Lydia Giménez-Llort

Autonomous University of Barcelona | UAB · Department of Psychiatry and Forensic Medicine

Translational research is the key to unlocking the mysteries of neurological and psychiatric disorders and developing new treatments. Disease models in vivo and in vitro have been critical in understanding complex disease mechanisms. The most recent research indicates that sex, gender, and aging all play important roles in the pathogenesis and clin...

Fibromyalgia (FM) is a condition characterized by musculoskeletal pain and multiple comorbidities. Our study aimed to identify four clusters of FM patients according to their core clinical symptoms and neuropsychological comorbidities to identify possible therapeutic targets in the condition. We performed a population-based cohort study on 251 adul...

Translational research is the key to unlocking the mysteries of neurological and psychiatric disorders and developing new treatments. Disease models in vivo and in vitro have been critical in understanding complex disease mechanisms. The most recent research indicates that sex, gender, and aging all play important roles in the pathogenesis and clin...

Pre-clinical research in aging is hampered by the scarcity of studies modeling its heterogeneity and complexity forged by pathophysiological conditions throughout the life cycle and under the sex perspective. In the case of Alzheimer’s disease, the leading cause of dementia in older adults, we recently described in female wildtype and APP23 mice a...

One key limitation in developing effective treatments for neurodegenerative diseases is the lack of models that accurately mimic the complex physiopathology of the human disease. Humans accumulate with age the pigment neuromelanin inside catecholaminergic neurons. Neurons reaching the highest neuromelanin levels preferentially degenerate in Parkins...

Background Standard neuropathologic analysis of Alzheimer’s brain relies on traditional fluorescence microscopy, which suffers from limited spatial resolution due to light diffraction. As a result, it fails to reveal intricate details of amyloid plaques. While electron microscopy (EM) offers higher resolution, its extensive sample preparation, invo...

The COVID-19 pandemic was one of this century’s deadliest and most widespread viral outbreaks, with higher mortality rates in men than women. Disruptions in funeral rituals and customs, no social recognition of the losses, and limited social support have complicated the grieving process and are linked to disenfranchised (not openly acknowledged, so...

Introduction The threat and preservation of the territorial integrity of Ukraine are not new issues. During the last decade, peacetime (Peace, until 2013) was disrupted by active hostility (AH, 2014–2015) and trench warfare (TW, 2016–2021). War exert acute and chronic impacts on mental health, may be a substrate for mental health disorders, especia...

Research on Alzheimer’s disease (AD) has classically focused on alterations that occur in the brain and their intra- and extracellular neuropathological hallmarks. However, the oxi-inflammation hypothesis of aging may also play a role in neuroimmunoendocrine dysregulation and the disease’s pathophysiology, where the liver emerges as a target organ...

Chronic administration of d ‐galactose ( d ‐gal) in rodents reproduces the overproduction of reactive oxygen species of physiological aging. The present research shows for the first time distinct signatures on d ‐gal‐induced aging (500 mg/kg, 6 weeks) and the preventive and protective potential of two vitamin D (50 IU) supplementation regimens (pre...

A sample of 351 adults (women/men 4:1) aged 18 to 60 participated in an online survey administered during the first two waves (15 March–25 April and 10 October–25 November 2020) of the COVID-19 pandemic in Ukraine. The user ethnography profile was Generation Z (born in the 1990s), female (81.2%), Instagrammer (60.3%), unmarried (56.9%) and student...

The COVID-19 pandemic is one of the past century's deadliest and most widespread viral outbreaks, with higher mortality rates in men than women. Disruptions in funeral rituals and customs, no social recognition of the loss, and limited social support intricate the grieving process and are linked with disenfranchised (not openly acknowledged, social...

Despite its robust proteopathic nature, the spatiotemporal signature of disrupted protein modules in sporadic Alzheimer’s disease (AD) brains remains poorly understood. This considered oxidative stress contributes to AD progression and early intervention with coenzyme Q10 or its reduced form, ubiquinol, delays the progression of the disease. Using...

The perception of body and social odours (SOP) is crucial for interpersonal chemosensory signalling and mate choice, yet little is known about the role of the SOP on the quality of partnerships and the attachment style. The aim of this study was to investigate the role of the SOP in women’s stress responses by considering the role of biopsychosocia...

