Alexandra J. Fiocco

Stress hormones and human memory function across the lifespan.

In this paper, we summarize the data obtained in our laboratory showing the effects of glucocorticoids on human cognitive function in older adults, young adults and children. We first present data obtained in the aged human population which showed that long-term exposure to high endogenous levels of glucocorticoids is associated with both memory impairments and a 14% smaller volume of the hippocampus. We then report on studies showing that in older adults with moderate levels of glucocorticoids, memory performance can be acutely modulated by pharmacological manipulations of glucocorticoids. In young adults, we present data obtained in our laboratory showing that cognitive processing sustained by the frontal lobes is also sensitive to acute increases of glucocorticoids. We also summarize studies showing that just as in older adults, memory performance in young adults can be acutely modulated by pharmacological manipulations of glucocorticoids. We then present a study in which we showed a differential involvement of adrenergic and glucocorticoid hormones for short- and long-term memory of neutral and emotional information. In the last section of the paper, we present data obtained in a population of young children and teenagers from low and high socioeconomic status (SES), where we showed that children from low SES present significantly higher levels of basal cortisol when compared to children from high SES. We then present new data obtained in this population showing that children and teenagers from low and high SES do not process the plausibility of positive and negative attributes in the same way. Children from low SES tended to process positive and negative attributes on a more negative note than children from high SES, and this type of processing was significantly related to basal cortisol at age 10, 12 and 14. Altogether, the results of these studies show that both bottom-up (effects of glucocorticoids on cognitive function), and top-down (effects of cognitive processing on glucocorticoid secretion) effects exist in the human population.

Predictors of maintaining cognitive function in older adults: The Health ABC Study

Background: Although several risk factors for cognitive decline have been identified, much less is known about factors that predict maintenance of cognitive function in advanced age. Methods: We studied 2,509 well-functioning black and white elders enrolled in a prospective study. Cognitive function was measured using the Modified Mini-Mental State Examination at baseline and years 3, 5, and 8. Random effects models were used to classify participants as cognitive maintainers (cognitive change slope ≥0), minor decliners (slope <0 and >1 SD below mean), or major decliners (slope ≤1 SD below mean). Logistic regression was used to identify domain-specific factors associated with being a maintainer vs a minor decliner. Results: Over 8 years, 30% of the participants maintained cognitive function, 53% showed minor decline, and 16% had major cognitive decline. In the multivariate model, baseline variables significantly associated with being a maintainer vs a minor decliner were age (odds ratio [OR] = 0.65, 95% confidence interval [CI] 0.55–0.77 per 5 years), white race (OR = 1.72, 95% CI 1.30–2.28), high school education level or greater (OR = 2.75, 95% CI 1.78–4.26), ninth grade literacy level or greater (OR = 4.85, 95% CI 3.00–7.87), weekly moderate/vigorous exercise (OR = 1.31, 95% CI 1.06–1.62), and not smoking (OR = 1.84, 95% CI 1.14–2.97). Variables associated with major cognitive decline compared to minor cognitive decline are reported. Conclusion: Elders who maintain cognitive function have a unique profile that differentiates them from those with minor decline. Importantly, some of these factors are modifiable and thus may be implemented in prevention programs to promote successful cognitive aging. Further, factors associated with maintenance may differ from factors associated with major cognitive decline, which may impact prevention vs treatment strategies.

Chronic stress, cognitive functioning and mental health.

This review aims to discuss the evidence supporting the link between chronic stress, cognitive function and mental health. Over the years, the associations between these concepts have been investigated in different populations. This review summarizes the findings that have emerged from older populations as well as from populations suffering from pathological aging, namely Mild Cognitive Impairment and Alzheimers Disease. Although older adults are an interesting population to study in terms of chronic stress, other stress-related diseases can occur throughout the lifespan. The second section covers some of these stress-related diseases that have recently received a great deal of attention, namely burnout, depression, and post-traumatic stress disorder. Given that chronic stress contributes to the development of certain pathologies by accelerating and/or exacerbating pre-existing vulnerabilities that vary from one individual to the other, the final section summarizes data obtained on potential variables contributing to the association between chronic stress and cognition.

