Searching for the trace: The influence of age, lexical activation and working memory on sentence processing

To investigate the stability of trace reactivation in healthy older adults, 22 older volunteers with no significant neurological history participated in a cross-modal priming task. Whilst both object relative center embedded (ORC) and object relative right branching (ORR) sentences is-ere employed, working memory load was reduced by limiting the number of wordy separating the antecedent front the gap for both sentence types. Analysis of the results did not reveal any significant trace reactivation for the ORC or ORR sentences. The results did reveal, however, a positive correlation between age and semantic printing at the pre-gap position and a negative correlation between age and semantic printing at the gap position for ORC sentences. In contrast, there was no correlation between age and priming effects for the ORR sentences. These results indicated that trace reactivation may be sensitive to a variety of age related factors, including lexical activation and working memory. The implications of these results for sentence processing in the older population arc discussed.

Dietary habits are major determinants of the plasma antioxidant status in healthy elderly subjects

Previous studies indicate that regular consumption of a diet rich in fruits and vegetables is associated with a lower risk for age-related diseases. The aim of the present study was to evaluate whether the often-reported age-related decrease of plasma antioxidants in man depends on differences in dietary intake or on other age- and gender-related factors. In this observational case-control study, thirty-nine community-dwelling healthy subjects aged 65 years and older consuming high intakes of fruits and vegetables daily (HI) and forty-eight healthy subjects aged 65 and older consuming low intakes of fruit and vegetables daily (LI) were enrolled. Plasma levels of retinol, tocopherols, carotenoids and malondialdehyde (MDA) as well as content of protein carbonyls in Ig G were measured. Plasma levels of retinol, tocopherols and carotenoids were significantly higher in group HI than in group LI subjects independent of age and gender. MDA levels were inversely correlated with vitamin A and α-carotene. Protein carbonyls were inversely correlated with γ-tocopherol. In the elderly, a higher daily intake of fruits and vegetables is associated with an improved antioxidant status in comparison to subjects consuming diets poor in fruits and vegetables. Modification of nutritional habits among other lifestyle changes should be encouraged to lower prevalence of disease risk factors in later life. © The Authors 2005.

Apparent motion photometry:evaluation and reliability of a novel method for the measurement of macular pigment

Background/aims Macular pigment is thought to protect the macula against exposure to light and oxidative stress, both of which may play a role in the development of age-related macular degeneration. The aim was to clinically evaluate a novel cathode-ray-tube-based method for measurement of macular pigment optical density (MPOD) known as apparent motion photometry (AMP). Methods The authors took repeat readings of MPOD centrally (0°) and at 3° eccentricity for 76 healthy subjects (mean (±SD) 26.5±13.2 years, range 18–74 years). Results The overall mean MPOD for the cohort was 0.50±0.24 at 0°, and 0.28±0.20 at 3° eccentricity; these values were significantly different (t=-8.905, p<0.001). The coefficients of repeatability were 0.60 and 0.48 for the 0 and 3° measurements respectively. Conclusions The data suggest that when the same operator is taking repeated 0° AMP MPOD readings over time, only changes of more than 0.60 units can be classed as clinically significant. In other words, AMP is not suitable for monitoring changes in MPOD over time, as increases of this magnitude would not be expected, even in response to dietary modification or nutritional supplementation.

The effect of ageing on macrophage Toll-like receptor-mediated responses in the fight against pathogens

The cellular changes during ageing are incompletely understood yet immune system dysfunction is implicated in the age-related decline in health. The acquired immune system shows a functional decline in ability to respond to new pathogens whereas serum levels of cytokines are elevated with age. Despite these age-associated increases in circulating cytokines, the function of aged macrophages is decreased. Pathogen-associated molecular pattern receptors such as Toll-like receptors (TLRs) are vital in the response of macrophages to pathological stimuli. Here we review the evidence for defective TLR signalling in normal ageing. Gene transcription, protein expression and cell surface expression of members of the TLR family of receptors and co-effector molecules do not show a consistent age-dependent change across model systems. However, there is evidence for impaired downstream signalling events, including inhibition of positive and activation of negative modulators of TLR induced signalling events. In this paper we hypothesize that despite a poor inflammatory response via TLR activation, the ineffective clearance of pathogens by macrophages increases the duration of their activation and contributes to perpetuation of inflammatory responses and ageing.

