Lutfu Hanoglu

Abnormalities of cortical neural synchronization mechanisms in patients with dementia due to Alzheimer's and Lewy body diseases: an EEG study

The aim of this retrospective exploratory study was that resting state eyes-closed electroencephalographic (rsEEG) rhythms might reflect brain arousal in patients with dementia due to Alzheimers disease dementia (ADD), Parkinsons disease dementia (PDD), and dementia with Lewy body (DLB). Clinical and rsEEG data of 42 ADD, 42 PDD, 34 DLB, and 40 healthy elderly (Nold) subjects were available in an international archive. Demography, education, and Mini-Mental State Evaluation score were not different between the patient groups. Individual alpha frequency peak (IAF) determined the delta, theta, alpha 1, alpha 2, and alpha 3 frequency bands. Fixed beta 1, beta 2, and gamma bands were also considered. rsEEG cortical sources were estimated by means of the exact low-resolution brain electromagnetic source tomography and were then classified across individuals, on the basis of the receiver operating characteristic curves. Compared to Nold, IAF showed marked slowing in PDD and DLB and moderate slowing in ADD. Furthermore, all patient groups showed lower posterior alpha 2 source activities. This effect was dramatic in ADD, marked in DLB, and moderate in PDD. These groups also showed higher occipital delta source activities, but this effect was dramatic in PDD, marked in DLB, and moderate in ADD. The posterior delta and alpha sources allowed good classification accuracy (approximately 0.85-0.90) between the Nold subjects and patients, and between ADD and PDD patients. In quiet wakefulness, delta and alpha sources unveiled different spatial and frequency features of the cortical neural synchronization underpinning brain arousal in ADD, PDD, and DLB patients. Future prospective cross-validation studies should test these rsEEG markers for clinical applications and drug discovery.

RIFAMPICIN: An antibiotic with brain protective function

Besides its well known antibiotic activity rifampicin exerts multiple brain protective functions in acute cerebral ischemia and chronic neurodegeneration. The present mini-review gives an update of the unique activity of rifampicin in different diseases including Parkinsons disease, meningitis, stroke, Alzheimers disease and optic nerve injury.

Does sleep disturbance affect the amyloid clearance mechanisms in alzheimer's disease?

Sleep is an important factor that plays a key role in Alzheimers disease pathogenesis. However, it is still unclear whether poor‐quality sleep may overlap with sleep disturbances in the underlying dysfunctional mechanisms of amyloid beta (Aβ) clearance metabolism. Here, we aimed to evaluate the current evidence on the role of sleep deprivation in Aβ clearance metabolism. To that end, we discuss possible mechanisms underlying the bidirectional interaction between the sleep deprivation and Aβ clearance pathways.

Abnormalities of Cortical Neural Synchronization Mechanisms in Subjects with Mild Cognitive Impairment due to Alzheimer's and Parkinson's Diseases: An EEG Study

The aim of this retrospective and exploratory study was that the cortical sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms might reveal different abnormalities in cortical neural synchronization in groups of patients with mild cognitive impairment due to Alzheimers disease (ADMCI) and Parkinsons disease (PDMCI) as compared to healthy subjects. Clinical and rsEEG data of 75 ADMCI, 75 PDMCI, and 75 cognitively normal elderly (Nold) subjects were available in an international archive. Age, gender, and education were carefully matched in the three groups. The Mini-Mental State Evaluation (MMSE) was matched between the ADMCI and PDMCI groups. Individual alpha frequency peak (IAF) was used to determine the delta, theta, alpha1, alpha2, and alpha3 frequency band ranges. Fixed beta1, beta2, and gamma bands were also considered. eLORETA estimated the rsEEG cortical sources. Receiver operating characteristic curve (ROC) classified these sources across individuals. Results showed that compared to the Nold group, the posterior alpha2 and alpha3 source activities were more abnormal in the ADMCI than the PDMCI group, while the parietal delta source activities were more abnormal in the PDMCI than the ADMCI group. The parietal delta and alpha sources correlated with MMSE score and correctly classified the Nold and diseased individuals (area under the ROC = 0.77-0.79). In conclusion, the PDMCI and ADMCI patients showed different features of cortical neural synchronization at delta and alpha frequencies underpinning brain arousal and vigilance in the quiet wakefulness. Future prospective cross-validation studies will have to test these rsEEG markers for clinical applications and drug discovery.

