Mixing energy drinks and alcohol during adolescence impairs brain function: a study of rat hippocampal plasticity.

In the last decades, the consumption of energy drinks has risen dramatically, especially among young people, adolescents and athletes, driven by the constant search for ergogenic effects, such as the increase in physical and cognitive performance. In parallel, mixed consumption of energy drinks and ethanol, under a binge drinking modality, under a binge drinking modality, has similarly grown among adolescents. However, little is known whether the combined consumption of these drinks, during adolescence, may have long-term effects on central function, raising the question of the risks of this habit on brain maturation. Our study was designed to evaluate, by behavioral, electrophysiological and molecular approaches, the long-term effects on hippocampal plasticity of ethanol (EtOH), energy drinks (EDs), or alcohol mixed with energy drinks (AMED) in a rat model of binge-like drinking adolescent administration. The results show that AMED binge-like administration produces adaptive hippocampal changes at the molecular level, associated with electrophysiological and behavioral alterations, which develop during the adolescence and are still detectable in adult animals. Overall, the study indicates that binge-like drinking AMED adolescent exposure represents a habit that may affect permanently hippocampal plasticity.

Multidisciplinary Management of Cutaneous Squamous Cell Carcinoma of the Scalp: An Algorithm for Reconstruction and Treatment.

Background: Scalp-associated cutaneous squamous cell carcinoma (cSCC) presents formidable treatment challenges, especially when it leads to full-thickness defects involving bone. Aggressive or recurring cases often demand a multidisciplinary approach. Leveraging our surgical experience and a literature review, we introduce a therapeutic algorithm to guide the selection of reconstruction methods, particularly for locally advanced lesions, furthermore showing the synergy between surgery and other therapies for comprehensive, multidisciplinary disease management. Methods: Our algorithm stems from a retrospective analysis of 202 patients undergoing scalp cSCC resection and reconstruction over a 7-year period, encompassing 243 malignancies. After rigorous risk assessment and documentation of surgical procedures, reconstruction methods were therefore related to malignancy extent, depth, and individual clinical status. Results: The documented reconstructions included 76 primary closures, 115 skin grafts, 7 dermal substitute reconstructions, 33 local flaps, 1 locoregional flap, and 1 microsurgical free flap. Patients unsuitable for surgery received radiotherapy or immunotherapy after histological confirmation. Precise analysis of tumor characteristics in terms of infiltration extent and depth guided the selection of appropriate reconstruction and treatment strategies Combining these insights with an extensive literature review enabled us to formulate our algorithm for managing scalp cSCCs. Conclusions: Effectively addressing scalp cSCC, especially in locally advanced or recurrent cases, demands a systematic approach integrating surgery, radiotherapy, and immunotherapy. Our multidisciplinary team's decision-making algorithm improved patient outcomes by offering a broader spectrum of therapeutic options that can synergistically achieve optimal results.

VGF modifications related to nigrostriatal dopaminergic neurodegeneration induced by the pesticide fipronil in adult male rats.

BACKGROUND: Dopamine is reduced in the brain of rats treated with fipronil, a broad-spectrum insecticide. VGF (no acronym) is a neurotrophin-inducible protein expressed as the 75 kDa form (precursor or pro-VGF) or its truncated peptides. VGF immunostaining has been revealed using an antibody against the C-terminal nonapeptide of the rat pro-VGF in the nerve terminals of the rat substantia nigra, where it was reduced after 6-hydroxydopamine treatment. It is unknown whether pro-VGF and/or its shortened peptides are present in these neurons. Therefore, the aim of this study was first to determine which types of VGF are expressed in the normal substantia nigra (and striatum) and then to determine VGF modulations and whether they occur in parallel with locomotor changes after fipronil injection. METHODS: Rats were divided into two groups that received a unilateral intranigral infusion of either fipronil (25 µg) diluted in dimethyl sulfoxide (DMSO) or DMSO alone, and then were tested for locomotor activity. An untreated group of rats (n=4) was used for identification of the VGF fragments using high performance liquid chromatography-mass spectrometry and western blot, while changes in treated groups (fipronil vs DMSO, each n=6) were investigated by immunohistochemistry using an antibody against the rat pro-VGF C-terminal nonapeptide in parallel with the anti-tyrosine hydroxylase antibody. RESULTS: In untreated rats, the VGF C-terminal antibody identified mostly a 75 kDa band in the substantia nigra and striatum, supporting the finding of high-resolution mass spectrometry, which revealed fragments covering the majority of the pro-VGF sequence. Furthermore, several shortened VGF C-terminal forms (varying from 10 to 55 kDa) were also found by western blot, while high-resolution mass spectrometry revealed a C-terminal peptide overlapping the immunogen used to create the VGF antibody in both substantia nigra and striatum. In the substantia nigra of fipronil-treated rats, immunostaining for tyrosine hydroxylase and VGF was reduced compared to DMSO-treated rat group, and this was related with significant changes in locomotor activity. CONCLUSION: Fipronil has the ability to modulate the production of pro-VGF and/or its C-terminal truncated peptides in the nigrostriatal system indicating its intimate interaction with the dopaminergic neurotransmission and implying a potential function in modulating locomotor activity.

