Thioredoxin as a putative biomarker and candidate target in age-related immune decline

The oxidoreductase Trx-1 (thioredoxin 1) is highly conserved and found intra- and extra-cellularly in mammalian systems. There is increasing interest in its capacity to regulate immune function based on observations of altered distribution and expression during ageing and disease. We have investigated previously whether extracellular T-cell or peripheral blood mononuclear cell Trx-1 levels serve as a robust marker of ageing. In a preliminary study of healthy older adults compared with younger adults, we showed that therewas a significant, butweak, relationshipwith age. Interestingly, patientswith rheumatoid arthritis and cancer have been described by others to secrete or express greater surface Trx-1 than predicted. It is interesting to speculate whether a decline in Trx-1 during ageing protects against such conditions, but correspondingly increases risk of disease associated with Trx-1 depletion such as cardiovascular disease. These hypotheses are being explored in the MARK-AGE study, and preliminary findings confirm an inverse correlation of surface Trx-1 with age. We review recent concepts around the role of Trx-1 and its partners in T-cell function on the cell surface and as an extracellular regulator of redox state in a secreted form. Further studies on the redox state and binding partners of surface and secreted Trx-1 in larger patient datasets are needed to improve our understanding of why Trx-1 is important for lifespan and immune function. © The Authors Journal compilation © 2014 Biochemical Society.

Differential effectiveness of two anxiety induction procedures in youth and older adult populations

In this study, we tested in older and younger adults the efficacy of two well-known procedures to experimentally induce anxiety: a) Velten self-statements combined with music; b) film scenes. We extended the pre-vious findings in this field to the understudied area of mood induction in older adults. Fifty-seven older adults and 94 college students were random-ly assigned to one of the experimental conditions or to a control group. Results indicated that both procedures were effective, according to a series of ANOVAs for several self-report, physiological, and behavioral measures. Likewise, the highest effect sizes were observed for the Velten procedure (g = .81 vs. g = .71), and the effects were significantly higher in younger (g = 1.0 in the Velten condition) than in older adults (g = .62), Q = 4.25, X2(1), p = .0392. Both procedures were effective to induce inducting anxiety in both age groups, especially the Velten procedure in younger adults. Therefore, Velten self-statements combined with music may be very useful anxiety induction procedure for further research in controlled situa-tions of emotions across the life-span.

Mobility changes in older age: neuropsychological, neurophysiological and cognitive predictors of successful adaptation in a real world scenario

