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.

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.

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ObjectivesOlder 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.MethodThe 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.ResultsAlthough 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.DiscussionYounger 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.

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.

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. Thirtythree caregivers (61.42 þ 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.

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The interaction of dopaminergic and cholinergic neurotransmission in, e.g., Parkinson’s disease has been well established. Here, D2 receptor antagonists were used to assess changes in [18F]-FEOBV binding to the vesicular acetylcholine transporter (VAChT) in rodents using positron emission tomography (PET). After pretreatment with either 10 mg/kg haloperidol, 1 mg/kg raclopride, or vehicle, 90 min dynamic PET scans were performed with arterial blood sampling. The net influx rate (K i) was obtained from Patlak graphical analysis, using a metabolite-corrected plasma input function and dynamic PET data. [18F]-FEOBV concentration in whole-blood or plasma and the metabolite-corrected plasma input function were not significantly changed by the pretreatments (adjusted p > 0.07, Cohen’s d 0.28–1.89) while the area-under-the-curve (AUC) of the parent fraction of [18F]-FEOBV was significantly higher after haloperidol treatment (adjusted p = 0.022, Cohen’s d = 2.51) than in controls. Compared to controls, the AUC of [18F]-FEOBV, normalized for injected dose and body weight, was nonsignificantly increased in the striatum after haloperidol (adjusted p = 0.4, Cohen’s d = 1.77) and raclopride (adjusted p = 0.052, Cohen’s d = 1.49) treatment, respectively. No changes in the AUC of [18F]-FEOBV were found in the cerebellum (Cohen’s d 0.63–0.74). Raclopride treatment nonsignificantly increased K i in the striatum 1.3-fold compared to control rats (adjusted p = 0.1, Cohen’s d = 1.1) while it reduced K i in the cerebellum by 28% (adjusted p = 0.0004, Cohen’s d = 2.2) compared to control rats. Pretreatment with haloperidol led to a nonsignificant reduction in K i in the striatum (10%, adjusted p = 1, Cohen’s d = 0.44) and a 40–50% lower K i than controls in all other brain regions (adjusted p < 0.0005, Cohen’s d = 3.3–4.7). The changes in K i induced by the selective D2 receptor antagonist raclopride can in part be quantified using [18F]-FEOBV PET imaging. Haloperidol, a nonselective D2/σ receptor antagonist, either paradoxically decreased cholinergic activity or blocked off-target [18F]-FEOBV binding to σ receptors. Hence, further studies evaluating the binding of [18F]-FEOBV to σ receptors using selective σ receptor ligands are necessary.