The Effect of nutritional supplementation on subjective and objective measures of visual and retinal function:a random controlled trial

In industrialised countries age-related macular disease (ARMD) is the leading cause of visual loss in older people. Because oxidative stress is purported to be associated with an increased risk of disease development the role of antioxidant supplementation is of interest. Lutein is a carotenoid antioxidant that accumulates within the retina and is thought to filter blue light. Increased levels of lutein have been associated with reduced risk of developing ARMD and improvements in visual and retinal function in eyes with ARMD. The aim of this randomised controlled trial (RCT) was to investigate the effect of a lutein-based nutritional supplement on subjective and objective measures of visual function in healthy eyes and in eyes with age-related maculopathy (ARM) – an early form of ARMD. Supplement withdrawal effects were also investigated. A sample size of 66 healthy older (HO), healthy younger (HY), and ARM eyes were randomly allocated to receive a lutein-based supplement or no treatment for 40 weeks. The supplemented group then stopped supplementation to look at the effects of withdrawal over a further 20 weeks. The primary outcome measure was multifocal electroretinogram (mfERG) N1P1 amplitude. Secondary outcome measures were mfERG N1, P1 and N2 latency, contrast sensitivity (CS), Visual acuity (VA) and macular pigment optical density (MPOD). Sample sizes were sufficient for the RCT to have an 80% power to detect a significant clinical effect at the 5% significance level for all outcome measures when the healthy eye groups were combined, and CS, VA and mfERG in the ARM group. This RCT demonstrates significant improvements in MPOD in HY and HO supplemented eyes. When HY and HO supplemented groups were combined, MPOD improvements were maintained, and mfERG ring 2 P1 latency became shorter. On withdrawal of the supplement mfERG ring 1 N1P1 amplitude reduced in HO eyes. When HO and HY groups were combined, mfERG ring 1 and ring 2 N1P1 amplitudes were reduced. In ARM eyes, ring 3 N2 latency and ring 4 P1 latency became longer. These statistically significant changes may not be clinically significant. The finding that a lutein-based supplement increases MPOD in healthy eyes, but does not increase mfERG amplitudes contrasts with the CARMIS study and contributes to the debate on the use of nutritional supplementation in ARM.

Drusen detection in retro-mode imaging by a scanning laser ophthalmoscope

Purpose: The Nidek F-10 is a scanning laser ophthalmoscope that is capable of a novel fundus imaging technique, so-called ‘retro-mode’ imaging. The standard method of imaging drusen in age-related macular degeneration (AMD) is by fundus photography. The aim of the study was to assess drusen quantification using retro-mode imaging. Methods: Stereoscopic fundus photographs and retro-mode images were captured in 31 eyes of 20 patients with varying stages of AMD. Two experienced masked retinal graders independently assessed images for the number and size of drusen, using purpose-designed software. Drusen were further assessed in a subset of eight patients using optical coherence tomography (OCT) imaging. Results: Drusen observed by fundus photography (mean 33.5) were significantly fewer in number than subretinal deposits seen in retro-mode (mean 81.6; p < 0.001). The predominant deposit diameter was on average 5 µm smaller in retro-mode imaging than in fundus photography (p = 0.004). Agreement between graders for both types of imaging was substantial for number of deposits (weighted ? = 0.69) and moderate for size of deposits (weighted ? = 0.42). Retro-mode deposits corresponded to drusen on OCT imaging in all eight patients. Conclusion: The subretinal deposits detected by retro-mode imaging were consistent with the appearance of drusen on OCT imaging; however, a larger longitudinal study would be required to confirm this finding. Retro-mode imaging detected significantly more deposits than conventional colour fundus photography. Retro-mode imaging provides a rapid non-invasive technique, useful in monitoring subtle changes and progression of AMD, which may be useful in monitoring the response of drusen to future therapeutic interventions.

Terminal galactose residues on transferrin are increased in mid-life adults compared to young adults

Humans undergo biological ageing at different rates. This associates with functional decline in a number of physiological systems and increasing incidence of age-related pathologies. The discovery of robust biomarkers of ageing could be used to identify early divergence from a path of healthy ageing towards age-related disease. In the present study, we undertook proteomic analysis of plasma from healthy young men (mean age = 21.4 ± 1.5 years) and healthy mid-life men (mean age = 57.0 ±1.6 years). We identified twelve spots including transferrin, complement C3b and transthyretin that differed in abundance between the age groups. Transferrin spots showed an acidic pI shift in older males. Sandwich ELISAs were used to investigate the changes further. C3b levels were below the level of detection by ELISA and plasma concentrations of total transferrin or transthyretin were not different between the age groups studied here. However, analysis of transferrin N-glycan structures showed an increase in terminal galactose residues in older men, suggesting that the loss of terminal N-acetyl neuraminic acid residues contributes to the more acid pI of transferrin spots observed with age. Terminal galactosylation of transferrin may be a biomarker of healthy ageing and is now under investigation in the MARKAGE study.

