High BMP4 expression in low/intermediate risk BCP-ALL identifies children with poor outcomes.

Pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) outcome has improved in the last decades, but leukemic relapses are still one of the main problems of this disease. Bone morphogenetic protein 4 (BMP4) was investigated as a new candidate biomarker with potential prognostic relevance, and its pathogenic role was assessed in the development of disease. A retrospective study was performed with 115 pediatric patients with BCP-ALL, and BMP4 expression was analyzed by quantitative reverse transcription polymerase chain reaction in leukemic blasts at the time of diagnosis. BMP4 mRNA expression levels in the third (upper) quartile were associated with a higher cumulative incidence of relapse as well as a worse 5-year event-free survival and central nervous system (CNS) involvement. Importantly, this association was also evident among children classified as having a nonhigh risk of relapse. A validation cohort of 236 patients with BCP-ALL supported these data. Furthermore, high BMP4 expression promoted engraftment and rapid disease progression in an NSG mouse xenograft model with CNS involvement. Pharmacological blockade of the canonical BMP signaling pathway significantly decreased CNS infiltration and consistently resulted in amelioration of clinical parameters, including neurological score. Mechanistically, BMP4 favored chemoresistance, enhanced adhesion and migration through brain vascular endothelial cells, and promoted a proinflammatory microenvironment and CNS angiogenesis. These data provide evidence that BMP4 expression levels in leukemic cells could be a useful biomarker to identify children with poor outcomes in the low-/intermediate-risk groups of BCP-ALL and that BMP4 could be a new therapeutic target to blockade leukemic CNS disease.

Correction to: Computational assembly of a human Cytomegalovirus vaccine upon experimental epitope legacy.

After publication of the original article [1], we were notified that legends of Fig. 1 and Fig. 2 have been swapped.

Computational assembly of a human Cytomegalovirus vaccine upon experimental epitope legacy.

BACKGROUND: Human Cytomegalovirus (HCMV) is a ubiquitous herpesvirus affecting approximately 90% of the world population. HCMV causes disease in immunologically naive and immunosuppressed patients. The prevention, diagnosis and therapy of HCMV infection are thus crucial to public health. The availability of effective prophylactic and therapeutic treatments remain a significant challenge and no vaccine is currently available. Here, we sought to define an epitope-based vaccine against HCMV, eliciting B and T cell responses, from experimentally defined HCMV-specific epitopes. RESULTS: We selected 398 and 790 experimentally validated HCMV-specific B and T cell epitopes, respectively, from available epitope resources and apply a knowledge-based approach in combination with immunoinformatic predictions to ensemble a universal vaccine against HCMV. The T cell component consists of 6 CD8 and 6 CD4 T cell epitopes that are conserved among HCMV strains. All CD8 T cell epitopes were reported to induce cytotoxic activity, are derived from early expressed genes and are predicted to provide population protection coverage over 97%. The CD4 T cell epitopes are derived from HCMV structural proteins and provide a population protection coverage over 92%. The B cell component consists of just 3 B cell epitopes from the ectodomain of glycoproteins L and H that are highly flexible and exposed to the solvent. CONCLUSIONS: We have defined a multiantigenic epitope vaccine ensemble against the HCMV that should elicit T and B cell responses in the entire population. Importantly, although we arrived to this epitope ensemble with the help of computational predictions, the actual epitopes are not predicted but are known to be immunogenic.

Descriptive analysis of the Test of Everyday Attention for Children in a Spanish Normative Sample.

