An update on the use of gamma (multi)sensory stimulation for Alzheimer’s disease treatment

Manippa, Valerio; Palmisano, Annalisa; Filardi, Marco; Vilella, Davide; Nitsche, Michael A.; Rivolta, Davide; Logroscino, Giancarlo

doi:10.3389/fnagi.2022.1095081

Cited by 28 publications

(12 citation statements)

References 76 publications

(101 reference statements)

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“…Numerous preclinical studies have shown that such gamma stimulation attenuates amyloid and tau pathology and promotes neuroprotection in mouse models of AD and that this coincides with improvements in cognitive function [7][8][9][10][11][12][13][14]. Based on these findings, multiple clinical trials have focused on assessing the therapeutic potential of gamma stimulation and encouragingly show gamma stimulation can also ameliorate aspects of neurodegeneration and dementia in patients with AD [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Audiovisual gamma stimulation for the treatment of neurodegeneration

Blanco‐Duque,

Chan,

Kahn

et al. 2023

J Intern Med

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Alzheimer's disease (AD) is the most common type of neurodegenerative disease and a health challenge with major social and economic consequences. In this review, we discuss the therapeutic potential of gamma stimulation in treating AD and delve into the possible mechanisms responsible for its positive effects. Recent studies reveal that it is feasible and safe to induce 40 Hz brain activity in AD patients through a range of 40 Hz multisensory and noninvasive electrical or magnetic stimulation methods. Although research into the clinical potential of these interventions is still in its nascent stages, these studies suggest that 40 Hz stimulation can yield beneficial effects on brain function, disease pathology, and cognitive function in individuals with AD. Specifically, we discuss studies involving 40 Hz light, auditory, and vibrotactile stimulation, as well as noninvasive techniques such as transcranial alternating current stimulation and transcranial magnetic stimulation. The precise mechanisms underpinning the beneficial effects of gamma stimulation in AD are not yet fully elucidated, but preclinical studies have provided relevant insights. We discuss preclinical evidence related to both neuronal and nonneuronal mechanisms that may be involved, touching upon the relevance of interneurons, neuropeptides, and specific synaptic mechanisms in translating gamma stimulation into widespread neuronal activity within the brain. We also explore the roles of microglia, astrocytes, and the vasculature in mediating the beneficial effects of gamma stimulation on brain function. Lastly, we examine upcoming clinical trials and contemplate the potential future applications of gamma stimulation in the management of neurodegenerative disorders.

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Section: Introductionmentioning

confidence: 99%

Audiovisual gamma stimulation for the treatment of neurodegeneration

Blanco‐Duque,

Chan,

Kahn

et al. 2023

J Intern Med

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“…The attempts to restore/influence gamma power in AD are still at an investigational stage, as no changes in AD biomarkers in humans after such treatment have been reported to date (Manippa et al, 2022). However, gamma‐patterned AD treatment has a clear clinical potential because a steady state gamma induced in sensory cortex can propagate into deeper brain areas in rodents (Adaikkan et al, 2019; Li et al, 2021; Martorell et al, 2019; Soula et al, 2023) and humans (Jones et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…Agents that directly pharmacologically target major neuropathological hallmarks of the disease including beta‐amyloid (Aß) plaques, tau‐containing neurofibrillary tangles and neuroinflammation are the main focus of attention (Cummings et al, 2022; van Dyck et al, 2023). In addition, the therapeutic potential of non‐pharmacological approaches, including those targeting brain network dysfunction, is gaining considerable traction (Chen et al, 2022; Manippa et al, 2022). Abnormal brain network activity in patients with AD includes a marked reduction in gamma band electroencephalogram oscillations (γ, 30–100 Hz) (Casula et al, 2022), a feature that also has been observed in many animal models (Bazzigaluppi et al, 2018; Driver et al, 2007; Iaccarino et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Gamma‐patterned sensory stimulation reverses synaptic plasticity deficits in rat models of early Alzheimer's disease

Yang,

Ondrejcak,

et al. 2023

Eur J of Neuroscience

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Non‐invasive sensory stimulation in the range of the brain's gamma rhythm (30–100 Hz) is emerging as a new potential therapeutic strategy for the treatment of Alzheimer's disease (AD). Here, we investigated the effect of repeated combined exposure to 40 Hz synchronized sound and light stimuli on hippocampal long‐term potentiation (LTP) in vivo in three rat models of early AD. We employed a very complete model of AD amyloidosis, amyloid precursor protein (APP)‐overexpressing transgenic McGill‐R‐Thy1‐APP rats at an early pre‐plaque stage, systemic treatment of transgenic APP rats with corticosterone modelling certain environmental AD risk factors and, importantly, intracerebral injection of highly disease‐relevant AD patient‐derived synaptotoxic beta‐amyloid and tau in wild‐type animals. We found that daily treatment with 40 Hz sensory stimulation for 2 weeks fully abrogated the inhibition of LTP in all three models. Moreover, there was a negative correlation between the magnitude of LTP and the level of active caspase‐1 in the hippocampus of transgenic APP animals, which suggests that the beneficial effect of 40 Hz stimulation was dependent on modulation of pro‐inflammatory mechanisms. Our findings support ongoing clinical trials of gamma‐patterned sensory stimulation in early AD.

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“…Although the exact mechanism of action of tACS is still under debate, the explicit aim of gamma-tACS is to restore disrupted endogenous gamma oscillations in AD patients. tACS is presumed to entrain or stimulation, can entrain gamma oscillations in AD patients for therapeutic purposes (Manippa et al, 2022). Indeed, the seminal study of Clements-Cortes and colleagues demonstrated that six 30-minute sessions of 40 Hz vibrotactile stimulation improve cognitive functioning in AD (Clements-Cortes et al, 2016).…”

Section: Proposed Mechanisms Of Action Of Gamma-tacsmentioning

confidence: 99%

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

et al. 2023

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

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An update on the use of gamma (multi)sensory stimulation for Alzheimer’s disease treatment

Cited by 28 publications

References 76 publications

Audiovisual gamma stimulation for the treatment of neurodegeneration

Audiovisual gamma stimulation for the treatment of neurodegeneration

Gamma‐patterned sensory stimulation reverses synaptic plasticity deficits in rat models of early Alzheimer's disease

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

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