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 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.

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.

Mediation of perceived stress and cortisol in the association between neuroticism and global cognition in older adults: A longitudinal study.

Neuroticism has been associated with a greater dementia risk, but its association with cognitive decline in healthy older adults remains unclear. Stress has been proposed as one of the mechanisms that could explain this relationship. Our aim was to analyse, in healthy older people, the mediating role of perceived stress and the Hypothalamic-Pituitary-Adrenal (HPA) axis in the association between neuroticism and global cognition. At Waves 1 and 2 (4-year follow-up), 87 older people (49.4% women; M age = 65.08, SD = 4.54 at Wave 1) completed a neuropsychological battery and the Perceived Stress Scale (PSS), and provided saliva samples on two (Wave 1) and three (Wave 2) consecutive days to measure the wake-to-bed slope. In Wave 2, neuroticism was assessed with the NEO-Five-Factor Inventory. PSS, but not the wake-to-bed slope, mediated the negative associations between neuroticism and global cognition (Waves 1, 2 and change). Regarding gender differences, PSS (Waves 1, 2 and change) and the wake-to-bed slope (Wave 2 and change) mediated these associations in men. Our results suggest that perceived stress and HPA-axis dysregulation could act as mechanisms underlying the association between neuroticism and cognitive functioning and decline, at least in older men.

Depression and Suicide Risk in Mild Cognitive Impairment: The Role of Alzheimer's Disease Biomarkers.

BACKGROUND: Patients with depression and mild cognitive impairment (MCI) are at greater risk of developing dementia. Depression involves a higher risk of suicidal ideation (SI) and suicide attempts (SA). Biomarkers of Alzheimer's Disease (AD) could help to clarify the role of depression and SI in AD. METHOD: Fifty-nine participants aged > 50 with criteria of MCI positive (MCI-AD) (n=22) and negative (MCI-Non AD) (n=24) AD and healthy controls (HC) (n=13) were evaluated. We used the Geriatric Depression Scale (GDS-30) and the GDS-SI factor to measure depression and indirect risk for suicide, respectively. Additionally, AD biomarkers such as amyloid-ß (Aß), hyperphosphorilated tau (P-tau), and total tau (T-tau) in cerebrospinal fluid (CSF) were analyzed. RESULTS: No significant differences between the groups were found in depression. However, in the MCI-AD group, lower P-tau and T-tau levels were related to higher GDS-SI scores, suggesting that MCI-AD patients with lower AD pathology are at a higher risk of suicide. CONCLUSIONS: The result highlights the importance of considering SI in the initial phases of AD, and the potential role of AD biomarkers in early detection of symptoms.

Diurnal cortisol secretion and health-related quality of life in healthy older people.

Several studies have demonstrated that a dysregulated hypothalamic-pituitary-adrenal (HPA) axis is related to worse health status (e.g., depression, posttraumatic stress, or diabetes, among others). However, less is known about the association between the individual's perception of their own health status and HPA-axis functioning in healthy older people. The aim of the present study was to examine the relationship between HPA-axis functioning and health-related quality of life (HRQoL) in healthy older people. To do this, 140 healthy older people (69 men and 71 women) from 56 to 76 years old collected eight saliva samples on two consecutive weekdays to measure the diurnal cortisol cycle (i.e. awakening cortisol levels, cortisol awakening response (CAR), overall morning cortisol levels, change in the cortisol levels during the day, and bedtime cortisol levels). In addition, they completed the SF-36 questionnaire to obtain a measure of HRQoL (i.e. reflecting physical and mental functional health status). Results showed that higher awakening and bedtime cortisol levels and the CAR were associated with a better perception of both physical and mental health. In addition, the wake-to-bed cortisol slope was only positively related to physical health. No sex differences were found. These findings suggest that the awakening and bedtime cortisol levels and the CAR are the most relevant indices of diurnal cortisol secretion for understanding the relationship between HPA-axis functioning and HRQoL status in older people.

Importance of Personality for Objective and Subjective-Physical Health in Older Men and Women.

