Early Clinical Exposure to Geriatric Psychiatry and Medical Students' Interest in Caring for Older Adults: A Randomized Controlled Trial.

OBJECTIVE: In the next 25 years, the population aged 65 and older will nearly double in many countries, with few new doctors wishing to care for older adults. The authors hypothesize that early clinical exposure to elderly patient care could increase student interest in caring for older adults during their future career. METHODS: The authors conducted a pragmatic medical education randomized controlled trial (RCT) at the Jewish General Hospital and the Douglas Mental Health Institute, McGill University, in Montreal, Canada. Third-year medical students undergoing their mandatory 16-week half-time clerkship rotation in psychiatry were randomly assigned to the equivalent of 2-4 weeks of full-time exposure to clinical geriatric psychiatry (n = 84). RESULTS: Being randomly assigned to geriatric psychiatry exposure (n = 44 of 84) was associated with increased "comfort in working with geriatric patients and their families" at 16-week follow-up (59.1% versus 37.5%, χ2 (1) = 3.9; p = 0.05). However, there was no significant association found between geriatric psychiatry exposure and change "in interest in caring for older adults," or change in "interest in becoming a geriatric psychiatrist." CONCLUSION: The results of this pragmatic education RCT suggest that exposing third-year medical students to 2-4 weeks of geriatric psychiatry did not increase their interest to care for older adults or become a geriatric psychiatrist. However, it did increase their comfort level in working with older adults and their families. However, more research is necessary to identify potential interventions that could inspire and increase medical student interest in caring for older adults as part of their future careers.

Depressive symptoms, cortisol, and cognition during human aging: the role of negative aging perceptions.

Depressive symptoms and memory impairments are associated with heightened stress hormone levels during aging. A factor that is related to memory deficits during aging is internalized negative aging stereotypes; the idea people have about the process of aging. In this study, we assessed the associations between internalized negative aging stereotypes, depressive symptoms, subjective and objective memory assessments, and cortisol concentration among older adults. Forty older adults aged between 58 and 85 years (18 females and 22 males; mean age ± SD: 71.25 ± 8.80 years) were assessed in this study. Measures of internalized negative aging stereotypes, depressive symptoms, and both subjective and objective memory performance were assessed. Salivary samples were obtained for measurement of cortisol concentration. Stepwise linear regressions were executed in our main analyses. Internalized negative aging stereotypes were associated with increased depressive symptoms and subjective memory complaints. No significant differences were observed for objective memory performance, or cortisol concentration. Internalized negative aging stereotypes are associated with increased depressive symptomatology and subjective complaints of memory; however, they do not predict increased cortisol concentration nor objective memory performance during aging. These results indicate that the mechanism underlying the association between internalized negative aging stereotypes and cognitive impairments may not be related to dysregulations of cortisol secretion among older adults.

Barrier enclosure in tracheostomy: a protective box for healthcare workers during the coronavirus disease 2019 pandemic.

BACKGROUND: Tracheostomy, being a high aerosol-generating procedure, poses a great challenge to surgeons, especially during the coronavirus disease 2019 pandemic. It is important to preserve staff numbers as this fight may go on for a long time. Personal protective equipment plays a key role in the protection of healthcare workers. Barrier enclosure has been attempted in procedures such as intubation and tracheostomy. The use of boxes became popularised for intubation and they have been utilised in many centres. METHODS: This paper describes the box designed by our team and presents our surgical experience with the box. The box is made of transparent acrylic. It is sealed at all ends, with a negative-pressure environment. The hand ports were designed to allow maximum manoeuvrability for surgeons, without restricting hand movements. CONCLUSION: The proposed box will provide more protection to healthcare workers during tracheostomy. However, the box is yet to be validated.

Acute and long-term associations between ApoE genetic polymorphism, cortisol levels, and declarative memory performance in older adults.