Supervisor-subordinate age dissimilarity and performance ratings:the buffering effects of supervisory relationship practice

Using 394 pairs of employees and their immediate supervisors working in the Information and Communication Technology (ICT) sector in three northern European countries, this study examined the effect of workplace moderators on the link between relational demography and supervisor ratings of performance. Directional age differences between superior and subordinate (i.e., status incongruence caused when the supervisor is older or younger than his/her subordinate) and non-directional age differences were used as predictors of supervisor ratings of occupational expertise. The quality of the supervisor-subordinate relationship and the existence of positive age-related supervisory practices were examined as moderators of this relationship. The results provide no support for a relationship between directional age differences and age-related stereotyping by supervisors in ratings of performance, neither for the effects of age-related supervisory practices. However, high quality supervisor-subordinate relationships did moderate the effects of age dissimilarity on supervisory ratings. The implications of these findings for performance appraisal methodologies and recommendations for further research are discussed.

Fatty acids, monocytes and ageing

Elevated free fatty acids (FFA) are a feature of ageing and a risk factor for metabolic disorders such as cardiovascular disease (CVD) and type-2 diabetes (T2D). Elevated FFA contribute to insulin resistance, production of inflammatory cytokines and expression of adhesion molecules on immune cells and endothelial cells, risk factors for CVD and T2D. Molecular mechanisms of FFA effects on monocyte function and how FFA phenotype is affected by healthy ageing remain poorly understood. This thesis evaluated the effects of the two major FFA in plasma, oleate and palmitate on monocyte viability, cell surface antigen expression, and inflammatory activation in THP-1 monocytes. Palmitate but not oleate increased cell surface expression of CD11b and CD36 after 24h, independent of mitochondrial superoxide, but dependent on de novo synthesis of ceramides. LPS-mediated cytokine production in THP-1 monocytes was enhanced and decreased following incubation with palmitate and oleate respectively. In a model of monocyte-macrophage differentiation, palmitate induced a pro-inflammatory macrophage phenotype which required de novo ceramide synthesis, whilst oleate reduced cytokine secretion, producing a macrophage with enhanced clearance apoptotic cells. Plasma fatty acid analysis in young and mid-life populations revealed age-related increases in both the SFA and MUFA classes, especially the medium and very long chain C14 and C24 fatty acids, which were accompanied by increases in the estimated activities of desaturase enzymes. Changes were independently correlated with increased PBMC CD11b, plasma TNF-a and insulin resistance. In conclusion, the pro-atherogenic phenotype, enhanced LPS responses in monocytes, and pro-inflammatory macrophage in the presence of palmitate but not oleate is reliant upon de novo ceramide synthesis. Age-related increases in inflammation, cell surface integrin expression are related to increases in both the MUFA and SFA fatty acids, which in part may be explained by altered de novo fatty acid synthesis.

25th RCOphth Congress, President's Session paper:25 years of progress in medical retina

The quarter century since the foundation of the Royal College of Ophthalmologists has coincided with immense change in the subspecialty of medical retina, which has moved from being the province of a few dedicated enthusiasts to being an integral, core part of ophthalmology in every eye department. In age-related macular degeneration, there has been a move away from targeted, destructive laser therapy, dependent on fluorescein angiography to intravitreal injection therapy of anti-growth factor agents, largely guided by optical coherence tomography. As a result of these changes, ophthalmologists have witnessed a marked improvement in visual outcomes for their patients with wet age-related macular degeneration (AMD), while at the same time developing and enacting entirely novel ways of delivering care. In the field of diabetic retinopathy, this period also saw advances in laser technology and a move away from highly destructive laser photocoagulation treatment to gentler retinal laser treatments. The introduction of intravitreal therapies, both steroids and anti-growth factor agents, has further advanced the treatment of diabetic macular oedema. This era has also seen in the United Kingdom the introduction of a coordinated national diabetic retinopathy screening programme, which offers an increasing hope that the burden of blindness from diabetic eye disease can be lessened. Exciting future advances in retinal imaging, genetics, and pharmacology will allow us to further improve outcomes for our patients and for ophthalmologists specialising in medical retina, the future looks very exciting but increasingly busy.

The influence on unaided vision of age, pupil diameter and spherocylindrical refractive error

Background - The aim was to derive equations for the relationship between unaided vision and age, pupil diameter, iris colour and sphero-cylindrical refractive error. Methods - Data were collected from 663 healthy right eyes of white subjects aged 20 to 70 years. Subjective sphero-cylindrical refractive errors ranged from -6.8 to +9.4 D (mean spherical equivalent), -1.5 to +1.9 D (orthogonal component, J0) and -0.8 to 1.0 D (oblique component, J45). Cylinder axis orientation was orthogonal in 46 per cent of the eyes and oblique in 18 per cent. Unaided vision (-0.3 to +1.3 logMAR), pupil diameter (2.3 to 7.5 mm) and iris colour (67 per cent light/blue irides) was recorded. The sample included mostly females (60 per cent) and many contact lens wearers (42 per cent) and so the influences of these parameters were also investigated. Results - Decision tree analysis showed that sex, iris colour, contact lens wear and cylinder axis orientation did not influence the relationship between unaided vision and refractive error. New equations for the dependence of the minimum angle of resolution on age and pupil diameter arose from step backwards multiple linear regressions carried out separately on the myopes (2.91.scalar vector +0.51.pupil diameter -3.14 ) and hyperopes (1.55.scalar vector + 0.06.age – 3.45 ). Conclusion - The new equations may be useful in simulators designed for teaching purposes as they accounted for 81 per cent (for myopes) and 53 per cent (for hyperopes) of the variance in measured data. In comparison, previously published equations accounted for not more than 76 per cent (for myopes) and 24 per cent (for hyperopes) of the variance depending on whether they included pupil size. The new equations are, as far as is known to the authors, the first to include age. The age-related decline in accommodation is reflected in the equation for hyperopes.