Communal nesting differentially attenuates the impact of pre-weaning social isolation on behavior in male and female rats during adolescence and adulthood.

Introduction: Early social isolation (ESI) disrupts neurodevelopmental processes, potentially leading to long-lasting emotional and cognitive changes in adulthood. Communal nesting (CN), i.e., the sharing of parental responsibilities between multiple individuals in a nest, creates a socially enriching environment known to impact social and anxiety-related behaviors. Methods: This study examines the effects of (i) the CN condition and of (ii) ESI during the 3rd week of life (i.e., pre-weaning ESI) on motor, cognitive, and emotional domains during adolescence and adulthood in male and female rats reared in the two different housing conditions, as well as (iii) the potential of CN to mitigate the impact of ESI on offspring. Results: We found that in a spontaneous locomotor activity test, females exhibited higher activity levels compared to males. In female groups, adolescents reared in standard housing (SH) condition spent less time in the center of the arena, suggestive of increased anxiety levels, while the CN condition increased the time spent in the center during adolescence, but not adulthood, independently from ESI. The prepulse inhibition (PPI) test showed a reduced PPI in ESI adolescent animals of both sexes and in adult males (but not in adult females), with CN restoring PPI in males, but not in adolescent females. Further, in the marble burying test SH-ESI adolescent males exhibited higher marble burying behavior than all other groups, suggestive of obsessive-compulsive traits. CN completely reversed this stress-induced effect. Interestingly, ESI and CN did not have a significant impact on burying behavior in adult animals of both sexes. Discussion: Overall, our findings (i) assess the effects of ESI on locomotion, sensorimotor gating, and compulsive-like behaviors, (ii) reveal distinct vulnerabilities of males and females within these domains, and (iii) show how early-life social enrichment may successfully counteract some of the behavioral alterations induced by early-life social stress in a sex-dependent manner. This study strengthens the notion that social experiences during early-life can shape emotional and cognitive outcomes in adulthood, and points to the importance of social enrichment interventions for mitigating the negative effects of early social stress on neurodevelopment.

The Atypical Dopamine Transporter Inhibitor CE-158 Enhances Dopamine Neurotransmission in the Prefrontal Cortex of Male Rats: A Behavioral, Electrophysiological, and Microdialysis Study.

BACKGROUND: Dopamine plays a key role in several physiological functions such as motor control, learning and memory, and motivation and reward. The atypical dopamine transporter inhibitor S,S stereoisomer of 5-(((S)-((S)-(3-bromophenyl)(phenyl)methyl)sulfinyl)methyl)thiazole (CE-158) has been recently reported to promote behavioral flexibility and restore learning and memory in aged rats. METHODS: Adult male rats were i.p. administered for 1 or 10 days with CE-158 at the dose of 1 or 10 mg/kg and tested for extracellular dopamine in the medial prefrontal cortex by means of intracerebral microdialysis and single unit cell recording in the same brain area. Moreover, the effects of acute and chronic CE-158 on exploratory behavior, locomotor activity, prepulse inhibition, working memory, and behavioral flexibility were also investigated. RESULTS: CE-158 dose-dependently potentiated dopamine neurotransmission in the medial prefrontal cortex as assessed by intracerebral microdialysis. Moreover, repeated exposure to CE-158 at 1 mg/kg was sufficient to increase the number of active pyramidal neurons and their firing frequency in the same brain area. In addition, CE-158 at the dose of 10 mg/kg stimulates exploratory behavior to the same extent after acute or chronic treatment. Noteworthy, the chronic treatment at both doses did not induce any behavioral alterations suggestive of abuse potential (e.g., motor behavioral sensitization) or pro-psychotic-like effects such as disruption of sensorimotor gating or impairments in working memory and behavioral flexibility as measured by prepulse inhibition and Y maze. CONCLUSIONS: Altogether, these findings confirm CE-158 as a promising pro-cognitive agent and contribute to assessing its preclinical safety profile in a chronic administration regimen for further translational testing.

