Gamma frequency sensory stimulation in mild probable Alzheimer’s dementia patients: Results of feasibility and pilot studies

PLoS ONE, Journal Year: 2022, Volume and Issue: 17(12), P. e0278412 - e0278412

Published: Dec. 1, 2022

Non-invasive Gamma ENtrainment Using Sensory stimulation (GENUS) at 40Hz reduces Alzheimer's disease (AD) pathology such as amyloid and tau levels, prevents cerebral atrophy, improves behavioral testing performance in mouse models of AD. Here, we report data from (1) a Phase 1 feasibility study (NCT04042922, ClinicalTrials.gov) cognitively normal volunteers (n = 25), patients with mild AD dementia 16), epilepsy who underwent intracranial electrode monitoring 2) to assess safety single brief GENUS session induce entrainment (2) single-blinded, randomized, placebo-controlled 2A pilot (NCT04055376) probable 15) safety, compliance, entrainment, exploratory clinical outcomes after chronic daily sensory for 3 months. Our showed that was safe effectively induced both cortical regions other subcortical structures the hippocampus, amygdala, insula, gyrus rectus. demonstrated light sound well-tolerated compliance equally high control active groups, participants inaccurate guessing their group assignments prior unblinding. Electroencephalography recordings show our device safely dementia. After months stimulation, receiving (i) lesser ventricular dilation hippocampal (ii) increased functional connectivity default mode network well medial visual network, (iii) better on face-name association delayed recall test, (iv) improved measures activity rhythmicity compared group. These results support further evaluation pivotal trial evaluate its potential novel disease-modifying therapeutic

Language: Английский

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Multisensory gamma stimulation promotes glymphatic clearance of amyloid

Nature, Journal Year: 2024, Volume and Issue: 627(8002), P. 149 - 156

Published: Feb. 28, 2024

Abstract The glymphatic movement of fluid through the brain removes metabolic waste 1–4 . Noninvasive 40 Hz stimulation promotes neural activity in multiple regions and attenuates pathology mouse models Alzheimer’s disease 5–8 Here we show that multisensory gamma influx cerebrospinal efflux interstitial cortex 5XFAD model disease. Influx was associated with increased aquaporin-4 polarization along astrocytic endfeet dilated meningeal lymphatic vessels. Inhibiting clearance abolished removal amyloid by stimulation. Using chemogenetic manipulation a genetically encoded sensor for neuropeptide signalling, found vasoactive intestinal peptide interneurons facilitate regulating arterial pulsatility. Our findings establish novel mechanisms recruit system to remove amyloid.

Language: Английский

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Alzheimer’s disease as a synaptopathy: Evidence for dysfunction of synapses during disease progression

Frontiers in Synaptic Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: March 9, 2023

The synapse has consistently been considered a vulnerable and critical target within Alzheimer’s disease, loss is, to date, one of the main biological correlates cognitive decline disease. This occurs prior neuronal with ample evidence that synaptic dysfunction precedes this, in support idea failure is crucial stage disease pathogenesis. two pathological hallmarks abnormal aggregates amyloid or tau proteins, have had demonstrable effects on physiology animal cellular models There also growing these proteins may synergistic effect neurophysiological dysfunction. Here, we review some findings alterations what know from models. First, briefly summarize human suggest synapses are altered, including how this relates network activity. Subsequently, considered, highlighting mouse pathology role play dysfunction, either isolation examining pathologies interact specifically focuses function observed models, typically measured using electrophysiology calcium imaging. Following loss, it would be impossible imagine not alter oscillatory activity brain. Therefore, discusses underpin aberrant patterns seen patients. Finally, an overview key directions considerations field covered. includes current therapeutics targeted at but methods modulate rescue patterns. Other important future avenues note include non-neuronal cell types such as astrocytes microglia, mechanisms independent will certainly continue for foreseeable future.

