Neuromodulatory interventions for Alzheimer's disease.
7 affiliations
- 1School of Advanced Technology, Algonquin College, Ottawa, ON, Canada.
- 2Department of Electrical and Computer Engineering, Western University, London, ON, Canada.
- 3Shenzhen Top-Tech Industrial Co., Ltd., Shenzhen, Guangdong, China.
- 4School of Information Technology, Carleton University, Ottawa, ON, Canada.
- 5Northern Innovation on Quantum Technologies Inc., Ottawa, ON, Canada.
- 6Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
- 7Human Health Therapeutics Research Center, National Research Council of Canada, Ottawa, ON, Canada.
Abstract
Alzheimer's disease (AD) and mild cognitive impairment (MCI) represent an escalating global public health challenge with major socioeconomic consequences. Although anti-amyloid monoclonal antibodies have introduced disease-modifying treatment options for early symptomatic AD, their benefits remain modest and must be balanced against cost, monitoring burden, and safety risks. Neuromodulatory interventions have therefore emerged as promising investigational strategies that may complement existing therapeutic approaches. This narrative review evaluates current clinical and neurophysiological evidence for seven major neuromodulation approaches: 40 Hz gamma rhythm sensory stimulation, also known as gamma entrainment using sensory stimulation (GENUS), transcranial alternating current stimulation (tACS), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), focused ultrasound (FUS), deep brain stimulation (DBS), and transcranial photobiomodulation (tPBM). Integrating clinical findings with mechanistic evidence, we examine synaptic plasticity, neuroinflammation, glymphatic clearance, oscillatory entrainment, and cholinergic signaling as candidate therapeutic mechanisms. A comparative matrix summarizes target specificity, invasiveness, stimulation parameters, and translational status. Finally, we discuss key barriers, including biological heterogeneity, protocol standardization, durability of benefit, caregiver burden, and the uncertain implications of continuous network stimulation for future personalized and closed-loop interventions.
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BibTeX
@article{wang2026neuromodulatory,
title = {{Neuromodulatory interventions for Alzheimer's disease.}},
author = {Ruofan Wang and Botao Zhu and Qingda Guo and Jun Steed Huang and Wandong Zhang},
journal = {Frontiers in aging neuroscience},
year = {2026},
month = oct,
doi = {10.3389/fnagi.2026.1925914},
url = {https://europepmc.org/article/MED/42923644},
note = {CC BY},
}
RIS
TY - JOUR
TI - Neuromodulatory interventions for Alzheimer's disease.
AU - Ruofan Wang
AU - Botao Zhu
AU - Qingda Guo
AU - Jun Steed Huang
AU - Wandong Zhang
PY - 2026
DA - 2026/10/08
JO - Frontiers in aging neuroscience
DO - 10.3389/fnagi.2026.1925914
UR - https://europepmc.org/article/MED/42923644
AB - Alzheimer's disease (AD) and mild cognitive impairment (MCI) represent an escalating global public health challenge with major socioeconomic consequences. Although anti-amyloid monoclonal antibodies have introduced disease-modifying treatment options for early symptomatic AD, their benefits remain modest and must be balanced against cost, monitoring burden, and safety risks. Neuromodulatory interventions have therefore emerged as promising investigational strategies that may complement existing therapeutic approaches. This narrative review evaluates current clinical and neurophysiological evidence for seven major neuromodulation approaches: 40 Hz gamma rhythm sensory stimulation, also known as gamma entrainment using sensory stimulation (GENUS), transcranial alternating current stimulation (tACS), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), focused ultrasound (FUS), deep brain stimulation (DBS), and transcranial photobiomodulation (tPBM). Integrating clinical findings with mechanistic evidence, we examine synaptic plasticity, neuroinflammation, glymphatic clearance, oscillatory entrainment, and cholinergic signaling as candidate therapeutic mechanisms. A comparative matrix summarizes target specificity, invasiveness, stimulation parameters, and translational status. Finally, we discuss key barriers, including biological heterogeneity, protocol standardization, durability of benefit, caregiver burden, and the uncertain implications of continuous network stimulation for future personalized and closed-loop interventions.
SN - 1663-4365
ER -