APOE genotype, hippocampal volume, and cognitive reserve predict improvement by cognitive training in older adults without dementia: a randomized controlled trial.

Cognitive training (CT) programs aim to improve cognitive performance and impede its decline. Thus, defining the characteristics of individuals who can benefit from these interventions is essential. Our objectives were to assess if the cognitive reserve (CR), APOE genotype (e4 carriers/non-carriers) and/or hippocampal volume might predict the effectiveness of a CT program. Participants were older adults without dementia (n = 226), randomized into parallel experimental and control groups. The assessment consisted of a neuropsychological protocol and additional data regarding total intracranial, gray matter, left/right hippocampus volume; APOE genotype; and Cognitive Reserve (CR). The intervention involved multifactorial CT (30 sessions, 90 min each), with an evaluation pre- and post-training (at six months); the control group simply following the center's routine activities. The primary outcome measures were the change in cognitive performance and the predictors of change. The results show that APOE-e4 non-carriers (79.1%) with a larger left hippocampal volume achieved better gains in semantic verbal fluency (R2 = .19). Subjects with a larger CR and a greater gray matter volume better improved their processing speed (R2 = .18). Age was correlated with the improvement in executive functions, such that older age predicts less improvement (R2 = .07). Subjects with a larger left hippocampal volume achieved more significant gains in general cognitive performance (R2 = .087). In conclusion, besides the program itself, the effectiveness of CT depends on age, biological factors like genotype and brain volume, and CR. Thus, to achieve better results through a CT, it is essential to consider the different characteristics of the participants, including genetic factors.Trial registration: Trial retrospectively registered on January 29th, 2020-(ClinicalTrials.gov -NCT04245579).

Predictive factors and risk and protection groups for loneliness in older adults: a population-based study.

BACKGROUND: Loneliness is considered a public health problem, particularly among older adults. Although risk factors for loneliness have been studied extensively, fewer studies have focused on the protected and risk groups that these factors configure. Our objective is to analyze the variables and latent factors that predict loneliness in older adults and that enable risk and protected groups to be configured. METHODS: We employed an epidemiological, cross-sectional survey that was carried out on a random sample of 2060 people over 65 years extracted from the census. A structured telephone interview was used to assess mental and physical health, habits, quality of life, and loneliness, applying the COOP-Wonca, Goldberg General Health (GHQ-12), and Barber Questionnaires. RESULTS: Predictors of loneliness were: mental health, living alone, quality of life, depressive symptoms, low educational level, and some deficiency situations such as having no one to turn to for help. The factors extracted (Factorial Analysis) were: a subjective experience of poor health, objective isolation, and psychological isolation. We established at risk and protected groups ("Decision Tree" procedure), and loneliness was referred to by 73.2% of the people living alone and with poor mental health and quality of life (risk group). By contrast, only 0.8% of people living with others, with good mental health and good quality of life felt loneliness (protected group). CONCLUSION: In a well-developed city, subjective and objective factors are associated with loneliness. These factors, especially those associated with at risk or protected groups, must be considered to develop strategies that address loneliness.

Myco-Phycobiont Interactions within the "Ramalina farinacea Group": A Geographical Survey over Europe and Macaronesia.

Ramalina farinacea is a widely distributed epiphytic lichen from the Macaronesian archipelagos to Mediterranean and Boreal Europe. Previous studies have indicated a specific association between R. farinacea and Trebouxia microalgae species. Here, we examined the symbiotic interactions in this lichen and its closest allies (the so-called "R. farinacea group") across ten biogeographic subregions, spanning diverse macroclimates, analyzing the climatic niche of the primary phycobionts, and discussing the specificity of these associations across the studied area. The most common phycobionts in the "R. farinacea group" were T. jamesii and T. lynnae, which showed a preference for continentality and insularity, respectively. The Canarian endemic R. alisiosae associated exclusively with T. lynnae, while the other Ramalina mycobionts interacted with both microalgae. The two phycobionts exhibited extensive niche overlap in an area encompassing Mediterranean, temperate Europe, and Macaronesian localities. However, T. jamesii occurred in more diverse climate types, whereas T. lynnae preferred warmer and more humid climates, often close to the sea, which could be related to its tolerance to salinity. With the geographical perspective gained in this study, it was possible to show how the association with different phycobionts may shape the ecological adaptation of lichen symbioses.

Social Loneliness in Older Adults with Mild Cognitive Impairment: Predictive Factors and Associated Clinical Characteristics.