Objective and subjective health generally have a positive relationship, although their association may be moderated by factors such as gender and personality. We aimed to analyze the association between personality and objective (metabolic syndrome (MetS)) and subjective-physical health in older men and women. For this purpose, in 138 participants (53.6% women, Mage = 66.85), neuroticism, conscientiousness, extraversion, openness, and agreeableness (NEO Five Factor Inventory), subjective-physical health (Short Form Health Survey, SF-36), and MetS (employing waist circumference, blood pressure, triglycerides, high-density lipoprotein cholesterol, and glycated hemoglobin) were assessed. Logistic regression analysis was performed to analyze whether personality was associated with MetS. Moreover, hierarchical regression analyses were conducted to analyze the relationship between personality or MetS, and subjective-physical health. Finally, gender and personality moderation analyses were performed with PROCESS. Results showed that higher neuroticism was associated with an increased likelihood of MetS, whereas higher neuroticism and lower extraversion were associated with lower subjective-physical health. Moreover, the negative relationship between MetS and subjective-physical health was stronger in individuals with low conscientiousness. Regarding gender differences, only in women, higher extraversion was related to a decreased likelihood of MetS, and MetS was related to lower subjective-physical health. In conclusion, higher neuroticism is the main vulnerability health factor, whereas to a lesser extent extraversion and conscientiousness are protective factors. Furthermore, the association between objective and subjective health is not direct, but it may vary depending on personality and gender.

Personality and Hypothalamic-Pituitary-Adrenal Axis in Older Men and Women.

Personality has been related to health and mortality risk, which has created interest in the biological pathways that could explain this relationship. Although a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been associated with health outcomes and aging, few studies have explored the association between personality and HPA axis functioning in older adults. In addition, it has been suggested that sex could moderate the relationship between personality and HPA axis functioning. Thus, our aim was to analyze the relationship between the big five personality traits and the diurnal cortisol pattern in older adults, as well as sex differences in this relationship. To do so, 79 older people (40 men and 39 women) from 59 to 81 years old (M = 69.19, SD = 4.60) completed the NEO-Five-Factor Inventory (FFI) to measure neuroticism, conscientiousness, extraversion, openness, and agreeableness. Saliva samples were provided on three consecutive days (awakening; 15, 30, and 45 min post-awakening; and bedtime) in order to analyze the diurnal cortisol pattern and, specifically, two cortisol indexes: the cortisol awakening response (CAR) and the diurnal cortisol slope (DCS). Results showed that neuroticism and conscientiousness moderated the diurnal cortisol pattern. Thus, individuals with higher neuroticism and lower conscientiousness scores showed higher bedtime cortisol levels, suggesting a less healthy diurnal cortisol pattern. Regarding the cortisol indexes, higher neuroticism and lower conscientiousness were related to greater CAR and DCS. Sex moderated the association between extraversion and the DCS. Specifically, higher extraversion was related to a lower DCS only in women. Openness and agreeableness were not related to the diurnal cortisol pattern. In conclusion, our results show that in older adults, neuroticism is a vulnerability factor for HPA axis dysregulation, with possible adverse effects on health. By contrast, conscientiousness, and extraversion only in women, appear to be protective factors of HPA axis functioning, with potential beneficial effects on health.

Relationship between Cortisol Changes during the Night and Subjective and Objective Sleep Quality in Healthy Older People.

The aim of this study was to investigate whether the nighttime cortisol release was associated with subjective and objective sleep quality and the discrepancy between them. Forty-five healthy older adults (age range from 56 to 75 years) collected salivary samples immediately before sleep and immediately after awakening on two consecutive nights. Actigraphy was used to assess objective sleep quality and quantity. A sleep diary was used to assess subjective sleep quality. Linear mixed models were performed using subjective and objective sleep quality data from 76 nights to investigate between-subject associations. We observed that larger changes in cortisol levels between sleep onset and awakening, reflecting a healthier circadian rhythm of the Hypothalamic-Pituitary-Adrenal (HPA) axis, were associated with better subjective sleep quality, but not with objective sleep quality. Moreover, smaller changes in nighttime cortisol were associated with lower subjective sleep quality relative to objective sleep quality. All these results were observed even after controlling for important confounders such as sleep quantity, age, sex, subjective socioeconomic status, stress perception, depression, physical activity, and adherence to the salivary sampling protocol. This study demonstrates that subjective sleep quality in older people may be explained, to some extent, by the activity of the HPA axis.