The Brain Protective Effect of rTMS (Repetitive Transcranial Magnetic Stimulation) in Depression: A Mini-Review in Animal Studies.

There are rapidly replicating human data suggesting the therapeutic and neurorestorative role of repetitive transcranial magnetic stimulation (rTMS) in clinical depression. However there are only limited experimental studies in the literature and the neurobiological mechanisms of the technique are still unclear. Studies have suggested that modulating of either excitatory or inhibitory neural circuitry may be responsible for the mechanism of action of rTMS while it is still unclear whether rTMS exerts a neuroprotective effect. In the light of these findings, we aimed to review the neuroprotective effect of rTMS in animal models of depression. We have shown that rTMS may exert significant neuroprotective effect through acting on the oxidative injury, stress hormones, dopamine and serotonin levels, Brain Derived Neurotrophic Factor expression, neuroinflamation and hippocampal cell proliferation.

The neuroprotective role of vesicular monoamine transporter 2 in neurodegenerative diseases.

Neuropharmacological relation of religious belief supports the role of dopaminergic activation as the leading neurochemical feature. However, vesicular monoamine transporter-2 (VMAT-2) has been shown to be responsible for removing of neurotransmitters such as dopamine that may secondarily lead to a neuroprotective activity by different neurodegeneration models. Moreover, there are interesting data showing that VMAT-2 may play an important role during religious belief and experience. In the light of these findings, we aimed to review the preclinical and clinical neuroprotective data of Vesicular monoamine transporter (VMAT-2) in different neurodegenerative and neuropsychiatric diseases. In respect of rapidly increasing evidences about the neurobiological and neuroimaging correlates of religious belief, we hypothesized that there is a link between belief and neuroprotection.

Therapeutic Effects Of Rivastigmine And Alfa-Lipoic Acid Combination In The Charles Bonnet Syndrome: Electroencephalography Correlates.

BACKGROUND Charles Bonnet Syndrome (CBS) is a rare clinical condition which is characterized by complex hallucinations in visually impaired patients. The pathophysiology of this disorder remains largely unknown, and there is still no proven treatment for this disease. In our study, we aimed to investigate the neural activity through Electroencephalography (EEG) power and evaluate the effect of rivastigmine in combination with alpha-lipoic acid on hallucination in two CBS patients with diabetic retinopathy. METHODS EEG data was recorded with standard routine EEG protocols for both patients in our electrophysiological research laboratory (REMER Clinical Electrophysiology and Neuromodulation Research and Application Laboratory) with Brain Vision Recorder (Brainproduct, Munich, Germany). All spectral analyses were processed by BrainVision Analyzer 2 (Brainproduct, Munich, Germany, 2.0.4 Version) in 128 Hz sample rates and the EEG recording and analysis was performed before the administration of rivastigmine (4.5 mg/daily and five patch daily for the first and second patients, respectively) in combination with alpha-lipoic acid (600 mg/daily) for both patients while they were not hallucinated during the time period recordings. Based on our measurement protocol, we have compared the patients in the study group with the three control subjects who were found to be normal except of visual disturbances secondary to significant diabetic retinopathy. RESULTS Highest theta power values were found in right occipital and left temporo-parietal regions for first and second CBS patients, respectively. Additionally, power spectra were lower in two cases as compared to their control groups in the alpha band for all electrodes. We have also shown that acid rivastigmine in combination with alpha-lipoic exerted significant anti-hallucinatory efficiency. CONCLUSION Our present findings could support the hypothesis that increased activation of specific areas in the source monitoring system plays an important role in the pathogenesis of CBS. In addition, rivastigmine in combination with alpha-lipoic acid could be a new valuable option for CBS patients.

