A high fat diet potentiates neonatal iron overload-induced memory impairments in rats.

PURPOSE: The present study aimed at evaluating possible synergistic effects between two risk factors for cognitive decline and neurodegenerative disorders, i.e. iron overload and exposure to a hypercaloric/hyperlipidic diet, on cognition, insulin resistance, and hippocampal GLUT1, GLUT3, Insr mRNA expression, and AKT phosporylation. METHODS: Male Wistar rats were treated with iron (30 mg/kg carbonyl iron) or vehicle (5% sorbitol in water) from 12 to 14th post-natal days. Iron-treated rats received a standard laboratory diet or a high fat diet from weaning to adulthood (9 months of age). Recognition and emotional memory, peripheral blood glucose and insulin levels were evaluated. Glucose transporters (GLUT 1 and GLUT3) and insulin signaling were analyzed in the hippocampus of rats. RESULTS: Both iron overload and exposure to a high fat diet induced memory deficits. Remarkably, the association of iron with the high fat diet induced more severe cognitive deficits. Iron overload in the neonatal period induced higher insulin levels associated with significantly higher HOMA-IR, an index of insulin resistance. Long-term exposure to a high fat diet resulted in higher fasting glucose levels. Iron treatment induced changes in Insr and GLUT1 expression in the hippocampus. At the level of intracellular signaling, both iron treatment and the high fat diet decreased AKT phosphorylation. CONCLUSION: The combination of iron overload with exposure to a high fat diet only led to synergistic deleterious effect on emotional memory, while the effects induced by iron and by the high fat diet on AKT phosphorylation were comparable. These findings indicate that there is, at least to some extent, an additive effect of iron combined with the diet. Further studies investigating the mechanisms associated to deleterious effects on cognition and susceptibility for the development of age-associated neurodegenerative disorders are warranted.

Behavior, BDNF and epigenetic mechanisms in response to social isolation and social support in middle aged rats exposed to chronic stress.

Social deprivation can be stressful for group-living mammals. On the other hand, an amazing response of these animals to stress is seeking social contact to give and receive joint protection in threatening situations. We explored the effects of social isolation and social support on epigenetic and behavioral responses to chronic stress. More specifically, we investigated the behavioral responses, corticosterone levels, BDNF gene expression, and markers of hippocampal epigenetic alterations (levels of H3K9 acetylation and methylation, H3K27 methylation, HDAC5, DNMT1, and DNMT3a gene expressions) in middle-aged adult rats maintained in different housing conditions (isolation or accompanied housing) and exposed to the chronic unpredictable stress protocol (CUS). Isolation was associated with decreased basal levels of corticosterone, impaired long-term memory, and decreased expression of the BDNF gene, besides altering the balance of H3K9 from acetylation to methylation and increasing the DNMT1 gene expression. The CUS protocol decreased H3K9 acetylation, besides increasing H3K27 methylation and DNMT1 gene expression, but had no significant effects on memory and BDNF gene expression. Interestingly, the effects of CUS on corticosterone and HDAC5 gene expression were seen only in isolated animals, whereas the effects of CUS on DNMT1 gene expression were more pronounced in isolated than accompanied animals. In conclusion, social isolation in middle age showed broader effects than chronic unpredictable stress on behavioral and epigenetic alterations potentially associated with decreased BDNF expression. Moreover, social support prevented the adverse effects of CUS on HPA axis functioning, HDAC5, and DNMT1 gene expressions.

Cannabidiol reverses memory impairments and activates components of the Akt/GSK3ß pathway in an experimental model of estrogen depletion.

Clinical and preclinical evidence has indicated that estrogen depletion leads to memory impairments and increases the susceptibility to neural damage. Here, we have sought to investigate the effects of Cannabidiol (CBD) a non-psychotomimetic compound from Cannabis sativa, on memory deficits induced by estrogen depletion in rats, and its underlying mechanisms. Adult rats were subjected to bilateral ovariectomy, an established estrogen depletion model in rodents, or sham surgery and allowed to recover for three weeks. After that, they received daily injections of CBD (10 mg/kg) for fourteen days. Rats were tested in the inhibitory avoidance task, a type of emotionally-motivated memory. After behavioral testing they were euthanized, and their hippocampi were isolated for analysis of components of the Akt/GSK3ß survival pathway and the antiapoptotic protein Bcl2. Results revealed that ovariectomy impaired avoidance memory, and CBD was able to completely reverse estrogen depletion-induced memory impairment. Ovariectomy also reduced Akt/GSK3ß pathway's activation by decreasing the phosphorylation levels of Akt and GSK3ß and Bcl2 levels, which were ameliorated by CBD. The present results indicate that CBD leads to a functional recovery accompanied by the Akt/GSK3ß survival pathway's activation, supporting its potential as a treatment for estrogen decline-induced deterioration of neural functioning and maintenance.

