Factors Influencing the Treatment Response of Pigment Epithelium Detachment in Age-Related Macular Degeneration.

PURPOSE: To study the effect of various baseline factors, particularly the type of drug (ranibizumab vs aflibercept), on the functional and anatomic response of treatment-naïve pigment epithelial detachment (PED) associated with neovascular age-related macular degeneration (neovascular AMD), after 3 intravitreal injections. DESIGN: Retrospective consecutive case series. METHODS: This study included 102 patients (n = 115 eyes) with treatment-naïve neovascular AMD and PED (>150 μm), who were treated with either ranibizumab (n = 68 eyes) or aflibercept (n = 47 eyes). A multivariate analysis using stepwise linear regression was performed in order to assess factors influencing visual acuity improvement, as well as treatment response of PED height after 3 monthly injections. RESULTS: Multivariate analysis revealed that better visual improvement was associated with lower best-corrected visual acuity (BCVA) at baseline (P = .001), presence of subretinal fluid (P = .001), and retinal angiomatous proliferation (P = .001); PED reduction was associated with higher PED at baseline (P = .001), predominantly serous PED (P = .003), and the use of aflibercept (P = .022). Drug type was not associated with change in BCVA at 3 months. CONCLUSION: Eyes with neovascular AMD and PED showed significant functional and anatomic response after 3 monthly intravitreal anti-VEGF injections. The functional response depended on baseline BCVA, presence of subretinal fluid, and retinal angiomatous proliferation, while anatomic response was influenced by baseline PED height, degree of vascularization, and drug type. Drug type was not associated with change in BCVA, but had a weak effect on anatomic response.

CONVERSION TO AFLIBERCEPT THERAPY VERSUS CONTINUING WITH RANIBIZUMAB THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION DEPENDENT ON MONTHLY RANIBIZUMAB TREATMENT.

PURPOSE: To compare the effects of converting to aflibercept therapy with continuing ranibizumab therapy in eyes with neovascular age-related macular degeneration requiring monthly ranibizumab treatment. METHODS: Patients were selected from the 104 patients (115 eyes) already enrolled in an "Observe and Plan" prospective case series that included treating neovascular age-related macular degeneration with ranibizumab for 24 months. Patients who still needed monthly retreatment at the end of a 2-year study were randomized to either continue ranibizumab therapy or to convert to aflibercept therapy. Outcome measures included average interval between treatments, resolution of exudative signs, number of retreatments, and change in visual acuity over 12 months (the third treatment year). RESULTS: Nineteen patients (21 eyes) met the inclusion criteria. Ten eyes were randomized to receive aflibercept, and 11 eyes remained on ranibizumab. Groups were balanced for baseline characteristics. Outcomes were similar in the 2 groups over a 12-month study duration, with no statistical difference. CONCLUSION: This comparative pilot study suggests that neovascular age-related macular degeneration requiring monthly retreatment with ranibizumab may respond in similar ways to both ranibizumab and aflibercept treatment. Larger sample sizes would be needed to confirm this observation.

Age-Related Tooth Wear Differs between Forest and Savanna Primates

Tooth wear in primates is caused by aging and ecological factors. However, comparative data that would allow us to delineate the contribution of each of these factors are lacking. Here, we contrast age-dependent molar tooth wear by scoring percent of dentine exposure (PDE) in two wild African primate populations from Gabonese forest and Kenyan savanna habitats. We found that forest-dwelling mandrills exhibited significantly higher PDE with age than savanna yellow baboons. Mandrills mainly feed on large tough food items, such as hard-shell fruits, and inhabit an ecosystem with a high presence of mineral quartz. By contrast, baboons consume large amounts of exogenous grit that adheres to underground storage organs but the proportion of quartz in the soils where baboons live is low. Our results support the hypothesis that not only age but also physical food properties and soil composition, particularly quartz richness, are factors that significantly impact tooth wear. We further propose that the accelerated dental wear in mandrills resulting in flatter molars with old age may represent an adaptation to process hard food items present in their environment.