Background and purpose: Therapies based on apolipoprotein A-I (ApoA-I), classically tested for cardiovascular diseases, were recently proposed for Alzheimer's disease (AD). Based on a drug reprofiling approach, our objective was to explore the use of a natural variant of ApoA-I form, ApoA-I-Milano (M), as a treatment for AD. ApoA-I-M contains the...

Gemfibrozil (GFZ) is a medication of the fibrate category with agonistic effects on PPAR‐α and is effective for hypertriglyceridemia and mixed dyslipidemia. This agent also has anti‐inflammatory and antioxidant properties. The current study investigated the effects of GFZ on hepatorenal damages in a D‐galactose (D‐gal)‐induced aging model. We used...

The severity of sensory involution during aging is critical for perceiving and recognizing the world. In addition, sensory deficits significantly increase the risk of older adults’ biological, mental, and social decline. Conversely, the loss of smell is an early biomarker of neurodegeneration in Alzheimer’s (AD) and Parkinson’s diseases. The worsen...

Burying and burrowing are promising rodent-typical behaviors to model neuropsychiatric symptoms (NPS). However, the original tests could be insufficient to conclude which NPS are modeled. Here, we propose methodological modifications such as the two-zone configuration and dual analysis in the Marble Burying Test (MB). Also, a new Brief Burrowing Te...

The impairment of basal forebrain cholinergic neurons (BFCN) is key to developing Alzheimer’s disease (AD). The endocannabinoid (eCB) system modulates these pathways, but the overall effect of cannabinoid compounds on memory remains unclear, since their dual neuroprotective-neurotoxic profile depends on factors such as dose and age of the subjects....

Bizarre behaviors (BB) are elicited in animals during stressful conditions and represent behavioral markers of disease/sickness relevant to animal welfare. These behaviors are disregarded in most experimental screenings due to their low incidence and short duration, despite their translational value mimicking disruptive behaviors associated with ne...

Alzheimer’s disease (AD) patients suffer from circadian rhythm alterations affecting their daily physical activity patterns with less willingness to perform a voluntary exercise. In preclinical studies, there is no clarity on whether animal models of AD can replicate these impairments. Here, we provide a proof of concept of the performance and beha...

The neuroimmunomodulation hypothesis for Alzheimer’s disease (AD) postulates that alterations in the innate immune system triggered by damage signals result in adverse effects on neuronal functions. The peripheral immune system and neuroimmunoendocrine communication are also impaired. Here we provide further evidence using a longitudinal design tha...

Alzheimer’s Disease (AD) patients suffer from circadian rhythm alterations involving sleep, thermoregulation, and movement activity disorders. The latter affects their daily patterns of physical activity (PA) and willingness to perform voluntary exercise, impeding benefit from routine PA practice. Neuropsychiatric symptoms (NPS) have been postulate...

Epidermolysis Bullosa (EB) is a chronic disease with multiple clinical presentations, depending on the subtype. It is characterized by the structural fragility of skin and tissues which results in lesions. Its low prevalence contributes to the lack of knowledge of the disease by the general population and the health sector. The disorder’s heterogen...

The crosstalk between obesity, diabetes, steatohepatitis, and dementia creates a controversial scenario when also studied using animal models. In the present work, this crosstalk was investigated in male and female 3xTg-AD mice for Alzheimer’s disease (AD) at different ages/stages and compared to sex- and age-matched counterparts with normal aging....

Epidermolysis bullosa (EB), also known as Butterfly skin, is a term for a heterogeneous group of rare genodermatosis disorders resulting in painful mucocutaneous blisters and extreme fragility with minor trauma or friction. The low prevalence and heterogeneity of EB, clinically classified into 4 major groups and over 30 subtypes, lead to significan...

Depression, stress, anxiety disorders, and PTSD are some of the mental health problems that are prevalent among immigrant populations despite being underdiagnosed. Stigma, difficulties in adapting, cultural barriers, and reduced access to mental health support can seriously hamper their ability to build resilience and recover. Other limitations inc...

A content analysis of an English Newspaper, The Times of India (the world’s largest newspaper by circulation) during the first national lockdown amid the COVID-19 pandemic identified nine different categories culled out from a total of 129 news categories reporting unprecedented COVID-19 stories. Half of them portrayed two sides of a coin: from dai...