INTRODUCTION: Test of Everyday Attention for Children (TEA-Ch) has been validated in different countries demonstrating that it is an instrument with a correct balance between reliability and duration. Given the shortage of trustworthy instruments of evaluation in our language for infantile population we decide to explore the Spanish version of the TEA-Ch. METHODS: We administered TEA-Ch (version A) to a sample control of 133 Spanish children from 6 to 11 years enrolled in school in the Community of Madrid. Four children were selected at random by course of Primary Education, distributing the sex of equivalent form. Descriptive analysis and comparison by ages and sex in each of the TEA-Ch´s subtests were conducted to establish a profile of the sample. In order to analyze the effect of the age, subjects were grouped in six sub-samples: 6, 7, 8, 9, 10 and 11 years-old. RESULTS: This first descriptive analysis demonstrates age exerted a significant effect on each measure, due to an important “jump” in children´s performance between 6 and 7 years-old. The effect of sex was significant only in two visual attention measures (Sky Search & Map) and interaction age and sex exerted a significant effect only in the dual task (Score DT). CONCLUSIONS: The results suggest that the Spanish version of the TEA-Ch (A) might be a useful instrument to evaluate attentional processes in Spanish child population.

Regional differences in low birth weight in Spain: biological, demographic and socioeconomic variables.

The geographic and demographic dimensions of Spain, in terms of surface and number of inhabitants, and its heterogeneous socioeconomic development offer an adequate opportunity to study the provincial differences in birth weight from 1996 to 2010, focusing on possible factors determining the relative frequency of low birth weight. The study analysed geographic differences with regard to biological, demographic and socioeconomic factors that interfere with the female reproductive pattern. The variables considered here were: birth order, proportion of premature deliveries, mother's age, multiparity, mother's country of origin and professional qualifications. Two periods (1996-2000 and 2006-2010) were compared by means of principal components analysis. An increase in the relative frequency of deliveries weighing less than 2500 g occurred in most of the 52 geographic units studied, differences being significant in 42. Only in five cases was there a non-significant reduction in the proportion of low weight births. The first component after principal component analysis indicated that low birth weight was positively related to maternal age and to multiple deliveries, and negatively to the mother's low professional qualification. The second component related positively to the incidence of premature deliveries and to non-Spanish status and negatively in the case of primiparous mothers. The progressive increase in low birth weight incidence observed in Spain from 1996 onwards has occurred with considerable variation in each province. In part, this diversity can be attributed to the unequal reproductive patterns of immigrant mothers.

Clinical and Demographic Characteristics of Binge Drinkers Associated with Lack of Efficacy of Brief Intervention and Medical Advice.

UNLABELLED: Brief Counseling Intervention (BCI) and Medical advice (MA) are psychotherapeutic approaches used for the treatment of binge drinkers in Primary Care. Although binge drinking is a common pattern of alcohol misuse in Europe and in the US, no studies have evaluated those subjects who do not respond to Brief Counseling Interventions or Medical Advice. OBJECTIVE: To determine the clinical and demographic characteristics of binge drinkers in whom BCI or MA are not effective in reducing harmful alcohol use. METHODS: This is a secondary analysis of data from a randomized alcohol brief intervention trial with a 12-month follow-up period. A total of 674 subjects (89%) participated right through to the end of the study. The primary outcome measure was change in harmful alcohol use from baseline to 12 months. RESULTS: The strongest baseline predictors of harmful alcohol use during follow-up were educational status, young adults, and high number of cigarettes smoked, present family history of alcoholism, treatment condition and number of drinks per episode of binge drinking. CONCLUSIONS: Binge drinkers are a heterogeneous group that responds to brief intervention or MA but in a subgroup of them these interventions fail to prevent harmful alcohol use. Other interventions should be implemented for these subjects.

