead to improvements in brain network synchronization. 

CITATION:

J.B. King ; K.G. Jones ; E. Goldberg ; M. Rollins ; K. MacNamee ; C. Moffit ; S.R. Naidu ; M.A. Ferguson ; E. Garcia-Leavitt ; J. Amaro ; K.R. Breitenbach ; J.M. Watson ; R.K. Gurgel ; J.S. Anderson1 ; N.L. Foster (2018): Increased Functional Connectivity After Listening to Favored Music in Adults With Alzheimer Dementia. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2018.19

¿Es terapéutico el «efecto Mozart» en la epilepsia?

Epilepsy, Mozart and his sonata K.448: is the «Mozart effect» therapeutic?

Abstract

To present a review of the so-called «Mozart effect», to explain why Mozart and his sonata K.448 were chosen, and to review the available literature on the treatment of epilepsy with that sonata.Profuse literature exists on the cerebral mechanisms that allow us to perceive, process and respond to the musical stimulus. Cerebral plasticity, especially in people with musical training, has also been demonstrated. The «Mozart effect» arose from the finding that hearing the sonata K.448 improved cognitive abilities, but the fact that these results may be due not to the music itself but to the listener increasing arousal or enjoyment generated controversy. In this context of debate, a large number of papers about the «Mozart effect» in the field of epilepsy were published, and are reviewed in this work.The «Mozart effect» has a scientific basis but its nature limits the methodological quality of the research. The music of Mozart, chosen for its exquisite structure, has been able to increase even more the controversy because also it is of the taste of a great majority. It is still far from being consolidated as a non-pharmacological antiepileptic treatment, but it could increase the scientific evidence with studies whose design minimizes the cited confounding factors.

Un estudio finlandés concluye que la sauna reduciría el riesgo de ictus

Sauna bathing reduces the risk of stroke in Finnish men and women: A prospective cohort study

Abstract

Objective To assess the association between frequency of sauna bathing and risk of future stroke.

Methods Baseline habits of sauna bathing were assessed in 1,628 adult men and women aged 53–74 years (mean age, 62.7 years) without a known history of stroke in the Finnish Kuopio Ischemic Heart Disease prospective cohort study. Three sauna bathing frequency groups were defined: 1, 2–3, and 4–7 sessions per week. Hazard ratios (HRs) (95% confidence intervals [CIs]) were estimated for incident stroke.

Results During a median follow-up of 14.9 years, 155 incident stroke events were recorded. Compared with participants who had one sauna bathing session per week, the age- and sex-adjusted HR (95% CI) for stroke was 0.39 (0.18–0.83) for participants who had 4–7 sauna sessions per week. After further adjustment for established cardiovascular risk factors and other potential confounders, the corresponding HR (95% CI) was 0.39 (0.18–0.84) and this remained persistent on additional adjustment for physical activity and socioeconomic status at 0.38 (0.18–0.81). The association between frequency of sauna bathing and risk of stroke was not modified by age, sex, or other clinical characteristics (p for interaction > 0.10 for all subgroups). The association was similar for ischemic stroke but modest for hemorrhagic stroke, which could be attributed to the low event rate (n = 34).

Conclusions This long-term follow-up study shows that middle-aged to elderly men and women who take frequent sauna baths have a substantially reduced risk of new-onset stroke.

El deterioro cognitivo contribuiría a la aparición de la congelación de la marcha en pacientes con enfermedad de Parkinson

Influence of cognitive impairment on the freezing of gait in non demented people with Parkinson's disease.

INTRODUCTION:

Freezing of gait (FOG) is a motor disturbance usually appearing in advanced Parkinson's disease (PD). Cognitive and executive function seems to play an important role in this phenomenon.

AIM:

To investigate if cognitive and kinematic parameters correlate with FOG in PD patients without dementia.

PATIENTS AND METHODS:

We conducted an observational cross-sectional study. Participants were classified in two groups: freezers and non-freezers. Clinical information was obtained by Hoehn and Yahr scale, Unified Parkinson's Disease Rating Scale and balance test of Short Physical Performance Battery. Cognitive function was evaluated using Minimental Examination and the Fuld Object Memory Evaluation; executive function was assessed with the Frontal Assessment Battery test. Battery kinematic parameters were assessed by means of gait speed, cadence, stride length and stride time.

RESULTS:

Twenty-five participants with PD without dementia completed the evaluation. Statistical significant differences between freezers and non-freezers were found in global cognition (p = 0,02), memory (p = 0,04), executive function (p = 0,04), cadence (p = 0,02), stride length (p = 0,04) and stride time (p = 0,01).

