[Cognitive reserve. A proposal for a new conceptual hypothesis]. / Reserva cognitiva. Propuesta de una nueva hipótesis conceptual.

INTRODUCTION: Currently, there is a lack of consensus on the definition of the concept of cognitive reserve, the elements that make it up and the relationship between them, despite the notable increase in the number of studies conducted on the subject. MATERIALS AND METHODS: A multi-domain conceptual model with two factors is proposed: general reserve and domain-specific reserve. The domain-specific reserve, in turn, would be divided into four areas: cognitive, behavioural, emotional and social. RESULTS: The proposed model seems to provide a more comprehensive explanation of the construct, with new elements of study to be taken into consideration. CONCLUSIONS: This proposal aims to introduce a new perspective into the study of cognitive reserve and to open up new lines of clinical and academic research with the aim of demonstrating its feasibility.

TITLE: Reserva cognitiva. Propuesta de una nueva hipótesis conceptual.Introducción. Actualmente, se observa una falta de consenso en la definición del concepto de reserva cognitiva, los elementos que la conforman y la relación entre ellos, a pesar del notable aumento de los estudios relacionados con ésta. Materiales y método. Se plantea un modelo conceptual multidominio de dos factores: reserva general y reserva específica de dominio. A su vez, la reserva específica de dominio quedaría dividida en cuatro áreas: cognitiva, conductual, emocional y social. Resultados. El modelo planteado parece dar una explicación más amplia del constructo, con nuevos elementos de estudio que se deben tener en consideración. Conclusiones. Con esta propuesta, se pretende aportar una nueva perspectiva al estudio de la reserva cognitiva y abrir nuevas líneas de investigación tanto a nivel clínico como académico para demostrar su viabilidad.

Reserva cognitiva. Propuesta de una nueva hipótesis conceptual / Cognitive reserve. A proposal for a new conceptual hypothesis

Introducción: Actualmente, se observa una falta de consenso en la definición del concepto de reserva cognitiva, los elementos que la conforman y la relación entre ellos, a pesar del notable aumento de los estudios relacionados con ésta. Materiales y método. Se plantea un modelo conceptual multidominio de dos factores: reserva general y reserva específica de dominio. A su vez, la reserva específica de dominio quedaría dividida en cuatro áreas: cognitiva, conductual, emocional y social. Resultados: El modelo planteado parece dar una explicación más amplia del constructo, con nuevos elementos de estudio que se deben tener en consideración. Conclusiones: Con esta propuesta, se pretende aportar una nueva perspectiva al estudio de la reserva cognitiva y abrir nuevas líneas de investigación tanto a nivel clínico como académico para demostrar su viabilidad.(AU)

INTRODUCTION: Currently, there is a lack of consensus on the definition of the concept of cognitive reserve, the elements that make it up and the relationship between them, despite the notable increase in the number of studies conducted on the subject. MATERIALS AND METHODS: A multi-domain conceptual model with two factors is proposed: general reserve and domain-specific reserve. The domain-specific reserve, in turn, would be divided into four areas: cognitive, behavioural, emotional and social. RESULTS: The proposed model seems to provide a more comprehensive explanation of the construct, with new elements of study to be taken into consideration. CONCLUSIONS: This proposal aims to introduce a new perspective into the study of cognitive reserve and to open up new lines of clinical and academic research with the aim of demonstrating its feasibility.(AU)

Circadian monitoring as an aging predictor.

The ageing process is associated with sleep and circadian rhythm (SCR) frailty, as well as greater sensitivity to chronodisruption. This is essentially due to reduced day/night contrast, decreased sensitivity to light, napping and a more sedentary lifestyle. Thus, the aim of this study is to develop an algorithm to identify a SCR phenotype as belonging to young or aged subjects. To do this, 44 young and 44 aged subjects were recruited, and their distal skin temperature (DST), activity, body position, light, environmental temperature and the integrated variable TAP rhythms were recorded under free-living conditions for five consecutive workdays. Each variable yielded an individual decision tree to differentiate between young and elderly subjects (DST, activity, position, light, environmental temperature and TAP), with agreement rates of between 76.1% (light) and 92% (TAP). These decision trees were combined into a unique decision tree that reached an agreement rate of 95.3% (4 errors out of 88, all of them around the cut-off point). Age-related SCR changes were very significant, thus allowing to discriminate accurately between young and aged people when implemented in decision trees. This is useful to identify chronodisrupted populations that could benefit from chronoenhancement strategies.