Family and Community Support, Brain-Derived Neurotrophic Factor, and Cognitive Performance in Older Adults: Findings From the Health, Wellbeing and Aging Study Population-Based Cohort.

Background: Social networks can modulate physiological responses, protects against the detrimental consequences of prolonged stress, and enhance health outcomes. Family ties represent an essential source of social networks among older adults. However, the impact of family support on cognitive performance and the biological factors influencing that relationship is still unclear. We aimed to determine the relationship between family support, cognitive performance and BDNF levels. Methods: Cross-sectional data from three-hundred, eight-six individuals aged on average 60 years enrolled in the Health, Wellbeing and Aging Study (SABE), a population-cohort study, were assessed for family support, community support and cognitive performance. Structural and functional family support was evaluated based on family size and interactions allied to scores in the Family APGAR questionnaire. Community assistance (received or provided) assessed the community support. Cognitive performance was determined using the Mini-Mental State Examination (MMSE), verbal fluency (animals per minute) and backward digital span. Blood samples were obtained to determine BDNF levels. Results: Multivariate analysis showed that functional family support, but not structural, was associated with higher MMSE, verbal fluency and digit span scores, even controlling for potential cofounders (p < 0.001). Providing support to the community, rather than receiving support from others, was associated with better cognitive performance (p < 0.001). BDNF concentration was not associated with community support, family function, or cognitive performance. Conclusion: These findings suggest that emotional components of functional family and community support (e.g., loving and empathic relationship) may be more significant to cognitive health than size and frequency of social interactions.

The G protein-coupled estrogen receptor (GPER) regulates recognition and aversively-motivated memory in male rats.

Estrogens, particularly 17ß-estradiol (estradiol, E2), regulate memory formation. E2 acts through its intracellular receptors, estrogen receptors (ER) ERα and ERß, as well as a recently identified G protein-coupled estrogen receptor (GPER). Although the effects of E2 on memory have been investigated, studies examining the effects of GPER stimulation are scarce. Selective GPER agonism improves memory in ovariectomized female rats, but little information is available regarding the effects of GPER stimulation in male rodents. The aim of the present study was to investigate the effects of the GPER agonist, G1, on consolidation and reconsolidation of inhibitory avoidance (IA) and object recognition (OR) memory in male rats. Animals received vehicle, G1 (15, 75, 150 µg/kg; i.p.), or the GPER antagonist G15 (100 µg/kg; i.p.) immediately after training, or G1 (150 µg/kg; i.p.) 3 or 6 h after training. To investigate reconsolidation, G1 was administered immediately after IA retention Test 1. Results indicated that G1 administered immediately after training at the highest dose enhanced both OR and IA memory consolidation, while GPER blockade immediately after training impaired OR. No effects of GPER stimulation were observed when G1 was given 3 or 6 h after training or after Test 1. The present findings provide evidence that GPER is involved in the early stages of memory consolidation in both neutral and emotional memory tasks in male adult rats.

Chronic harmine treatment has a delayed effect on mobility in control and socially defeated rats.

