Hair cortisol and dehydroepiandrosterone and their associations with optimism and pessimism in older people.

The cumulative negative effects of prolonged Hypothalamic-Pituitary-Adrenal axis (HPA axis) activation are associated with several age-related diseases. Some psychological traits such as optimism and pessimism have been shown to be related to both health and the stress response, although their relationship with the HPA axis is inconclusive. More stable HPA axis biomarkers, such as hair samples of cortisol (HC) and dehydroepiandrosterone (HDHEA), would help to clarify the association between these psychological traits and HPA axis functioning. The main aim of this study was to test the relationships between optimism and pessimism and chronic stress biomarkers measured in hair (HC and HDHEA). Additionally, a secondary objective was to explore sex differences in HC and HDHEA levels and their relationship with these psychological traits. We measured optimism, pessimism, and their combination (dispositional optimism) using the Life Orientation Test Revised (LOT-R) and chronic stress biomarkers (HC and HDHEA) in 119 healthy participants (46 men and 73 women) between 56 and 81 years old who belonged to a university program. Regression analyses controlling for perceived stress and BMI indicated that higher dispositional optimism was related to lower HC and HC:HDHEAratio (ß = -0.256, p = .008 and ß = -0.300, p = .002, respectively). More specifically, higher pessimism was related to higher HC (ß = 0.235; p = .012) and HC:HDHEAratio (ß = 0.240; p = .011), whereas higher optimism was associated with a lower HC:HDHEAratio(ß = -0.205; p = .031). Moderation analyses showed no sex differences. To date, this is the first study to investigate the link between these traits and HC and HDHEA in older people. Our results confirm that positive and negative expectations about the future (i.e. optimism and pessimism) may play an important role in health due to their relationship with the HPA axis. They also strengthen the idea that the negative effects of pessimism have a greater weight than the protective effects of optimism in their relationship with HPA axis regulation.

The effects of left dorsolateral prefrontal transcranial direct current stimulation on episodic future thinking following acute psychosocial stress.

INTRODUCTION: Research on stress-related disorders and brain imaging suggests that (acute) stress might impact the capacity to mentally simulate specific episodic future events (EFT) through the effects of cortisol on brain regions supporting this cognitive function, such as the prefrontal cortices. This study aims to examine the mechanisms underlying this link, using transcranial Direct Current Stimulation (tDCS) over the left dorsolateral prefrontal cortex. METHODS: 60 healthy participants were subjected to the Montreal Imaging Stress Task (MIST), followed by either active or sham tDCS. After stimulation, the EFT task was administered. Salivary cortisol was measured throughout the protocol. RESULTS: Higher cortisol AUCi values were linked to less specific episodic future thoughts. Moreover, active tDCS enhanced EFT specificity irrespective of cortisol, especially in high trait ruminators. We did not observe an effect from active tDCS on cortisol AUCi, and equally there was no interaction effect between cortisol AUCi and stimulation condition predictive for EFT specificity. CONCLUSION: Although we did not find evidence for the effects of tDCS on the HPA-system, our data reveal a crucial link between two critical predictors of mental health for the first time, and provide a solution to help rehabilitate EFT deficits.Trial registration: Netherlands National Trial Register identifier: ntr004..

Hormonal changes of intimate partner violence perpetrators in response to brief social contact with women.

This study investigated whether men with a history of real-life aggressive, dominant behavior show increases in testosterone and cortisol levels after brief social contact with women. Furthermore, we tested the prediction that such changes in hormones would be larger than those observed previously in young male students. Sixty-seven male participants convicted of intimate partner violence (IPV) either had brief social contact with a female confederate (experimental condition) or a male confederate (control condition). We also performed meta-analyses to investigate whether IPV perpetrators' hormonal responses were larger than the typical responses of young male students in prior studies. All statistical analyses were preregistered. Change in testosterone did not differ across experimental conditions, and testosterone in the IPV perpetrators actually declined from baseline in the female confederate condition. Our meta-analysis showed that this testosterone decrease was different from the testosterone increase typically observed in young male students. The cortisol levels of IPV perpetrators did not change in response to contact with women. This result was consistent with our meta-analysis since young male students also did not experience a cortisol change in response to interactions with women. In sum, our findings provide no evidence that male IPV perpetrators exhibit larger hormone increases to brief interactions with women, although it is possible that the men in this sample did not perceive the social contact period as a courtship opportunity. These results suggest that hormone reactivity to social encounters may differ across subject populations and depend on how subjects perceive social situations within laboratory settings.

