Lydia Giménez-Llort

Introduction: Gait alterations have been proposed as functional indicators of neural dysfunction in Alzheimer's disease; however, their ability to capture disease-associated locomotor changes in preclinical models remains insufficiently characterized. Methods: In this study, we applied a neuroinformatics framework combining markerless pose estimation, kinematic feature extraction, conventional statistical analysis, supervised machine learning, and model interpretability to characterize gait alterations in the 3xTg-AD mouse model. Two complementary analyses were performed: cross-sectional genotype classification at 12 months of age in 46 mice (3xTg-AD, n = 22; 3xTg-WT, n = 24) and longitudinal assessment of 31 paired surviving animals re-evaluated at 16 months (3xTg-AD, n = 15; 3xTg-WT, n = 16). Results: At 12 months, gait features provided moderate-to-good genotype discrimination, with Logistic Regression achieving the highest balanced performance (AUC = 0.82) and showing relevant contributions from Duty Factor, Allometric Stride Length, Allometric Step Width, and Speed. In the longitudinal cohort, classification performance was more limited (Random Forest, AUC = 0.61), likely reflecting the combined influence of physiological aging, genotype-associated change, selective survival, and task re-exposure. Nevertheless, conventional statistical analysis and SHAP-based model interpretation consistently identified longitudinal changes in Allometric Stride Length and Normalized Coordination Instability as relevant contributors to genotype-associated locomotor divergence. Discussion: These findings suggest that computational gait analysis can capture relevant alterations in locomotor organization in the 3xTg-AD model, with cross-sectional differences associated with distributed spatiotemporal features and longitudinal changes showing a stronger contribution of stride- and coordination-related variables.

Cultural differences in odor perception shape human sensory experience, influencing both social interaction and self‐perception. This study examined the relationship between olfactory imagery, body odor perception, and cultural variation in odor evaluation among participants from Italy, Spain, and Mongolia. Across the sample, the most preferred odors were the sea, coffee, bread, and books, while fish, smog, and waste were consistently disliked. Italian and Spanish participants showed overlapping preferences, reflecting a shared Mediterranean olfactory profile, with the sea rated most positively. Mongolian participants instead favored coffee, bread, books, and wood, but rated the sea significantly lower, likely due to limited ecological exposure. The exploration of self‐perception of body odor revealed that European participants showed greater olfactory awareness and more positive evaluations of self‐attributed odors, whereas no group differences emerged in odor intensity perception. These results support the hypothesis that while basic sensory perception may be relatively stable across cultures, cultural familiarity and environmental exposure shape odor preferences and evaluative aspects of olfactory self‐perception.

Background: Obesity involves an excessive buildup of adipose tissue and is linked to chronic inflammation and oxidative stress, both of which contribute to immunosenescence. Obesity and aging share common features, including immune system impairment and oxidative and inflammatory states, suggesting that obesity may represent a model for accelerated immunosenescence. Objectives/Methods: The aim of this research was to evaluate in Zucker fatty (fa/fa) rats, a well-established genetic model of obesity, multiple immune function parameters (phagocytic activity, natural killer cell function, lymphocyte proliferation in response to mitogens, and cytokine profiles), as well as redox parameters (total antioxidant capacity, glutathione levels, activities of glutathione peroxidase and reductase, and xanthine oxidase activity) in peritoneal leukocytes, spleen, thymus, and liver at adult age (24 weeks). Comparisons were made with Zucker lean controls (fa/+), commonly used as standard controls, and Wistar rats as an independent control group. Results: Zucker fa/fa rats displayed significant physiological disorders, including increased body and organ weights, premature immunosenescence characterized by impaired innate and adaptive immune responses, reduced IL-2 and IL-10 secretion, elevated TNF-α production upon mitogen stimulation, and oxidative stress evidenced by redox imbalance in the spleen, thymus, and liver. Conclusions: These immune dysfunctions and oxidative imbalances are comparable to those observed during the aging process. Given that the immune parameters analyzed are considered indicators of health, aging rate, and longevity, our findings suggest that adult Zucker fa/fa rats could exhibit features of premature aging.