INTRODUCTION: Depression is characterized by behavioral, cognitive and physiological changes, imposing a major burden on the overall wellbeing of the patient. Some evidence indicates that social stress, changes in growth factors (e.g., brain-derived neurotrophic factor (BDNF)), and neuroinflammation are involved in the development and progression of the disease. The monoamine oxidase A inhibitor drug harmine was suggested to have both antidepressant and anti-inflammatory properties and may, therefore, be a potential candidate for treatment of depression. AIM: The goal of this study was to assess the effects of harmine on behavior, brain BDNF levels, and microglia activation in control rats and a rat model of social stress. MATERIAL AND METHODS: Rats were submitted to 5 consecutive days of repeated social defeat (RSD) or control conditions. Animals were treated daily with harmine (15 mg/kg) or vehicle from day 3 until the end of the experiment. To assess the effects of harmine treatment on behavior, the sucrose preference test (SPT) was performed on days 1, 6, and 15, the open field test (OFT) on days 6 and 14, and the novel object recognition test (NOR) on day 16. Brain microgliosis was assessed using [11C]PBR-28 PET on day 17. Animals were terminated on day 17, and BDNF protein concentrations in the hippocampus and frontal cortex were analyzed using ELISA. RESULTS: RSD significantly decreased bodyweight and increased anxiety and anhedonia-related parameters in the OFT and SPT on day 6, but these behavioral effects were not observed anymore on day 14/15. Harmine treatment caused a significant reduction in bodyweight gain in both groups, induced anhedonia in the SPT on day 6, and significantly reduced the mobility and exploratory behavior of the animals in the OFT mainly on day 14. PET imaging and the NOR test did not show any significant effects on microglia activation and memory, respectively. BDNF protein concentrations in the hippocampus and frontal cortex were not significantly affected by either RSD or harmine treatment. DISCUSSION: Harmine was not able to reverse the acute effects of RSD on anxiety and anhedonia and even aggravated the effect of RSD on bodyweight loss. Moreover, harmine treatment caused unexpected side effects on general locomotion, both in RSD and control animals, but did not influence glial activation status and BDNF concentrations in the brain. In this model, RSD-induced stress was not strong enough to induce long-term effects on the behavior, neuroinflammation, or BDNF protein concentration. Thus, the efficacy of harmine treatment on these delayed parameters needs to be further evaluated in more severe models of chronic stress.

Iron Overload Impairs Autophagy: Effects of Rapamycin in Ameliorating Iron-Related Memory Deficits.

Over the years, iron accumulation in specific brain regions has been observed in normal aging and related to the pathogenesis of neurodegenerative disorders. Many neurodegenerative diseases may involve cognitive dysfunction, and we have previously shown that neonatal iron overload induces permanent cognitive deficits in adult rats and exacerbates age-associated memory decline. Autophagy is a catabolic pathway involved in the removal of toxic protein aggregates, which are a hallmark of neurodegenerative events. In the present study, we investigated whether iron accumulation would interfere with autophagy and also sought to determine the effects of rapamycin-induced stimulation of autophagy in attenuating iron-related cognitive deficits. Male Wistar rats received a single daily oral dose of vehicle or iron carbonyl (30 mg/kg) at postnatal days 12-14. In adulthood, they received daily intraperitoneal injections of vehicle or rapamycin (0.25 mg/kg) for 14 days. Results showed that iron given in the neonatal period impaired inhibitory avoidance memory and induced a decrease in proteins critically involved in the autophagy pathway, Beclin-1 and LC3, in the hippocampus. Rapamycin in the adulthood reversed iron-induced memory deficits, decreased the ratio phospho-mTOR/total mTOR, and recovered LC3 II levels in iron-treated rats. Our results suggest that iron accumulation, as observed in neurodegenerative disorders, hinders autophagy, which might play a role in iron-induced neurotoxicity. Rapamycin, by inducing authophagy, was able to ameliorate iron-induced cognitive impairments. These findings support the use of rapamycin as a potential neuroprotective treatment against the cognitive decline associated to neurodegenerative disorders.

Long-term environmental modifications affect BDNF concentrations in rat hippocampus, but not in serum.

The role of mBDNF on the beneficial effects of cognitive stimulation on the brain remains controversial, as well as the potential of peripheral mBDNF as a biomarker of environmental effects on its central status. We investigated the effect of different environmental conditions on recognition memory, proBDNF, mBDNF and synaptophysin levels in the hippocampus, and on mBDNF levels in blood. Male Wistar rats (6 and 17 months-old) were assigned to cognitively enriched (EE), standard (SE) and impoverished (IE) environmental conditions for twelve weeks. Novel object recognition was performed at week 10. When the animals were 9 and 20-months old, hippocampus was collected for mBDNF, proBDNF and synaptophysin analysis; serum was analyzed for mBDNF levels. The cognitively EE improved recognition memory, resulted in a trend to increased hippocampal mBDNF and augmented synaptophysin levels. Accordingly, hippocampal mBDNF, proBDNF and synaptophysin were significantly higher in EE than IE animals. Hippocampal mBDNF was positively correlated to proBDNF, cellular and behavioral plasticity markers. No effect of age was seen on the studied variables. Moreover, no significant effects of EE or IE on serum mBDNF were observed. Serum mBDNF also failed to correlate with hippocampal mBDNF, proBDNF and with the cellular and behavioral plasticity markers. These findings indicate that mBDNF is involved in neuronal and behavioral plasticity mechanisms induced by cognitively enriched environments, and that peripheral mBDNF may not always be a reliable biomarker of the effects of environmental settings on central mBDNF and plasticity, which is of special interest from a translational research perspective.