BACKGROUND: Loneliness and social isolation are considered public health problems among older individuals. In addition, both increase the risk of developing cognitive impairment and dementia. The Social Loneliness construct has been proposed to refer to these harmful social interaction-related factors. OBJECTIVE: To define the risk factors of Social Loneliness in individuals with mild cognitive impairment (MCI) and to analyze cognitive, emotional, and functional differences according to the participant's degree of Social Loneliness. METHODS: Through convenience sampling, 105 participants over 60 diagnosed with MCI were selected. The evaluation consisted of anamnesis and a comprehensive neuropsychological examination. The ESTE-II questionnaire was used to assess Social Loneliness and its three factors: perceived social support, social participation, and use of communication technologies. Personality was measured with the NEO-FFI questionnaire. RESULTS: The predictors of the Social Loneliness factors were as follows; 1) perceived social support (R2 = 0.33): Neuroticism (ß= 0.353), depression (ß= 0.205), and perceived health (ß= 0.133); 2) social participation (R2 = 0.24): Conscientiousness (ß= -0.344) and Extraversion (ß= -0.263); 3) use of communication technologies (R2 = 0.44): age (ß= 0.409), type of cohabitation (ß= 0.331), cognitive reserve (ß= -0.303), and Conscientiousness (ß= -0.247); all p < 0.05. The participants with a higher degree of Social Loneliness showed more depressive symptoms (R2 = 0.133), more memory complaints (R2 = 0.086), worse perceived health (R2 = 0.147), lower attentional performance/processing speed (R2 = 0.094), and more naming difficulties (R2 = 0.132); all p < 0.05. CONCLUSIONS: This research represents an advance in detecting individuals with MCI and an increased risk of developing Social Loneliness, which influences the configuration of the clinical profile of MCI.

Multiple bHLH/MYB-based protein complexes regulate proanthocyanidin biosynthesis in the herbage of Lotus spp.

MAIN CONCLUSION: The complexes involving MYBPA2, TT2b, and TT8 proteins are the critical regulators of ANR and LAR genes to promote the biosynthesis of proanthocyanidins in the leaves of Lotus spp. The environmental impact and health of ruminants fed with forage legumes depend on the herbage's concentration and structure of proanthocyanidins (PAs). Unfortunately, the primary forage legumes (alfalfa and clover) do not contain substantial levels of PAs. No significant progress has been made to induce PAs to agronomically valuable levels in their edible organs by biotechnological approaches thus far. Building this trait requires a profound knowledge of PA regulators and their interplay in species naturally committed to accumulating these metabolites in the target organs. Against this background, we compared the shoot transcriptomes of two inter-fertile Lotus species, namely Lotus tenuis and Lotus corniculatus, polymorphic for this trait, to search for differentially expressed MYB and bHLH genes. We then tested the expression of the above-reported regulators in L. tenuis x L. corniculatus interspecific hybrids, several Lotus spp., and different L. corniculatus organs with contrasting PA levels. We identified a novel MYB activator and MYB-bHLH-based complexes that, when expressed in Nicotiana benthamiana, trans-activated the promoters of L. corniculatus anthocyanidin reductase and leucoanthocyanidin reductase 1 genes. The last are the two critical structural genes for the biosynthesis of PAs in Lotus spp. Competition between MYB activators for the transactivation of these promoters also emerged. Overall, by employing Lotus as a model genus, we refined the transcriptional network underlying PA biosynthesis in the herbage of legumes. These findings are crucial to engineering this trait in pasture legumes.

Genetic Predictors of Change in Episodic Verbal Memory by Cognitive Intervention: ACT, PICALM, BDNF, NRG1, APOE Genes and Their Interactions in Situations of Cognitive Demand.

BACKGROUND: Cognitive interventions (CIs) in the elderly are activities that seek to improve cognitive performance and delay its deterioration. Our objectives were to study potential genetic predictors of how a CI program may influence immediate and delayed episodic verbal memory (EVM). METHODS: 162 participants were elderly individuals without dementia who were randomized into parallel control and experimental groups. Participants underwent genetic testing to analyze the PICALM, ACT, NRG1, BDNF and APOE genes. We performed a broad neuropsychological assessment before and 6 months after the CI. The CI involved multifactorial training (30 sessions). The control group undertook the centre's standard activities. The main outcome measures were the genotype studied as a predictor of post-intervention changes in EVM. RESULTS: We found the CI was associated with improvements in several cognitive functions, including immediate and delayed EVM. While no individual gene was associated with any such change, the interaction between PICALM/ACT (p = 0.008; Eta2 = 0.23) and PICALM/NRG1 (p = 0.029; Eta2 = 0.19) was associated with improved immediate EVM, and the NRG1/BDNF interaction was associated with improved delayed EVM (p = 0.009; Eta2 = 0.21). The APOEε4 genotype was not associated with any change in EVM. CONCLUSIONS: Our study shows that the participants' genotype can have an impact on the results of CIs. Cognitive stress may stimulate the interaction of various genes and as such, different types of CI should be established for distinct groups of people taking into account the individual's characteristics, like genotype, to improve the results of this type of health prevention and promotion activity.

