Search

Background and Objective: Cognitive impairment is among the most burdensome non-motor symptoms in Parkinson's disease (PD) and has been associated with hippocampal atrophy. Exercise has been reported to enhance neuroplasticity in the hippocampus in correlation with an improvement of cognitive function. We present data from the Training-PD study, which was designed to evaluate effects of an "" training protocol on neuronal plasticity in PD., Methods: We initiated a 6-week exergaming training program, combining visually stimulating computer games with physical exercise in 17 PD patients and 18 matched healthy controls. Volumetric segmentation of hippocampal subfields on T1- and T2-weighted magnetic resonance imaging and brain-derived neurotrophic factor (BDNF) serum levels were analyzed before and after the training protocol., Results: The PD group showed a group-dependent significant volume increase of the left hippocampal subfields CA1, CA4/dentate gyrus (DG) and subiculum after the 6-week training protocol. The effect was most pronounced in the left DG of PD patients, who showed a significantly smaller percentage volume compared to healthy controls at baseline, but not at follow-up. Both groups had a significant increase in serum BDNF levels after training., Conclusions: The results of the present study indicate that exergaming might be a suitable approach to induce hippocampal volume changes in PD patients. Further and larger studies are needed to verify our findings., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

The neurotrophin brain-derived neurotrophic factor (BDNF) plays a critical role in neuronal survival, synaptic plasticity, and memory. Several recent studies have demonstrated altered BDNF serum levels in Alzheimer's disease (AD) patients. However, the association of BDNF serum levels with the rate of cognitive decline in AD patients is still unclear. We demonstrate that BDNF serum levels are significantly decreased in AD patients with fast cognitive decline [decrease of Mini-Mental State Examination (MMSE) score >4/yr; n=12] compared to AD patients with slow cognitive decline (decrease of MMSE score ≤4/yr, n=28) and show a significant correlation with the rate of cognitive decline during 1 yr follow-up. These results suggest that higher BDNF serum levels are associated with a slower rate of cognitive decline in AD patients. Further longitudinal studies are necessary to elucidate the kinetics and the potential role of serum BDNF as a surrogate marker of disease progression in AD patients.

Major depression (MD) has been associated with decreased brain-derived neurotrophic factor (BDNF) serum levels, while antidepressant drugs were found to increase these decreased BDNF levels. We investigated if this is also caused by a single exercise session in elderly women with remitted MD. In our study 35 elderly women with a (partially) remitted depressive episode of unipolar depression according to DSM-IV criteria within the last year and 20 age-matched healthy female controls were included. Depression severity was assessed by HAMD. Serum levels of BDNF were measured by ELISA. Blood samples were taken during the rest period before beginning the exercise including spiroergometry, at the end of the exercise and after a 30-min recovery period. At baseline MD patients showed significantly decreased BDNF serum levels compared to healthy female controls. After a single 30-min exercise period, we found a significant increase of BDNF serum levels in MD patients towards values comparable with the baseline levels of the healthy controls, followed by a significant decrease after 30 min rest, while the healthy controls showed only a mild but non-significant increase. In conclusion, a single exercise session leads to a significant up-regulation and transient normalization of BDNF serum levels in elderly women with remitted MD. This mechanism may contribute to the beneficial therapeutic and relapse-preventing effects of physical activity on MD.

Preclinical and clinical studies gave evidence that lithium could be useful in the treatment of Alzheimer's disease (AD). In experimental investigations, lithium induces brain-derived neurotrophic factor (BDNF). Recent studies have found a decrease of BDNF in the serum and brains of AD patients with potentially consecutive lack of neurotrophic support. We assessed the influence of a lithium treatment on BDNF serum concentration in a subset of a greater sample recruited for a randomized, single-blinded, placebo-controlled, parallel-group multicenter 10-week study, investigating the efficacy of lithium treatment in AD patients. In AD patients treated with lithium, a significant increase of BDNF serum levels, and additionally a significant decrease of ADAS-Cog sum scores in comparison to placebo-treated patients, were found. Diminution of cognitive impairment was inversely correlated with lithium serum concentration. Upregulation of BDNF might be part of a neuroprotective effect of lithium in AD patients. The results of the present investigation encourage performing studies with longer treatment phases to observe potential positive long-term effects of lithium in AD patients.

