INEU

Baseline Results Investigate APOE‐Memory Connection in Latin‐American Population at Risk for Dementia ‐ LatAm‐FINGERS Initial Insights

Sun, 21 Dec 2025 00:00:00 GMT

Baseline Results Investigate APOE‐Memory Connection in Latin‐American Population at Risk for Dementia ‐ LatAm‐FINGERS Initial Insights Vasconcelos Friedlaender, Clarisse; Cruz de Souza, Leonardo; Tonidandel Barbosa, Maira; Braga Gomes, Karina; Gonçalves Tosatti, Jéssica Abdo; de Faria Rocha, João Victor; Melillo Cardoso, Davi; Machado Prates, Marcelo; Lopes, Andre Luis; Silva Vieira, Vitoria; Ribeiro Jeunon, Vinicius; Ferreira de Souza, Letícia Maria; Soares Figueiredo, Lais; Andrades, Andreia; Crivelli, Lucía; Calandri, Ismael Luis; Martin, Maria Eugenia; Allegri, Ricardo Francisco; Sevlever, Gustavo Emilio; Surace, Ezequiel Ignacio Background: Latin America (LA) faces heightened vulnerability to modifiable dementia risk factors. Early identification of at‐risk individuals is crucial for implementing effective preventive strategies. The Free and Cued Selective Reminding Test with Immediate Recall (FCSRT‐IR) is promising in early detection of mnemonic impairment, with high sensitivity and specificity for Alzheimer's Disease (AD) risk. While sociodemographic and genetic factors, including APOE ε4 genotype, are associated with elevated dementia risk, their influence on cognitive performance in LA populations remains unclear. We aim to investigate sociodemographic factors and APOE ε4 genotype influence on mnemonic performance in high‐risk LA individuals. Method: Cross‐sectional analysis of LatAm‐FINGERS baseline data, a randomized, multicenter trial evaluating non‐pharmacological interventions for cognitive decline prevention in LA. Inclusion criteria: age 60‐77 years; CAIDE ≥ 6; ‐1.5 ≤ z score ≤ 0 on MMSE or CERAD word list. Exclusion criteria: MMSE < 20; dementia; illiteracy. Participants from Argentina, Brazil, Chile, and Uruguay were included. Memory assessment used FCSRT‐IR and SOMI (Stages of Objective Memory Impairment) classification. APOE genotyping was performed on blood samples using PCR‐RFLP analysis. Jamovi software (v2.3) analyzed correlations and associations (p < 0.05). Result: Sample (N = 358 participants): age 67.75 ± 4.86 years; education 13.41 ± 3.14 years; 72.3% female; 61.2% white; 22.3% APOE ε4 carriers. FCSRT‐IR scores correlated significantly with sociodemographics (p < .001) and varied among countries (p < .001). SOMI distribution: 58% SOMI‐0 (preserved memory), 27.6% SOMI‐1/2 (mild impairment). Argentina showed 36% in SOMI‐3/4 (severe impairment); Uruguay 75% in SOMI‐0. No significant sociodemographic differences were found between APOE ε4 carriers/non‐carriers. Non‐carriers performed better on FCSRT‐IR, significant only for identification score (p = .017). No significant APOE ε4‐SOMI association. Conclusion: Sociodemographic profile significantly influences memory performance, while APOE ε4 genotype shows limited association. This suggests environmental and social factors may play a more central role in cognitive performance than genetic predisposition in LA populations.

Ageism in a Latin American Cohort: The Role of Cognition and Gender

Fri, 26 Dec 2025 00:00:00 GMT

Ageism in a Latin American Cohort: The Role of Cognition and Gender Arruabarrena, Micaela María; Corvalán, Nicolás; Morello García, Florentina; Keller, Greta; Martinez, Carlos; Crivelli, Lucía Background: Ageism, a form of discrimination based on age‐related stereotypes, encompasses both negative (e.g., older adults as burdensome or incapable) and positive (e.g., older adults as wise or nurturing) stereotypes. According to the Stereotype Embodiment Theory (SET), these cultural stereotypes, internalized throughout life, shape self‐perceptions, behaviors, and health outcomes as individuals age. The objective of this study is to evaluate the differences in perceived ageism between individuals with Mild Cognitive Impairment (MCI) and normal controls (NC). Additionally, it aims to analyze whether men and women perceive ageism differently, considering gender effects and potential interactions with cognitive status. Method: Our study included 188 participants (57.4% women) aged 60 to 88 years (72.2±6.7). According to the Clinical Dementia Rating (CDR), 136 participants were classified as NC (CDR=0) and 52 as MCI (CDR=0.5). All the participants completed the 8‐item Perceived Ageism Questionnaire (PAQ) to evaluate positive and negative ageism. Generalized linear models assessed the relationship between ageism perceptions and cognitive status, gender, age, and their interactions. Result: No significant differences in Positive Ageism (p = .548) or Negative Ageism (p = .079) were found between MCI and NC. In the Positive Ageism model, lower cognitive status (𝛃=‐3.278, SE=0.4657, p = .0155) and the interaction between gender and cognitive status (𝛃=2.3821, SE=0.8812, p = .0075) were significant predictors. Intragroup comparisons and post‐hoc analysis showed that in the MCI group, men perceived higher Positive Ageism than women (p = .028), which was not present in the NC group (p = 0.897). In addition, no significant gender differences in Negative Ageism were observed in either the MCI or NC groups. Conclusion: Our findings highlight distinct patterns in positive and negative ageism according to the interaction between gender and cognitive status. Men with MCI perceive significantly higher Positive Ageism, suggesting that aging in men is perceived as an advantage, reinforcing notions of wisdom and social value. In contrast, women with MCI do not share this positive perception, likely reflecting societal attitudes that devalue aging in women. Future studies should explore these interactions to understand better the impact of ageism on older adults with MCI.