Acute psychosocial stress effects on memory performance: Relevance of age and sex.

In recent decades, there has been a growing interest in investigating the effects of chronic and acute stress on cognitive processes, especially memory performance. However, research focusing on acute stress effects has reported contradictory findings, probably due to the many factors that can moderate this relationship. In addition to factors related to the individual, such as sex and age, other factors, such as the type of memory assessed, can play a critical role in the direction of these effects. This review summarizes the main findings of our research group and others about the effects of acute psychosocial stress on memory performance in young and older people of both sexes, taking into account the type and phase of memory assessed. In our opinion, an approach that addresses individual factors and other factors related to the type of stressor and temporal relationship between exposure to the stressor and performance will contribute to better understanding the mechanisms underlying the complex relationship between acute stress and memory. Finally, some new directions for future studies on this research topic are suggested.

Cortisol and trait anxiety as relevant factors involved in memory performance in people with drug-resistant epilepsy.

People with drug-resistant epilepsy are exposed to unpredictable and uncontrollable seizures, which can be considered as a chronic stress condition. Additionally, these patients present memory deficits and a high prevalence of depression and anxiety. Cortisol, the main stress hormone, has a modulatory role on memory in healthy individuals and patients with emotional disorders, but its role in memory and emotional processes remains unclear in people with epilepsy. This study analyzes the differences in cortisol levels in people with epilepsy with high and low memory performance, and the relationships among cortisol levels, epilepsy-related factors, memory, anxiety, and depression. Fifty-two adults with drug-resistant epilepsy underwent a neuropsychological evaluation, in which nine saliva samples were collected to analyze the ability of the hypothalamic-pituitary-adrenal axis to descend in accordance with the circadian rhythm. Cortisol area under the curve (AUC) was computed to study the global cortisol changes. Patients with low immediate and delayed memory performance and left-hemisphere focus showed higher cortisol levels. Additionally, patients with low memory scores had higher cortisol AUC, and therefore slower declining levels in the afternoon. Memory performance was negatively related to the cortisol AUC and trait anxiety, being both reliable predictors of memory performance, especially in patients with left-hemisphere focus. These results suggest that memory deficits in people with drug-resistant epilepsy may be influenced by exposure to cortisol derived from chronic stress. Additionally, trait anxiety could contribute to increasing the vulnerability to stress.

The relationship between cortisol and cognitive function in healthy older people: The moderating role of Apolipoprotein E polymorphism.

The Apolipoprotein E4 (ApoE-ε4) allele has been suggested as the main risk factor for late onset Alzheimer's disease (AD), whereas the ApoE-ε2 allele has been proposed as a protective factor. These proposals have increased the interest in the effect of the ApoE genotype in healthy people. Additionally, high cortisol levels have been related to negative effects on cognition. However, few studies have investigated the relationship between cognitive performance and cortisol, taking into account the different ApoE alleles. For this reason, the aim of this study was to evaluate different cognitive domains (declarative and working memory, attention, and executive function) and their relationship with cortisol, considering the ApoE-ε2, ApoE-ε3, and ApoE-ε4 alleles in healthy older people (55-77 years old). Two saliva samples were collected during the neuropsychological session to obtain cortisol levels and the ApoE genotype. Results showed an association between the ApoE genotype and declarative memory, specifically learning ability, where ApoE-ε2 group performed better than ApoE-ε4 and ApoE-ε3 groups. No differences in cortisol levels were obtained considering the ApoE genotype. In addition, higher mean cortisol levels were related to a worse performance on declarative memory, for the whole sample, and when considering the three allelic variation, for the ApoE-ε4 group. On the contrary, an increase of cortisol levels during the neuropsychological session was associated to a better performance on declarative memory for the whole sample, and for the ApoE-ε3 group when considering the three alleles. Besides, ApoE-ε3 group also showed an association between higher mean cortisol levels and a better attention performance. Therefore, our results suggest that carrying the ApoE-ε4 allele may be a vulnerability factor in the adverse effects of Hypothalamic-Pituitary-Adrenal (HPA) axis dysregulation on cognition during aging, while ApoE-ε3 allele could be associated to a more adaptive HPA axis response.