Coping with emotional stressors strongly impacts older people due to their age-related impaired neuroendocrine and immune systems. Elevated cortisol levels seem to be associated with an increased risk of cognitive decline and dementia. In Alzheimer’s disease (AD), alterations in the innate immune system result in crosstalk between immune mediators...

Ukrainian Military Hospital retrospective analysis during a decade of conflicts (3995 records) unveils specific mental health ICD-10-CM distribution per rank and the long-lasting impact of active conflict or trench warfare. Most hospitalizations in all years of observation were among soldiers. Anxiety-related disorders have been present since ‘peac...

Motor performance facilitates the understanding of the functional state related to the progression of Alzheimer's disease (AD). At the translational level, this brief report refines the characterization of the motor dysfunction of the 3xTg-AD mouse model in different motor tasks, focusing on the abnormal clasping reflex and coordination impairments...

Misophonia is a poorly understood and underdiagnosed disorder. People who suffer from this condition without knowing it has a notable deterioration in their quality of life, affecting their personal and social relationships. The present study characterized the self-concept of 82 people (women:men, 3:2) attending a medical psychology center in Barce...

In the present study, the health-protective and therapeutic properties of MET are revisited, giving focusing on the effect of MET on the Nrf2 expression in patients with different pathological conditions. Metformin (MET) regulates high blood glucose, thus being an integral part of the antidiabetic medications used to treat type 2 diabetes mellitus....

Misophonia is a scarcely known disorder. This systematic review (1) offers a quantitative and qualitative analysis of the literature since 2001, (2) identifies the most relevant aspects but also controversies, (3) identifies the theoretical and methodological approaches, and (4) highlights the outstanding advances until May 2022 as well as aspects...

Imidazoline receptors (IR) are classified into three receptor subtypes (I1R, I2R, and I3R) and previous studies showed that regulation of I2R signaling has neuroprotective potential. In order to know if I2R has a role in modulating vascular tone in health and disease, we evaluated the putative vasoactive effects of two recently synthesized I2R liga...

Longitudinal approaches for disease-monitoring in old animals face survival and frailty limitations, but also assessment and re-test bias on genotype and sex effects. The present work investigated these effects on 56 variables for behavior, functional profile, and biological status of male and female 3xTg-AD mice and NTg counterparts using two desi...

Collective mourning is an expression of societal maturity, cohesion, and respect. The world is in grief, but in early January 2020, before nobody could even imagine that SARS-CoV-2 would turn into the COVID-19 pandemic, a music video version of a pop ballad about love and isolation was spread across a Chinese social network. The song ‘You Are Not A...

Subjective cognitive complaints correspond to a heterogeneous construct that frequently occurs in the early stages of older adult life. Despite being a common source of worry for middle-aged people, it can be underestimated when clinical and neuropsychological assessments discard any underlying pathological processes. Negative age stereotyping but...

Storage of aversive memories is of utmost importance for survival, allowing animals to avoid upcoming similar stimuli. However, without reinforcement, the learned avoidance response gradually decreases over time. While the molecular mechanisms controlling this extinction process are not well known, there is evidence that the endocannabinoid system...

Calcium dobesilate (CaD) is used for the treatment of diabetic retinopathy and nephropathy. This agent exerts antioxidant effects. In the present study, we evaluated the protective effects of oral administration of CaD against hepatorenal damages in a mice model of aging induced by D‐galactose (D‐gal). We used twenty‐eight male albino mice, which e...

The phenotypic transformation of astrocytes in Alzheimer's disease (AD) is still not well understood. Recent analyses based on single-nucleus RNA sequencing of postmortem Alzheimer's disease (AD) samples are limited by the low number of sequenced astrocytes, small cohort sizes, and low number of differentially expressed genes detected. To optimize...

Gemfibrozil (GFZ) is a lipid-lowering drug with several other effects, such as antioxidant and anti-inflammatory activities. In the current study, chronic D-galactose treatment (D-gal, 150 mg/kg/day; i.p., 6 weeks) induced a model of accelerated aging in male mice, and was used to study the behavioral, anti-oxidative, and neuroprotective effects of...