Social isolation and social support at adulthood affect epigenetic mechanisms, brain-derived neurotrophic factor levels and behavior of chronically stressed rats.

Epigenetic modulation of brain-derived neurotrophic factor (BDNF) provides one possible explanation for the dysfunctions induced by stress, such as psychiatric disorders and cognitive decline. Interestingly, social support can be protective against some of these effects, but the mechanisms of social buffering are poorly understood. Conversely, early isolation exacerbates the responses to stressors, although its effects in adulthood remain unclear. This study investigated the effects of social isolation and social buffering on hippocampal epigenetic mechanisms, BDNF levels and behavioral responses of chronically stressed young adult rats. Male Wistar rats (3 months) were assigned to accompanied (paired) or isolated housing. After one-month half of each group was submitted to a chronic unpredictable stress (CUS) protocol for 18 days. Among accompanied animals, only one was exposed to stress. Behavioral analysis encompassed the Open field, plus maze and inhibitory avoidance tasks. Hippocampal H3K9 and H4K12 acetylation, HDAC5 expression and BDNF levels were evaluated. Isolated housing increased HDAC5 expression, decreased H3K9 and H4K12 acetylation, reduced BDNF levels, and impaired long-term memory. Stress affected weight gain, induced anxiety-like behavior and decreased AcK9H3 levels. Interactions between housing conditions and social stress were seen only for HDAC5 expression, which showed a further increase in the isolated + CUS group but remained constant in accompanied animals. In conclusion, social isolation at adulthood induced epigenetic alterations and exacerbated the effects of chronic stress on HDAC5. Notwithstanding, social support counteracted the adverse effects of stress on HDAC5 expression.

Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation.

Brain-derived neurotrophic factor (BDNF) is one of the most studied neurotrophins in the healthy and diseased brain. As a result, there is a large body of evidence that associates BDNF with neuronal maintenance, neuronal survival, plasticity, and neurotransmitter regulation. Patients with psychiatric and neurodegenerative disorders often have reduced BDNF concentrations in their blood and brain. A current hypothesis suggests that these abnormal BDNF levels might be due to the chronic inflammatory state of the brain in certain disorders, as neuroinflammation is known to affect several BDNF-related signaling pathways. Activation of glia cells can induce an increase in the levels of pro- and antiinflammatory cytokines and reactive oxygen species, which can lead to the modulation of neuronal function and neurotoxicity observed in several brain pathologies. Understanding how neuroinflammation is involved in disorders of the brain, especially in the disease onset and progression, can be crucial for the development of new strategies of treatment. Despite the increasing evidence for the involvement of BDNF and neuroinflammation in brain disorders, there is scarce evidence that addresses the interaction between the neurotrophin and neuroinflammation in psychiatric and neurodegenerative diseases. This review focuses on the effect of acute and chronic inflammation on BDNF levels in the most common psychiatric and neurodegenerative disorders and aims to shed some light on the possible biological mechanisms that may influence this effect. In addition, this review will address the effect of behavior and pharmacological interventions on BDNF levels in these disorders.

Mental health in familial caregivers of Alzheimer's disease patients: are the effects of chronic stress on cognition inevitable?