La Intervención Breve (IB) y el Consejo Médico simple (CM) son intervenciones psicoterapéuticas usadas para el tratamiento del consumo de alcohol por atracones en Atención Primaria. A pesar de la frecuencia de este patrón de abuso en Europa y en los Estados Unidos, ningún estudio ha evaluado las características de los sujetos que no responden a esas dos técnicas. Objetivo. Determinar las características demográficas y clínicas de los bebedores por atracones en los que la IB y el CM no son efectivos para la reducción del consumo perjudicial de alcohol. Métodos. Se trata de un análisis secundario de los datos obtenidos en un ensayo aleatorizado de intervención breve en alcohol con un período de seguimiento de 12 meses. Un total de 674 sujetos (89%) participaron durante todo el estudio hasta el final. La variable principal fue el cambio en el uso perjudicial de alcohol tras 12 meses de seguimiento. Resultados. Para ambos grupos de tratamiento las variables que predecían la continuidad en el consumo perjudicial tras el seguimiento eran: bajo nivel educativo, ser jóvenes, el número de cigarrillos fumados, la historia familiar de alcoholismo y la gravedad del consumo de alcohol basalmente. Conclusiones. Las características clínicas y sociodemográficas de los sujetos con un patrón de consumo de alcohol por atracones atendidos en Atención primaria influyen en el pronóstico de las Intervenciones breves y del Consejo Médico.

S-Adenosylmethionine Decreases Bacterial Translocation, Proinflammatory Cytokines, Oxidative Stress and Apoptosis Markers in Hepatic Ischemia-Reperfusion Injury in Wistar Rats.

Hepatic ischemia/reperfusion injury (IRI) can seriously impair liver function. It is initiated by oxidative stress, resulting in inflammation and apoptosis-induced cellular damage. Glutathione (GSH) prevents oxidative stress. S-Adenosylmethionine (SAMet) is a GSH synthesis precursor that avoids the deficit in SAMet-synthetase activity and contributes to intracellular ATP repletion. It also acts as a methyl group donor, stabilizing hepatocyte membranes, among other functions. This study investigated the effect of SAMet on bacterial translocation and levels of proinflammatory cytokines, oxidative stress and apoptosis markers in male Wistar rats subjected to hepatic IRI. Animals were randomly divided into six groups: (1) sham operation, (3) animals undergoing 60 min of ischemia of the right lateral lobe for temporary occlusion of the portal vein and hepatic artery plus 10 min of reperfusion, and (5) the same as (3) but with a reperfusion period of 120 min. Groups 2, 4 and 6, respectively, are the same as (1), (3) and (5), except that animals received SAMet (20 mg/kg) 15 min before ischemia. GSH, ATP, lipid peroxidation (LPO), TNF-α, IL-1ß, IL-6, total caspase-1 and caspase-9, total and cleaved caspase-3, and phosphatidylcholine were determined in the liver. Endotoxin, TNF-α, IL-1ß, IL-6, IL-10 and LPO in vena cava and portal vein blood samples were also measured. Endotoxin and LPO levels as well as proinflammatory cytokines and apoptotic markers increased significantly in animals undergoing IRI, both after 10 and 120 min of reperfusion. IRI produced a significant decrease in GSH, ATP, portal IL-10 and phosphatidylcholine. SAMet treatment prevented these effects significantly and increased survival rate. The study suggests that SAMet exerts protective effects in hepatic IRI.

The effects of adiponectin and leptin on human endothelial cell proliferation: a live-cell study.

The effect of adiponectin and leptin on the proliferation of the human microvascular endothelial cell line (HMEC-1) was studied in the absence or presence of fetal bovine serum (FBS). The participation of extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase/Akt (PI-3K/Akt) pathways in this effect were evaluated. We studied the effect of both adipokines on the motility, mitosis, proliferation and cell death processes of HMEC-1 cells using live-cell imaging techniques. Adiponectin but not leptin further increased the proliferative effect induced by FBS on HMEC-1. This effect seems to be the consequence of an increase in the mitotic index in adiponectin-treated cells when compared to untreated ones. The presence of either the mitogen-activated protein kinase (MAPK) inhibitor (PD98059), or PI-3K inhibitor (LY294002), reduced the effect of adiponectin in a dose-dependent manner. Neither adipokine was able to affect HMEC-1 proliferation in FBS-free conditions. Duration of mitosis, cell motility and the cell death process were similar in all conditions. These data suggest that adiponectin and leptin exert different effects on endothelial cell function. Adiponectin was able to potentiate proliferation of HMEC-1. This effect involves the activation of both PI3-K/Akt and ERK/MAPK pathways. However, it seems to exert minimal effects on HMEC-1 function in the case of leptin.