CFH Y402H polymorphism and response to intravitreal Ranibizumab in brazilian patients with neovascular age-related macular degeneration

Objective: To investigate the association between CFH gene polymorphism and response to ranibizumab in Brazilian patients with neovascular age-related macular degeneration (AMD).Methods: 95 patients were genotyped for the CFH rs1061170 (Y402H) single nucleotide polymorphism. Patients with neovascular AMD initially received intravitreal ranibizumab injections for three months and were retreated as needed. Visual acuity (VA) and central retinal thickness (CRT) were measured before treatment and at 1, 3, 6, and 12 months post-treatment.Results: For patients with the TT and TC genotypes, paired comparisons of VA showed a statistically significant improvement when the data obtained at all visits were compared with baseline. Patients homozygous for the risk genotype (CC) did not show a statistically significant improvement when VA obtained at visits 1, 3, 6 and 12 were compared with baseline. For all genotypes, paired comparisons of CRT showed a statistically significant improvement when the data obtained at visits 1, 3, 6 and 12 were compared with baseline.Conclusion: Patients with the CC genotype showed poorer long-term functional response to intravitreal ranibizumab.

Age-related changes of the multidrug resistance P-glycoprotein function in normal human peripheral blood T lymphocytes

The multidrug resistance P-glycoprotein is a transmembrane efflux pump expressed by lymphocytes and is involved in their cytolytic activity. In the present study, we investigated the age-related changes of P-glycoprotein function in normal peripheral blood lymphocytes. Blood samples from 90 normal volunteers (age range, 0 to 86 years) were analyzed. P-glycoprotein function was assessed by the flow cytometric rhodamine 123 assay. P-glycoprotein function was highest in cord blood and progressively declined with age in peripheral blood T CD4+ and CD8+ cells. In contrast, P-glycoprotein function did not vary with age in CD19+ B or CD16+CD56+ natural killer cells. These data suggest that the decline in P-glycoprotein function in T CD4+ and CD8+ lymphocytes as a function of age may contribute to the decrease in T cell cytolytic activity with aging.

Age-related changes in radiation-induced micronuclei among healthy adults

The aim of the present study was to establish the extent of in vitro radioresponse of lymphocytes among 62 healthy adults of both genders and to estimate the distribution of baseline micronuclei and radiosensitivity among individuals of the study population using the cytochalasin block micronucleus test. A younger study group consisted of 10 males (mean age, 22.4 years; range, 21-27) and 12 females (mean age, 24.8 years; range, 20-29), whereas an older study group consisted of 18 males (mean age, 35.1 years; range, 30-44) and 22 females (mean age, 38.5 years; range, 30-48). For evaluation of radiosensitivity blood samples were irradiated in vitro using 60Co g-ray source. The radiation dose employed was 2 Gy, the dose rate 0.45 Gy/min. The study revealed a significant gender effect on baseline micronuclei favoring females (Z = 3.25, P < 0.001), while yields of radiation-induced micronuclei did not differ significantly (Z = 0.56, P < 0.56) between genders. The distribution of baseline micronuclei among the individuals tested followed Poisson distribution in both study groups and in both genders, whereas the distribution of radiosensitivity among individuals of the older study group did not fulfill Poisson expectations (Kolmogorov-Smirnof test, P < 0.01). In contrast to a nonsignificant difference in radiosensitivity between males and females of the same age group (Z = 1.97, P < 0.56), a statistically significant difference in radiosensitivity between younger and older group for both genders was found (Z = 3.03, P < 0.03). Since the individuals tested were healthy, the observed variability in radiation response is considered to be an early effect of ageing.

Age-related changes in ERPs associated with context-based and response-based interference

Age-related differences in information processing have often been explained through deficits in older adults' ability to ignore irrelevant stimuli and suppress inappropriate responses through inhibitory control processes. Functional imaging work on young adults by Nelson and colleagues (2003) has indicated that inferior frontal and anterior cingulate cortex playa key role in resolving interference effects during a delay-to-match memory task. Specifically, inferior frontal cortex appeared to be recruited under conditions of context interference while the anterior cingulate was associated with interference resolution at the stage of response selection. Related work has shown that specific neural activities related to interference resolution are not preserved in older adults, supporting the notion of age-related declines in inhibitory control (Jonides et aI., 2000, West et aI., 2004b). In this study the time course and nature of these inhibition-related processes were investigated in young and old adults using high-density ERPs collected during a modified Sternberg task. Participants were presented with four target letters followed by a probe that either did or did not match one of the target letters held in working memory. Inhibitory processes were evoked by manipulating the nature of cognitive conflict in a particular trial. Conflict in working memory was elicited through the presentation of a probe letter in immediately previous target sets. Response-based conflict was produced by presenting a negative probe that had just been viewed as a positive probe on the previous trial. Younger adults displayed a larger orienting response (P3a and P3b) to positive probes relative to a non-target baseline. Older adults produced the orienting P3a and 3 P3b waveforms but their responses did not differentiate between target and non-target stimuli. This age-related change in response to targetness is discussed in terms of "early selection/late correction" models of cognitive ageing. Younger adults also showed a sensitivity in their N450 response to different levels of interference. Source analysis of the N450 responses to the conflict trials of younger adults indicated an initial dipole in inferior frontal cortex and a subsequent dipole in anterior cingulate cortex, suggesting that inferior prefrontal regions may recruit the anterior cingulate to exert cognitive control functions. Individual older adults did show some evidence of an N450 response to conflict; however, this response was attenuated by a co-occurring positive deflection in the N450 time window. It is suggested that this positivity may reflect a form of compensatory activity in older adults to adapt to their decline in inhibitory control.