A transdisciplinary perspective of chronic stress in relation to psychopathology throughout life span development.

The allostatic load (AL) model represents an interdisciplinary approach to comprehensively conceptualize and quantify chronic stress in relation to pathologies throughout the life cycle. This article first reviews the AL model, followed by interactions among early adversity, genetics, environmental toxins, as well as distinctions among sex, gender, and sex hormones as integral antecedents of AL. We next explore perspectives on severe mental illness, dementia, and caregiving as unique human models of AL that merit future investigations in the field of developmental psychopathology. A complimenting transdisciplinary perspective is applied throughout, whereby we argue that the AL model goes beyond traditional stress-disease theories toward the advancement of person-centered research and practice that promote not only physical health but also mental health.

The role of cognitive deficits in the development of eating disorders.

Eating disorders (ED), including anorexia and bulimia nervosa, are chronic illnesses with periods of symptom exacerbation and remission. Because symptoms are usually present from 6 to 24 months before a diagnosis is made, aetiological agents are believed to be active well before symptoms appear. It is proposed that neuropsychological deficits in various cognitive domains preexist and underlie the aetiology of ED. This paper provides a comprehensive review of the literature relevant to neuropsychological deficits in ED patients and explores the relationship between cognitive deficits, psychosocial development, and the development of ED. Although the role of neuropsychological deficits in the evolution of ED requires further research, the proposed association has significant implications for clinical practice.

Anxiolytic-like effects of antidepressants after acute administration in a four-plate test in mice.

The four-plate test (FPT) is an animal model of anxiety based on stress caused by unconditioned fear. An increase of spontaneous punished behavior was used as a measure to determine the anxiolytic effects of various antidepressants (ADs). In the present study. ADs with different mechanisms of action, including tricyclics, selective serotonin reuptake inhibitors (SSRIs), a monoamine oxidase inhibitor (MAOI), and atypicals, were studied in the FPT to evaluate their anxiolytic-like effects following acute administration. The number of punished crossings was dramatically increased by the SSRIs citalopram, fluvoxamine, and paroxetine, but not fluoxetine. The mixed 5-HT/NE reuptake inhibitors, milnacipran and venlafaxine, also demonstrated strong antipunishment effects. The specific NE reuptake inhibitors, desipramine and maprotiline, and the atypical AD trazodone, enhanced freezing behavior, suggesting anxiogenic-like behavior. It was concluded that, in the FPT, a model based on spontaneous response, where animals are exposed to an aversive environment from which they can only escape by being motionless, this kind of behavior might be related to anticipatory anxiety. In this situation, ADs acting preferentially on 5-HT transmission possessed clear anxiolytic like effects. The balance between the two transmitters, 5-HT and NE, seemed to be a crucial factor.

Diurnal cycle of salivary cortisol in older adult men and women with subjective complaints of memory deficits and/or depressive symptoms: Relation to cognitive functioning

In populations of young and older adults, it has been shown that individuals may be categorized into one of three diurnal subgroups when salivary cortisol levels are assessed over a 2-day period and compared for their consistency across days: a typical subgroup, a flat subgroup, and an inconsistent subgroup. Interestingly, recent studies have reported that the typical subgroup represents the majority of the young and older adult population, a finding that is difficult to reconcile with previous studies showing increased cortisol levels in older adults with depression or cognitive impairments. In order to assess whether a typical diurnal cortisol profile is representative across different subgroups of older adults, we assessed diurnal cortisol cycle representation in a sample of older adults with subjective complaints of depression and/or memory problems. Furthermore, given the robust relationship between cortisol and cognitive function, the present study examined the association between the three diurnal subgroups and cognitive performance. Forty-two older individuals were recruited on the basis of reporting subjective complaints of either memory problems and/or depressive mood. Participants were asked to sample their saliva over a 2-day period and were then asked to undergo a neuropsychological evaluation that taps into short-term memory, declarative memory and language. The results showed that 69% of the sample presented a Flat cycle of salivary cortisol over a 2-day period while 19% presented an inconsistent pattern and 12% presented a typical pattern. Participants in the flat subgroup were significantly impaired on letter verbal fluency. Furthermore, a relationship was found between diurnal cortisol subgroup representation and subjective complaint profile. These findings show that older adults with complaints of memory problems and/or depressive symptoms do not present the typical profile of the diurnal cortisol cycle, and they provide a preliminary view of how diurnal cortisol profile relates to cognitive function during human aging.