The aims of this thesis were to investigate the neuropsychological, neurophysiological, and cognitive contributors to mobility changes with increasing age. In a series of studies with adults aged 45-88 years, unsafe pedestrian behaviour and falls were investigated in relation to i) cognitive functions (including response time variability, executive function, and visual attention tests), ii) mobility assessments (including gait and balance and using motion capture cameras), iii) motor initiation and pedestrian road crossing behavior (using a simulated pedestrian road scene), iv) neuronal and functional brain changes (using a computer based crossing task with magnetoencephalography), and v) quality of life questionnaires (including fear of falling and restricted range of travel). Older adults are more likely to be fatally injured at the far-side of the road compared to the near-side of the road, however, the underlying mobility and cognitive processes related to lane-specific (i.e. near-side or far-side) pedestrian crossing errors in older adults is currently unknown. The first study explored cognitive, motor initiation, and mobility predictors of unsafe pedestrian crossing behaviours. The purpose of the first study (Chapter 2) was to determine whether collisions at the near-side and far-side would be differentially predicted by mobility indices (such as walking speed and postural sway), motor initiation, and cognitive function (including spatial planning, visual attention, and within participant variability) with increasing age. The results suggest that near-side unsafe pedestrian crossing errors are related to processing speed, whereas far-side errors are related to spatial planning difficulties. Both near-side and far-side crossing errors were related to walking speed and motor initiation measures (specifically motor initiation variability). The salient mobility predictors of unsafe pedestrian crossings determined in the above study were examined in Chapter 3 in conjunction with the presence of a history of falls. The purpose of this study was to determine the extent to which walking speed (indicated as a salient predictor of unsafe crossings and start-up delay in Chapter 2), and previous falls can be predicted and explained by age-related changes in mobility and cognitive function changes (specifically within participant variability and spatial ability). 53.2% of walking speed variance was found to be predicted by self-rated mobility score, sit-to-stand time, motor initiation, and within participant variability. Although a significant model was not found to predict fall history variance, postural sway and attentional set shifting ability was found to be strongly related to the occurrence of falls within the last year. Next in Chapter 4, unsafe pedestrian crossing behaviour and pedestrian predictors (both mobility and cognitive measures) from Chapter 2 were explored in terms of increasing hemispheric laterality of attentional functions and inter-hemispheric oscillatory beta power changes associated with increasing age. Elevated beta (15-35 Hz) power in the motor cortex prior to movement, and reduced beta power post-movement has been linked to age-related changes in mobility. In addition, increasing recruitment of both hemispheres has been shown to occur and be beneficial to perform similarly to younger adults in cognitive tasks (Cabeza, Anderson, Locantore, & McIntosh, 2002). It has been hypothesised that changes in hemispheric neural beta power may explain the presence of more pedestrian errors at the farside of the road in older adults. The purpose of the study was to determine whether changes in age-related cortical oscillatory beta power and hemispheric laterality are linked to unsafe pedestrian behaviour in older adults. Results indicated that pedestrian errors at the near-side are linked to hemispheric bilateralisation, and neural overcompensation post-movement, 4 whereas far-side unsafe errors are linked to not employing neural compensation methods (hemispheric bilateralisation). Finally, in Chapter 5, fear of falling, life space mobility, and quality of life in old age were examined to determine their relationships with cognition, mobility (including fall history and pedestrian behaviour), and motor initiation. In addition to death and injury, mobility decline (such as pedestrian errors in Chapter 2, and falls in Chapter 3) and cognition can negatively affect quality of life and result in activity avoidance. Further, number of falls in Chapter 3 was not significantly linked to mobility and cognition alone, and may be further explained by a fear of falling. The objective of the above study (Study 2, Chapter 3) was to determine the role of mobility and cognition on fear of falling and life space mobility, and the impact on quality of life measures. Results indicated that missing safe pedestrian crossing gaps (potentially indicating crossing anxiety) and mobility decline were consistent predictors of fear of falling, reduced life space mobility, and quality of life variance. Social community (total number of close family and friends) was also linked to life space mobility and quality of life. Lower cognitive functions (particularly processing speed and reaction time) were found to predict variance in fear of falling and quality of life in old age. Overall, the findings indicated that mobility decline (particularly walking speed or walking difficulty), processing speed, and intra-individual variability in attention (including motor initiation variability) are salient predictors of participant safety (mainly pedestrian crossing errors) and wellbeing with increasing age. More research is required to produce a significant model to explain the number of falls.

Sexual risk behaviors and HIV risk among Americans aged 50 years or older: a review.

Although HIV-related sexual risk behaviors have been studied extensively in adolescents and young adults, there is limited information about these behaviors among older Americans, which make up a growing segment of the US population and an understudied population. This review of the literature dealing with sexual behaviors that increase the risk of becoming HIV-infected found a low prevalence of condom use among older adults, even when not in a long-term relationship with a single partner. A seminal study by Schick et al published in 2010 reported that the prevalence of condom use at last intercourse was highest among those aged 50-59 years (24.3%; 95% confidence interval, 15.6-35.8) and declined with age, with a 17.1% prevalence among those aged 60-69 years (17.1%; 95% confidence interval, 7.3-34.2). Studies have shown that older Americans may underestimate their risk of becoming HIV-infected. Substance use also increases the risk for sexual risk behaviors, and studies have indicated that the prevalence of substance use among older adults has increased in the past decade. As is the case with younger adults, the prevalence of HIV infections is elevated among ethnic minorities, drug users (eg, injection drug users), and men who have sex with men. When infected, older adults are likely to be diagnosed with HIV-related medical disorders later in the course of illness compared with their younger counterparts. Physicians are less likely to discuss sexual risk behaviors with older adults and to test them for HIV compared with younger adults. Thus, it is important to educate clinicians about sexual risk behaviors in the older age group and to design preventive interventions specifically designed for older adults.