Age-Related Changes in Visual Spatial Working Memory Cognits: Frontal-Parietal EEG Coherence During Delay

This study explored changes in scalp electrophysiology across two Working Memory (WM) tasks and two age groups. Continuous electroencephalography (EEG) was recorded from 18 healthy adults (18-34 years) and 12 healthy adolescents (14-17) during the performance of two Oculomotor Delayed Response (ODR) WM tasks; (i.e. eye movements were the metric of motor response). Delay-period, EEG data in the alpha frequency was sampled from anterior and parietal scalp sites to achieve a general measure of frontal and parietal activity, respectively. Frontal-parietal, alpha coherence was calculated for each participant for each ODR-WM task. Coherence significantly decreased in adults moving across the two ODR tasks, whereas, coherence significantly increased in adolescents moving across the two ODR tasks. The effects of task in the adolescent and adult groups were large and medium, respectively. Within the limits of this study, the results provide empirical support that WM development during adolescence include complex, qualitative, change.

Age-related eye disease and cognitive function

Objectif: Évaluer la relation entre la fonction cognitive chez les personnes âgées atteintes de dégénérescence maculaire reliée à l’âge (DMLA), de glaucome ou de dystrophie cornéenne de Fuchs et les comparer avec les personnes âgées n’ayant pas de maladie oculaire. Devis: Étude transversale de population hospitalière. Participants: 420 participants (113 avec la DMLA, 66 avec la dystrophie cornéenne de Fuchs, 130 avec le glaucome et 111 témoins). Méthodes: Nous avons recruté les patients à partir de la clinique d’ophtalmologie de l’Hôpital Maisonneuve-Rosemont (Montréal, Canada) de septembre 2009 à septembre 2013. Les patients atteints de la DMLA ou de la maladie de Fuchs ont une acuité visuelle inférieure à 20/40 dans les deux yeux, tandis que les patients avec du glaucome ont un champ visuel dans le pire œil inférieur ou égal à -4dB. Les patients contrôles, qui ont été recrutés à partir des mêmes cliniques, ont une acuité visuelle et un champ visuel normaux. Nous avons colligé des données concernant la fonction cognitive à partir du test Mini-Mental State Exam (MMSE)-version aveugle. Pour mesurer la fonction visuelle, nous avons mesuré l’acuité visuelle, la sensibilité au contraste et le champ visuel. Nous avons également révisé le dossier médical. Pour les analyses statistiques, nous avons utilisé la régression linéaire. Critère de jugement principal: MMSE-version aveugle. Résultats: Les trois maladies oculaires ont été associées à une limitation de la cognition. Le score de MMSE-version aveugle se situe de 0.7 à 0.8 unités plus basses par rapport au groupe contrôle. Comparativement aux contrôles, les patients avec maladies oculaires ont eu un score moyen diminué (P < 0.05). Le niveau d’éducation élevé est associé à une meilleure cognition (P < 0.001). Conclusions: Nos résultats suggèrent que les maladies oculaires sont associées à une diminution de la fonction cognitive chez les personnes âgées. De futures études sont nécessaires pour évaluer l’impact des maladies oculaires sur le déclin cognitif chez cette population pour pouvoir envisager des interventions ciblées qui pourraient les aider à maintenir leur indépendance le plus longtemps possible.