CONTEXT: For the past two decades, researchers have shown that elevated levels of circulating stress hormones may negatively impact cognitive performance in older adults. As well, genetic polymorphism of the apolipoprotein E gene (APOE) has been found to contribute to impairment in cognitive performance in old age. To date, only one study has reported a relationship between APOE status and cortisol levels, however the relationship was only found to be significant in dementia patients, with a trend observed in healthy controls. OBJECTIVE: The goal of the present investigation was to examine the acute and long-term relationship between APOE status, cortisol secretion, and declarative memory performance in older adults. DESIGN: Two sample cohorts were assessed. In the first cohort, 24-h basal serum cortisol levels were obtained once a year over eight years to assess changes in basal cortisol levels over time. Declarative memory was also obtained in this group at three time-points over five years. In the second cohort, basal and stress-induced cortisol levels as well as basal declarative memory was tested. RESULTS: In the first cohort, E4 carriers were found to secrete higher serum cortisol levels than non-E4 carriers during the first 24-h visit (p=0.04) to the laboratory. However, this group difference did not remain over subsequent years. Furthermore, declarative memory performance over years did not significantly differ according to APOE status. In the second cohort, no significant group differences were found for basal or reactive cortisol levels (ps>0.05), and no group difference was found for acute declarative memory performance. CONCLUSION: The findings in this study suggest minimal to no significant effect of APOE status on cortisol secretion or declarative memory in non-demented older adults.

Cortisol levels during human aging predict hippocampal atrophy and memory deficits.

Elevated glucocorticoid levels produce hippocampal dysfunction and correlate with individual deficits in spatial learning in aged rats. Previously we related persistent cortisol increases to memory impairments in elderly humans studied over five years. Here we demonstrate that aged humans with significant prolonged cortisol elevations showed reduced hippocampal volume and deficits in hippocampus-dependent memory tasks compared to normal-cortisol controls. Moreover, the degree of hippocampal atrophy correlated strongly with both the degree of cortisol elevation over time and current basal cortisol levels. Therefore, basal cortisol elevation may cause hippocampal damage and impair hippocampus-dependent learning and memory in humans.

Childhood sexual abuse in relation to neurobiological challenge tests in patients with borderline personality disorder and normal controls.

This study examined whether abnormal responses to neurobiological challenge tests in borderline personality disorder (BPD) are related to a history of childhood sexual abuse (CSA). We compared patients meeting BPD criteria (n=24), with and without histories of CSA, with normal controls (n=12) on the results of challenges with meta-chlorphenylpiperazine (m-CPP), pyridostigmine and clonidine. No differences were found between abused and non-abused patients with BPD. These results do not support the hypothesis that CSA is directly related to neurobiological abnormalities in BPD.

Impaired platelet [3H]paroxetine binding in female patients with borderline personality disorder.

RATIONALE: There have been few studies of platelet paroxetine binding in borderline personality disorder (BPD). OBJECTIVE: Our aim was to determine whether female BPD subjects show abnormalities in platelet paroxetine binding. METHODS: Twenty-one female BPD subjects and 16 age- and gender-matched normal control subjects were assessed using the following: (1) Diagnostic Interview for Borderlines, Revised, (2) Diagnostic Assessment for Personality Pathology: Brief Questionnaire, and (3) Barratt Impulsivity Scale. Platelets were collected and assayed for platelet paroxetine binding. RESULTS: Bmax was lower in the BPD group (p < 0.0001), but differences in Kd only reached a trend level. There were no associations with trait dimensions independent of diagnosis. CONCLUSIONS: Reduced platelet paroxetine binding in female BPD patients may reflect presynaptic serotonin dysfunction.

Stress-induced declarative memory impairment in healthy elderly subjects: relationship to cortisol reactivity.

A group of 14 healthy elderly subjects was submitted to a nonstressful (attentional task) and a stressful (public speaking task) condition. Declarative (conscious recollection of learned information) and nondeclarative (retrieved information without conscious or explicit access) memory as well as salivary cortisol levels were measured before and after each condition. The results showed that the stressful condition significantly decreased declarative memory performance, whereas the nonstressful condition did not. Nondeclarative memory performance was not affected by either condition. Further analyses separating the subjects into responders and nonresponders in terms of stress-induced cortisol changes revealed a very different pattern of cortisol secretion and declarative memory performance in both populations. We showed that the responders presented increased cortisol levels 60 min before the actual stressor, whereas the nonresponders presented increased cortisol levels 25 min before the actual stressor. Although the responders did not differ from the nonresponders in declarative memory performance before and after the nonstressful condition, they presented a lower declarative memory performance when measured before and after the stressful condition. The early increase in cortisol levels observed in the responder group suggests that the anticipation of the stress, rather than the actual stressor per se, may have played a more significant role in the stress-induced declarative memory deficits observed in this subgroup. Together, these results show that the cortisol response to anticipation of stress and/or to stress in the elderly specifically affects those memory functions that are dependent on hippocampal activity. They also suggest that an altered cortisol responsivity to acute and/or chronic stress, with its detrimental effects on memory, could be an important factor explaining the genesis of memory deficits in aged populations.