Language: Английский

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40 Hz light flickering promotes sleep through cortical adenosine signaling

Cell Research, Journal Year: 2024, Volume and Issue: 34(3), P. 214 - 231

Published: Feb. 8, 2024

Abstract Flickering light stimulation has emerged as a promising non-invasive neuromodulation strategy to alleviate neuropsychiatric disorders. However, the lack of neurochemical underpinning hampered its therapeutic development. Here, we demonstrate that flickering triggered an immediate and sustained increase (up 3 h after flickering) in extracellular adenosine levels primary visual cortex (V1) other brain regions, function frequency intensity, with maximal effects observed at 40 Hz 4000 lux. We uncovered cortical (glutamatergic GABAergic) neurons, rather than astrocytes, cellular source, intracellular generation from AMPK-associated energy metabolism pathways (but not SAM-transmethylation or salvage purine pathways), efflux mediated by equilibrative nucleoside transporter-2 (ENT2) molecular pathway responsible for generation. Importantly, 20 80 Hz) 30 min enhanced non-rapid eye movement (non-REM) REM sleep 2–3 mice. This somnogenic effect was abolished ablation V1 superior colliculus) neurons genetic deletion gene encoding ENT2 ENT1), but recaptured chemogenetic inhibition focal infusion into dose-dependent manner. Lastly, also promoted children insomnia decreasing onset latency, increasing total time, reducing waking onset. Collectively, our findings establish ENT2-mediated signaling basis flickering-induced unravel novel treatment insomnia, condition affects 20% world population.

Language: Английский

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Cognitive and Neuropathophysiological Outcomes of Gamma-tACS in Dementia: A Systematic Review

Neuropsychology Review, Journal Year: 2023, Volume and Issue: 34(1), P. 338 - 361

Published: March 6, 2023

Abstract Despite the numerous pharmacological interventions targeting dementia, no disease-modifying therapy is available, and prognosis remains unfavorable. A promising perspective involves tackling high-frequency gamma-band (> 30 Hz) oscillations involved in hippocampal-mediated memory processes, which are impaired from early stages of typical Alzheimer’s Disease (AD). Particularly, positive effects entrainment on mouse models AD have prompted researchers to translate such findings into humans using transcranial alternating current stimulation (tACS), a methodology that allows endogenous cortical frequency-specific manner. This systematic review examines state-of-the-art use gamma-tACS Mild Cognitive Impairment (MCI) dementia patients shed light its feasibility, therapeutic impact, clinical effectiveness. search two databases yielded 499 records resulting 10 included studies total 273 patients. The results were arranged single-session multi-session protocols. Most demonstrated cognitive improvement following gamma-tACS, some showed neuropathological markers, suggesting feasibility these anyhow far strong evidence available for models. Nonetheless, small number their wide variability terms aims, parameters, measures, make it difficult draw firm conclusions. We discuss methodological limitations studies, proposing possible solutions future avenues improve research dementia.

Language: Английский

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Non-pharmacological interventions for sleep disturbances in people with dementia

Cochrane library, Journal Year: 2023, Volume and Issue: 2023(1)

Published: Jan. 3, 2023

Language: Английский

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Gamma entrainment using audiovisual stimuli alleviates chemobrain pathology and cognitive impairment induced by chemotherapy in mice

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(737)

Published: March 6, 2024

Patients with cancer undergoing chemotherapy frequently experience a neurological condition known as chemotherapy-related cognitive impairment, or “chemobrain,” which can persist for the remainder of their lives. Despite growing prevalence chemobrain, both its underlying mechanisms and treatment strategies remain poorly understood. Recent findings suggest that chemobrain shares several characteristics neurodegenerative diseases, including chronic neuroinflammation, DNA damage, synaptic loss. We investigated whether noninvasive sensory stimulation we term gamma entrainment using stimuli (GENUS), has been shown to alleviate aberrant immune pathologies in mouse models neurodegeneration, could also mitigate phenotypes mice administered chemotherapeutic drug. When concurrently agent cisplatin, GENUS alleviated cisplatin-induced brain pathology, promoted oligodendrocyte survival, improved function model chemobrain. These effects persisted up 105 days after treatment, suggesting potential long-lasting benefits. However, when 90 chemotherapy, only provided limited benefits, indicating it was most effective used prevent progression pathology. Furthermore, demonstrated were not but extended methotrexate-induced Collectively, these may represent versatile approach treating induced by different agents.