Squamous cell carcinoma of the scalp: a combination of different therapeutic strategies.

A case study of a 71-year-old man with a giant cutaneous squamous cell carcinoma of the scalp and calvaria is presented, where a combination of surgical excision, reconstruction with a latissimus dorsi muscular free flap, immunotherapy, and radiotherapy were used to control the disease for two years without recurrence.

Effects of the Phenethylamine 2-Cl-4,5-MDMA and the Synthetic Cathinone 3,4-MDPHP in Adolescent Rats: Focus on Sex Differences.

The illicit drug market of novel psychoactive substances (NPSs) is expanding, becoming an alarming threat due to increasing intoxication cases and insufficient (if any) knowledge of their effects. Phenethylamine 2-chloro-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA) and synthetic cathinone 3,4-methylenedioxy-α-pyrrolidinohexanophenone (3,4-MDPHP) are new, emerging NPSs suggested to be particularly dangerous. This study verified whether these two new drugs (i) possess abuse liability, (ii) alter plasma corticosterone levels, and (iii) interfere with dopaminergic transmission; male and female adolescent rats were included to evaluate potential sex differences in the drug-induced effects. Findings show that the two NPSs are not able to sustain reliable self-administration behavior in rats, with cumulatively earned injections of drugs being not significantly different from cumulatively earned injections of saline in control groups. Yet, at the end of the self-administration training, females (but not males) exhibited higher plasma corticosterone levels after chronic exposure to low levels of 3,4-MDPHP (but not of 2-Cl-4,5-MDMA). Finally, electrophysiological patch-clamp recordings in the rostral ventral tegmental area (rVTA) showed that both drugs are able to increase the firing rate of rVTA dopaminergic neurons in males but not in females, confirming the sex dimorphic effects of these two NPSs. Altogether, this study demonstrates that 3,4-MDPHP and 2-Cl-4,5-MDMA are unlikely to induce dependence in occasional users but can induce other effects at both central and peripheral levels that may significantly differ between males and females.

Dopamine, Erectile Function and Male Sexual Behavior from the Past to the Present: A Review.

Early and recent studies show that dopamine through its neuronal systems and receptor subtypes plays different roles in the control of male sexual behavior. These studies show that (i) the mesolimbic/mesocortical dopaminergic system plays a key role in the preparatory phase of sexual behavior, e.g., in sexual arousal, motivation and reward, whereas the nigrostriatal system controls the sensory-motor coordination necessary for copulation, (ii) the incertohypothalamic system is involved in the consummatory aspects of sexual behavior (penile erection and copulation), but evidence for its role in sexual motivation is also available, (iii) the pro-sexual effects of dopamine occur in concert with neural systems interconnecting the hypothalamus and preoptic area with the spinal cord, ventral tegmental area and other limbic brain areas and (iv) D2 and D4 receptors play a major role in the pro-sexual effects of dopamine. Despite some controversy, increases or decreases, respectively, of brain dopamine activity induced by drugs or that occur physiologically, usually improves or worsens, respectively, sexual activity. These findings suggest that an altered central dopaminergic tone plays a role in mental pathologies characterized by aberrant sexual behavior, and that pro-erectile D4 receptor agonists may be considered a new strategy for the treatment of erectile dysfunction in men.

A Novel and Selective Dopamine Transporter Inhibitor, (S)-MK-26, Promotes Hippocampal Synaptic Plasticity and Restores Effort-Related Motivational Dysfunctions.