Education modulates cortisol reactivity to the Trier Social Stress Test in middle-aged adults

The present study assessed the modulating effect of education level on cortisol reactivity to the Trier Social Stress Test (TSST) in a sample of 101 middle-aged adults (22 males, 79 females) between the ages of 50 and 65. The TSST involves a public speech and mental arithmetic task in front of an audience. No previous studies have assessed whether education level can have an impact on cortisol reactivity to this psychosocial stressor. It is plausible that greater exposure to academia may impact how one perceives and responds to the demands of the speech and arithmetic task. Should education have an impact on cortisol reactivity to the TSST, future studies will be required to control for this factor in order to reduce both statistical error and false interpretations. In addition to completing the TSST, participants were administered a battery of neurocognitive tests and personality questionnaires, including a report on education level (i.e. number of years total and degree: High School, Junior College, Technical, University). Results showed that adults with post-secondary education above Junior College tended to secrete higher cortisol levels overall, as measured by total area under the curve. However, it was the group with lower educational attainment who showed a greater stress response specific to the TSST, as measured by percentage increase in cortisol from pre- to post-TSST. Analyses also found that higher educated adults performed better than their less educated peers on verbal fluency. Considering that the TSST is an oral task, it is suggested that middle-aged individuals with a lower level of education may find the TSST more stressful due to lower verbal capacity, which may lead to an increased cortisol response to the TSST when compared to individuals with a higher level of education.

Aging and Alzheimer’s Disease

Publisher Summary This chapter discusses aging and Alzheimers disease. The possibility that aging-associated alterations of neuroendocrine systems contribute to the pathophysiology of behavioral changes and disorders of later life has long intrigued clinicians and investigators. This possibility was largely an inference from the substantial aging-associated reduction in concentrations of several important hormones such as estrogen, testosterone, growth hormone, and thyroid stimulating hormone (TSH). However, establishing causality for decreased neuroendocrine activity in the pathophysiology of such later-life behavioral problems as impaired cognition and depression has proved difficult. For example, attempts to treat major neuropsychiatric disorders of later life with gonadal hormones have been largely disappointing. Furthermore, the direction in which several behaviorally relevant neuroendocrine systems are altered in late life is inconsistent with the assumption that aging is always associated with reduced neuroendocrine activity.

Sodium intake and physical activity impact cognitive maintenance in older adults: the NuAge Study.

This study examines the association between sodium intake and its interaction with physical activity on cognitive function over 3 years in older adults residing in Québec, Canada. We analyzed a subgroup from the NuAge cohort (aged 67-84 years) with nutrient intake data, including sodium, from a food frequency questionnaire administered at baseline. Baseline physical activity was assessed using the Physical Activity Scale for the Elderly (PASE; high-low). Modified Mini Mental State Examination (3MS) was administered at baseline and annually for 3 additional years. Controlling for age, sex, education, waist circumference, diabetes, and dietary intakes, analyses showed an association between sodium intake and cognitive change over time in the low PASE group only. Specifically, in the low PASE group, elders in the low sodium intake tertile displayed better cognitive performance over time (mean decline in 3MS over years: mean [M] = -0.57, standard error [SE] = 0.002) compared with the highest (M = -1.72, SE = 0.01) and mid sodium intake (M = -2.07, SE = 0.01) groups. This finding may have significant public health implications, emphasizing the importance of addressing multiple lifestyle factors rather than a single domain effect on brain health.