Apolipoprotein E ɛ4-related effects on cognition are limited to the Alzheimer's disease spectrum.

Whether the deleterious effects of APOE4 are restricted to the Alzheimer's disease (AD) spectrum or cause cognitive impairment irrespectively of the development of AD is still a matter of debate, and the focus of this study. Our analyses included APOE4 genotype, neuropsychological variables, amyloid-ßeta (Aß) and Tau markers, FDG-PET values, and hippocampal volumetry data derived from the healthy controls sample of the ADNI database. We formed 4 groups of equal size (n = 30) based on APOE4 carriage and amyloid-PET status. Baseline and follow-up (i.e., 48 months post-baseline) results indicated that Aß-positivity was the most important factor to explain poorer cognitive performance, while APOE4 only exerted a significant effect in Aß-positive subjects. Additionally, multiple regression analyses evidenced that, within the Aß-positive sample, hippocampal volumetry explained most of the variability in cognitive performance for APOE4 carriers. These findings represent a strong support for the so-called preclinical/prodromal hypothesis, which states that the reported differences in cognitive performance between healthy carriers and non-carriers are mainly due to the APOE4's capability to increase the risk of AD. Moreover, our results reinforce the notion that a synergistic interaction of Aß and APOE4 elicits a neurodegenerative process in the hippocampus that might be the main cause of impaired cognitive performance.

Brain signal complexity in adults with Down syndrome: Potential application in the detection of mild cognitive impairment.

Background: Down syndrome (DS) is considered the most frequent cause of early-onset Alzheimer's disease (AD), and the typical pathophysiological signs are present in almost all individuals with DS by the age of 40. Despite of this evidence, the investigation on the pre-dementia stages in DS is scarce. In the present study we analyzed the complexity of brain oscillatory patterns and neuropsychological performance for the characterization of mild cognitive impairment (MCI) in DS. Materials and methods: Lempel-Ziv complexity (LZC) values from resting-state magnetoencephalography recordings and the neuropsychological performance in 28 patients with DS [control DS group (CN-DS) (n = 14), MCI group (MCI-DS) (n = 14)] and 14 individuals with typical neurodevelopment (CN-no-DS) were analyzed. Results: Lempel-Ziv complexity was lowest in the frontal region within the MCI-DS group, while the CN-DS group showed reduced values in parietal areas when compared with the CN-no-DS group. Also, the CN-no-DS group exhibited the expected pattern of significant increase of LZC as a function of age, while MCI-DS cases showed a decrease. The combination of reduced LZC values and a divergent trajectory of complexity evolution with age, allowed the discrimination of CN-DS vs. MCI-DS patients with a 92.9% of sensitivity and 85.7% of specificity. Finally, a pattern of mnestic and praxic impairment was significantly associated in MCI-DS cases with the significant reduction of LZC values in frontal and parietal regions (p = 0.01). Conclusion: Brain signal complexity measured with LZC is reduced in DS and its development with age is also disrupted. The combination of both features might assist in the detection of MCI within this population.

Quantitative modeling of peptide binding to TAP using support vector machine.