Assessing the antecedents and consequences of threat appraisal of an acute psychosocial stressor: the role of optimism, displacement behavior, and physiological responses.

The feeling of stress is increasing in today's societies, particularly in young adults subjected to social evaluative situations in highly competitive academic and work contexts. Threat appraisal is a primary and fundamental reaction when people face a stressful situation. The aim of this study was to investigate the role of dispositional optimism as an antecedent and displacement behavior as a consequence of threat appraisal of a social-evaluative situation of stress. A second objective was to verify the moderating role of physiological responses to stress (heart rate and cortisol reactivity) in the relationship between threat appraisal and displacement behavior. To do this, we combined the Trier Social Stress Test (TSST) with ethological analysis, self-report questionnaires, and physiological data. As expected, people who scored higher on dispositional optimism perceived stress as less threatening, and a higher perception of threat was positively related to displacement behavior patterns. Moreover, the results showed that threat appraisal fully mediates the relationship between dispositional optimism and displacement behavior, and that only heart rate reactivity (not cortisol) moderates the relationship between threat appraisal and displacement behavior.

Autonomic markers associated with generalized social phobia symptoms: heart rate variability and salivary alpha-amylase.

The study of autonomic nervous system changes associated with generalized social phobia (GSP) disorder has increased in recent years, showing contradictory results. The present study aimed to evaluate how young people with GSP reacted before, during, and after exposure to the Trier Stress Social Test (TSST), focusing on their autonomic changes (heart rate variability (HRV) and salivary alpha-amylase (sAA)) compared to a control group (non-GSP). Some psychological variables were also considered. Sex was specifically studied as a possible modulator of autonomic fluctuations and psychological state. Eighty young people were randomly distributed into two counterbalanced situations: stress condition (N = 18 and 21 for GSP and non-GSP, respectively) and control condition (N = 21 and 20 for GSP and non-GSP, respectively), where cardiovascular variables were continuously recorded. Psychological questionnaires about mood and perceived stress were filled out, and five saliva samples were collected to analyze sAA. GSP participants showed higher values on low- and high-frequency ratios (HR domains), compared to non-GSP people, during exposure to the TSST, but no differences were observed after the stressor. Furthermore, the two groups did not differ in sAA. Importantly, positive affect in GSP participants was modulated by sex. The present study suggests that the balance between high- and low-frequency domains of HRV is a key cardiovascular marker reflecting the stress response of GSP people, as well the importance of sex in positive affect when facing a stressful situation.

Causal attribution and psychobiological response to competition in young men.

