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.

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.