Dopamine (DA), the most abundant human brain catecholaminergic neurotransmitter, modulates key behavioral and neurological processes in young and senescent brains, including motricity, sleep, attention, emotion, learning and memory, and social and reward-seeking behaviors. The DA transporter (DAT) regulates transsynaptic DA levels, influencing all these processes. Compounds targeting DAT (e.g., cocaine and amphetamines) were historically used to shape mood and cognition, but these substances typically lead to severe negative side effects (tolerance, abuse, addiction, and dependence). DA/DAT signaling dysfunctions are associated with neuropsychiatric and progressive brain disorders, including Parkinson's and Alzheimer diseases, drug addiction and dementia, resulting in devastating personal and familial concerns and high socioeconomic costs worldwide. The development of low-side-effect, new/selective medicaments with reduced abuse-liability and which ameliorate DA/DAT-related dysfunctions is therefore crucial in the fields of medicine and healthcare. Using the rat as experimental animal model, the present work describes the synthesis and pharmacological profile of (S)-MK-26, a new modafinil analogue with markedly improved potency and selectivity for DAT over parent drug. Ex vivo electrophysiology revealed significantly augmented hippocampal long-term synaptic potentiation upon acute, intraperitoneally delivered (S)-MK-26 treatment, whereas in vivo experiments in the hole-board test showed only lesser effects on reference memory performance in aged rats. However, in effort-related FR5/chow and PROG/chow feeding choice experiments, (S)-MK-26 treatment reversed the depression-like behavior induced by the dopamine-depleting drug tetrabenazine (TBZ) and increased the selection of high-effort alternatives. Moreover, in in vivo microdialysis experiments, (S)-MK-26 significantly increased extracellular DA levels in the prefrontal cortex and in nucleus accumbens core and shell. These studies highlight (S)-MK-26 as a potent enhancer of transsynaptic DA and promoter of synaptic plasticity, with predominant beneficial effects on effort-related behaviors, thus proposing therapeutic potentials for (S)-MK-26 in the treatment of low-effort exertion and motivational dysfunctions characteristic of depression and aging-related disorders.

Neuroplastic changes in c-Fos, ΔFosB, BDNF, trkB, and Arc expression in the hippocampus of male Roman rats: differential effects of sexual activity.

Sexual activity causes differential changes in the expression of markers of neural activation (c-Fos and ΔFosB) and neural plasticity (Arc and BDNF/trkB), as determined either by Western Blot (BDNF, trkB, Arc, and ΔFosB) or immunohistochemistry (BDNF, trkB, Arc, and c-Fos), in the hippocampus of male Roman high (RHA) and low avoidance (RLA) rats, two psychogenetically selected rat lines that display marked differences in sexual behavior (RHA rats exhibit higher sexual motivation and better copulatory performance than RLA rats). Both methods showed (with some differences) that sexual activity modifies the expression levels of these markers in the hippocampus of Roman rats depending on: (i) the level of sexual experience, that is, changes were usually more evident in sexually naïve than in experienced rats; (ii) the hippocampal partition, that is, BDNF and Arc increased in the dorsal but tended to decrease in the ventral hippocampus; (iii) the marker considered, that is, in sexually experienced animals BDNF, c-Fos, and Arc levels were similar to those of controls, while ΔFosB levels increased; and (iv) the rat line, that is, changes were usually larger in RHA than RLA rats. These findings resemble those of early studies in RHA and RLA rats showing that sexual activity influences the expression of these markers in the nucleus accumbens, medial prefrontal cortex, and ventral tegmental area, and show for the first time that also in the hippocampus sexual activity induces neural activation and plasticity, events that occur mainly during the first phase of the acquisition of sexual experience and depend on the genotypic/phenotypic characteristics of the animals.

Correlation between olfactory function, age, sex, and cognitive reserve index in the Italian population.

PURPOSE: Loss of smell decreases the quality of life and contributes to the failure in recognizing hazardous substances. Given the relevance of olfaction in daily life, it is important to recognize an undiagnosed olfactory dysfunction to prevent these possible complications. Up to now, the prevalence of smell disorders in Italy is unknown due to a lack of epidemiological studies. Hence, the primary aim of this study was to evaluate the prevalence of olfactory dysfunction in a sample of Italian adults. METHODS: Six hundred and thirty-three participants (347 woman and 286 men; mean age 44.9 years, SD 17.3, age range 18-86) were recruited from 10 distinct Italian regions. Participants were recruited using a convenience sapling and were divided into six different age groups: 18-29 years (N = 157), 30-39 years (N = 129), 40-49 years (N = 99), 50-59 years (N = 106), > 60 years (N = 142). Olfactory function, cognitive abilities, cognitive reserve, and depression were assessed, respectively, with: Sniffin' Sticks 16-item Odor Identification Test, Montreal Cognitive Assessment, Cognitive Reserve Index, and the Beck Depression Inventory. Additionally, socio-demographic data, medical history, and health-related lifestyle information were collected. RESULTS: About 27% of participants showed an odor identification score < 12 indicating hyposmia. Multiple regression analysis revealed that OI was significantly correlated with age, sex, and cognitive reserve index, and young women with high cognitive reserve index showing the highest olfactory scores. CONCLUSION: This study provides data on the prevalence of olfactory dysfunction in different Italian regions.