The transport of peptides to the endoplasmic reticulum by the transporter associated with antigen processing (TAP) is a necessary step towards determining CD8 T cell epitopes. In this work, we have studied the predictive performance of support vector machine models trained on single residue positions and residue combinations drawn from a large dataset consisting of 613 nonamer peptides of known affinity to TAP. Predictive performance of these TAP affinity models was evaluated under 10-fold cross-validation experiments and measured using Pearson's correlation coefficients (R(p)). Our results show that every peptide position (P1-P9) contributes to TAP binding (minimum R(p) of 0.26 +/- 0.11 was achieved by a model trained on the P6 residue), although the largest contributions to binding correspond to the C-terminal end (R(p) = 0.68 +/- 0.06) and the P1 (R(p) = 0.51 +/- 0.09) and P2 (0.57 +/- 0.08) residues of the peptide. Training the models on additional peptide residues generally improved their predictive performance and a maximum correlation (R(p) = 0.89 +/- 0.03) was achieved by a model trained on the full-length sequences or a residue selection consisting of the first 5 N- and last 3 C-terminal residues of the peptides included in the training set. A system for predicting the binding affinity of peptides to TAP using the methods described here is readily available for free public use at http://imed.med.ucm.es/Tools/tapreg/.

Temporal and territorial analysis of multiple deliveries in Spain (1900-2006).

Temporal variations in the frequency of multiple maternities in many Western European countries have been described. However, within a single country, regional differences are observed. Urban industrialized regions and rural agricultural areas have experienced in recent decades a distinct decline in multiple deliveries, which in cases have been related to maternal age and parity changes. Research on multiple deliveries in Spain is scarce and none of the studies go back to the beginning of the 20th century or consider regional variation over an extended period of time. The present paper is a yearly study on multiple deliveries in Spain since 1900 including a geographical analysis. Rather than dealing with recent changes in multi-parity, this paper is concerned with Spain's long-term national variation (between 1900 and 2006). The changing pattern of double and triple deliveries was analyzed using data from the Spanish National Statistics Institute (INE). Twinning rates in Spain are low in comparison to those of equivalent periods in other countries, and the minimum rates correspond to the 1980s decade. Results were interpreted by taking into account the influence of age at maternity and reproductive variation up to 1990. A good fit between observed and predicted rates was obtained after the application of models, which besides maternal age and parity, include their interaction. Regarding territorial variability, the values corresponding to southern, northern and insular Spanish provinces are consistent with an earlier reduction of the crude birth rate in the north-east regions and latter in the southern regions and the Canary Islands.

Mate choice in Olivenza: influence of border change on Spanish-Portuguese lineages.

The mating pattern in a population determines the next generation gene pool and therefore its genetic structure. Besides socio-cultural and geographic factors, political barriers may influence the formation of couples. The present paper studies how the change of national border affected the mating pattern of Olivenza in Badajoz Province (Spain), which experienced a change of domain from Portugal to Spain in 1801. For the period analysed (1750-1850), 954 Catholic marriage records were transcribed. Data were sorted by decades in order to make a temporal study possible and analysed by means of diversity and repeated-pairs of surnames. Following the change of border the mating pattern modified. Coinciding with a larger number of mixed marriages with Spaniards, there was a progressive rise in the diversity of surnames. From 1811 to 1820 the analysis of repeated-pairs of surnames indicates the existence of preferential matings within Spanish and Portuguese lineages. After 1821 the above pattern became less clear due to the disappearance of the Spanish-Portuguese restrictions on choice of mate.

Immunocytochemical detection of synaptophysin in C57BL/6 mice cochlea during aging process.

Aged mammals frequently exhibit a bilateral, progressive, and symmetric deafness related to the degeneration of auditory receptor. However, little is still known about aging effects on synapses in this receptor. Synaptophysin (Syp) is a 38 kDa Ca2+ binding glycoprotein widely found in presynaptic membrane and vesicles. The Syp has been found in presynaptic buttons of efferent auditory fibers, within the developing and adult auditory receptor. The detection of Syp in aged cochleae could provide relevant information about synaptic changes and receptor degeneration process observed in old animals. This paper focuses on aging linked changes related to the presence of Syp in cochleae of C57BL/6J mice (from 1 to 24 months old). Results showed that during the first months of age, no significant changes were observed in the Syp distribution under the basal pole of inner (IHCs) neither the outer (OHCs) hair cells. At six months of age, a significant decrease of Syp immunocytochemical detection appeared in fibers under the most external row of OHCs, but restricted to the cochlear basal coil. Only a very scarce reduction of Syp was noted under the IHC and the other OHC rows, also at the basal coil. From mice 9 months old on, a progressive decrease of the presence of Syp was found under IHC and all OHC rows starting at the basal coil and reaching the apical coil in the oldest mice. All these data could indicate that the cochlea aging process early affects to presynaptic membrane proteins of efferent endings fibers. This early alteration of cochleae efferent synapses could be involved in the whole degeneration of the Corti's organ.