The subgranular zone of the dentate gyrus is an adult neurogenic niche where new neurons are continuously generated. A dramatic hippocampal neurogenesis decline occurs with increasing age, contributing to cognitive deficits. The process of neurogenesis is intimately regulated by the microenvironment, with inflammation being considered a strong nega...

Oxaliplatin, the first-line chemotherapeutic agent against colorectal cancer (CRC), induces peripheral neuropathies, which can lead to dose limitation and treatment discontinuation. Downregulation of potassium channels, which involves histone deacetylase (HDAC) activity, has been identified as an important tuner of acute oxaliplatin-induced hyperse...

Background Deposition of amyloid plaques and neurofibrillary tangles composed of abnormally phosphorylated tau are the neuropathological hallmarks of Alzheimer's disease (AD). However, years before the accumulation of protein aggregates, the abnormal intraneuronal accumulation of heparan sulfates (HS) is observed. This phenomenon breaks a dogma, si...

In the next few years, the prevalence of diabetes mellitus (DM) is projected to dramatically increase globally, but most of the cases will occur in low-to-middle-income countries. Some of the major risk factors for diabetes accelerate the development of dementia in African-Americans, thus leading to a higher prevalence of dementia than Caucasians....

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia in aging populations. Recently, the regulation of neurolipid-mediated signaling and cerebral lipid species was shown in AD patients. The triple transgenic mouse model (3xTg-AD), harboring βAPPSwe, PS1M146V, and tauP301L transgenes, mimics many...

Facial expression is a key aspect in observational scales developed to improve pain assessment in individuals with cognitive impairments. Although these scales are used internationally in individuals with different types of cognitive impairments, it is not known whether observing facial expressions of pain might differ between regions or between di...

Gait impairments in Alzheimer’s disease (AD) result from structural and functional deficiencies that generate limitations in the performance of activities and restrictions in individual’s biopsychosocial participation. In a translational way, we have used the conceptual framework proposed by the International Classification of Disability and Health...

The temporal course and the severity of the involution of sensory systems through aging can be critical since they ensure the ability to perceive and recognize the world. In older people, sensory impairments significantly increase their risk of biological, psychological, and social impoverishment. Besides this, olfactory loss is considered an early...

The secondary impacts of the COVID-19 pandemic are distress triggers and risk factors for mental health. Conversely, self-compassion skills and compassionate thoughts/behaviors towards suffering may contribute to their alleviation. Both psychological constructs are interrelated in life-threatening diseases such as multiple sclerosis (MS). The Terue...

Ageism can be seen as systematic stereotypes, prejudice, and discrimination of people because of their age. For a long time, society has accepted negative stereotypes as a norm. When referring to older adults, the United Nations Global Report on Ageism warns about a severe impact. The Intergenerational Study for a Healthy Aging, a questionnaire abo...

The shorter life spans of mice provide an exceptional experimental gerontology scenario. We previously described increased bizarre (disruptive) behaviors in the 6-month-old 3xTg-AD mice model for Alzheimer's disease (AD), compared to C57BL/6J wildtype (NTg), when confronting new environments. In the present work, we evaluated spontaneous gait and e...

The marble burying (MB) test, a classical test based on the natural tendency of rodents to dig in diverse substrates and to bury small objects, is sensitive to some intrinsic and extrinsic factors. Here, under emerging neuroethological quantitative and qualitative analysis, the MB performance of 12-month-old male and female 3xTg-AD mice for Alzheim...

Nesting behavior in rodents, used to assess animal welfare/illness and instrumental tasks, is also proposed as valuable for disease monitoring, evaluating potential risk factors and interventions. The reliability of Deacon’s 5-point ordinal scale to score nests at 24 h is well-recognized. However, previous work with the 3xTg-AD mice model of Alzhei...

A decline in learning and remembering a spatial route often accompanies the normal ageing process. Impairments in spatial orientation manifest from the early stages of disabling cognitive diseases such as Alzheimer’s Disease (AD). In the preclinical field, detecting behavioural signs that help differentiate both entities improve understanding of th...

The impact of isolation has become a critical worldwide issue since the outbreak of the COVID-19 pandemic. In nursing homes, the physical distance measures forced the separation of old patients in restricted areas and rooms to avoid the spread of the virus. Similarly, older people living at home face severe restrictions as the best preventive strat...