Familial caregivers of Alzheimer's disease (AD) patients experience an emotional and physical burden which characterizes a chronic stress condition. The resulting hypothalamic-pituitary-adrenal axis dysfunction favors an imbalance of neurotoxic/neuroprotective factors and causes cognitive impairments, increasing the caregivers' risk for cognitive decline and compromising their ability to provide adequate care of the patient. Therefore, the present study aimed to investigate the reversibility of the cognitive impairments of familial caregivers of AD patients during their caregiving-related chronic stress condition. Thirty-three caregivers (61.42 + 2.68 years; 27 women) and thirty-four controls (57.91 ± 2.16 years, 20 women) were evaluated for their cognitive functioning (attention, executive function, processing speed and memory) with a neuropsychological battery (Digit-span, Trail Making, Stroop and the Logical Memory tests). Subjects' cortisol/dehydroepiandrosterone (DHEA) ratios were determined by radioimmunoassay, and their brain-derived neurotrophic factor (BDNF) levels were analyzed by ELISA. An incidental contextual memory task, with or without an associative encoding instruction, was used to investigate if caregivers have a cognitive reserve prone to rehabilitation. The contextual memory impairment of caregivers was associated with prefrontal and hippocampal cognitive dysfunctions, alterations of the cortisol/DHEA ratio and lower BDNF levels. Even so, the contextual memory impairment could be improved by the associative encoding condition. This study suggests that the cognitive impairments of caregivers are not necessarily irreversible, as indicated by the results obtained for contextual memory, which could be improved despite the ongoing chronic stress and associated hormonal and neurotrophin dysfunctions. Lay summary The support of a relative with Alzheimer's Disease submits the familial caregivers to a chronic stress condition that increases their own risk of cognitive decline. This study suggests that, irrespective to their alterations on cortisol/DHEA ratio and BDNF levels, caregivers have a cognitive reserve that could probably be engaged to limit the negative effects of chronic stress on cognition.

Episodic memory boosting in older adults: exploring the association of encoding strategies and physical activity.

Background: Contextual memory is susceptible to the effects of aging and its impairment compromises episodic memories and quality of life in older adults. Objective: Compare the effects of cognitive support on incidental contextual memory free recall and recognition with a naturalistic experimental paradigm and explore the association of encoding strategies and physical activity on memory improvement. Methods: Subjects (≥60 years, n = 52) were assigned to one of two encoding conditions for the contextual memory task: with or without an incidental associative instruction to encourage association of an item to its spatial context. Immediate free recall and recognition tests were run to assess the encoding instruction efficiency. The association of memory performance and physical activity was analyzed using the scores on the International Physical Activity Questionnaire (IPAQ) to subdivide each experimental group into Low IPAQ (below median) and High IPAQ (above median) subgroups. Results: The associative encoding instruction increased contextual memory free recall and recognition, with greater effects on free recall. The most robust associations between physical activity and contextual memory were also seen on free recall, in which higher levels of physical activity corresponded to increased baseline performance (non-associative encoding condition) and greater improvement of memory by the encoding support (associative encoding condition). Conclusion: Cognitive support at encoding can improve contextual memory free recall and recognition, suggesting they are prone to rehabilitation. Moreover, higher physical activity levels were positively associated with encoding strategies on contextual memory improvement, increasing the availability of latent process-based components of the cognitive reserve.

Multimodal physical activity increases brain-derived neurotrophic factor levels and improves cognition in institutionalized older women.

Physical activity has been proposed as a promising intervention to improve cognition and decrease the risk of dementia in older adults. Brain-derived neurotrophic factor (BDNF) appears to mediate, at least partially, these effects of exercise. However, intervention studies of the effects of multimodal exercises on cognition and BDNF levels are scarce and composed by small samples. Thus, the generalization of the conclusions of these studies depends on the reproducibility of the results. In order to contribute to the knowledge on the field, the present study evaluated the effects of a physical activity intervention composed by muscle strengthening and aerobic conditioning on BDNF levels and cognition in older women. Independent and non-demented subjects (≥75 years) were assigned to a 3-month physical activity intervention (n = 22, 60 min exercise sessions three times a week) or to a control condition (n = 10, no exercise). Clinical (anxiety and depression symptoms), neuropsychological (Digit Span, Stroop, Trail Making, and Contextual Memory tests), physical (upper and lower limb strength, aerobic conditioning), and physiological (serum BDNF) parameters were evaluated immediately before, 1 month, and 3 months after starting intervention. Results indicated that controls had stable levels for all measured variables, whereas the intervention group improved on physical fitness, depressive symptoms, cognitive performance, and BDNF levels. Moreover, a linear regression identified an association between aerobic conditioning and BDNF levels. In conclusion, combined muscle strengthening and aerobic conditioning was able to improve cognitive performance and increase BDNF levels. Aerobic conditioning seems to be an important mediator of these outcomes.

Age Effects on Cognitive and Physiological Parameters in Familial Caregivers of Alzheimer's Disease Patients.