A contribution to a special issue on Hormones and Human Competition. Psychoneuroendocrine effects of competition have been widely accepted as a clear example of the relationship between androgens and aggressive/dominant behavior in humans. However, results about the effects of competitive outcomes are quite heterogeneous, suggesting that personal and contextual factors play a moderating role in this relationship. To further explore these dimensions, we aimed to examine (i) the effect of competition and its outcome on the psychobiological response to a laboratory competition in young men, and (ii) the moderating role of some cognitive dimensions such as causal attributions. To do so, we compared the responses of 56 healthy young men faced with two competitive tasks with different instructions. Twenty-eight men carried out a task whose instructions led subjects to think the outcome was due to their personal performance ("merit" task), whereas 28 other men faced a task whose outcome was attributable to luck ("chance" task). In both cases, outcome was manipulated by the experimenter. Salivary steroid hormones (testosterone and cortisol), cardiovascular variables (heart rate and blood pressure), and emotional state (mood and anxiety) were measured at different moments before, during and after both tasks. Our results did not support the "winner-loser effect" because no significant differences were found in the responses of winners and losers. However, significantly higher values on the testosterone and cardiovascular variables, along with slight decreases in positive mood, were associated with the merit-based competition, but not the chance-based condition. In addition, an exploratory factorial analysis grouped the response components into two patterns traditionally related to more active or more passive behaviors. Thus, our results suggest that the perception of contributing to the outcome is relevant in the psychobiological response to competition in men. Overall, our results reveal the importance of the appraisal of control and causal attribution in understanding human competitive interactions.

Cortisol awakening response and cognitive performance in hypertensive and normotensive older people.

Healthy older people with a cortisol awakening response (CAR) of decreased magnitude show worse frontal cortex-related cognitive performance. Systemic hypertension has been related to a CAR of decreased magnitude. Additionally, worse executive function and processing speed have been observed in older people with systemic hypertension. This is the first study to examine the relationship between the CAR (measured with six saliva samples at home on two consecutive weekdays) and cognitive performance, in both hypertensive (n=26) and normotensive (n=28) older people (from 56 to 78years old). Hypertensive participants showed lower morning cortisol secretion, and they also woke up earlier. No differences in CAR were observed. A CAR of decreased magnitude was related to worse executive function in both hypertensive and normotensive participants, but to slower processing speed only in normotensive participants. Being treated with antihypertensive for a longer period of time was related to a CAR of increased magnitude and better performance on executive function. Our findings suggest that earlier awakening time in hypertensive older people might underlie the lower overall morning cortisol secretion observed in previous studies. Additionally, this study confirms that a dysregulation of the CAR is related to worse executive function, and it extends this association to hypertensive older people. Finally, it is worth noting that hypertension may moderate the relationship between CAR and processing speed.

Acute stress and working memory in older people.

Several studies have shown that acute stress affects working memory (WM) in young adults, but the effect in older people is understudied. As observed in other types of memory, older people may be less sensitive to acute effects of stress on WM. We performed two independent studies with healthy older men and women (from 55 to 77 years old) to investigate the effects of acute stress (Trier Social Stress Test; TSST) and cortisol on WM. In study 1 (n = 63), after the TSST women (but not men) improved their performance on Digit Span Forward (a measure of the memory span component of WM) but not on Digit Span Backward (a measure of both memory span and the executive component of WM). Furthermore, in women, cortisol levels at the moment of memory testing showed a positive association with the memory span component of WM before and after the TSST, and with the executive component of WM only before the stress task. In study 2 (n = 76), although participants showed a cortisol and salivary alpha-amylase (sAA) response to the TSST, stress did not affect performance on Letter-Number Sequencing (LNS; a task that places a high demand on the executive component of WM). Cortisol and sAA were not associated with WM. The results indicate that circulating cortisol levels at the moment of memory testing, and not the stress response, affect memory span in older women, and that stress and the increase in cortisol levels after stress do not affect the executive component of WM in older men and women. This study provides further evidence that older people may be less sensitive to stress and stress-induced cortisol response effects on memory processes.

Acute stress impairs recall after interference in older people, but not in young people.

Stress has been associated with negative changes observed during the aging process. However, very little research has been carried out on the role of age in acute stress effects on memory. We aimed to explore the role of age and sex in the relationship between hypothalamus-pituitary-adrenal axis (HPA-axis) and sympathetic nervous system (SNS) reactivity to psychosocial stress and short-term declarative memory performance. To do so, sixty-seven participants divided into two age groups (each group with a similar number of men and women) were exposed to the Trier Social Stress Test (TSST) and a control condition in a crossover design. Memory performance was assessed by the Rey Auditory Verbal Learning Test (RAVLT). As expected, worse memory performance was associated with age; but more interestingly, the stressor impaired recall after interference only in the older group. In addition, this effect was negatively correlated with the alpha-amylase over cortisol ratio, which has recently been suggested as a good marker of stress system dysregulation. However, we failed to find sex differences in memory performance. These results show that age moderates stress-induced effects on declarative memory, and they point out the importance of studying both of the physiological systems involved in the stress response together.