Age-related and sex-related alterations in f3-adrenergic receptors in different regions of rat brain

The binding of (-)[ 3H ]dihydroalprenolol , an antagonist of norepinephrine , to $-adrenergic receptors in different regions of the brain of male and female rats of various ages was measured . The binding to the synaptosomal fraction of corpus striatum , hypothalamus, cerebral cortex, cerebellum and the brainstems shows a significant decrease in the binding in old rats of both sexes . Only in the female corpus striatal region, the binding in the adult and the old is the same . In the case of females, the highest binding is seen in the young. In the male, an increase in binding occurs up to adulthood , after which it declines, suggesting a definite sex-related difference in the Q-adrenergic receptor.

Non-invasive Studies on Age Related Parameters Using a Blood Volume Pulse Sensor

A non-invasive technique is implemented to measure a parameter which is closely related to the distensibility of large arteries, using the second derivative of the infrared photoplethysmographic waveform. Thirty subjects within the age group of 20-61 years were involved in this pilot study. Two new parameters, namely the area of the photoplethysmographic waveform under the systolic peak, and the ratio of the time delay between the systolic and the diastolic peaks and the time period of the waveform ( T/T) were studied as a function of age. It was found that while the parameter which is supposed to be a marker of distensibility of large arteries and T /T values correlate negatively with age, the area under the systolic peak correlates positively with age. The results suggest that the derived parameters could provide a simple, non-invasive means for studying the changes in the elastic properties of the vascular system as a function of age.

Escala de ajuste a la pérdida visual relacionada con la edad : adaptación española de la Age-related Vision Loss Scale (AVL Scale) de A. Horowitz y J. P. Reinhardt.

Resumen tomado de la publicación

Comparison of long term cochlear noise injury and age-related cochlear degeneration in mice

This paper studies and compares age related hearing loss and noise-induced hearing loss in mice, and the different cell types that are affected by aging and noise.

Investigating age related changes in taste and affects on sensory perceptions of oral nutritional supplements

Background: sip feeds are oral nutritional supplements (ONSs) that are commonly prescribed to malnourished patients to improve their nutritional and clinical status. However, ONSs are poorly consumed and frequently wasted, with sweetness being identified as one of the factors leading to patients’ dislike of ONSs. Objectives: to investigate if age affects sweetness thresholds and if this impacts upon perceived sweetness intensity, hedonic (sweetness and overall) and ranked preference of ONS products. Design: prospective, observational. Subjects: thirty-six young adults (18–33 years) and 48 healthy older adults (63–85 years). Setting: Department of Food and Nutritional Sciences and the Clinical Health Sciences at the University of Reading. Methods: detection and recognition threshold levels, basic taste identification and ‘just about right’ level of sweetness were examined. Three ONSs (chocolate, vanilla, strawberry) and sucrose solutions were evaluated for hedonic sweetness, overall hedonic liking, sweetness intensity and rank preference. Results: significant differences were found in both sweetness detection and recognition thresholds (P = 0.0001) between young and older adults, with older adults more likely to incorrectly identify the taste (P = 0.0001). Despite the deterioration in sweetness sensitivity among the older adults, there were no significant differences found in sweetness intensity perceived for the ONS products presented (P > 0.05) when compared with the young adults. However, across both groups sweetness intensity was found to be correlated with overall product dislike across all flavour variants tested (R = 0.398, P = 0.0001). Conclusions: sweetness appears to be one of many factors contributing to the dislike of ONSs. Manufacturers are encouraged to reconsider the formulations of these products so that beneficial effects of ONSs can be delivered in a more palatable and acceptable form and wastage reduced.

Age-related effects of Ginkgo biloba extract on synaptic plasticity and excitability

EGb 761 is a standardized extract from the Ginkgo biloba leaf and is purported to improve age-related memory impairment. The acute and chronic effect of EGb 761 on synaptic transmission and plasticity in hippocampal slices from young adult (8-12 weeks) and aged (18-24 months) C57B1/6 mice was tested because hippocampal plasticity is believed to be a key component of memory. Acutely applied EGb 761 significantly increased neuronal excitability in slices from aged mice by reducing the population spike threshold and increased the early phase of long-term potentiation, though there was no effect in slices from young adults. In chronically treated mice fed for 30 days with an EGb 761-supplemented diet, EGb 761 significantly increased the population spike threshold and long-term potentiation in slices from aged animals, but had no effect on slices from young adults. The rapid effects of EGb 761 on plasticity indicate a direct interaction with the glutamatergic system and raise interesting implications with respect to a mechanism explaining its effect on cognitive enhancement in human subjects experiencing dementia. (C) 2003 Elsevier Inc. All rights reserved.