CONCLUSION:

Cognitive parameters may have an important contribution to the manifestation of freezing of gait in PD. These results may have important clinical implications for developing future non-pharmacological and cognitive interventions strategies targeted to PD patients with FOG.

Los dímeros estables de β-amiloide, posible biomarcador de la enfermedad de Alzheimer

Direct Evidence of the Presence of Cross-Linked Aβ Dimers in the Brains of Alzheimer’s Disease Patients

Brain-derived amyloid-β (Aβ) dimers are associated with Alzheimer’s disease (AD). However, their covalent nature remains controversial. This feature is relevant, as a covalent cross-link has been proposed to make brain-derived dimers (brain dimers) more synaptotoxic than Aβ monomers and would also make them suitable candidates for biomarker development. To resolve this controversy, we here present a three-step approach. First, we validated a type of synthetic cross-linked Aβ (CL Aβ) dimers, obtained by means of the photoinduced cross-linking of unmodified proteins (PICUP) reaction, as well-defined mimics of putative brain CL Aβ dimers. Second, we used these PICUP CL Aβ dimers as standards to improve the isolation of brain Aβ dimers and to develop state-of-the-art mass spectrometry (MS) strategies to allow their characterization. Third, we applied these MS methods to the analysis of brain Aβ dimer samples allowing the detection of the CL [Aβ(6–16)]2peptide comprising a dityrosine cross-link. This result demonstrates the presence of CL Aβ dimers in the brains of patients with AD and opens up avenues for establishing new therapeutic targets and developing novel biomarkers for this disease.

Una investigación revela el impacto de las variantes genéticas raras en la herencia del autismo

Paternally inherited cis-regulatory structural variants are associated with autism

Inherited variation contributes to autism

About one-quarter of genetic variants that are associated with autism spectrum disorder (ASD) are due to de novo mutations in protein-coding genes. Brandler et al. wanted to determine whether changes in noncoding regions of the genome are associated with autism. They applied whole-genome sequencing to ∼2600 families with at least one affected child. Children with ASD had inherited structural variants in noncoding regions from their father. Regulatory regions of some specific genes were disrupted among multiple families, supporting the idea that a component of autism risk involves inherited noncoding variation.

Abstract

The genetic basis of autism spectrum disorder (ASD) is known to consist of contributions from de novo mutations in variant-intolerant genes. We hypothesize that rare inherited structural variants in cis-regulatory elements (CRE-SVs) of these genes also contribute to ASD. We investigated this by assessing the evidence for natural selection and transmission distortion of CRE-SVs in whole genomes of 9274 subjects from 2600 families affected by ASD. In a discovery cohort of 829 families, structural variants were depleted within promoters and untranslated regions, and paternally inherited CRE-SVs were preferentially transmitted to affected offspring and not to their unaffected siblings. The association of paternal CRE-SVs was replicated in an independent sample of 1771 families. Our results suggest that rare inherited noncoding variants predispose children to ASD, with differing contributions from each parent.

Vinculan una noche con privación de sueño y la acumulación de β-amiloide

β-Amyloid accumulation in the human brain after one night of sleep deprivation

Significance

There has been an emerging interest in sleep and its association with β-amyloid burden as a risk factor for Alzheimer’s disease. Despite the evidence that acute sleep deprivation elevates β-amyloid levels in mouse interstitial fluid and in human cerebrospinal fluid, not much is known about the impact of sleep deprivation on β-amyloid burden in the human brain. Using positron emission tomography, here we show that acute sleep deprivation impacts β-amyloid burden in brain regions that have been implicated in Alzheimer’s disease. Our observations provide preliminary evidence for the negative effect of sleep deprivation on β-amyloid burden in the human brain.

Abstract

The effects of acute sleep deprivation on β-amyloid (Aβ) clearance in the human brain have not been documented. Here we used PET and 18F-florbetaben to measure brain Aβ burden (ABB) in 20 healthy controls tested after a night of rested sleep (baseline) and after a night of sleep deprivation. We show that one night of sleep deprivation, relative to baseline, resulted in a significant increase in Aβ burden in the right hippocampus and thalamus. These increases were associated with mood worsening following sleep deprivation, but were not related to the genetic risk (APOE genotype) for Alzheimer’s disease. Additionally, baseline ABB in a range of subcortical regions and the precuneus was inversely associated with reported night sleep hours. APOE genotyping was also linked to subcortical ABB, suggesting that different Alzheimer’s disease risk factors might independently affect ABB in nearby brain regions. In summary, our findings show adverse effects of one-night sleep deprivation on brain ABB and expand on prior findings of higher Aβ accumulation with chronic less sleep.