Inflammatory-oxidative stress generated by immune cells plays an important role in aging and in age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Triple-transgenic mice for AD (3xTg-AD) are a suitable model for mimicking this disease in an age-dependent manner. We previously showed that peritoneal leukocyte functions and their redox-inflammatory state are altered early in female 3xTg-AD mice, which exhibit premature aging compared to non-transgenic (NTg) animals. However, their characteristics at 9 months of age, when they present an early neuropathological state, and the sex differences are not known. Here, we analyzed several spleen and thymus leukocyte functions (chemotaxis, natural killer activity, and lymphoproliferation in response to mitogens), pro-inflammatory (IL-1B, TNF-alpha) and anti-inflammatory (IL-10) released cytokine concentrations, and redox parameters (glutathione concentrations and glutathione peroxidase, glutathione reductase, and xanthine oxidase activities) in male and female 3xTg-AD mice compared to age-matched controls. We also analyzed the effects of voluntary physical exercise on immune functions. Our results show that 9-month-old male and female 3xTg-AD mice have worse immune functions, redox state, and inflammation than NTg counterparts. Physical exercise improves immune function. Thus, accelerated aging reflected by peripheral immunosenescence and oxidation-inflammation in 3xTg-AD mice precedes hallmark neuropathology, and exercise can slow down AD progression.

Background/Objectives: Homeostatic (nervous, immune and endocrine) systems and their communications network are crucial for health and aging rate. We previously reported behavioral and peritoneal leukocyte function alterations and oxidative-inflammatory stress in young female triple-transgenic (3xTg) mice for Alzheimer’s disease (AD). Here, the deterioration of the homeostatic systems and their interplay was investigated, in an integrated way, at prodromal stages and in both sexes of 3xTg-AD mice. Methods: An integrative analysis of the behavioral profile, peripheral immune splenic and thymic leukocyte functions, splenic oxidative-inflammatory state, and plasmatic corticosterone in both sexes of 3xTg-AD mice at 4 months of age was compared to that of age- and sex-matched NTg counterparts. Results: The prodromal stage of 3xTg-AD, characterized by anxiety-like behaviors and disrupted exploration, was aligned with reduced chemotaxis, natural killer activity, and lymphoproliferation—especially in the spleen. In addition, 3xTg-AD mice exhibited lower anti-inflammatory (IL-10) and higher pro-inflammatory (IL-2, IL-1β, and TNF-α) cytokine concentrations and oxidative stress (higher oxidants and lower antioxidants). Several of these alterations displayed sex-dependent differences (worse in males). However, no differences in corticosterone were found. Conclusions: These findings suggest that neuroimmune and redox-inflammatory dysfunctions, indicative of premature aging, emerge at the prodromal stage of AD, preceding corticosterone changes, unveiling a time lag in the neuroimmunoendocrine alterations in these animals. They may act as early indicators of premature aging in AD pathology and provide potential targets for sex-specific prodromal intervention.

Homeostatic systems (nervous, immune, and endocrine) and their communications network are crucial for health and aging rate. The triple transgenic mice for Alzheimer´s disease (3xTg-AD) offer a valuable model to study the pathogenesis of AD, in which oxidative-inflammatory stress is involved. We previously reported behavioral and peritoneal leukocyte function alterations and oxidative-inflammatory stress in young female 3xTg-AD compared to age-matched non-transgenic (NTg) controls. However, it is not known how the deterioration of the homeostatic system interplay occurs at prodromal stages and the effects of sex. Here, we carried out an integrative analysis of the behavioral profile, splenic and thymic leukocyte functions, splen-ic oxidative-inflammatory state and plasmatic corticosterone in male and female 3xTg-AD at 4 months, compared to NTg counterparts. At this prodromal stage, char-acterized by anxiety-like behaviors and disrupted exploration, the 3xTg-AD mice ex-hibited reduced chemotaxis, natural killer activity, and lymphoproliferation—especially in the spleen. These changes were accompanied by lower anti-inflammatory and higher pro-inflammatory cytokine concentrations, and oxidative (higher oxidants and lower antioxidants) stress, indicating a breakdown of neuroimmune and redox-inflammatory homeostasis. Notably, several of these alterations displayed sex-dependent differences. These findings suggest that neuroimmune and redox-inflammatory dysfunctions emerge at the prodromal stage, preceding endocrine changes, and may act as early in-dicators of premature aging in Alzheimer’s pathology.

Background/Objectives: Neuropsychological testing is key in defining cognitive profiles at early stages of dementia. More importantly, the detection of subtle cognitive changes, such as subjective cognitive complaints (SCCs), an understudied phenomenon, is critical for early detection and preventive interventions. Methods: This systematic review analyzes the empirical data on the cognitive domains and neuropsychological tests used in studies addressing SCC in the last 15 years (2009–2024). Results: A selection of 15 papers with exploratory, cross-sectional, and prospective scope in this field was obtained from PubMed and Embase databases. They used screening tests (17%) and a broad spectrum of neurocognitive domains. Yet, we identified three main targeted cognitive domains: executive functions (28%), language (17%), and memory (17%). Myriad assessment tools were also applied, but the most commonly used was a set of eight tests: Mini-mental Scale Examination (MMSE), Trail Making Test (A-B), Stroop test, Digit span test (DST), Semantic and Phonological fluency test, Rey Auditory Verbal Learning Test (RAVLT), Weschler Memory Scale (WMS), and Boston Naming Test (BNT). New approaches involved including the Geriatric Depression Scale (GDS) and self/informant reports. Conclusions: Despite scarce agreement in the assessment protocols, the identification of early neurocognitive symptoms to objectivate the SCC phenomenon envisions a broad field of research.

