Progress of clinical therapies for dry age-related macular degeneration

Dry age-related macular degeneration (AMD) is a progressive blinding disease that currently affects millions of people worldwide with no successful treatment available. Significant research efforts are currently underway to develop therapies aimed at slowing the progression of this disease or, more notably, reversing it. Here the therapies which have reached clinical trial for treatment of dry AMD were reviewed. A thorough search of PubMed, Embase, and Clinicaltrials.gov has led to a comprehensive collection of the most recent strategies being evaluated. This review also endeavors to assess the status and future directions of therapeutics for this debilitating condition.

L2 attitude and motivation of secondary, undergraduate, and postgraduate ESL learners in India

Second language (L2) attitude and motivation-related studies focusing on differences caused by age have mostly highlighted the temporal dimension of L2 attitude and motivation. Age-related L2 motivation studies have also been gainfully employed at comparisons between L2 learners of different age groups recruited from different L2 learning environments. Such studies have not, however, attempted an analysis of the L2 attitudinal and motivational differences that may exist among L2 learners within a closer age range, e.g., 18 to 25 years. This article presents the findings of an L2 attitude and motivation survey, using a modified version of Dӧrnyei et al. (2006) and Ryan (2005), conducted among secondary, undergraduate, and postgraduate English as a second language (ESL) learners (N210) in India. It primarily presents a comparative analysis of the L2 attitudinal and motivational constructs of integrativeness, instrumentality, cultural interest, linguistic self-confidence, and L2 anxiety attested in the sample. Additionally, it offers a description of the correlation between the five L2 attitudinal and motivational constructs concerning the different ESL groups. As the ESL learners across the academic levels demonstrated ESL motivation more on the side of instrumentality, they also reported linguistic self-confidence more in the familiar environment of an L2 classroom than outside of it. Since better motivational strategies enhance learner dedication to the learning of a certain L2, an elaborated understanding of the specific differences in L2 attitude and motivation within this important age range should help design more useful and effective L2 pedagogical methods.

Inter- and Intra-Hemispheric Age-Related Remodeling in Visuo-Spatial Working Memory

Electroencephalography (EEG) studies investigating visuo-spatial working memory (vWM) in aging typically adopt an event-related potential (ERP) analysis approach that has shed light on the age-related changes during item retention and retrieval. However, this approach does not fully enable a detailed description of the time course of the neural dynamics related to aging. The most frequent age-related changes in brain activity have been described by two influential models of neurocognitive aging, the Hemispheric Asymmetry Reduction in Older Adults (HAROLD) and the Posterior-Anterior Shift in Aging (PASA). These models posit that older adults tend to recruit additional brain areas (bilateral as predicted by HAROLD and anterior as predicted by PASA) when performing several cognitive tasks. We tested younger (N = 36) and older adults (N = 35) in a typical vWM task (delayed match-to-sample) where participants have to retain items and then compare them to a sample. Through a data-driven whole scalp EEG analysis we aimed at characterizing the temporal dynamics of the age-related activations predicted by the two models, both across and within different stages of stimulus processing. Behaviorally, younger outperformed older adults. The EEG analysis showed that older adults engaged supplementary bilateral posterior and frontal sites when processing different levels of memory load, in line with both HAROLD and PASA-like activations. Interestingly, these age-related supplementary activations dynamically developed over time. Indeed, they varied across different stages of stimulus processing, with HAROLD-like modulations being mainly present during item retention, and PASA-like activity during both retention and retrieval. Overall, the present results suggest that age-related neural changes are not a phenomenon indiscriminately present throughout all levels of cognitive processing.

Association of mitochondrial DNA haplogroup and hearing impairment with aging in Japanese general population of the Iwaki Health Promotion Project

Age-related hearing loss (ARHL) is a complex multifactorial disorder. Studies in animals, including mitochondria-mutator mice, and in human suggest that oxidative stress and mitochondrial disturbance play an important role in the pathoetiology of ARHL. Mitochondrial DNA (mtDNA) haplogroups are populations with genetically similar traits, and they have been reported to affect the mitochondrial function of oxidative phosphorylation. To gain further insights into the relationships between mitochondrial haplotypes and the susceptibility to cochlear aging, in this study, we aimed to elucidate how the differences in mtDNA haplogroups may affect ARHL development in Japanese general population. We focused on early onset ARHL, as the same mtDNA haplogroup can show either a negative or positive effect on systemic co-morbidities of ARHL that appear later in life. A total of 1167 participants of the Iwaki Health Promotion Project were surveyed in 2014, and 12 major haplotype groups (D4a, D4b, D5, G1, G2, M7a, M7b, A, B4, B5, N9, and F) were selected for the analysis. A total of 698 subjects aged 30 to 65 years were included in the statistical analysis, and the hearing loss group consisted of 112 males (40.3%) and 111 females (26.4%). Multiple logistic regression analysis showed that the male subjects belonging to haplogroup A had a significantly increased risk of hearing loss, whereas the female subjects belonging to haplogroup N9 had a significantly decreased risk of hearing loss. These results suggested that the mtDNA haplogroup may be an indicator for future risk of morbidity associated with ARHL.

Efficacy and Safety of Ketone Supplementation or Ketogenic Diets for Alzheimer's Disease: A Mini Review

Alzheimer's disease (AD) is the most frequent age-related neurodegenerative disorder, with no curative treatment available so far. Alongside the brain deposition of β-amyloid peptide and hyperphosphorylated tau, neuroinflammation triggered by the innate immune response in the central nervous system, plays a central role in the pathogenesis of AD. Glucose usually represents the main fuel for the brain. Glucose metabolism has been related to neuroinflammation, but also with AD lesions. Hyperglycemia promotes oxidative stress and neurodegeneration. Insulinoresistance (e.g., in type 2 diabetes) or low IGF-1 levels are associated with increased β-amyloid production. However, in the absence of glucose, the brain may use another fuel: ketone bodies (KB) produced by oxidation of fatty acids. Over the last decade, ketogenic interventions i.e., ketogenic diets (KD) with very low carbohydrate intake or ketogenic supplementation (KS) based on medium-chain triglycerides (MCT) consumption, have been studied in AD animal models, as well as in AD patients. These interventional studies reported interesting clinical improvements in animals and decrease in neuroinflammation, β-amyloid and tau accumulation. In clinical studies, KS and KD were associated with better cognition, but also improved brain metabolism and AD biomarkers. This review summarizes the available evidence regarding KS/KD as therapeutic options for individuals with AD. We also discuss the current issues and potential adverse effects associated with these nutritional interventions. Finally, we propose an overview of ongoing and future registered trials in this promising field.