Emotional Intelligence as an Evolutive Factor on Adult With ADHD.

Objective: ADHD adults exhibit deficits in emotion recognition, regulation, and expression. Emotional intelligence (EI) correlates with better life performance and is considered a skill that can be learned and developed. The aim of this study was to assess EI development as ability in ADHD adults, considering the effect of comorbid psychiatric disorders and previous diagnosis of ADHD. Method: Participants (n = 116) were distributed in four groups attending to current comorbidities and previous ADHD diagnosis, and administered the Mayer-Salovey-Caruso Emotional Intelligence Test version 2.0 to assess their EI level. Results: ADHD adults with comorbidity with no previous diagnosis had lower EI development than healthy controls and the rest of ADHD groups. In addition, ADHD severity in childhood or in adulthood did not influence the current EI level. Conclusion: EI development as a therapeutic approach could be of use in ADHD patients with comorbidities.

Evaluation of the Feasibility of a Two-Week Course of Aquatic Therapy and Thalassotherapy in a Mild Post-Stroke Population.

Strokes are a leading cause of disability in developed countries. Patients with disabilities need rehabilitation to improve their physical functioning, mental status, and quality of life. Currently, no high-quality evidence can be found attesting the benefits of any of the interventions that are nowadays used. Water-based exercise may improve the physical conditions and quality of life of people in the post-stroke phase. The objective of this study is to test whether aquatic therapy in an enriched environment at the seaside (a thalassotherapy center) could play a role in this condition. A quasi-experimental prospective study consisting of a specific program assessed 62 patients with a mild-moderate disability pre- and post-2 weeks of intensive treatment. They followed a thalassotherapy regimen including aquatic therapy in a sea water pool at 32-34 °C for 45 min daily five times a week. The outcomes measured were the Berg Balance scale, the Timed Up and Go test, the 10-meter walking test, the 6-min walking test, the Pain Visual Analogue Scale, the WHO Well-being index, EuroQoL VAS and EuroQoL 5D. We observed a significant improvement in all outcomes measured (p < 0.001, except mobility EuroQoL p < 0.05), except in the other four dimensions of the EuroQoL 5D and 10-metre walking test (NS). Conclusion: A two-week intensive course of aquatic therapy and thalassotherapy may be beneficial in the short term by reducing pain and improving the functional status and overall well-being of post-stroke patients.

The Impact of Adult ADHD in the Quality of Life Profile.

OBJECTIVE: In this multicenter, cross-sectional study, we aimed to investigate the quality of life (QoL) and the neuropsychological and clinical characteristics of adults with ADHD with different developmental pathways. METHOD: Our study sample included 25 control (healthy) participants, 31 patients with newly diagnosed ADHD without comorbidities (ADHD-C-D), 31 with newly diagnosed ADHD with comorbidities (ADHD+C-D), and 29 with previously diagnosed ADHD with comorbidities (ADHD+C+D). RESULTS: Compared with controls, ADHDs had little differences in the attentional performance but showed higher impulsivity, more severe symptoms of depression and anxiety, and lower QoL. The ADHD+C-D group showed more severe symptoms of depression and anxiety than the ADHD+C+D group ( p = .037 and p = .008, respectively), and poorer QoL in the psychological health sphere ( p = .003). CONCLUSION: Differences between ADHD and control subjects were particularly remarkable in mood symptoms and QoL. Previous diagnosis might have a positive impact on mood symptoms and QoL in ADHD adults.