Influence du vieillissement et de la scolarité sur la compréhension du discours : apport de l’imagerie optique

La compréhension du discours, et son évolution au cours du vieillissement, constitue un sujet d’une grande importance par sa complexité et sa place dans la préservation de la qualité de vie des aînés. Les objectifs de cette thèse étaient d’évaluer l’influence du vieillissement et du niveau de scolarité sur les capacités de compréhension du discours et sur l’activité cérébrale s’y rattachant. Pour ce faire, trois groupes (jeunes adultes ayant un niveau universitaire de scolarité, personnes âgées ayant un niveau universitaire de scolarité et personnes âgées ayant un niveau secondaire de scolarité) ont réalisé une tâche où ils devaient lire de courtes histoires, puis estimer la véracité d’une affirmation concernant cette histoire. Les capacités de compréhension correspondant aux traitements de trois niveaux du modèle de construction-intégration de Kintsch (la microstructure, la macrostructure et le modèle de situation) ont été évaluées. L’imagerie optique (NIRS) a permis d’estimer les variations d’oxyhémoglobine (HbO) et de déoxyhémoglobine (HbR) tout au long de la tâche. Les résultats ont démontré que les personnes âgées étaient aussi aptes que les plus jeunes pour rappeler la macrostructure (essentiel du texte), mais qu’ils avaient plus de difficulté à rappeler la microstructure (détails) et le modèle de situation (inférence et intégration) suite à la lecture de courts textes. Lors de la lecture, les participants plus âgés ont également montré une plus grande activité cérébrale dans le cortex préfrontal dorsolatéral gauche, ce qui pourrait être un mécanisme de compensation tel que décrit dans le modèle CRUNCH. Aucune différence significative n’a été observée lors de la comparaison des participants âgés ayant un niveau universitaire de scolarité et ceux ayant un niveau secondaire, tant au niveau des capacités de compréhension que de l’activité cérébrale s’y rattachant. Les deux groupes ont cependant des habitudes de vie stimulant la cognition, entre autres, de bonnes habitudes de lecture. Ainsi, ces habitudes semblent avoir une plus grande influence que l’éducation sur les performances en compréhension et sur l’activité cérébrale sous-jacente. Il se pourrait donc que l’éducation influence la cognition en promouvant des habitudes favorisant les activités cognitives, et que ce soit ces habitudes qui aient en bout ligne un réel impact sur le vieillissement cognitif.

Aging and semantic integration in sentence processing: Testing the cognitive workload of wrap-up

The current study investigated the cognitive workload of sentence and clause wrap-up in younger and older readers. A large number of studies have demonstrated the presence of wrap-up effects, peaks in processing time at clause and sentence boundaries that some argue reflect attention to organizational and integrative semantic processes. However, the exact nature of these wrap-up effects is still not entirely clear, with some arguing that wrap-up is not related to processing difficulty, but rather is triggered by a low-level oculomotor response or the implicit monitoring of intonational contour. The notion that wrap-up effects are resource-demanding was directly tested by examining the degree to which sentence and clause wrap-up affects the parafoveal preview benefit. Older and younger adults read passages in which a target word N occurred in a sentence-internal, clause-final, or sentence-final position. A gaze-contingent boundary change paradigm was used in which, on some trials, a non-word preview of word N+1 was replaced by a target word once the eyes crossed an invisible boundary located between words N and N+1. All measures of reading time on word N were longer at clause and sentence boundaries than in the sentence-internal position. In the earliest measures of reading time, sentence and clause wrap-up showed evidence of reducing the magnitude of the preview benefit similarly for younger and older adults. However, this effect was moderated by age in gaze duration, such that older adults showed a complete reduction in the preview benefit in the sentence-final condition. Additionally, sentence and clause wrap-up were negatively associated with the preview benefit. Collectively, the findings from the current study suggest that wrap-up is cognitively demanding and may be less efficient with age, thus, resulting in a reduction of the parafoveal preview during normal reading.