Loneliness in the elderly: association with health variables, pain, and cognitive performance. A population-based study / La soledad en personas mayores: asociación con las variables de salud, el dolor y el rendimiento cognitivo. Estudio poblacional

The aim of this population-based study is to analyze the association of loneliness and physical health, pain, health-related quality of life, mental health, cognitive performance, morbidity, and use of health services. Based on the census, a stratified random sampling was chosen. A telephone interview was conducted with 2,060 people over 65 years old, using the GHQ-12 and the COOP-Wonca. An association of loneliness with General Mental Health (GHQ-12) was found, OR = 1.43 (1.34, 1.52) and depression, OR = 2.34 (1.54, 3.53). In cognitive performance the highest effect variable was “memory problems disturb your daily life”, OR = 3.11 (1.25, 7.72); illnesses-related variables: the highest effect variables were perception of health status, OR = 1.37 (1.13, 1. 67) and quality of life (COOP-Wonca), OR = 3.03 (2.32, 3.94); pain-related variables: the highest effect variables were non-localized pain, OR = 2.67 (1.87, 3.83) and arthritis/arthrosis, OR = 1.94 (1.38, 2.72); impaired vision, OR = 2. 62 (1.84, 3.73) and hearing, OR = 1.81 (1.21, 2.72). It is concluded that loneliness is a complex phenomenon associated with variables of different nature. This fact should be taken into account at the time of planning possible solutions. (AU)

El objetivo de este estudio poblacional es analizar la asociación de la soledad no deseada (SND) con salud física, dolor, calidad de vida relacionada con la salud, salud mental, rendimiento cognitivo, morbilidad y uso de servicios de salud. Recurriendo al censo, se realizó un muestreo aleatorio estratificado en Madrid. Se llevó a cabo una entrevista telefónica a 2,060 mayores de 65 años utilizando el GHQ-12 y el COOP-Wonca. Encontramos asociación de la SND y la salud mental general (GHQ-12), OR = 1.43 (1.34, 1.52) y depresión, OR = 2.34 (1.54, 3.53). En rendimiento cognitivo, la variable de mayor efecto fue “los problemas de memoria alteran su vida cotidiana”, OR = 3.11 (1.25, 7.72); variables relacionadas con enfermedad: las de mayor efecto fueron “percepción del estado de salud”, OR = 1.37 (1.13, 1.67) y calidad de vida (COOP-Wonca), OR = 3.03 (2.32, 3.94); variables de dolor: dolor general, OR = 2.67 (1.87, 3.83) y artritis/artrosis, OR = 1.94 (1.38, 2.72); dificultades para ver, OR = 2.62 (1.84, 3.73) y oír, OR = 1.81 (1.21, 2.72). Se concluye que la SND es una situación compleja, lo que debe considerarse al programar soluciones que sean efectivas. (AU)

A genetic approach reveals different modes of action of prefoldins.

The prefoldin complex (PFDc) was identified in humans as a co-chaperone of the cytosolic chaperonin T-COMPLEX PROTEIN RING COMPLEX (TRiC)/CHAPERONIN CONTAINING TCP-1 (CCT). PFDc is conserved in eukaryotes and is composed of subunits PFD1-6, and PFDc-TRiC/CCT folds actin and tubulins. PFDs also participate in a wide range of cellular processes, both in the cytoplasm and in the nucleus, and their malfunction causes developmental alterations and disease in animals and altered growth and environmental responses in yeast and plants. Genetic analyses in yeast indicate that not all of their functions require the canonical complex. The lack of systematic genetic analyses in plants and animals, however, makes it difficult to discern whether PFDs participate in a process as the canonical complex or in alternative configurations, which is necessary to understand their mode of action. To tackle this question, and on the premise that the canonical complex cannot be formed if one subunit is missing, we generated an Arabidopsis (Arabidopsis thaliana) mutant deficient in the six PFDs and compared various growth and environmental responses with those of the individual mutants. In this way, we demonstrate that the PFDc is required for seed germination, to delay flowering, or to respond to high salt stress or low temperature, whereas at least two PFDs redundantly attenuate the response to osmotic stress. A coexpression analysis of differentially expressed genes in the sextuple mutant identified several transcription factors, including ABA INSENSITIVE 5 (ABI5) and PHYTOCHROME-INTERACTING FACTOR 4, acting downstream of PFDs. Furthermore, the transcriptomic analysis allowed assigning additional roles for PFDs, for instance, in response to higher temperature.

Metabolic Profiling and Metabolite Correlation Network Analysis Reveal That Fusarium solani Induces Differential Metabolic Responses in Lotus japonicus and Lotus tenuis against Severe Phosphate Starvation.

Root fungal endophytes are essential mediators of plant nutrition under mild stress conditions. However, variations in the rhizosphere environment, such as nutrient depletion, could result in a stressful situation for both partners, shifting mutualistic to nonconvenient interactions. Mycorrhizal fungi and dark septate endophytes (DSEs) have demonstrated their ability to facilitate phosphate (Pi) acquisition. However, few studies have investigated other plant-fungal interactions that take place in the root environment with regard to phosphate nutrition. In the present research work, we aimed to analyze the effect of extreme Pi starvation and the fungal endophyte Fusarium solani on the model Lotus japonicus and the crop L. tenuis. We conducted metabolomics analysis based on gas chromatography-mass spectrometry (GC-MS) on plant tissues under optimal conditions, severe Pi starvation and F.solani presence. By combining statistical and correlation network analysis strategies, we demonstrated the differential outcomes of the two plant species against the combination of treatments. The combination of nutritional stress and Fusarium presence activated significant modifications in the metabolism of L. japonicus affecting the levels of sugars, polyols and some amino acids. Our results display potential markers for further inspection of the factors related to plant nutrition and plant-fungal interactions.