• beta amyloid
• sleep
• hippocampus
• Alzheimer’s disease
• glymphatic system

Los niños con autismo tienen demasiadas neuronas en la amígdala y las pierden a medida que maduran

Neuron numbers increase in the human amygdala from birth to adulthood, but not in autism

Significance

We demonstrate that the number of mature neurons in the human amygdala increases from childhood into adulthood. This trajectory may be due to the incorporation of immature neurons from the paralaminar nucleus in the ventral amygdala. In contrast, individuals with autism spectrum disorder (ASD) show an initial excess of mature neurons followed by a decline into adulthood. Our results suggest a degenerative component in ASD and highlight the need for a more comprehensive understanding of the protracted cellular development of the human amygdala for multiple psychiatric disorders.

Abstract

Remarkably little is known about the postnatal cellular development of the human amygdala. It plays a central role in mediating emotional behavior and has an unusually protracted development well into adulthood, increasing in size by 40% from youth to adulthood. Variation from this typical neurodevelopmental trajectory could have profound implications on normal emotional development. We report the results of a stereological analysis of the number of neurons in amygdala nuclei of 52 human brains ranging from 2 to 48 years of age [24 neurotypical and 28 autism spectrum disorder (ASD)]. In neurotypical development, the number of mature neurons in the basal and accessory basal nuclei increases from childhood to adulthood, coinciding with a decrease of immature neurons within the paralaminar nucleus. Individuals with ASD, in contrast, show an initial excess of amygdala neurons during childhood, followed by a reduction in adulthood across nuclei. We propose that there is a long-term contribution of mature neurons from the paralaminar nucleus to other nuclei of the neurotypical human amygdala and that this growth trajectory may be altered in ASD, potentially underlying the volumetric changes detected in ASD and other neurodevelopmental or neuropsychiatric disorders.

El flujo sanguíneo periférico se vería también afectado en la enfermedad de Alzheimer

Crosstalk between Peripheral Small Vessel Properties and Anxious-like Profiles: Sex, Genotype, and Interaction Effects in Mice with Normal Aging and 3×Tg-AD mice at Advanced Stages of Disease

Authors: Jiménez-Altayó, Francesca; b; * | Sánchez-Ventura, Juditha | Vila, Elisabeta; b | Giménez-Llort, Lydiab; c; *

Affiliations: [a] Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona, Barcelona, Spain | [b] Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, Spain | [c] Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain

Correspondence: [*] Correspondence to: Lydia Giménez-Llort, PhD, Translational Behavioral Neuroscience Lab, Unitat de Psicologia Mèdica, Departament de Psiquiatria i Medicina Legal, Facultat de Medicina, Universitat Autònoma de Barcelona, Avinguda Can Domènech, Edifici M, s/n. Campus Bellaterra, Cerdanyola del Vallès, 08193 Bellatterra, Spain. Tel.: +34 93 581 2378; Fax: +34 93 581 1435; E-mail: lidia.gimenez@uab.cat and Francesc Jiménez-Altayó, PhD, Departament de Farmacologia, Terapèutica i Toxicologia, Facultat de Medicina, Universitat Autònoma de Barcelona, Avinguda Can Domènech, Edifici M, s/n. Campus Bellaterra, Cerdanyola del Vallès, 08193 Bellatterra, Spain. Tel.: +34 93 581 1952; Fax: +34 93 581 1953; E-mail: francesc.jimenez@uab.cat.

Abstract: Cardiovascular disease resulting from oxidative stress and inflammation can exacerbate Alzheimer’s disease. This brief report provides the first evidence of compromised small peripheral mesenteric resistance artery (MRA) properties in 15-month-old 3xTg-AD mice. Females showed worse physiologically relevant MRA structural (increased passive external and internal diameters, cross sectional area) and functional (increased active internal diameters) alterations suggesting sex-dependent dysfunctions. At both physiological and high intraluminal pressures, vascular alterations correlated with the anxious-like behavioral profile, in a sex-dependent manner. Finally, the results unveil a crosstalk between peripheral small vessel properties and behavior in both 3xTg-AD mice and age-matched counterparts with normal aging.

Keywords: 3×Tg-AD mice, aging, Alzheimer’s disease, cardiovascular disease, emerging concepts, gender medicine, oxidative stress, peripheral inflammation, small mesenteric resistance arteries, vascular remodeling.