When it comes to neurodegenerative disorders, Alzheimer’s disease (AD) is one of the main causes of dementia in older people. Until now, studies have focused on alterations occurring in the brain. However, it has been shown that along with the accumulation of beta-amyloid plaques and tau proteins, oxidative stress and inflammation also play a role...

In Western societies, death is a social and educational taboo. Poor education about death and mourning processes and overprotective family and social attitudes move children away from death to avoid “unnecessary suffering.” The COVID-19 outbreak highlighted these shortcomings and the difficult management of grief's complexity under sudden and unexp...

The increase of the aging population, where quite chronic comorbid conditions are associated with pain, draws growing interest across its investigation and the underlying nociceptive mechanisms. Burn injuries associated problems might be of relevance in the older adult’s daily life, but in people with dementia, exposure to high temperatures and hea...

According to the Research Domain Criteria (RDoC), phenotypic differences among disorders may be explained by variations in the nature and degree of neural circuitry disruptions and/or dysfunctions modulated by several biological and environmental factors. We recently demonstrated the in vivo behavioral translation of tweaking the PI3K/Akt signaling...

The wide heterogeneity and complexity of Alzheimer’s disease (AD) patients’ clinical profiles and increased mortality highlight the relevance of personalized-based interventions and the need for end-of-life/survival predictors. At the translational level, studying genetic and age interactions in a context of different levels of expression of AD-gen...

New evidence refers to a high degree of heterogeneity in normal but also Alzheimer’s disease (AD) clinical and temporal patterns, increased mortality, and the need to find specific end-of-life prognosticators. This heterogeneity is scarcely explored in very old male AD mice models due to their reduced survival. In the present work, using 915 (432 A...

The extreme, unprecedented situations in the current COVID-19 pandemic are risk factors for psychosocial stress for the entire population. However, strict confinement had a particular impact on people suffering from misophonia and their families. Misophonia is a condition in which hearing certain sounds triggers intense anger, disgust and even seve...

Forced strict confinement to hamper the COVID-19 pandemic seriously affected people suffering from misophonia (M+) and those living with them. Misophonia is a complex neurophysiological and behavioral disorder of multifactorial origin, characterized by an intense physiological and emotional response produced by intolerance to auditory stimuli of th...

The long-term treatment of mice with D-galactose (D-gal) induces the overproduction of reactive oxygen species (ROS) and is a well-accepted experimental model of oxidative stress-linked cognitive disorders in physiological aging. Calcium dobesilate (CaD, Doxium®) is an established vasoactive and angioprotective drug commonly used for the clinical t...

Background Recent gene profiling of human AD astrocytes using single-nucleus RNA sequencing is limited by the low number of differentially expressed genes detected, and the small size of cohorts. We improved on prior studies with a novel systems-biology-based approach that can be used with available data from large cohorts. Methods Brain-cell speci...

Background Our understanding of the impact of astrocytes in Alzheimer’s disease (AD) is hindered by the lack of astrocyte-specific omics data from patients diagnosed with dementia due to AD. Studies aiming to profile human AD astrocytes—including single-nucleus RNA sequencing—were limited by the low number of differentially expressed genes detected...

The assessment of welfare and disease progression in animal models is critical. Most tools rely on evaluating individual subjects, whereas social behaviors, also sensitive to acute illness, chronic diseases, or mental health, are scarcely monitored because they are complex and time-consuming. We propose the evaluation of social nesting, a species-t...

A new hypothesis highlights sleep-dependent learning/memory consolidation and regards the sleep-wake cycle as a modulator of β-amyloid and tau Alzheimer’s disease (AD) pathologies. Sundowning behavior is a common neuropsychiatric symptom (NPS) associated with dementia. Sleep fragmentation resulting from disturbances in sleep and circadian rhythms i...

The assessment of welfare and disease progression in animal models is critical. Most tools rely on evaluating individual subjects, whereas social behaviors, also sensitive to acute illness, chronic diseases, or mental health, are scarcely monitored because of their complexity, are invasive, and time-consuming. We propose the evaluation of social ne...

One year after the start of the COVID-19 pandemic, its secondary impacts can be globally observed. Some of them result from physical distancing and severe social contact restrictions by policies still imposed to stop the fast spread of new variants of this infectious disease. People with Alzheimer's disease (AD) and other dementias can also be sign...