Therapeutic role of rifampicin in Alzheimer's disease: Rifampicin in Alzheimer's disease

Rifampicin exerts significant brain protective functions in multiple experimental models. Here we summarize the underlying mechanisms of the neuroprotective and pro‐cognitive effects of rifampicin that are mediated by its anti‐inflammatory, anti‐tau, anti‐amyloid, and cholinergic effects. Beyond suggesting that rifampicin shows strong brain protective effects in preclinical models of Alzheimers disease, we also provide substantial clinical evidence for the neuroprotective and pro‐cognitive effects of rifampicin. Future neuroimaging studies combined with clinical assessment scores are the following steps to be taken in this field of research.

Cognitive Impairment in Parkinson’s Disease Is Reflected with Gradual Decrease of EEG Delta Responses during Auditory Discrimination

Parkinson’s disease (PD) is a neurodegenerative disease that is characterized by loss of dopaminergic neurons in the substantia nigra. Mild Cognitive impairment (MCI) and dementia may come along with the disease. New indicators are necessary for detecting patients that are likely to develop dementia. Electroencephalogram (EEG) Delta responses are one of the essential electrophysiological indicators that could show the cognitive decline. Many research in literature showed an increase of delta responses with the increased cognitive load. Furthermore, delta responses were decreased in MCI and Alzheimer disease in comparison to healthy controls during cognitive paradigms. There was no previous study that analyzed the delta responses in PD patients with cognitive deficits. The present study aims to fulfill this important gap. 32 patients with Parkinson’s disease (12 of them were without any cognitive deficits, 10 of them were PD with MCI, and 10 of them were PD with dementia) and 16 healthy subjects were included in the study. Auditory simple stimuli and Auditory Oddball Paradigms were applied. The maximum amplitudes of each subject’s delta response (0.5–3.5 Hz) in 0–600 ms were measured for each electrode and for each stimulation. There was a significant stimulation × group effect [F(df = 6,88) = 3,21; p < 0.015; ηp2 = 0.180], which showed that the difference between groups was specific to the stimulation. Patients with Parkinson’s disease (including PD without cognitive deficit, PD with MCI, and PD with dementia) had reduced delta responses than healthy controls upon presentation of target stimulation (p < 0.05, for all comparisons). On the other hand, this was not the case for non-target and simple auditory stimulation. Furthermore, delta responses gradually decrease according to the cognitive impairment in patients with PD. Conclusion: The results of the present study showed that cognitive decline in PD could be represented with decreased event related delta responses during cognitive stimulations. Furthermore, the present study once more strengthens the hypothesis that decrease of delta oscillatory responses could be the candidate of a general electrophysiological indicator for cognitive impairment.

Functional cortical source connectivity of resting state electroencephalographic alpha rhythms shows similar abnormalities in patients with mild cognitive impairment due to Alzheimer's and Parkinson's diseases

OBJECTIVE This study tested the hypothesis that markers of functional cortical source connectivity of resting state eyes-closed electroencephalographic (rsEEG) rhythms may be abnormal in subjects with mild cognitive impairment due to Alzheimers (ADMCI) and Parkinsons (PDMCI) diseases compared to healthy elderly subjects (Nold). METHODS rsEEG data had been collected in ADMCI, PDMCI, and Nold subjects (N = 75 for any group). eLORETA freeware estimated functional lagged linear connectivity (LLC) from rsEEG cortical sources. Area under receiver operating characteristic (AUROC) curve indexed the accuracy in the classification of Nold and MCI individuals. RESULTS Posterior interhemispheric and widespread intrahemispheric alpha LLC solutions were abnormally lower in both MCI groups compared to the Nold group. At the individual level, AUROC curves of LLC solutions in posterior alpha sources exhibited moderate accuracies (0.70-0.72) in the discrimination of Nold vs. ADMCI-PDMCI individuals. No differences in the LLC solutions were found between the two MCI groups. CONCLUSIONS These findings unveil similar abnormalities in functional cortical connectivity estimated in widespread alpha sources in ADMCI and PDMCI. This was true at both group and individual levels. SIGNIFICANCE The similar abnormality of alpha source connectivity in ADMCI and PDMCI subjects might reflect common cholinergic impairment.