Alzheimer's disease (AD) can be treated with inhibitors of the enzyme acetylcholinesterase (AChE). Recent pre-clinical and clinical studies gave evidence that AChE-inhibitors have neuroprotective effects and thereby a disease-modifying potential. The mechanism of this action is still discussed. In an animal model oral administration of an AChE-inhibitor lead to an increase of brain derived neurotrophic factor (BDNF) in hippocampus and cortex. Recent studies have found a decrease of BDNF in the serum and brain of AD patients with potentially consecutive lack of neurotrophic support and contribution to progressive neurodegeneration. BDNF serum concentrations were assessed by ELISA in 19 AD patients and 20 age-matched healthy controls at baseline and in the AD patients after 15 months of treatment with donepezil 10 mg per day (one patient received just 5 mg). Before treatment with donepezil we found in AD significantly decreased BDNF serum concentrations (19.2 +/- 3.7 ng/ml) as compared to healthy controls (23.2 +/- 6.0 ng/ml, P = 0.015). After 15 months of treatment the BDNF serum concentration increased significantly in the AD patients (23.6 +/- 7.0 ng/ml, P = 0.001) showing no more difference to the healthy controls (P = 0.882). The results of the present study confirm data of prior investigations that a down-regulation of BDNF in serum and brain of AD patients seems to begin with the first clinical symptoms and to be persistent. A treatment with the AChE-inhibitor donepezil is accompanied with an increase of BDNF serum concentration in AD patients reaching the level of healthy controls. Thus, up-regulation of BDNF might be part of a neuroprotective effect of AChE-inhibitors. The molecular mechanism of this potentially disease-modifying mechanism of action of donepezil should be clarified.

Fibromyalgia (FM) is still often viewed as a psychosomatic disorder. However, the increased pain sensitivity to stimuli in FM patients is not an "imagined" histrionic phenomena. Pain, which is consistently felt in the musculature, is related to specific abnormalities in the CNS pain matrix. Brain-derived neurotrophic factor (BDNF) is an endogenous protein involved in neuronal survival and synaptic plasticity of the central and peripheral nervous system (CNS and PNS). Several lines of evidence converged to indicate that BDNF also participates in structural and functional plasticity of nociceptive pathways in the CNS and within the dorsal root ganglia and spinal cord. In the latter, release of BDNF appears to modulate or even mediate nociceptive sensory inputs and pain hypersensitivity. We were interested, if BDNF serum concentration may be altered in FM. The present pilot study assessed to our knowledge for the first time BDNF serum concentrations in 41 FM patients in comparison to 45 age-matched healthy controls. Mean serum levels of BDNF in FM patients (19.6 ng/ml; SD 3.1) were significantly increased as compared to healthy controls (16.8 ng/ml; SD 2.7; p<0.0001). In addition, BDNF serum concentrations in FM patients were independent from age, gender, illness duration, preexisting recurrent major depression and antidepressive medication in low doses. In conclusion, the results from our study indicate that BDNF may be involved in the pathophysiology of pain in FM. Nevertheless, how BDNF increases susceptibility to pain is still not known.

Alzheimer's disease (AD) and normal pressure hydrocephalus (NPH) are common forms of dementia in the elderly. Recent findings have suggested an involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of AD. BDNF is an endogenous protein involved in the maintenance of neuronal function, synaptic plasticity and structural integrity in the adult brain. BDNF serum and cerebrospinal fluid (CSF) concentrations were assessed by a sensitive ELISA in 27 AD patients in comparison to 9 NPH patients and 28 age-matched healthy controls (10 CSF samples). We found a significant decrease of BDNF serum concentration in AD (18.6ng/ml) and NPH patients (18.1ng/ml) as compared to healthy controls (21.3ng/ml; p=0.041/p=0.017). BDNF serum concentrations did not correlate with CSF levels, age or MMSE scores both in AD and NPH patients. In unconcentrated CSF samples, BDNF could be detected in AD patients in 8/27 cases (29.6%; mean of 4.6pg/ml), in NPH patients in 1/9 cases (11.1%; mean of 6.4pg/ml) and in the control subjects in 5/10 cases (50%; mean of 1.6pg/ml) with no significant differences as regards mean concentration and frequency of detectable BDNF in CSF. The decrease of BDNF serum levels in AD and NPH may reflect a lack of trophic support and thus contribute to progressive degeneration in both diseases. In contrast to serum, CSF seems to be no useful source to determine BDNF in AD or NPH because of too low concentrations. Further examinations have to follow to elucidate the potential sources and the meaning of reduced BDNF levels in the blood in AD and NPH.