La semiología de las crisis no resulta útil para caracterizar la epilepsia infantil benigna

Frequency, semiology and prognosis of benign infantile epilepsy

iNTRODUCTION:

Benign infantile epilepsy is an epileptic syndrome of infancy. Until now, only a small number of case-series have been published.

AIM:

To study the frequency, semiology and prognosis of benign infantile epilepsy.

PATIENTS AND METHODS:

The 827 patients with one or more epileptic seizures seen at our hospital between 1 June 1994 and 1 March 2011 were included and prospectively followed. A diagnosis of benign infantile epilepsy was made in patients that fulfilled the following criteria at six month of evolution: one or more focal and/or generalised seizures, onset before 24 months, no neurological deficit and normal neuroimaging and interictal EEG.

RESULTS:

77 cases (9%) met the diagnostic criteria. Semiology of the seizures was similar to that of other focal seizures in children under 24 months. 25% of the patients remained as isolated seizures. Among those with two or more seizures, the probability of achieving a 3 year initial remission without antiepileptic treatment was 86%. In the subgroup of patients with focal seizures without family history the probability was 74% and in five cases a global developmental delay/intellectual disability was detected thereafter.

CONCLUSIONS:

Benign infantile epilepsy is a frequent epileptic syndrome. Semiology of seizures is not useful to characterize the syndrome. A diagnosis of benign infantile epilepsy at six month of evolution implies a reasonably good prognosis, but possibly not as good as for other self-limited epilepsies of infancy.

Imágenes de resonancia magnética aportan nueva información sobre redes cerebrales asociadas al autismo

Alterations of White Matter Connectivity in Preschool Children with Autism Spectrum Disorder

Abstract

Purpose

To investigate the topologic architecture of white matter connectivity networks in preschool-aged children with a diagnosis of autism spectrum disorder (ASD) versus typical development (TD).

Materials and Methods

Forty-two participants were enrolled, including 21 preschool children with ASD (14 male children and seven female children; mean age, 4.56 years ± 0.97 [standard deviation]) and 21 children with TD (11 males and 10 females; mean age, 5.13 years ± 0.82). The diagnosis of ASD was determined according to the Diagnostic and Statistical Manual of Mental Disorders Global Assessment of Functioning scores (mean score, 8.00 ± 0.50). All participants underwent diffusion-tensor imaging (DTI) and T2-weighted imaging on a 3-T magnetic resonance system. A graph theoretical analysis was applied to investigate the topologic organization of the brain network including global and local topologic parameters. Statistical analysis was then performed for the comparison between the groups.

Results

Compared with the TD group, children with ASD demonstrated shortened characteristic path length (t1 = 0.536, t2 = 0.534, t3 = 0.523, t4 = 0.510, and t5 = 0.501; P < .05) and increased global efficiency (t1 = 0.499, t2 = 0.497, t3 = 0.486, t4 = 0.473, and t5 = 0.465; P < .05) and clustering coefficient (t1 = 0.673, t2 = 0.750, t3 = 0.757, t4 = 0.738, and t5 = 0.741; P < .05). Significant increases in nodal efficiency were mainly found in left pallidum (0.037 vs 0.032, respectively; P < .01) and right caudate nucleus (0.037 vs 0.032, respectively; P < .01) of the basal ganglia network.

Conclusion

Significantly altered patterns of global and local brain network topography may underlie the abnormal brain development in preschool children with ASD compared with those who have TD. The identification of altered structural connectivity in basal ganglia and paralimbic-limbic networks may point toward potential imaging biomarkers for preschool-age patients with ASD.

Detectan alteraciones cerebrales en personas sanas con riesgo de sufrir enfermedad de Alzheimer

Effects of APOE-ε4 allele load on brain morphology in a cohort of middle-aged healthy individuals with enriched genetic risk for Alzheimer's disease

Abstract

Introduction

Apolipoprotein E (APOE)-ε4 is the major genetic risk factor for Alzheimer's disease. However, the dose-dependent impact of this allele on brain morphology of healthy individuals remains unclear.

Methods

We analyzed gray matter volumes (GMvs) in a sample of 533 healthy middle-aged individuals with a substantial representation of ε4-carriers (207 heterozygotes and 65 homozygotes).

Results

We found APOE-ε4 additive GMv reductions in the right hippocampus, caudate, precentral gyrus, and cerebellar crus. In these regions, the APOE genotype interacted with age, with homozygotes displaying lower GMv after the fifth decade of life. APOE-ε4 was also associated to greater GMv in the right thalamus, left occipital gyrus, and right frontal cortex.