No Effects of Acute Psychosocial Stress on Working Memory in Older People With Type 2 Diabetes.

Type 2 diabetes (T2D) has been considered a public health threat due to its growing prevalence, particularly in the older population. It is important to know the effects of psychosocial stress and its potential consequences for some basic cognitive processes that are important in daily life. Currently, there is very little information about how people with T2D face acute psychosocial stressors, and even less about how their response affects working memory (WM), which is essential for their functionality and independence. Our aim was to characterize the response to an acute laboratory psychosocial stressor and its effects on WM in older people with T2D. Fifty participants with T2D from 52 to 77 years old were randomly assigned to a stress (12 men and 12 women) or control (12 men and 14 women) condition. Mood and physiological (cortisol, C, and salivary alpha-amylase, sAA) responses to tasks were measured. In addition, participants completed a WM test before and after the stress or control task. Our results showed that the TSST elicited higher negative affect and greater C and sAA responses than the control task. No significant differences in WM were observed depending on the exposure to stress or the control task. Finally, participants who showed higher C and sAA responses to the stressor had lower WM performance. Our results indicate that medically treated older adults with T2D show clear, typical mood and physiological responses to an acute psychosocial stressor. Finally, the lack of acute psychosocial stress effects on WM suggests that it could be related to aging and not to this disease, at least when T2D is adequately treated.

The relationship between loneliness and cognition in healthy older men and women: The role of cortisol.

Loneliness has been associated with an increased risk of cognitive decline and dementia in older people, as well as a dysregulation of Hypothalamic-Pituitary-Adrenal (HPA) axis functioning. In addition, it has been suggested that women are more vulnerable to the negative effects of loneliness on health. Our aim was to analyze the effect of HPA-axis functioning as a mediator in the relationship between loneliness and cognitive function, and interactions depending on sex, in healthy older people. To do so, 86 healthy older people (52.3% female) from 60 to 80 years old (M = 67.44, SD = 4.37) completed the revised UCLA loneliness scale. A neuropsychological battery was administered to assess global cognition, processing speed, attention and executive function, working memory, and verbal memory immediate and delayed recall. Saliva samples were provided on two consecutive weekdays to obtain awakening and bedtime cortisol levels, the diurnal cortisol slope (DCS), and the area under the curve with respect to the ground (AUCg). Our results showed that loneliness was not directly associated with cognitive performance. Furthermore, loneliness was related to higher bedtime cortisol levels, but not to awakening cortisol, the DCS, or the AUCg. In addition, loneliness was associated with worse performance on attention and processing speed, executive function, and verbal memory immediate recall, via bedtime cortisol levels. Therefore, we suggest that HPA-axis functioning is one of the biological mechanisms that mediate the relationship between loneliness and poorer cognitive function. No sex differences were observed in these associations.

Acute Cortisol Levels and Memory Performance in Older People with High and Normal Body Mass Index.

Previous studies have shown that healthy older adults may be less sensitive to the effects of acute cortisol levels on memory performance than young adults. Importantly, being overweight has recently been associated with an increase in both cortisol concentration and cortisol receptors in central tissues, suggesting that Body Mass Index (BMI) may contribute to differences in the relationship between memory and acute cortisol. This study investigates the role of BMI in the relationship between memory performance and acute cortisol levels in older people (M = 64.70 years; SD = 4.24). We measured cortisol levels and memory performance (working memory and declarative memory) in 33 participants with normal BMI (normal BMI = 18.50-24.99) and 36 participants with overweight BMI (overweight BMI = 25-29.99). Overweight BMI participants showed worse performance on word-list learning (p = .036, 95% CI [0.08, 2.18], η2p = 0.07). Higher cortisol levels were related to higher proactive interference (ß = .364, p = .016, 95% CI [0.07, 0.66]), and BMI did not moderate any of the relationships investigated. In accordance with previous studies, our results show worse memory performance in individuals with overweight BMI. However, our results do not support the idea that memory performance in older people with higher BMI may be more sensitive to differences in acute cortisol levels than in older people with normal BMI. More research is needed to test this hypothesis with obese individuals (BMI > 30 Kg/cm2).