Impact of a shift work-like lighting schedule on the functioning of the circadian system in the short-lived fish Nothobranchius furzeri.

Adult Nothobranchius furzeri of the MZM-04/10 strain were individually kept and subjected to a "5 + 2" shifting lighting schedule (SHIFT) for 8 weeks in order to evaluate the desynchronizing effects of a simulated human-like shift-work schedule on the functioning of the circadian system (CS). With this aim, sixteen 21-week-old N. furzeri were placed into a Morning, Night and Evening schedule (lights on from 08:00 to 16:00, 00:00 to 08:00 and 16:00 to 00:00 h, respectively) and fed once a day in the middle of the corresponding photophase (12:00, 04:00 and 20:00 h, respectively). Then, in the weekends (2 days), fish were always returned to the Morning shift. As controls, 16 fish were maintained under a non-shifting LD cycle condition (CONTROL) throughout the whole experiment, with lights on from 08:00 to 16:00 h. Rest-activity rhythm (RAR) of fish subjected to SHIFT showed several symptoms of chronodisruption, such as a decrease in the percentage of diurnal activity and a reduction of the relative amplitude and the circadian function index with time. When a periodogram analysis was performed, RAR of N. furzeri under SHIFT conditions showed up to three separate circadian components: one longer than 24 h (26.5 h) that followed the weekly 8 h delays; a short-period component (~23 h) that was related to the weekend's phase advances, and finally, a 24 h component. The shifting LD schedule also affected fish CS at a molecular level, with several significant differences in the expression of core genes of the molecular clock (bmal1, clock, rorα, rev-erbα) between SHIFT and CONTROL animals. RAR impairment along with changes in clock gene expression could be associated with high stress and accelerated aging in these fish.

Ontogeny and aging of the distal skin temperature rhythm in humans.

In circadian terms, human ontogeny is characterized by the emergence of a daily pattern, from a previous ultradian pattern, for most variables during the first 6 months of life. Circadian aging in humans is characterized by a phase advance, accompanied by rhythm fragmentation and flattening. Despite an expanding body of literature focused on distal skin temperature, little information is available about the ontogeny and practically nothing about age-related changes in this rhythm. Thus, the aim was to evaluate the degree of maturation and aging of the circadian pattern of distal skin temperature to identify those parameters that are modified throughout life and could be used to differentiate subjects according to their age. For this, distal skin temperature was measured in 197 volunteers (55 % women), including babies aged 15 days (30 subjects), 1 month (28 subjects), 3 months (31 subjects), and 6 months (10 subjects); young adults aged 19 years (37 subjects); middle-aged persons aged 46 years (27 subjects); older people aged 72 (34 subjects). Circadian system maturation was associated with an increase in amplitude and a reduction in skin temperature during sleep. During adulthood, women showed a more robust pattern (lower fragmentation, and higher night-time temperature, amplitude, circadian function index, and first harmonic relative power); however, these differences were lost with aging, a period of life that was consistently associated with a phase advance of the rhythm. In summary, distal skin temperature pattern can be used as a robust variable to discern between different ages throughout the life.

