Abnormalities of Cortical Neural Synchronization Mechanisms in Patients With Dementia Due to Parkinson’s and Sintomatic Huntington’s Diseases

\ua9 2024 The Alzheimer\u27s Association. Alzheimer\u27s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer\u27s Association. BACKGROUND: Parkinson\u27s disease and Huntington\u27s disease are both neurodegenerative conditions involving the basal ganglia area of the brain. Both conditions can cause symptoms that affect movement. Cognitive decline or dementia can also occur in both. Resting state EEG (rsEEG) rhythms reflect neurophysiological mechanisms and operational functions related to the fluctuation of brain arousal and quiet vigilance in humans. The hypothesis was that rsEEG sources may be more abnormal in Huntington\u27s disease patients in symptomatic stage (S-HD) than patients with dementia due to Parkinson\u27s disease. METHOD: Clinical and rsEEG datasets in 16 PDD, 18 S-HD, and 25 matched cognitively unimpaired (Nold) participants - matched as demography, education, and gender - were taken from an international archive. The eLORETA freeware was used to estimate cortical rsEEG sources at delta, theta, alpha1, alpha2, alpha3, beta1, beta2, and gamma frequency bands. RESULT: Results showed lower amplitude of the posterior alpha activities and higher amplitude of widespread low frequencies bands (i.e., delta and theta) in the PDD and S-HD groups than in the Healthy group. As compared to the PDD group, the S-HD showed greater reductions in the rsEEG alpha 2 rhythms in the frontal and temporal regions (see Figure 1). CONCLUSION: These results suggest that cortical sources of rsEEG rhythms might reflect different abnormalities of the core neurophysiological mechanisms underlying brain arousal in quiet wakefulness and low vigilance in PDD, and S-HD patients. The mentioned rsEEG markers might be clinically useful in the disease staging, monitoring over time, and drug discovery

Abnormal electroencephalographic rhythms from quiet wakefulness to light sleep in Alzheimer\u27s disease patients with mild cognitive impairment

\ua9 2025 International Federation of Clinical NeurophysiologyObjectives: Alzheimer\u27s disease patients with mild cognitive impairment (ADMCI) show abnormal resting-state eyes-closed electroencephalographic (rsEEG) alpha rhythms (8–12 Hz) and may suffer from daytime sleepiness. Our exploratory study tested the hypothesis that they may present characteristic EEG rhythms from quiet wakefulness to light sleep during diurnal recordings. Methods: Datasets of 34 ADMCI and 22 matched healthy elderly (Nold) subjects were obtained from international archives. EEG recordings lasted approximately 30 min. Transitions of EEG activity from quiet wakefulness (alpha-dominant) to light sleep (theta-dominant ripples) were scored according to Hori\u27s vigilance stages. Cortical source activities were computed using the eLORETA software. Results: ADMCI (t-ADMCI, N = 18) over Nold (t-Nold, N = 11) participants were characterized by greater frontal EEG delta source activities and a lesser reduction (reactivity) in the posterior alpha source activities from quiet wakefulness to ripples. Notably, EEG delta source activities during quiet wakefulness were also greater in the ADMCI group transitioning to light sleep as compared to patients without said vigilance reduction. Conclusions: These results suggest that ADMCI patients with a greater susceptibility to daytime sleepiness may show characteristic EEG delta and alpha rhythms in the transition from quiet vigilance to daytime sleep. Significance: Our study showed a derangement of EEG rhythms during the transition to sleep possibly specific to AD

Alpha rhythm and Alzheimer\u27s disease: Has Hans Berger\u27s dream come true?

\ua9 2025 The Author(s)In this “centenary” paper, an expert panel revisited Hans Berger\u27s groundbreaking discovery of human restingstate electroencephalographic (rsEEG) alpha rhythms (8–12 Hz) in 1924, his foresight of substantial clinical applications in patients with “senile dementia,” and new developments in the field, focusing on Alzheimer\u27s disease (AD), the most prevalent cause of dementia in pathological aging. Clinical guidelines issued in 2024 by the US National Institute on Aging-Alzheimer\u27s Association (NIA-AA) and the European Neuroscience Societies did not endorse routine use of rsEEG biomarkers in the clinical workup of older adults with cognitive impairment. Nevertheless, the expert panel highlighted decades of research from independent workgroups and different techniques showing consistent evidence that abnormalities in rsEEG delta, theta, and alpha rhythms (< 30 Hz) observed in AD patients correlate with wellestablished AD biomarkers of neuropathology, neurodegeneration, and cognitive decline. We posit that these abnormalities may reflect alterations in oscillatory synchronization within subcortical and cortical circuits, inducing cortical inhibitory-excitatory imbalance (in some cases leading to epileptiform activity) and vigilance dysfunctions (e.g., mental fatigue and drowsiness), which may impact AD patients’ quality of life. Berger\u27s vision of using EEG to understand and manage dementia in pathological aging is still actual

The GTPase Rac Regulates the Proliferation and Invasion of Fibroblast-Like Synoviocytes from Rheumatoid Arthritis Patients

Fibroblast-like synoviocytes (FLS) isolated from joints of rheumatoid arthritis (RA) patients display proliferative and invasive properties reminiscent of those of malignant tumor cells. Rac small GTPases play an important role in tumor cell proliferation and invasion. We therefore investigated the potential role of Rac proteins in the proliferative and invasive behavior of RA-FLS. We showed that inhibiting Rac activity with the Rac-specific small molecule inhibitor NSC23766 causes a strong inhibition of RA-FLS proliferation, without affecting cell survival. Rac inhibition also results in a strong reduction in RA-FLS invasion through reconstituted extracellular matrix and a less marked inhibition of two-dimensional migration as measured by monolayer wound healing. We also showed that small interfering RNA-mediated depletion of Rac1 inhibits RA-FLS proliferation and invasion to a similar extent as NSC23766. These results demonstrate for the first time that Rac proteins play an important role in the aggressive behavior of FLS isolated from RA patients. In addition, we observed that inhibiting Rac proteins prevents JNK activation and that the JNK inhibitor SP600125 strongly inhibits RA-FLS invasion, suggesting that Rac-mediated JNK activation contributes to the role of Rac proteins in the invasive behavior of RA-FLS. In conclusion, Rac-controlled signaling pathways may present a new source of drug targets for therapeutic intervention in RA