A role for epigenetic modulation of the innate immune response during aging

The ageing process results from a complex interplay between genes and the environment that can precipitate an uncontrolled inflammation. Epigenetic changes are believed to provide a link between the environment and nutrition to gene expression by altering the activity of some histone-modifying protein. Epigenetic modifications of DNA and histone proteins have been proposed as important contributory mechanisms to the retention of metabolic memory over time. A thorough understanding of the posttranscriptional and epigenetic factors involved in both normal ageing and age-related disease may inform new strategies and approaches to diagnose, treat, or suppress many aspects of age-dependent frailty.

Age differences in associative and strategic processes in human conditional learning

Research indicates associative and strategic deficits mediate age related deficits in memory, whereas simple associative processes are independent of strategic processing and strategic processes mediate resistance to interference. The present study showed age-related deficits in a contingency learning task, although older participants' resistance to interference was not disproportionately affected. Recognition memory predicted discrimination, whereas general cognitive ability predicted resistance to interference, suggesting differentiation between associative and strategic processes in learning and memory, and age declines in associative processes. Older participants' generalisation of associative strength from existing to novel stimulus-response associations was consistent with elemental learning theories, whereas configural models predicted younger participants' responses. This is consistent with associative deficits and reliance on item-level representations in memory during later life. © 2011 Psychology Press Ltd.

'Their tummys don't really suit that food':children and young teenagers understanding of food allergy

Background: Food allergy (FA) is aunique chronic condition as sufferers aregenerally well unless they accidentally ingest an allergen, whereupon symptoms can be life threatening. A good under-standing of the condition is essential forsuccessful self-management, however little is known about children and young teenagers' understanding. This study aimed toexplore understanding of FA in childrenwith and without FA and whether under-standing changes as children get older.Method: Participants aged 6–14 years (53with FA; 89 without), recruited from loc evidence of a prospective associationbetween maternal, perinatal or infant VDIand subsequent IgE-mediated FA schools and allergy clinics took part insemi-structured interviews; data were analysed using thematic analysis.Results: Three themes were identified fromthe data across the different age groups andallergy statuses: food allergy as a sickness, food allergy as an illness and food allergy asintolerance to food. Children aged 6–8 years described FA as a sickness; you were not allowed the food because it makes youpoorly. Children aged 9–11 years also talked about FA as something that makesyou poorly, but many also described it as anillness and understood that symptoms were caused by food. Children aged 12–14 yearsdescribed it as an intolerance or that FA was your body's response to a particularfood. These age-related differences wereseen in children with and without FA. Conclusion: Although sophistication ofknowledge of FA increases with age, it is still a little understood condition by chil-dren and young teenagers. Clear, age-re-lated information about food allergy andhow it should be managed is needed forthose with and without allergy, to avoidmisunderstanding, and aid awareness andbetter self-management of the condition

Perceivers' impressions of self -presentation tactics: The effects of age and gender

Eighty-four young and 84 older men and women participants, read scenarios in which a male or female target uses either a self-enhancement or a self-deprecation tactic to present him/herself in front of either a close friend or a new acquaintance. Then participants i.e., perceivers) rated their impressions of the self-enhancing or self-deprecating target on six scales: likable, self-knowledgeable, honest, depressed, happy, and anxious. Overall, both young and old perceivers gave more favorable ratings to self-enhancing targets than to self-deprecating targets. Both young and old perceivers' impressions did not differ for a target who presented him/herself in front of a friend or in front of an acquaintance. Also, perceivers completed Singelis' (1994) Self-Construal Measurement, which measures both interdependent and independent self-construals. As predicted, older perceivers had a higher level of interdependent self-construal than did young perceivers. Unexpectedly, female perceivers had a higher level of independent self-construal than did male perceivers. Neither the age-related nor gender-related differences in self-construals were associated with any age-related or gender-related differences in perceivers' impressions of the self-enhancing and self-deprecating targets. That is, the moderator effects of self-construals on the relationships between self-presentation tactic conditions and ratings of targets were not-significant. ^