Loneliness during the post-confinement period: The significance of social living conditions for stress biomarkers and memory.

In the aftermath of the COVID-19 lockdown, concerns about the impact of loneliness and reduced social interactions on mental health have arisen. This study explored the repercussions of post-lockdown social restrictions across psychological (loneliness, perceived stress, and depressive symptoms), biological (hair cortisol and cardiovascular activity), and cognitive dimensions (subjective memory complaints and working, declarative, and prospective memory), with a specific emphasis on perceived loneliness and the living situation. The study included 45 students: 23 (mean age = 25.69 years) in the Alone Group (AG), who experienced significant family changes and international relocation, and 22 (mean age = 25.50 years) in the Not Alone Group (NAG), who maintained their nuclear family and did not move from their home country. We assessed heart rate variability (HRV) before, during, and after immediate memory evaluations using time-domain (the square root of the mean, RMSSD) measures. The analysis revealed no significant group differences in telematic contact with family and friends, perceived stress, or depression. However, the AG participants reported fewer face-to-face interactions and greater perceived loneliness compared to the NAG. Additionally, the AG group exhibited slightly higher hair cortisol levels and worse working memory (WM) and prospective memory (PM) performance. Importantly, no significant associations were observed between memory outcomes and stress biomarkers. However, a significant interaction effect of loneliness in the relationship between hair cortisol levels and PM was found. That is, hair cortisol concentrations were negatively related to PM when participants perceived high and moderate loneliness. This interaction was absent in the working and declarative memory domains. In summary, these findings underscore the intricate interplay between loneliness, cortisol, and memory, emphasizing the need for comprehensive research on the complex mechanisms governing these multifaceted relationships.

EEG frequency bands in subjective cognitive decline: A systematic review of resting state studies.

As the older population continues to expand, there is a growing prevalence of individuals who experience subjective cognitive decline (SCD), characterized by self-reported failures in cognitive function and an increased risk of cognitive impairment. Recognizing that preventive interventions are typically more effective in preclinical stages, current research endeavors to focus on identifying early biological markers of SCD using resting-state electroencephalogram (rsEEG) methods. To do so, a systematic literature review covering the past 20 years was conducted following PRISMA guidelines, in order to consolidate findings on rsEEG frequency bands in individuals with SCD. Pubmed and Web of Science databases were searched for rsEEG studies of people with SCD. Quality assessments were completed using a modified Newcastle-Ottawa scale. A total of 564 articles published from December 2003 to December 2023 were reviewed, and significant aspects of these papers were analyzed to provide a general overview of the research on this technique. After removing unrelated articles, nine articles were selected for the present study. The review emphasizes patterns in frequency band activity, revealing that individuals classified as SCD exhibited increased theta power than healthy controls, but decreased than MCI. However, findings for the alpha, delta, and beta bands were inconsistent, demonstrating variability across studies and highlighting the need for further research. Although the rsEEG of frequency bands emerges as a promising early biomarker, there is a noteworthy need to establish uniform standards and consistent measurement approaches in order to ensure the reliability and comparability of the results obtained in the research.

Biomarkers of Alzheimer's Disease and Cerebrovascular Disease in Relation to Depressive Symptomatology in Individuals With Subjective Cognitive Decline.