Language: Английский

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Safety, tolerability, and efficacy estimate of evoked gamma oscillation in mild to moderate Alzheimer’s disease

Frontiers in Neurology, Journal Year: 2024, Volume and Issue: 15

Published: March 6, 2024

Background Alzheimer’s Disease (AD) is a multifactorial, progressive neurodegenerative disease that disrupts synaptic and neuronal activity network oscillations. It characterized by loss, brain atrophy decline in cognitive functional abilities. Cognito’s Evoked Gamma Therapy System provides an innovative approach for AD inducing EEG-verified gamma oscillations through sensory stimulation. Prior research has shown promising disease-modifying effects experimental models. The present study (NCT03556280: OVERTURE) evaluated the feasibly, safety efficacy of evoked oscillation treatment using medical device (CogTx-001) participants with mild to moderate AD. Methods was randomized, double blind, sham-controlled, 6-months clinical trial enrolled 76 participants, aged 50 or older, who met criteria baseline MMSE scores between 14 26. Participants were randomly assigned 2:1 receive self-administered daily, one-hour, therapy, evoking sham treatment. CogTx-001 use at home help care partner, over 6 months. primary outcome measures safety, physical neurological exams monthly assessments adverse events (AEs) MRI, tolerability, measured use. Although not statistically powered evaluate potential outcomes, secondary included several endpoints. Results Total AEs similar groups, there no unexpected serious related AEs, treatment-emergent led discontinuation. MRI did show Amyloid-Related Imaging Abnormalities (ARIA) any participant. High adherence rates (85–90%) observed participants. There statistical separation active arm measure MADCOMS CDR-SB ADAS-Cog14. However, some including ADCS-ADL, MMSE, whole volume demonstrated reduced progression compared treated achieved nominal significance. Conclusion Our results demonstrate 1-h daily safe well-tolerated benefits Clinical Trial Registration: www.ClinicalTrials.gov , identifier: NCT03556280.

Language: Английский

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Memory enhancement by transcranial radiofrequency wave treatment occurs without appreciably increasing brain temperature

Physical and Engineering Sciences in Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

Language: Английский

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Monitoring Sleep Quality Through Low α-Band Activity in the Prefrontal Cortex Using a Portable Electroencephalogram Device: Longitudinal Study

Journal of Medical Internet Research, Journal Year: 2025, Volume and Issue: 27, P. e67188 - e67188

Published: March 10, 2025

Background The pursuit of sleep quality has become an important aspect people’s global quest for overall health. However, the objective neurobiological features corresponding to subjective perceptions remain poorly understood. Although previous studies have investigated relationship between electroencephalogram (EEG) and sleep, lack longitudinal follow-up raises doubts about reproducibility their findings. Objective Currently, there is a gap in research regarding stable associations EEG data assessed through multiple collection sessions, which could help identify potential targets related quality. Methods In this study, we used portable device collect resting-state prefrontal cortex over 3-month period from 42 participants (27 first month, 25 second 40 third month). Each participants’ was using Pittsburgh Sleep Quality Index (PSQI) estimate recent Results We found that significant consistent positive correlation low α band activity PSQI scores (r=0.45, P<.001). More importantly, remained across all recordings (P<.05), regardless whether considered same cohort or expanded sample size. Furthermore, discovered periodic component primarily contributed association with PSQI. Conclusions These findings represent identification reliable target sessions. Our results provide solid foundation future applications devices monitoring screening disorders broad population.

Language: Английский

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