Factors associated with recent increase of multiple births in Spain.

The increased incidence of multiple deliveries in Spain, in addition to changes in age at maternity and parity, is attributed to assisted reproductive treatments, but the relative contribution of the latter to this rise remains uncertain, due to the scarce information provided by clinics practicing those treatments. Population based data (1984-2004), including information on mother's age, nationality, marital status, date of delivery, and the characteristics of each (parity, single or multiple), and sex of newborns were provided by the Spanish Institute of Statistics. Twinning and triplet deliveries relate to maternal age, parity, and nationality. For younger ages (or= 40) rates increased after 1994. From 1984 to 2004 the percentage of twins of opposite sex increased from 24.31 to 36.58 per cent. Since 1997, Spanish and non-Spanish mothers differentiate with respect to multiple maternity at ages over 30. In addition to unmarried Spanish women, immigrants constitute a reliable reference group that determines the convenience of segregating information on multiple deliveries respecting origin. The proportion of twins and triplets of opposite sex, maternal age, and parity patterns observed are concordant with a differential access to reproductive treatments depending on the woman's age. The present norm regulating the maximum number of fertilizations per cycle and the demand for these treatments explain the high incidence of multiple deliveries in Spain. A modified logistic curve predicts a stabilization of multiple deliveries, which will probably continue to be high in Spain.

Physical activity effects on the individual alpha peak frequency of older adults with and without genetic risk factors for Alzheimer's Disease: A MEG study.

OBJECTIVE: Since a cure for Alzheimer's Disease (AD) is yet to be discovered, attention has shifted towards prevention. Physical activity (PA) emerged as a notorious lifestyle factor that could influence brain structure and function. The individual alpha peak frequency (IAPF) is a measure that summarizes the spectral content of brain signals and has been proven to be sensitive to both AD pathology and PA interventions. Therefore, our goal was to unravel whether chronic PA modulates IAPF and if APOE ɛ4 carriage moderates this relationship. METHODS: We analyzed 4-minutes of resting-state magnetoencephalographic recordings from 100 healthy elders that provided self-reported measures of PA, and the IAPF was calculated. RESULTS: We found that IAPF was negatively influenced by age and APOE and positively influenced by PA. The effect of PA on IAPF only remained significant for the ɛ4 non-carriers group. CONCLUSIONS: PA is positively associated to higher IAPF in healthy older adults and could potentially act as a protective factor against cognitive decline. Nevertheless, such effect is non-significant among elders who are more vulnerable to developing AD due to their genetic carriage. SIGNIFICANCE: This investigation offers the first neurophysiological evidences on the combined effects of APOE genotype and PA in healthy elders.

Magnetoencephalographic parietal delta dipole density in mild cognitive impairment: preliminary results of a method to estimate the risk of developing Alzheimer disease.

BACKGROUND: Subjects with mild cognitive impairment (MCI) are at a higher risk of experiencing Alzheimer disease (AD). Magnetoencephalographic temporoparietal dipole densities of low-frequency activity are good predictors of individuals' cognitive status, and might be a useful tool to investigate the conversion from MCI to AD. OBJECTIVE: To investigate the role of low-frequency dipole densities as predictors of the risk of developing AD. DESIGN: Whole-head magnetoencephalographic recordings were obtained from 19 probable AD patients, 17 MCI patients, and 17 healthy control subjects. The generators of focal magnetic slow waves were located using a single moving dipole model. RESULTS: Left parietal delta dipole density permitted a reliable classification of AD and MCI patients. The MCI patients were divided into 2 groups based on the median left parietal delta dipole density, and were followed up for 2 years. The estimated relative risk of conversion to AD was increased by 350% in those MCI patients with high left parietal delta dipole density scores. CONCLUSIONS: Results confirmed the important role of parietal delta dipole density in the evaluation of AD and MCI. A magnetoencephalographic-based assessment of AD and MCI patients might be considered a useful clinical test in the near future.