Use of an exogenous DNA-free system to generate MSTN-KO calves by CRISPR/Cas9 and SCNT

Thu, 25 Sep 2025 00:00:00 GMT

Use of an exogenous DNA-free system to generate MSTN-KO calves by CRISPR/Cas9 and SCNT Suvá, Mariana; Bastón, Juan Ignacio; Wiedenmann, Elisabet Astrid; Pose Ortiz de Rozas, María Belén; Roberto, Jordán; Ghetti, Alberto; Viale, Diego Luis; Moro, Lucía Natalia; Vichera, Gabriel Damián This study aimed to obtain myostatin (MSTN)-knockout calves, while avoiding the risk of exogenous DNA integration during gene editing. To achieve this, we combined CRISPR/Cas9 ribonucleoprotein gene editing with somatic cell nuclear transfer (SCNT) technology. In the first experiment (E1), we compared the gene editing efficiency of four gRNAs targeting different coding regions of the MSTN gene using plasmid-based CRISPR/Cas9 in bovine fetal fibroblasts (BFF-E1 cells). The highest bioinformatically-predicted editing rate (BPE) was obtained with gRNA2 (96 %), which was subsequently used for further experiments. Next, embryos were produced by SCNT using BFF-E1-edited cells as nuclear donors. Sanger sequencing of the embryos showed biallelic MSTN editing. In the second experiment (E2), plasmid-based editing was replaced with CAS9 protein and trac:crRNA oligoribonucleotides. Editing efficiency was assessed on one edited bovine fetal fibroblast line (BFF-E2-maleed) and two edited bovine mesenchymal stem lines (MSC-E2-maleed and MSC-E2-femed) derived from price-winning animals. BPEs were 58.8 %, 31 % and 59 % in fibroblast and MSC cells, and 64 %, 73.3 %, and 66.6 % in SCNT embryos derived from BFF-E2-maleed, MSC-E2-maleed and MSC-E2-femed, respectively. Transfer of 35 MSC-E2-femed embryos to recipient cows, resulted in the birth of one MSTN-edited calf with a heterozygous genotype. A second-generation clone was subsequently produced, using a fibroblast sample as nuclear donor. In conclusion, we established an efficient protocol for generating high rates of edited blastocysts with a desirable genetic background, resulting in the birth of two MSTN-knockout calves. This study provides a foundation for gene editing to improve productive or biomedical traits.

Structural connectivity correlates of response to electroconvulsive therapy in treatment-resistant depression

Wed, 01 Apr 2026 00:00:00 GMT

Structural connectivity correlates of response to electroconvulsive therapy in treatment-resistant depression Samman, María Eugenia; Fiorentini, Leticia; Lahitou Herlyn, Delfina; Tsuchiyagaito, Aki; Castro, Mariana Nair; Costanzo, Elsa; Brusco, Luis Ignacio; Camprodon, Joan A.; Forcato, Cecilia; Guinjoan, Salvador Martín; Villarreal, Mirta Fabiana Electroconvulsive therapy (ECT) remains the most effective intervention for treatment-resistant depression (TRD). We investigated whether cortico-limbic structural connectivity is associated with ECT response. Twenty-nine TRD patients underwent bifrontal ECT and baseline probabilistic tractography assessing connectivity between amygdala, anterior insula (aINS), orbitofrontal cortex (OFC), posterior cingulate cortex (PCC), posterior ventrolateral (VLPFC) and dorsolateral prefrontal cortex (DLPFC), subgenual cingulate cortex (SGCC) and thalamus. Stronger connectivity within a subnetwork comprising bilateral OFC, bilateral aINS, left SGCC and right DLPFC was associated with poorer ECT response showing predictive value for treatment outcome. Conversely, thalamus-PCC connectivity is related to greater baseline severity and better ECT response. In TRD, depressive symptom scores negatively correlated with fronto-limbic-thalamic connectivity. Our findings highlight a fronto-limbic subnetwork whose hyperconnectivity may reflect maladaptive regulation limiting neuromodulation efficacy. In contrast, thalamic connectivity may act as a hub linking fronto-limbic and default mode network circuits, potentially facilitating receptive pathways supporting therapeutic response and guiding anatomically precise neuromodulation strategies.