OBJECTIVES: Older familial caregivers of Alzheimer's disease patients are subjected to stress-related cognitive and psychophysiological dysfunctions that may affect their quality of life and ability to provide care. Younger caregivers have never been properly evaluated. We hypothesized that they would show qualitatively similar cognitive and psychophysiological alterations to those of older caregivers. METHOD: The cognitive measures of 17 young (31-58 years) and 18 old (63-84 years) caregivers and of 17 young (37-57 years) and 18 old (62-84 years) non-caregiver controls were evaluated together with their salivary cortisol and dehydroepiandrosterone (DHEA) levels, as measured by radioimmunoassays and ELISA assays of brain-derived neurotrophic factor (BDNF) in serum. RESULTS: Although younger caregivers had milder impairments in memory and executive functions than older caregivers, their performances fell to the same or lower levels as those of the healthy older controls. Decreases in DHEA and BDNF levels were correlated with the cognitive dysfunctions observed in the older and younger caregivers, respectively. Cortisol at 10PM increased in both caregiver groups. DISCUSSION: Younger caregivers were prone to cognitive impairments similar to older caregivers, although the degree and the neuropsychological correlates of the cognitive dysfunctions were somewhat different between the two groups. This work has implications for caregiver and care-recipient health and for research on the neurobiology of stress-related cognitive dysfunctions.

Could BDNF be involved in compensatory mechanisms to maintain cognitive performance despite acute sleep deprivation? An exploratory study.

BACKGROUND: Neuroimaging studies suggest that acute sleep deprivation can lead to adaptations, such as compensatory recruitment of cerebral structures, to maintain cognitive performance despite sleep loss. However, the understanding of the neurochemical alterations related to these adaptations remains incomplete. OBJECTIVE: Investigate BDNF levels, cognitive performance and their relations in healthy subjects after acute sleep deprivation. METHODS: Nineteen sleep deprived (22.11±3.21years) and twenty control (25.10±4.42years) subjects completed depression, anxiety and sleep quality questionnaires. Sleep deprived group spent a full night awake performing different playful activities to keep themselves from sleeping. Attention, response inhibition capacity and working memory (prefrontal cortex-dependent) were assessed with Stroop and Digit Span tests. Declarative memory (hippocampus-dependent) was assessed with Logical Memory test. Serum BDNF was measured by sandwich ELISA. Data were analyzed with independent samples T-test, ANOVA, ANCOVA and curve estimation regressions. p<0.05 was deemed statistically significant. RESULTS: The sleep deprived group showed higher BDNF levels and normal performance on attention, response inhibition capacity and working memory. However, declarative memory was impaired. A sigmoidal relation between BDNF and Stroop Test scores was found. CONCLUSIONS: Increased BDNF could be related, at least in part, to the maintenance of normal prefrontal cognitive functions after sleep deprivation. This potential relation should be further investigated.

The role of encoding strategies in contextual memory deficits in patients with bipolar disorder.

Contextual memory is important for the encoding and retrieval of episodic memory, which is often impaired in euthymic patients with bipolar disorder (BD). The objective was to investigate the effect of low and high cognitive support on encoding in an incidental contextual memory task in euthymic patients with BD. Twenty-three patients with a BD type I diagnosis (aged 23-63 years, 17 women and 6 men) and 29 healthy controls completed a recognition memory task for context (location of a recognised object). Participants were assigned to one of two incidental encoding conditions: (1) with a binding cue to encourage the association of the object to its location (judging the degree of appropriateness of an object in relation to its location) or (2) without a binding cue (judging daily use of objects). Patients showed a deficit in incidental contextual memory in the absence of a binding cue at encoding. Under incidental encoding with the binding cue, no differences were observed between the groups for contextual memory. Contextual memory deficits in BD patients were reduced by providing cognitive support at encoding. The role of this strategy should be investigated in larger samples to evaluate its use for cognitive remediation in BD patients.

Characterization of cognitive and motor performance during dual-tasking in healthy older adults and patients with Parkinson's disease.