Depression and Suicide Risk in Mild Cognitive Impairment: The Role of Alzheimer’s Disease Biomarkers / Depresión y Riesgo de Suicidio en el Deterioro Cognitivo Leve: el Rol de los Biomarcadores de la Enfermedad de Alzheimer

Background: Patients with depression and mild cognitive impairment (MCI) are at greater risk of developing dementia. Depression involves a higher risk of suicidal ideation (SI) and suicide attempts (SA). Biomarkers of Alzheimer’s Disease (AD) could help to clarify the role of depression and SI in AD. Method: Fifty-nine participants aged > 50 with criteria of MCI positive (MCI-AD) (n=22) and negative (MCI-Non AD) (n=24) AD and healthy controls (HC) (n=13) were evaluated. We used the Geriatric Depression Scale (GDS-30) and the GDS-SI factor to measure depression and indirect risk for suicide, respectively. Additionally, AD biomarkers such as amyloid-ß (Aß), hyperphosphorilated tau (P-tau), and total tau (T-tau) in cerebrospinal fluid (CSF) were analyzed. Results: No significant differences between the groups were found in depression. However, in the MCI-AD group, lower P-tau and T-tau levels were related to higher GDS-SI scores, suggesting that MCI-AD patients with lower AD pathology are at a higher risk of suicide. Conclusions: The result highlights the importance of considering SI in the initial phases of AD, and the potential role of AD biomarkers in early detection of symptoms.(AU)

Antecedentes: Los pacientes con depresión y deterioro cognitivo leve (DCL) tienen un alto riesgo de desarrollar demencia. La depresión implica un alto riesgo de ideación suicida (IS) e intentos de suicidio (AS). Los biomarcadores de la enfermedad de Alzheimer (EA) pueden clarificar el papel de la depresión e IS en la EA. Método: Cincuenta y nueve participantes >50 años con criterios de DCL-EA positivo (DCL-EA; 22) y negativo (DCL-NoEA; 24) y 13 controles sanos. La depresión fue evaluada con la Escala Geriátrica de Depresión (GDS-30) y la IS con el factor GDS-IS. Además, se midieron los siguientes biomarcadores en el líquido cefalorraquídeo: ß-amiloide (ß-A), tau hiperfosforilada (H-tau) y total (T-tau). Resultados: No se encontraron diferencias significativas entre los tres grupos de participantes en depresión o en IS. Sin embargo, en el grupo DCL-EA, niveles más bajos de H-tau y T-tau, indicadores de menor patología EA, se relacionaron significativamente con mayor riesgo de suicidio indirecto. Conclusiones: Este resultado subraya la importancia de considerar la IS en fases iniciales de EA, y el potencial papel de los biomarcadores de EA para detectar sus síntomas.(AU)

Acute cortisol levels and memory performance in older people with high and normal body mass index

Previous studies have shown that healthy older adults may be less sensitive to the effects of acute cortisol levels on memory performance than young adults. Importantly, being overweight has recently been associated with an increase in both cortisol concentration and cortisol receptors in central tissues, suggesting that Body Mass Index (BMI) may contribute to differences in the relationship between memory and acute cortisol. This study investigates the role of BMI in the relationship between memory performance and acute cortisol levels in older people (M = 64.70 years; SD = 4.24). We measured cortisol levels and memory performance (working memory and declarative memory) in 33 participants with normal BMI (normal BMI = 18.50-24.99) and 36 participants with overweight BMI (overweight BMI = 25-29.99). Overweight BMI participants showed worse performance on word-list learning (p = .036, 95% CI [0.08, 2.18], η2p = 0.07). Higher cortisol levels were related to higher proactive interference (β = .364, p = .016, 95% CI [0.07, 0.66]), and BMI did not moderate any of the relationships investigated. In accordance with previous studies, our results show worse memory performance in individuals with overweight BMI. However, our results do not support the idea that memory performance in older people with higher BMI may be more sensitive to differences in acute cortisol levels than in older people with normal BMI. More research is needed to test this hypothesis with obese individuals (BMI > 30 Kg/cm2)

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