Acute modulation of aged human memory by pharmacological manipulation of glucocorticoids.

In a previous longitudinal study of basal cortisol levels and cognitive function in humans, we showed that elderly humans with 4- to 7-yr cumulative exposure to high levels of cortisol present memory impairments, compared with elderly humans with moderate cortisol levels over years. Here, we measured whether memory performance in two groups of elderly humans separated on the basis of their cortisol history over a 5-yr period could be modulated by a hormone-replacement protocol in which we inhibited cortisol secretion by the administration of metyrapone and then restored baseline cortisol levels by infusion of hydrocortisone. We showed that in elderly subjects with a 5-yr history of moderate cortisol levels (n = 8), metyrapone treatment significantly impaired memory performance, a deficit that was reversed following hydrocortisone replacement. In the elderly subjects with a 5-yr history of high cortisol levels and current memory deficits (n = 9), metyrapone treatment did not have any significant effect on memory performance, but hydrocortisone treatment significantly decreased delayed memory. These results suggest that memory function in elderly humans can be intensely modulated by pharmacological manipulation of glucocorticoids, although the direction of these effects depends on the cortisol history of each individual.

The effect of electroconvulsive therapy on endorphins in depression.

The time course study of the endorphin response to electroconvulsive therapy (ECT) was carried out in 10 patients (including one control who did not receive active ECT) at the first and sixth ECT. Results showed a significant rise of plasma endorphin levels after ECT. This increase returned to the pre-ECT level within 1 hr after ECT. There was a pre-rise of plasma endorphin level, which probably was stress related and which was also observed in the control case.

Effect of lithium and neuroleptic combination on lithium transport, blood pressure, and weight in bipolar patients.

Patients treated with a combination of lithium (Li) and neuroleptics are reported to be at greater risk for toxicity. Previous findings suggested that treatment with a combination of Li and neuroleptics would increase the lithium ratio (LR) and intraerythrocyte Li levels. We studied 67 bipolar patients who were treated with Li alone (20 patients) or Li combined with haloperidol (17 patients), or Li combined with chlorpromazine (30 patients). Results revealed that the neuroleptic groups showed significantly lower LR and intracellular Li concentration as compared with those on Li alone. There was no significant difference in Li dosage among these three groups. No difference was found among these three groups with respect to mean blood pressure and weight. The number of hypertensive patients in the Li only group was twice as high as that in either of the two other groups, and the LR of the former was significantly higher than those of the latter groups.

Plasma melatonin--an index of brain aging in humans?

We investigated the age-related changes in the circadian rhythm of plasma melatonin as a potential index of brain aging in man. The subjects were 5 young men aged 19-25 years, 11 older men aged 51-65 years, 6 elderly men aged 66-89 years, 7 young women aged 19-25 years, 5 premenopausal women aged 45-50 years, 8 postmenopausal women aged 51-65 years, and 5 elderly women aged 66-75 years. They were all physically and psychiatrically normal. Serial blood samples were drawn from 8:00 AM until 8:00 AM on the next day, with the indoor illumination set at 300 Lux from 7:00 AM until 4:00 PM and at 50 Lux thereafter. Plasma melatonin was estimated by radioimmunoassay. The results show that there is a significant negative correlation between age and 24-hr secretion of plasma melatonin (r = -0.952, p less than 0.0001), between age and peak levels of plasma melatonin (r = -0.937, p less than 0.00001), and between age and the lag in time from sunset to the onset of significant elevation of plasma melatonin over daytime values (r = 0.916, p less than 0.0001). It is concluded that study of the circadian rhythm of plasma melatonin may prove to be a useful index of the aging process.

Circadian rhythms of melatonin and cortisol in aging.