The primary purpose of this study was to investigate the effect of dual-tasking on cognitive performance and gait parameters in patients with idiopathic Parkinson's disease (PD) without dementia. The impact of cognitive task complexity on cognition and walking was also examined. Eighteen patients with PD (ages 53-88, 10 women; Hoehn and Yahr stage I-II) and 18 older adults (ages 61-84; 10 women) completed two neuropsychological measures of executive function/attention (the Stroop Test and Wisconsin Card Sorting Test). Cognitive performance and gait parameters related to functional mobility of stride were measured under single (cognitive task only) and dual-task (cognitive task during walking) conditions with different levels of difficulty and different types of stimuli. In addition, dual-task cognitive costs were calculated. Although cognitive performance showed no significant difference between controls and PD patients during single or dual-tasking conditions, only the patients had a decrease in cognitive performance during walking. Gait parameters of patients differed significantly from controls at single and dual-task conditions, indicating that patients gave priority to gait while cognitive performance suffered. Dual-task cognitive costs of patients increased with task complexity, reaching significantly higher values then controls in the arithmetic task, which was correlated with scores on executive function/attention (Stroop Color-Word Page). Baseline motor functioning and task executive/attentional load affect the performance of cognitive tasks of PD patients while walking. These findings provide insight into the functional strategies used by PD patients in the initial phases of the disease to manage dual-task interference.

Contextual recognition memory deficits in major depression are suppressed by cognitive support at encoding.

OBJECTIVES: To investigate the effect of cognitive support (an associative orienting instruction at encoding) on contextual memory in depressed patients. METHODS: Seventeen patients (age 20-40 years, 14 women) diagnosed with major depressive disorder (MDD) and 22 healthy controls matched for age, gender and education completed a recognition memory task for item (object) and context (location), with or without an incidental binding cue at encoding. In addition, participants completed the vocabulary subtest of the Wechsler Adult Intelligence Scale (WAIS III) and the Wisconsin Card Sorting Test (WCST). Salivary samples were collected at 7 AM, 4 PM and 10 PM on the day of testing for cortisol and DHEA level measurement. RESULTS: Depressed patients showed a deficit in contextual memory in the absence of a binding cue but did not differ from healthy controls in item memory or when a binding cue was present. Cortisol and cortisol/DHEA ratios were lower in depressed patients compared to healthy controls and correlated with memory deficits. CONCLUSIONS: Contextual memory deficits in MDD patients can be reduced by providing cognitive support at encoding.

Emotional memory deficit and its psychophysiological correlate in family caregivers of patients with dementia.

This study examined the cortisol secretion pattern and declarative memory performance of dementia caregivers. An illustrated story paradigm memory task was used to evaluate the effects of emotional arousal on memory and assess the caregivers' cognitive compensation capacity. Younger (n=19) and elderly (n=24) noncaregivers and elderly caregivers (n=14) took part in 2 experiments to elucidate the effects of aging (experiment 1) and chronic stress (experiment 2) on memory performance and cortisol levels. Each group was divided in 2 subgroups: one that was exposed to an emotionally neutral story, and one that was exposed to a similar, but emotionally arousing story. Participants completed a multiple-choice questionnaire in the test session. Salivary cortisol samples were collected at 8:00 AM, 4:00 PM, and 10:00 PM, 1 day after memory testing. Experiment 1 showed that, despite an age-related memory deficit, arousal manipulation produced a similar effect in both age groups. Experiment 2 showed that, in addition to the characteristic memory decline of aging, elderly caregivers did not benefit from emotionally arousing material as their noncaregiver counterparts did. This impairment correlated with elevated nighttime cortisol levels, indicating a potential worsening impact of caregiver burden on age-related cognitive decline.

Subjective mild depressive symptoms are associated with abnormal diurnal cycle of salivary cortisol in older adults.

BACKGROUND: Alterations in cortisol secretion pattern seem to be involved in the associations between aging, depression, and cognitive decline. OBJECTIVE: The aim of this study was to mainly assess cortisol circadian profile in older adults with subjective depressive symptoms. METHODS: Salivary cortisol samples from healthy young (n = 22) and old adults (n = 22), and from older adults who self-reported depressive symptoms in Geriatric Depression Scale (n = 22) were collected at 7 AM, 4 PM, and 10 PM and were analyzed by radioimmunoassay. RESULTS: Older adults with depressive symptoms presented the characteristic cortisol circadian pattern, but they showed higher cortisol levels at 10 PM than healthy young and elderly controls. CONCLUSIONS: Our data suggest that mild depressive symptoms could be associated with a cortisol secretion pattern previously described as being predictive of cognitive decline.