Parámetros y Tendencias Genéticas para Característica de Crecimiento Predestete en una Población Bovina Multirracial en Colombia / Parameters and Genetic Trends for Preweaning Growth Traits in a Multibreed Cattle Population in Colombia

El presente estudio tuvo como objetivo estimar las heredabilidades, correlaciones, heterosis y tendencias genéticas para peso al nacer (PN) y al destete ajustado (PDA; 270 d) en una población multirracial Angus×Brahman en el Trópico bajo colombiano. Se utilizaron 561 registros de pesos al nacer y al destete entre los años 1999 al 2010. Los datos fueron analizados mediante un modelo bivariado que incluyó los efectos fijos de grupo contemporáneo (año-época de nacimiento-sexo), edad de la madre, efectos genéticos directos y maternos de raza, heterosis individual y materna; y los efectos aleatorios genéticos directos y maternos del animal, ambiente permanente materno y residual. Los componentes de varianza se estimaron por el método de máxima verosimilitud restringida, mediante el programa AIREML. Las heredabilidades directas estimadas para PN y PDA fueron 0,08 ± 0,005 y 0,10 ± 0,006, respectivamente. La heredabilidad materna para PN fue de 0,04 ± 0,002 y 0,08 ± 0,005 para PDA. Se encontraron correlaciones genéticas negativas entre efectos directos y maternos para PN (-0,51 ± 0,02) y PDA (-0,21 ± 0,03) y entre efectos directos para PN y maternos para PDA (-0,50 ± 0,02). Las tendencias genéticas para efectos directos y maternos fueron cercanas a cero y no significativas (P>0,05). Las heredabilidades directas y maternas para ambas características, sugieren que se deben mejorar y homogenizar en la población las condiciones de nutrición y manejo para mejorar el crecimiento de los animales en la fase predestete. Las tendencias genéticas indican, que la intensidad de selección aplicada a esta población multirracial no fue suficiente para influir sobre los valores de cría directos y maternos durante los años de estudio.

The aim of this study was to estimate heritabilities, correlations, heterosis, and genetic trends for birth weight (BW) and adjusted weight at weaning (AWW, 270 d) in a multibreed Angus × Brahman population in the Colombian tropical lowlands. A total of 561 records of BW and weaning weight from 1999 to 2010 were used. Data were analyzed using a bivariate model, which included the fixed effects of contemporary group (year-season of birth-sex), age of mother, direct genetic effects and maternal effects of breed, individual and maternal heterosis; and the direct and maternal genetic random effects of the animal, maternal permanent environment, and residuals. Variance components were estimated by the restricted maximum likelihood method, using the AIREML program. Estimates of direct heritability for BW and AWW were 0.08 ± 0.005 and 0.10 ± 0.006, respectively. The maternal heritability for BW was 0.04 ± 0.002 and 0.08 ± 0.005 for AWW. Negative genetic correlations were found between direct and maternal effects for BW (-0.51 ± 0.02) and AWW (-0.21 ± 0.03), and between direct effects for BW and maternal for AWW (-0.50 ± 0.02). The genetic trends for direct and maternal effects were closed to zero and not statistically significant (P>0.05). The direct and maternal heritabilities for both traits suggest that nutrition conditions and management should be improved and homogenize in the population to improve animal growth in the pre-weaning phase. Genetic trends indicate that the selection intensity applied to this multiracial population was not enough to exert an influence on the direct breeding and maternal values during the years of the study.

Circadian rhythmicity as a predictor of weight-loss effectiveness.

OBJECTIVES: Some of the major challenges associated with successful dietary weight management include the identification of individuals not responsive to specific interventions. The aim was to investigate the potential relationship between weight loss and circadian rhythmicity, using wrist temperature and actimetry measurements, in women undergoing a weight-loss program, in order to assess whether circadian rhythmicity could be a marker of weight-loss effectiveness. METHODS: Participants were 85 overweight and obese women (body mass index, BMI: 30.24±4.95 kg m(-2)) subjected to a weight-reduction program. Efficacy of the treatment was defined as total weight loss, percentage of initial weight and weekly weight loss rates. Circadian rhythmicity in wrist temperature motor activity and position were analyzed using different sensors. RESULTS: Lower weight loss was related with a more flattened pattern measured as amplitude from cosinor (r=0.235, P=0.032), a higher fragmentation of rhythms determined by higher intradaily variability (IV) (r=-0.339, P=0.002), and an impaired wrist temperature circadian rhythm determined by the means of Circadian Function Index (r=0.228, P=0.038). Further analyses showed that low responders displayed lower amplitude (0.71±0.36 versus 1.24±0.62, P=0.036) and higher fragmentation of the circadian rhythm (0.24±0.11 versus 0.15±0.07, P=0.043) than high responders. Whereas we did not find significant differences in total activity rates between high responders and low responders, we found significant differences for the mean values of body position for high responders (39.12±3.79°) as compared with low responder women (35.31±2.53°, P=0.01). CONCLUSIONS: Circadian rhythms at the beginning of the treatment are good predictors of future weight loss. Further treatment should consider chronobiological aspects to diagnose obesity and effectiveness of treatments.