Preliminary finding of a randomized, double-blind, placebo-controlled, crossover study to evaluate the safety and efficacy of 5-hydroxytryptophan on REM sleep behavior disorder in Parkinson's disease.

PURPOSE: Altered serotonergic neurotransmission may contribute to the non-motor features commonly associated with Parkinson's disease (PD) such as sleep disorders. The 5-hydroxytryptophan (5-HTP) is the intermediate metabolite of L-tryptophan in the production of serotonin and melatonin. The purpose of this study was to compare the effects of 5-HTP to placebo on REM sleep behavior disorder (RBD) status in patients with PD. METHODS: A single-center, randomized, double-blind placebo-controlled crossover trial was performed in a selected population of 18 patients with PD and RBD. The patients received a placebo and 50 mg of 5-HTP daily in a crossover design over a period of 4 weeks. RESULTS: 5-HTP produced an increase in the total percentage of stage REM sleep without a related increase of RBD episodes, as well as a marginal, non-significant reduction in both arousal index and wake after sleep onset. The self-reported RBD frequency and clinical global impression (CGI) were improved during 5-HTP and placebo treatment in comparison to baseline. 5-HTP significantly improved our patients' motor experiences of daily living as rated by the Unified Parkinson's Disease Rating Scale (UPDRS) part II. CONCLUSIONS: This study provides evidence that 5-HTP is safe and effective in improving sleep stability in PD, contributing to ameliorate patients' global sleep quality. Larger studies with higher doses and longer treatment duration are needed to corroborate these preliminary findings.

Oxytocin-conjugated saporin injected into the substantia nigra of male rats alters the activity of the nigrostriatal dopaminergic system: A behavioral and neurochemical study.

Saporin conjugated to oxytocin (OXY-SAP) destroys neurons expressing oxytocinergic receptors. When injected unilaterally in the substantia nigra of male rats, OXY-SAP causes a dose-dependent decrease up to 55 % in nigral Tyrosine Hydroxylase (TH)-immunoreactivity compared to control mock peptide BLANK-SAP- and PBS-treated rats or the contralateral substantia nigra. TH decrease was parallel to a dopamine content decrease in the ipsilateral striatum compared to BLANK-SAP- or PBS-treated rats or the contralateral striatum. OXY-SAP-treated rats showed a small but significant increase of locomotor activity 28 days after intranigral injection in the Open field test compared to BLANK-SAP- or PBS-treated rats, in line with an inhibitory role of nigral oxytocin on locomotor activity. OXY-SAP-, but not BLANK-SAP- or PBS-treated rats, also showed marked dose-dependent rotational turning ipsilateral to the injected substantia nigra when challenged with d-amphetamine, but not with apomorphine. Under isoflurane anesthesia OXY-SAP-treated rats showed levels of extracellular dopamine in the dialysate from the ipsilateral striatum only half those of BLANK-SAP- or PBS-treated rats or the contralateral striatum. When treated with d-amphetamine, OXY-SAP_60/120 rats showed increased extracellular dopamine levels in the dialysate from the ipsilateral striatum two third/one third only of those found in BLANK-SAP- or PBS-treated rats or the contralateral striatum, respectively. These results show that OXY-SAP destroys nigrostriatal dopaminergic neurons expressing oxytocin receptors leading to a reduced striatal dopamine function.

Activation of Antioxidant and Proteolytic Pathways in the Nigrostriatal Dopaminergic System After 3,4-Methylenedioxymethamphetamine Administration: Sex-Related Differences.