BACKGROUND: Subjective cognitive decline (SCD) has gained recent interest as a potential harbinger of neurodegenerative diseases such as Alzheimer's disease (AD) and cerebrovascular disease (CVD). In addition, SCD can be related to depressive symptomatology. However, the association between AD and CVD biomarkers, depressive symptomatology, and SCD is still unclear. We investigated the association of AD and CVD biomarkers and depressive symptomatology with SCD in individuals with subjective memory complaints (SCD-memory group) and individuals with subjective concentration complaints (SCD-concentration group). METHODS: We recruited a population-based cohort of 217 individuals (all aged 70 years, 53% female participants, 119 SCD-memory individuals, 23 SCD-concentration individuals, and 89 controls). AD and CVD were assessed through cerebrospinal fluid levels of the Aß42/40 ratio and phosphorylated tau, and white matter signal abnormalities on magnetic resonance imaging, respectively. Associations between biomarkers, depressive symptomatology, and SCD were tested via logistic regression and correlation analyses. RESULTS: We found a significant association between depressive symptomatology with SCD-memory and SCD-concentration. Depressive symptomatology was not associated with AD and CVD biomarkers. Both the phosphorylated tau biomarker and depressive symptomatology predicted SCD-memory, and the Aß42/40 ratio and depressive symptomatology predicted SCD-concentration. CONCLUSIONS: The role of depressive symptomatology in SCD may differ depending on the stage within the spectrum of preclinical AD (as determined by amyloid-beta and tau positivity), and does not seem to reflect AD pathology. Our findings contribute to the emerging field of subclinical depressive symptomatology in SCD and clarify the association of different types of subjective complaints with distinct syndromic and biomarker profiles.

Acute stress does not impair long-term memory retrieval in older people.

Previous studies have shown that stress-induced cortisol increases impair memory retrieval in young people. This effect has not been studied in older people; however, some findings suggest that age-related changes in the brain can affect the relationships between acute stress, cortisol and memory in older people. Our aim was to investigate the effects of acute stress on long-term memory retrieval in healthy older people. To this end, 76 participants from 56 to 76 years old (38 men and 38 women) were exposed to an acute psychosocial stressor or a control task. After the stress/control task, the recall of pictures, words and stories learned the previous day was assessed. There were no differences in memory retrieval between the stress and control groups on any of the memory tasks. In addition, stress-induced cortisol response was not associated with memory retrieval. An age-related decrease in cortisol receptors and functional changes in the amygdala and hippocampus could underlie the differences observed between the results from this study and those found in studies performed with young people.

Acute pre-learning stress and declarative memory: impact of sex, cortisol response and menstrual cycle phase.

This study explores the influence of pre-learning stress on performance on declarative memory tasks in healthy young adults in relation to sex and menstrual cycle phase. The sample was composed of 119 students (32 men and 87 women) from 18 to 25 years of age. The women were tested in different hormonal stages (30 in follicular phase, 34 in luteal phase, and 23 using oral contraceptives). The participants were exposed to the Trier Social Stress Test (TSST) or a control condition. Afterwards, their memory performance was measured using a standardized memory test (Rey's Auditory Verbal Learning Test). In the control condition, all groups of women recalled more words than men, but these differences disappeared in the group exposed to TSST because men's performance on the memory test improved, but only to the level of women. In addition, our data suggest that in women the relationship between cortisol and memory can be modulated by sex hormone levels, since in luteal women a negative relationship was found between memory performance and peak cortisol level. These results confirm that sex differences need to be considered in the relationship between pre-learning stress and memory performance.

Openness to experience and cognitive functioning and decline in older adults: The mediating role of cognitive reserve.