Differences in circadian rhythmicity in CLOCK 3111T/C genetic variants in moderate obese women as assessed by thermometry, actimetry and body position.

INTRODUCTION: Genetics is behind our circadian machinery. CLOCK (Circadian Locomotor Output Cycles Kaput) 3111T/C single-nucleotide polymorphism (SNP) has been previously related to obesity and weight loss. However, phenotypic association and functionality of CLOCK 3111 locus is still unknown. The aim of this study was to determine, in free-living conditions, if the presence of CLOCK 3111C in overweight women could be related to (a) circadian disorders, and (b) changes in sleep quality, to improve understanding of the previously demonstrated associations with obesity and reduced weight loss of the C carriers. METHODS: Wrist temperature, actimetry and position (TAP) and TAP variables were measured as markers of circadian functionality during 8 consecutive days. A rest-activity and food diary was also completed, whereas sleep quality was determined by domiciliary polysomnography. We recruited 85 women who were overweight with body mass index (BMI) of 28.59±4.30 kg m(-2) and age 43±12 years. From this sample, we found that 43 women were carrying the minor allele (C) for CLOCK 3111T/C SNP and 42 women were TT carriers (major allele carriers). Both groups of patients were matched for number, age, obesity parameters and energy intake. RESULTS: Compared with TT subjects, who showed more robust circadian rhythm profiles, patients with the C allele displayed significant circadian abnormalities: lower amplitude and greater fragmentation of the rhythm, a less stable circadian pattern and a significantly weakened circadian function, as assessed by the circadian function index (CFI). C subjects were also less active, started their activities later in the morning and were sleepier during the day, showing a delayed acrophase that characterizes 'evening-type' subjects. CONCLUSION: C genetic variants in CLOCK 3111T/C display a less robust circadian rhythm than TT and a delayed acrophase that characterizes 'evening-type' subjects. We support the notion that identifying CLOCK genotypes in patients may assist the therapist in characterization of the roots of the metabolic problem.

Wrist skin temperature, motor activity, and body position as determinants of the circadian pattern of blood pressure.

Although the circadian blood pressure (BP) pattern has been extensively studied, the determinants of this rhythm are not fully understood. Peripheral vasodilatation is a regulatory mechanism for BP maintenance. However, it remains to be established whether the increase of nocturnal distal skin temperature associated with heat loss could also reflect the dipping status. For the first time, this paper investigates the relationship between BP and skin wrist temperature (WT), to evaluate whether the WT circadian rhythm can serve as screening procedure to detect dipping/non-dipping BP patterns. In addition, the authors compare the relationship between WT and other variables previously described as determinants of the BP pattern, such as physical activity and body position. Measurements of WT, motor activity, and body position for 5 d, plus ambulatory BP for 24-h during that span, were obtained from 28 diurnally active normotensive volunteers. WT was negatively correlated, whereas activity and body position were positively correlated, with systolic and diastolic BPs. However, these relationships were stronger during the rest than activity phase. In addition, a 78.6% concordance was detected between the observed dips in BP and the predicted BP pattern calculated based on the WT rhythm. Thus, these results suggest that the increase in WT produced by heat loss during the rest phase through peripheral skin blood vessels is the result of blood vessel vasodilatation reflexes in response to a shift from a standing to a supine position, together with shift in the circadian sympathetic/parasympathetic balance (nocturnal parasympathetic activation). In conclusion, WT could be considered as a potential new screening procedure to implement the diagnosis of non-dipping BP pattern.