Influence du vieillissement et de la scolarité sur la compréhension du discours : apport de l’imagerie optique

La compréhension du discours, et son évolution au cours du vieillissement, constitue un sujet d’une grande importance par sa complexité et sa place dans la préservation de la qualité de vie des aînés. Les objectifs de cette thèse étaient d’évaluer l’influence du vieillissement et du niveau de scolarité sur les capacités de compréhension du discours et sur l’activité cérébrale s’y rattachant. Pour ce faire, trois groupes (jeunes adultes ayant un niveau universitaire de scolarité, personnes âgées ayant un niveau universitaire de scolarité et personnes âgées ayant un niveau secondaire de scolarité) ont réalisé une tâche où ils devaient lire de courtes histoires, puis estimer la véracité d’une affirmation concernant cette histoire. Les capacités de compréhension correspondant aux traitements de trois niveaux du modèle de construction-intégration de Kintsch (la microstructure, la macrostructure et le modèle de situation) ont été évaluées. L’imagerie optique (NIRS) a permis d’estimer les variations d’oxyhémoglobine (HbO) et de déoxyhémoglobine (HbR) tout au long de la tâche. Les résultats ont démontré que les personnes âgées étaient aussi aptes que les plus jeunes pour rappeler la macrostructure (essentiel du texte), mais qu’ils avaient plus de difficulté à rappeler la microstructure (détails) et le modèle de situation (inférence et intégration) suite à la lecture de courts textes. Lors de la lecture, les participants plus âgés ont également montré une plus grande activité cérébrale dans le cortex préfrontal dorsolatéral gauche, ce qui pourrait être un mécanisme de compensation tel que décrit dans le modèle CRUNCH. Aucune différence significative n’a été observée lors de la comparaison des participants âgés ayant un niveau universitaire de scolarité et ceux ayant un niveau secondaire, tant au niveau des capacités de compréhension que de l’activité cérébrale s’y rattachant. Les deux groupes ont cependant des habitudes de vie stimulant la cognition, entre autres, de bonnes habitudes de lecture. Ainsi, ces habitudes semblent avoir une plus grande influence que l’éducation sur les performances en compréhension et sur l’activité cérébrale sous-jacente. Il se pourrait donc que l’éducation influence la cognition en promouvant des habitudes favorisant les activités cognitives, et que ce soit ces habitudes qui aient en bout ligne un réel impact sur le vieillissement cognitif.

EFFECTS OF AGING ON MIDBRAIN AND CORTICAL SPEECH-IN-NOISE PROCESSING

Older adults frequently report that they can hear what they have been told but cannot understand the meaning. This is particularly true in noisy conditions, where the additional challenge of suppressing irrelevant noise (i.e. a competing talker) adds another layer of difficulty to their speech understanding. Hearing aids improve speech perception in quiet, but their success in noisy environments has been modest, suggesting that peripheral hearing loss may not be the only factor in the older adult’s perceptual difficulties. Recent animal studies have shown that auditory synapses and cells undergo significant age-related changes that could impact the integrity of temporal processing in the central auditory system. Psychoacoustic studies carried out in humans have also shown that hearing loss can explain the decline in older adults’ performance in quiet compared to younger adults, but these psychoacoustic measurements are not accurate in describing auditory deficits in noisy conditions. These results would suggest that temporal auditory processing deficits could play an important role in explaining the reduced ability of older adults to process speech in noisy environments. The goals of this dissertation were to understand how age affects neural auditory mechanisms and at which level in the auditory system these changes are particularly relevant for explaining speech-in-noise problems. Specifically, we used non-invasive neuroimaging techniques to tap into the midbrain and the cortex in order to analyze how auditory stimuli are processed in younger (our standard) and older adults. We will also attempt to investigate a possible interaction between processing carried out in the midbrain and cortex.