Sub-Saharan Africans and Afro-Americans face 2-to-8 times higher risk of dementia compared to Caucasians, with Nigerian people being the highest population-at-risk. Adding to this challenge, their unique lipid profile increases their susceptibility to type 2 diabetes mellitus (DM-2), which further raises the risk of cognitive impairment (CI) by 1.5 times. Recently, we demonstrated a strong Diabetes/Dementia tandem in Nigerians, with increased cognitive vulnerability in illiterate, short-height, and diabetic Nigerian women in the eye of the storm. The combination of factors within this population makes it the optimal scenario to understand the relationship between CI and DM-2. Here, we further studied the blood biochemical analysis of our Makurdi cohort and searched for correlations with standard anthropometric measures, educational level, cognitive status (as assessed with MMSE, 6-CIT) and DM-2. CI was prevalent across all groups, with higher incidence in DM-2 subjects and a marked sexual dimorphism. Thus, women exhibited a greater risk, especially those with low educational attainment. In the search for potential blood-based biomarkers for cognitive function, we identified those related to renal function. In particular, elevated uric acid and urea levels were associated with poorer cognitive performance, highlighting a potential kidney-brain axis connection. Renal function blood metabolites in this Nigerian cohort have been identified as possible kidney-brain axis biomarkers of CI. Moreover, illiteracy, female sex, and DM-2 pose them a compounded risk of developing CI. These findings advocate that targeted interventions addressing educational disparities and metabolic health could be proposed to mitigate cognitive decline in these vulnerable sub-groups. The integration of these factors provides a comprehensive understanding of CI incidence in Nigeria’s population, offering new avenues for diagnosis, prevention, and treatment strategies. Not applicable.

The state of frailty is a clinical–biological syndrome that affects the older population with a higher risk of functional dependence. Animal models can provide a tool to study this complex scenario. In the present work, we analyzed the physical and behavioral hallmarks of end-point status in 16-month-old mice (C57BL/6J) according to animal welfare regulations compared to age-matched counterparts with normal aging. A group of 6-month-old mice was added to control for age bias. First, we identified ‘structural kyphosis’ (visible and unmodifiable deformation in locomotion) correlated with piloerection as the hallmarks of the physical frailty phenotype compared to the ‘postural kyphosis’ (adjustment to counteract increased visceral volume but attenuated during locomotion) of old mice with normal aging. Alopecia (barbering) was presented in both old groups. Normal levels of exploratory activity in the corner test for neophobia and triceps surae muscle weight but an increased latency of rearing indicated the poorest emotional phenotype, with a possible contribution of structural kyphosis. The presence of hepatomegaly and splenomegaly counteracted the significant WAT loss commonly associated with end-of-life traits, which should have a normal body weight but preserved muscle mass.

Introduction. Frailty is a common condition among older individuals and is associated with increased vulnerability to adverse health outcomes. The COVID-19 pandemic further highlighted the impact of viral infections on frail populations. The present work aimed to determine frailty, functional and cognitive status, and clinical analysis of older persons in a long-term care facility in Chile, before and following the outbreak of COVID-19. Methods. A single-center, pre–post, and Pearson’s correlational study was conducted in a cohort of 20 persons positive for COVID-19 from a total of 45 residents. Data on demographic, clinical, functional (Barthel Index (BI) and Katz) and cognitive (Mini mental Examination) status, and physiological function (hematology, lipidic and biochemical profiles) were collected. Results. The mean age was 84 ± 2.4 years, and 80% were females. The most common comorbidities were Arterial Hypertension, Diabetes Mellitus type II, and Alzheimer’s disease. Physical frailty was confirmed by body weight, body mass index, and calf circumference. Pre-infection, BI was negatively correlated with lipidic profile and erythrocyte sedimentation rate (ESR), and positively with frailty (calf circumference). Pre–post analysis showed that frailty and most analytical results were not modified. However, functional dependence on daily live activities significantly increased as measured by BI, with worse grooming and bowel and bladder controls. Post-infection, correlations were lost except between BI and ESR, and decreased albumin levels were found. Conclusions. The worsening of specific functional limitations emphasizes the need for targeted interventions that can be correlated with ESR. Albumin appears as a potential biomarker for physiological dysfunction associated with their infectious/inflammatory processes.