Discussion

Our data indicate that APOE-ε4 exerts additive effects on GMv in regions relevant for Alzheimer's disease pathophysiology already in healthy individuals. These findings elucidate the mechanisms underlying the increased Alzheimer's disease risk in ε4-carriers, suggesting a dose-dependent disease vulnerability on the brain structure level.

Keywords

Alzheimer's disease

APOE-ε4

Healthy individuals

Voxel-based morphometry

Gray matter volumes

Aging

Background

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder characterized by progressive cognitive impairment and a characteristic pattern of regional brain atrophy that starts in the hippocampus and medial temporal regions and then spreads to other cortical areas [1]. The two major neuropathologic features of AD are extracellular fibrillary amyloid β (Aβ) plaques and intracellular neurofibrillary tau tangles. AD pathology develops slowly with a protracted preclinical phase characterized by abnormal cerebral Aβ deposition in cognitively intact individuals [2]. The apolipoprotein E (APOE)-ε4 represents the major genetic risk factor for late-onset AD, with increasing copies of the ε4 allele being associated to greater AD risk and younger age of disease onset [3,4]. Three common polymorphic alleles referred as ε2, ε3, and ε4 code, respectively, three distinct apoeE isoforms, which differ among each other by a single amino acid, and depending on the allele pairs, they result in six possible diploid haplotypes. In the brain, apoE mediates neuronal delivery of cholesterol, which is an essential component for axonal growth, synaptic formation, and remodeling, and has an important role in Aβ metabolism. The apoE4 isoform (coded by the APOE-ε4 allele) has been shown to be less efficient in Aβ clearance and cholesterol transport than the other isoforms (apoE2 > apoE3 > apoE4) [4]. APOE-ε4-homozygous (HO) individuals are therefore an interesting population for studying the long-term effects of the lack of expression of the more efficient apoE isoform. Regarding the pathogenesis of AD, the mechanisms through which APOE-ε4 increases risk can be regarded as conferring a loss of neuroprotective function, gain of neurotoxic function, or both [4]. APOE-ε4 allele dose effects on memory decline have been reported in cognitively healthy individuals [5], and a dose-dependent hippocampal gray matter (GM) degeneration has been observed in AD patients [6,7]. However, only a few reports have assessed the impact of APOE-ε4 homozygosity on the brain morphology of healthy middle-aged subjects. One cross-sectional studyfound significantly reduced hippocampal volume in healthy APOE-ε4 homozygotes, as compared to ε4-heterozygotes and noncarriers (NC), without however reporting any ε4 dose-dependent effects [8]. In the follow-up of this study, an age-related hippocampal volume loss was found only in homozygotes, again not supporting for APOE-ε4 additive effects in this region [9]. On the other hand, Chen et al. [10]reported a significant correlation between APOE-ε4 gene dose and higher annualized rates of whole-brain atrophy in healthy individuals.

Aside from these reports, most of the studies in the literature pooled together APOE-ε4 homozygotes and heterozygotes into a single APOE-ε4 carrier category. Although longitudinal studies reported significantly faster decays of regional gray matter volume (GMv) in healthy carriers compared to NC [11,12], most cross-sectional studies which determined volumes in a priori–defined AD-sensitive cerebral regions did not find significant group differences [13–15]. Similarly, null findings were reported in studies using voxelwise techniques, such as voxel-based morphometry (VBM) [16–18]. By contrast, two studies using VBM reported GMv differences in brain regions including the hippocampus, lingual gyrus, and precuneus, when comparing carriers to NC [19,20]. More recently, Ten Kate et al. [21] reported decreased volume in the precuneus and insula in healthy middle-aged carriers of the risk allele as well as an interaction between APOE status and age in determining GMv in temporal and occipital regions. Discrepancies among studies might be in part due to the volumetric technique adopted and the difference in the samples' age, where studies including relatively older individuals tend to report significant differences compared to those including younger samples.

In the present study, we sought to determine the effects of APOE-ε4 allele load on brain morphology to better characterize the mechanisms through which APOE-ε4 confers an increased risk to develop AD in the healthy population. To this end, we used VBM in a cohort of healthy middle-aged individuals enriched for this genetic risk for AD (261 NC, 207 APOE-ε4 heterozygotes, and 65 APOE-ε4 homozygotes). We also sought to determine potential interactions between APOE status and age in determining GMv variability.