Sequestro pulmonar : trabalho de revisão

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Lingual kinematic strategies used to increase speech rate: Comparisons between younger and older adults

The primary objective of this study was to assess the lingual kinematic strategies used by younger and older adults to increase rate of speech. It was hypothesised that the strategies used by the older adults would differ from the young adults either as a direct result of, or in response to a need to compensate for, age-related changes in the tongue. Electromagnetic articulography was used to examine the tongue movements of eight young (M526.7 years) and eight older (M567.1 years) females during repetitions of /ta/ and /ka/ at a controlled moderate rate and then as fast as possible. The younger and older adults were found to significantly reduce consonant durations and increase syllable repetition rate by similar proportions. To achieve these reduced durations both groups appeared to use the same strategy, that of reducing the distances travelled by the tongue. Further comparisons at each rate, however, suggested a speed-accuracy trade-off and increased speech monitoring in the older adults. The results may assist in differentiating articulatory changes associated with normal aging from pathological changes found in disorders that affect the older population.

Perceptions of younger, middle-aged, and older adults in Australia and Japan: Stereotypes and age group vitality

This study investigated the perceptions of young adults in Japan and Australia about their own age group, as well as middle-aged and older adults. Using a self-administered questionnaire, 155 Japanese and 171 Australian students rated people in the three age groups on traits of personal vitality and benevolence, and also rated their age group vitalities. Results indicated that Australians perceived both middle-aged and older adults in more positive terms than did Japanese and also perceived the vitality of these age groups as higher. On the other hand, both Japanese and Australian young people judged the vitality of their own group as lower than that of middle-aged adults. These results suggest that norms of filial piety, especially its respect dimension, in Japan may be eroding, whereas older Australians may be gaining in social stature.

Visual speech perception: a comparison between younger and older adults

This paper examines the visual speech processing abilities of older adults and the age-related effects on speechreading abilities.

Electromyographic patterns of lower limb muscles during apprehensive gait in younger and older female adults

Objective: Investigate the influence of apprehensive gait on activation and cocontraction of lower limb muscles of younger and older female adults. Methods: Data of 17 younger (21.47±2.06 yr) and 18 older women (65.33±3.14. yr) were considered for this study. Participants walked on the treadmill at two different conditions: normal gait and apprehensive gait. The surface electromyographic signals (EMG) were recorded during both conditions on: rectus femoris (RF), vastus lateralis (VL), vastus medialis (VM), biceps femoris (BF), tibialis anterior (TA), gastrocnemius lateralis (GL), and soleus (SO). Results: Apprehensive gait promoted greater activation of thigh muscles than normal gait (F=5.34 and p=0.007, for significant main effect of condition; RF, p=0.002; VM, p<0.001; VL, p=0.003; and BF, p=0.001). Older adults had greater cocontraction of knee and ankle stabilizer muscles than younger women (F=4.05 and p=0.019, for significant main effect of groups; VM/BF, p=0.010; TA/GL, p=0.007; and TA/SO, p=0.002). Conclusion: Apprehensive gait promoted greater activation of thigh muscles and older adults had greater cocontraction of knee and ankle stabilizer muscles. Thus, apprehensive gait may leads to increased percentage of neuromuscular capacity, which is associated with greater cocontraction and contribute to the onset of fatigue and increased risk of falling in older people. © 2013 Elsevier Ltd.