OBJECTIVE: Openness to experience has been consistently associated with better cognitive functioning in older people, but its association with cognitive decline is less clear. Cognitive reserve has been proposed as a mechanism underlying this relationship, but previous studies have reported mixed findings, possibly due to the different ways of conceptualizing cognitive reserve. We aimed to analyze the potential mediating role of cognitive reserve in the association between openness and cognitive functioning and decline in healthy older people. METHOD: In Wave 1 and at the four-year follow-up (Wave 2), 87 healthy older people (49.4% women; M age = 65.08, SD = 4.54) completed a neuropsychological battery to assess cognitive functioning and a questionnaire to assess cognitive reserve. Openness was measured with the NEO- Five-Factor Inventory. Mediation models were proposed to investigate the relationship between openness and cognitive function or decline through cognitive reserve or its change. RESULTS: Cognitive reserve mediated the openness-cognitive functioning association. Thus, individuals with higher openness showed greater cognitive reserve, and this greater cognitive reserve was associated with better cognitive functioning. Moreover, greater cognitive reserve at baseline also mediated the association between higher openness and slower cognitive decline. However, change in cognitive reserve did not mediate the association between openness and change in cognitive functioning. CONCLUSIONS: Cognitive reserve is a mechanism underlying the association between openness and cognitive functioning and decline. These findings support the differential preservation hypothesis, suggesting that healthy older adults who engage in more cognitively stimulating activities would show less age-related cognitive decline.

Female students' personality and stress response to an academic examination.

BACKGROUND: Women are vulnerable to stress-related disorders. Examinations are a source of stress, triggering emotional, cognitive, and hormonal responses. We examined women's psychological and hormonal stress responses and academic performance according to personality during a real-life examination. METHODS: Female students (N = 66) were divided into two groups based on hierarchical cluster analysis: one cluster characterized by high neuroticism and moderate extraversion (HN-ME; n = 42) and the other by low neuroticism and high extraversion (LN-HE; n = 24). Academic performance, perceived stress, and emotional dysregulation were analyzed. State anxiety, affect, and cortisol release were measured before and on the examination day. RESULTS: The HN-ME cluster was high in perceived stress, emotional dysregulation, and negative affect. This cluster also had higher state anxiety levels two days before and shortly after the examination compared to the LN-HE cluster. Students' cortisol levels were higher on the examination day, and there was a marginal significance of the Cluster factor in the cortisol release regardless of the day of measurement. CONCLUSIONS: Women with high neuroticism and moderate extraversion may be more vulnerable to psychological stress in academic settings but similar to other women in their cortisol response.

Association between olfactory dysfunction and mood disturbances with objective and subjective cognitive deficits in long-COVID.

Background and purpose: The coronavirus disease 2019 (COVID-19) has been associated with olfactory dysfunction. The persistent symptoms of anosmia or hyposmia were associated in previous studies with the development of memory impairment and mood disturbances. We aimed to investigate the association between the chronicity of reported olfactory dysfunction and subjective and objective cognitive performance in long-COVID patients and to explore whether their emotional symptoms are related to their cognition. Methods: One hundred twenty-eight long-COVID participants were recruited. Reported symptomatology, subjective memory complaints, anxiety and depression symptomatology, and trait-anxiety were assessed. Subjective memory complaints and mood disturbances were compared among groups of participants with olfactory dysfunction as an acute (AOD), persistent (POD), or nonexistent (NOD) symptom. Seventy-six of the volunteers also participated in a face-to-face session to assess their objective performance on tests of general cognitive function and verbal declarative memory. Objective cognitive performance and mood disturbances were compared among the AOD, POD, and NOD groups. Results: The subjective memory complaints and the anxiety and depression symptoms were similar among the groups, but the score in general cognitive function was lower in the participants with symptoms of acute olfactory dysfunction than in those with no olfactory symptoms at any time. Participants' memory complaints were positively related to their emotional symptoms. The relationship between depressive symptomatology and memory complaints interacted with the olfactory dysfunction, as it only occurred in the participants without symptoms of olfactory dysfunction. Depressive symptomatology and acute olfactory symptoms were negatively associated with general cognitive function and delayed memory performance. The months elapsed from diagnosis to assessment also predicted delayed memory performance. Anxious symptomatology was negatively associated with the immediate ability to recall verbal information in participants who did not present olfactory dysfunction in the acute phase of the infection. Conclusion: Olfactory dysfunction in the acute phase of the infection by COVID-19 is related to cognitive deficits in objective tests, and mood disturbances are associated with self-reported and objective memory. These findings may contribute to further understanding the neuropsychological and emotional aspects of long-COVID.