The relationship of age to the circadian rhythms of melatonin and cortisol was investigated in 44 men and 27 women (age range 19-89 years). Subjects were physically and psychiatrically normal. Four hourly serial blood samples were drawn from 8:00 AM until 8:00 AM the next day, with additional samples at 10:00 PM and 2:00 AM. The indoor illumination was restricted to 300 lux during day and 50 lux during the night. Plasma melatonin and cortisol were estimated by radioimmunoassay. Results show that the means of melatonin and cortisol values decreased significantly with age when the subjects were divided into three age groups, i.e., 19-25 years, 42-65 years, and 66-89 years. They also showed a significant negative correlation with age. The acrophases of the two hormonal rhythms, however, showed different relationships to age. The acrophase of melatonin rhythm showed a positive correlation with age (r = 0.38, p less than 0.001), and cortisol showed a negative correlation with age (r = -0.56, p greater than 0.001). It is suggested that this may indicate a weakened responsiveness of the circadian system in the elderly to the day-night cycle and an altered relationship between the pacemakers driving melatonin and cortisol circadian rhythms. This may thus represent a biomarker for the intrinsic process of the aging of the brain.

Studies of a neurochemical link between depression, anxiety, and stress from [3H]imipramine and [3H]paroxetine binding on human platelets.

We measured platelet [3H]imipramine and [3H]paroxetine binding in patients with major depression (n = 11), dysthymia (n = 9), generalized anxiety (n = 18) and panic disorder (n = 10), and in healthy controls (n = 13). The [3H]imipramine binding capacity (Bmax) was lower in all patient groups; [3H]paroxetine binding was reduced in anxiety disorders, however, decreases in depression and dysthymia were not significant. There were no differences in the affinity constant (Kd) for either radioligand. We also examined the effects of examination stress on platelet binding in medical students. Compared to after vacation, when binding was similar to controls, [3H]imipramine (n = 19) and [3H]paroxetine (n = 14) Bmax values were significantly decreased during examinations and similar to patient values. Examinations were also associated with an increase in plasma cortisol levels. These findings suggest that there is a neurochemical link between depression, anxiety, and stress, and that disturbances in neurochemical functioning may be associated with specific symptomatology, independent of psychiatric diagnosis.

Cardiovascular, neuroendocrine, and monoaminergic responses to psychological stressors: possible differences between remitted panic disorder patients and healthy controls.

Both clinical symptomatology and stress research suggest that panic attacks might be partially attributable to exaggerated psychophysiological responses to environmental stressors. In the present study, we aimed to explicitly test this idea by measuring the physiological responses to a mild psychological stressor in both healthy controls (n = 8) and fully remitted, medication-free panic disorder patients (n = 8). One hour before the stressor, former patients, compared to healthy controls, exhibited higher diastolic blood pressure. From a blood sample taken 30 min before the stressor, patients, compared to controls, had lower paroxetine platelet binding site densities. During the stressor, patients, compared to controls, had greater increases in plasma levels of cortisol. These preliminary findings suggest that remitted panic disorder patients might have disturbed physiological responses to mild psychological stressors. These disturbances might be related to the development of future episodes.

The dexamethasone suppression test and treatment outcome in elderly depressed patients participating in a placebo-controlled multicenter trial involving moclobemide and nortriptyline.

The dexamethasone suppression test (DST) was conducted in 95 elderly DSM-III-R depressed patients randomized for treatment with moclobemide (MOC; 400 mg daily), nortriptyline (NT; 75 mg daily), or placebo (PBO) in a 7-week double-blind multicenter study. Patients were assessed weekly using various clinical scales, including the 17-item Hamilton Depression Rating Scale. The DST was administered at baseline and at the end of treatment. At baseline, no relationship was found between DST status and the various clinical scales used. At the end of treatment, suppressors (DST-) had significantly improved clinical ratings compared to nonsuppressors (DST+), and were mostly found among those treated with NT (71%) as compared to MOC (41%) or PBO (33%) (p < .03). On the other hand, baseline DST measures influenced treatment outcome; DST+ patients had a greater number of treatment responders to NT (48%) than MOC (19%) or PBO (20%) (p < .07). For DST- patients, the situation was reversed: NT, 7%; MOC, 31%. Postdexamethasone cortisol levels were lower in MOC responders (p < .07). An interaction was found between DST and drug-specific response. The DST may be a useful adjunct for predicting and evaluating the outcome of antidepressant therapy.