3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is an amphetamine-related drug that may damage the dopaminergic nigrostriatal system. To investigate the mechanisms that sustain this toxic effect and ascertain their sex-dependence, we evaluated in the nigrostriatal system of MDMA-treated (4 × 20 mg/kg, 2 h apart) male and female mice the activity of superoxide dismutase (SOD), the gene expression of SOD type 1 and 2, together with SOD1/2 co-localization with tyrosine hydroxylase (TH)-positive neurons. In the same mice and brain areas, activity of glutathione peroxidase (GPx) and of ß2/ß5 subunits of the ubiquitin-proteasome system (UPS) were also evaluated. After MDMA, SOD1 increased in striatal TH-positive terminals, but not nigral neurons, of males and females, while SOD2 increased in striatal TH-positive terminals and nigral neurons of males only. Moreover, after MDMA, SOD1 gene expression increased in the midbrain of males and females, whereas SOD2 increased only in males. Finally, MDMA increased the SOD activity in the midbrain of females, without affecting GPx activity, decreased the ß2/ß5 activities in the striatum of males and the ß2 activity in the midbrain of females. These results suggest that the mechanisms of MDMA-induced neurotoxic effects are sex-dependent and dopaminergic neurons of males could be more sensitive to SOD2- and UPS-mediated toxic effects.

The potential role of oxytocin in addiction: What is the target process?

Oxytocin regulates a variety of centrally-mediated functions, ranging from socio-sexual behavior, maternal care, and affiliation to fear, stress, anxiety. In the past years, both clinical and preclinical studies characterized oxytocin for its modulatory role on reward-related neural substrates mainly involving the interplay with the mesolimbic and mesocortical dopaminergic pathways. This suggests a role of this nonapeptide on the neurobiology of addiction raising the possibility of its therapeutic use. Although far from a precise knowledge of the underlying mechanisms, the putative role of the bed nucleus of the stria terminalis as a key structure where oxytocin may rebalance altered neurochemical processes and neuroplasticity involved in dependence and relapse has been highlighted. This view opens new opportunities to address the health problems related to drug misuse.

Exploring the variability of radiomic features of lung cancer lesions on unenhanced and contrast-enhanced chest CT imaging.

PURPOSE: The aim of this methods work is to explore the different behavior of radiomic features resulting by using or not the contrast medium in chest CT imaging of non-small cell lung cancer. METHODS: Chest CT scans, unenhanced and contrast-enhanced, of 17 patients were selected from images collected as part of the staging process. The major T1-T3 lesion was contoured through a semi-automatic approach. These lesions formed the lesion phantoms to study features behavior. The stability of 94 features of the 3D-Slicer package Radiomics was analyzed. Feature discrimination power was quantified by means of Gini's coefficient. Correlation between distance matrices was evaluated through Mantel statistic. Heatmap, cluster and silhouette plots were applied to find well-structured partitions of lesions. RESULTS: The Gini's coefficient evidenced a low discrimination power, <0.05, for four features and a large discrimination power, around 0.8, for five features. About 90% of features was affected by the contrast medium, masking tumor lesions variability; thirteen features only were found stable. On 8178 combinations of stable features, only one group of four features produced the same partition of lesions with the silhouette width greater than 0.51, both on unenhanced and contrast-enhanced images. CONCLUSIONS: Gini's coefficient highlighted the features discrimination power in both CT series. Many features were sensitive to the use of the contrast medium, masking the lesions intrinsic variability. Four stable features produced, on both series, the same partition of cancer lesions with reasonable structure; this may merit being objects of further validation studies and interpretative investigations.

Age-Related Cognitive Decline and the Olfactory Identification Deficit Are Associated to Increased Level of Depression.

PURPOSE: Previous studies reported a correlation between olfactory function and depression. However, in literature, no data are available for the correlation between depression and all other factors such as age, sex, olfactory, gustatory, and cognitive function in healthy subjects taken together. The aim of this study was to provide a systematic account regarding the association between those variables in a non-clinical population. METHODS: Two hundred and seventy-three participants were recruited with an age range of 19-84 years. Olfactory, gustatory, cognitive function, and depression level were evaluated by means of the following tests: the Sniffin' Sticks test, Taste Strips test, Montreal Cognitive Assessment (MoCA), and Beck Depression Inventory (BDI). RESULTS: In our data, an age-related decrease in olfactory and gustatory function and a decline in cognitive functions such as attention, memory, and language were observed. Instead, no significant differences were observed for the depression level in relation to the different age ranges. However, our results indicated that the depression level could be associated to sex, odor identification impairment, and decreased attention and language. CONCLUSION: Sex, the odor identification impairment, and an age-related decrease in attention and language are associated with increased level of depression in healthy subjects. Our data can be useful and informative for health care workers, that is, to have adequate preventive strategies to be used whenever these conditions are detected and recognized.