'Catching the spike and tracking the flow': Holter-temperature monitoring in patients admitted in a general internal medicine ward.

OBJECTIVE: To study if a 24-h continuous monitoring of temperature reveals information not accessible through conventional care. This included omitted fever peaks and circadian and complexity characteristics that may correlate with specific aetiologies. DESIGN: Ours was a prospective, observational study. A total of 62 patients, admitted to a general internal medicine ward, in whom a temperature > 38 °C had been observed the day before inclusion underwent a 24-h long continuous monitoring of both central and peripheral temperatures. The time series were recorded in a file, while they otherwise followed conventional care. Time series were analysed for standard statistics, chronobiological analysis (amplitude, mesor, acrophase, intra-daily variability) and complexity analysis (Approximate Entropy of both central and peripheral temperature, cross-ApEn). A month after discharge, the clinical reports were reviewed and a definitive diagnosis of the febrile syndrome was established. RESULTS: A total of 62 patients were initially included. In six cases, no time series could be obtained because of technical problems, leaving 56 patients accessible for analysis. In 10 cases, no definitive diagnosis was established. Continuous monitoring detected a mean of 0.7 (CI = 0.27-1.33) peaks of fever (central temperature > 38.0 °C) unobserved by conventional care per patient. A proportion of 16% (CI = 6-26) of patients considered afebrile by conventional care had at least one fever peak detected by continuous monitoring. Circadian rhythm persisted or was exacerbated in febrile patients. Circadian amplitude was increased in patients with tuberculosis. Complexity analysis did not differ among different diagnostic groups, although in subgroup analysis, viral infections had a higher complexity than other infectious diseases. CONCLUSIONS: Temperature Holter monitoring reveals fever peaks that pass otherwise unobserved. Furthermore, chronobiological and complexity analysis of the temperature profile may provide quick and easy 'hidden information', not available to conventional care.

El sistema circadiano en el anciano: valoración clínica e intervenciones terapéuticas / No disponible

Todos los seres vivos en el planeta Tierra estamos sometidos a un entorno cambiante y cíclico que ha contribuido al desarrollo de un reloj biológico que les permite la anticipación a estos cambios. Este reloj necesita un conjunto de sincronizadores externos (zeitgebers) que lo pongan en hora cada día. Algunos de estos sincronizadores son la luz, el horario regular de comidas, ejercicio moderado, contactos sociales... Durante el envejecimiento, el reloj biológico va perdiendo paulatinamente su capacidad de marcar el ritmo al organismo. Es por ello que las terapias cronobiológicas que tratan de potenciar las señales sincronizadoras tienen mucho interés, no sólo por su eficacia, sino también por su bajo costo y la ausencia de efectos secundarios. En primer lugar y teniendo en cuenta que el mejor sincronizador para el reloj biológico es la luz, la terapia más eficaz es la luminoterapia con luz brillante. En segundo lugar habría que recomendar el mantenimiento de un horario estable de comidas, de ejercicio físico moderado y relaciones sociales. Todas estas son medidas que mejoran las entradas al reloj pero también podemos mejorar las salidas. El reloj marca el ritmo al organismo a través de una hormona, la melatonina. Con el envejecimiento, los niveles de melatonina endógena van disminuyendo y por ello, una terapia útil es la administración de melatonina exógena o de alguno de sus agonistas farmacológicos. Esta hormona actúa como señal temporal, pero igualmente como inductora del sueño, hormona antienvejecimiento, oncostática frente a ciertos tipos de tumores e inmunomoduladora. Para conocer el estado del sistema circadiano (el reloj biológico) y poder optimizar las terapias, es necesario medir algunos ritmos que se denominan «marcadores». Se trata de ritmos muy estables y que están controlados directamente por el reloj. Algunos ejemplos de estos ritmos son el de temperatura periférica y el de actividad motora. En ambos casos se trata de ritmos que se determinan mediante el empleo de técnicas no invasivas (AU)

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