Growth hormone response to apomorphine, a dopamine receptor agonist, in normal aging and in dementia of the Alzheimer type.

The growth hormone (GH) response to the dopamine (DA) receptor agonist, apomorphine HCl (Apo) (0.5 mg SC) was studied in young and elderly normal subjects as well as in patients with dementia of the Alzheimer type (DAT) and controls matched for age, gender and Quetelet index. The GH response was significantly decreased in normal elderly men (mean age 67.3 years; N = 16) compared with young men (mean age 21.2 years; N = 12) and in elderly women (mean age 65.4 years; N = 9) compared with young women (mean age 25.5 years; N = 6) in the luteal phase but not in the early follicular phase. Young men had a significantly greater GH response than young women in either phase of the menstrual cycle. The decline in GH response with normal aging may be related to a decrease in sex steroid activity. There was no significant difference in GH response between DAT patients (N = 15) and paired controls. This suggests that hypothalamic D2 receptor function regulating GH secretion is not altered in DAT.

Longitudinal study of basal cortisol levels in healthy elderly subjects: evidence for subgroups.

A group of 51 healthy elderly volunteer subjects participated in a 3- to 6-year longitudinal study of basal cortisol levels. Once per year basal cortisol levels were examined using hourly sampling over a 24-h period. Analyses of three cortisol measures (last measure obtained, mean cortisol levels across years, and the cortisol slope) revealed that the slope of the regression line measuring cortisol levels at each year was the most predictive measure of cortisol secretion over the years in this elderly population. Cortisol levels were shown to increase with years in one subgroup, to decrease in another, and to remain stable in a third. The age of the subjects was not related to either cortisol levels or to the pattern of change in cortisol secretion over years. Free and total cortisol levels were highly correlated and the groups did not differ with regard to plasma corticosteroid binding globulin. No group differences were observed for weight, height, body mass index, pulse, blood pressure and glucose. However, significant group differences were reported for plasma triglycerides levels as well as high density lipoproteins levels. Positive correlations were reported between the obsession/compulsion subscale of the SCL-90 questionnaire and the cortisol slope of subjects. Finally, previously reported group differences in neuropsychological performance are summarized. Thus, there exists considerable variation in hypothalamo-pituitary-adrenal function amongst aged humans. These results are consistent with recent animal studies showing the existence of subpopulations of aged rats which differ in hypothalamo-pituitary-adrenal activity and cognitive efficiency.

CSF acetylcholinesterase in dementia and in sequential samples of lumbar CSF.

Acetylcholinesterase (AchE) activity (nmol/ml/min) was measured in lumbar CSF from 11 patients with dementia of the Alzheimer type (DAT), 8 patients with Korsakoff psychosis and 33 patients with low back pain who were undergoing myelography (controls). There was no significant difference in enzyme activity between the three groups. There was no significant correlation between age and AchE activity. AchE was also measured in 20 two-ml samples of CSF collected sequentially by lumbar puncture in two neurosurgical patients who had been recumbent for at least 8 hours. Variations in AchE between samples were small. In neither patient was there an increase in AchE activity with progressive sampling. These data indicate that (1) AchE is unchanged in Korsakoff psychosis (2) decreases in brain AchE which are found in DAT are not readily reflected in lumbar CSF (3) AchE in lumbar CSF has a diffuse origin including spinal cord (4) CSF AchE activity is unlikely to be a useful clinical marker for DAT.

beta-Endorphin and naloxone in psychiatric patients: clinical and biological effects.

The authors conducted single- and double-blind studies of the responses of 7 chronic male schizophrenic patients to 10 mg of naloxone. BPRS ratings were made before and 6 hours after the injection; ACTH blood levels were determined before and 1 1/2 and 6 hours after injection. Statistically significant improvement of psychotic behavior occurred after 6 hours. The greatest improvement occurred in the patient who showed the most pronounced diurnal variation of ACTH levels, and there was no improvement in the patient who had no diurnal changes. Prolactin plasma levels following endorphin injections were apparently dose-dependent and peaked at approximately 30 minutes. The mean half-life of elimination of exogenous beta-endorphin was between 12 and 35 minutes. The authors theorize that positive and negative behavioral responses to naloxone depend--as possibly do many placebo responses in general--on the relative stress produced by experimental or therapeutic interventions.