Neurostimulation in Alzheimer’s
Can this groundbreaking treatment enhance cognitive
abilities in Alzheimer’s dementia?
Alzheimer’s disease is the most common neurodegenerative disorder and accounts for 60-80% of dementia cases. It affects the memory, behavior, thinking, and social abilities of those affected. New innovative therapies are focusing on neurostimulation for Alzheimer’s dementia, a non-invasive and non-pharmacological approach with promising potential to positively influence the course of the disease.
In particular, transcranial alternating current stimulation (tACS) and direct current stimulation (tDCS) can be employed in early stages to break or slow down the harmful disease cycle. The goal is to restore neural functions and alleviate cognitive deficits.
Alzheimer's Disease
Pathophysiology and Effects
The Alzheimer’s disease is characterized by the accumulation of amyloid-beta (Aβ) peptides outside the nerve cells and hyperphosphorylated tau proteins (p-tau) inside the cells, which damage the brain in the form of plaques and neurofibrillary tangles. These pathological processes lead to disturbances in neuronal oscillations, neurotoxicity, brain atrophy, and progressive cognitive deficits.1
In particular, the pathological accumulation of amyloid β and p-tau is toxic to parvalbumin-positive (PV+) interneurons2, which are essential for normal gamma oscillations in the brain. Disturbances in gamma rhythm cause an hyperexcitability of glutamatergic neurons and throw the balance of excitation and inhibition (E/I) out of equilibrium. This imbalance leads to excitotoxicity – a dangerous overstimulation of nerve cells due to excess calcium3 – as well as triggering inflammatory processes4. This is accompanied by reduced cerebral blood flow5,6 and a decreased brain metabolism, further accelerating cognitive decline7,8.
These interconnected factors reinforce each other in a vicious cycle that leads to increasing destruction of neural structures, limited functional connectivity, and ultimately to cell death.
Brain Stimulation for Alzheimer's: Treatment Methods and Effectiveness
Transcranial Alternating Current Stimulation (tACS) as an Innovative Therapy for Alzheimer’s
The transcranial alternating current stimulation (brain stimulation for Alzheimer’s) is a promising alternative treatment for Alzheimer’s that is specifically applied at 40 Hz (gamma band frequency) to normalize the disrupted gamma oscillations. The therapy aims to restore the balance between neuronal excitability and inhibition (E/I) and to promote the synchronization of parvalbumin-positive interneurons (PV-IN)9,10,11.
By restoring the balance and neuronal synchrony, personalized neurostimulation can interrupt the pathological process. Positive effects on neuronal activity are observed particularly in the Default Mode Network (DMN)12, which is central to memory, attention, and other cognitive functions. Changes in the DMN are strongly linked to memory loss, attention disorders, and neurotoxicity.13,14,15
Direct current stimulation (tDCS) as an adjunct treatment for Alzheimer’s
Another proven alternative treatment for Alzheimer’s is transcranial direct current stimulation (tDCS). Unlike alternating current stimulation, tDCS applies a constant current that modulates the excitability of nerve cells depending on the direction of flow – either by excitation or inhibition.
The targeted use of tDCS as a complementary treatment for Alzheimer’s in early stages has led to improvements in various cognitive functions in clinical studies, including memory16,17,18, language, attention19, and spatial orientation20. The treatment is non-invasive, well-tolerated, and can be conveniently performed on an outpatient basis.
Personalized Neurostimulation
Benefits and Outlook
Neurostimulation for Alzheimer’s dementia represents a promising complementary treatment alongside existing therapies. Through non-drug, non-invasive brain stimulation in Alzheimer’s, harmful cellular processes can be interrupted and neural networks can be strengthened.
The Swiss innovation Brain Stimulator Miamind® is being studied in clinical trials and has the potential to contribute to improving the quality of life for Alzheimer’s patients, especially in the early stages of the disease. Personalized neurostimulation allows for an individualized treatment approach that can be used as an alternative or supplementary treatment for Alzheimer’s.
The current research findings on tACS and tDCS are promising, although further clinical studies are needed to investigate the optimal application and long-term effects more precisely.
Swiss New Development: The Personalized Miamind®
Neurostimulator
As a Swiss innovation, the young Basel neurology start-up Bottneuro, a spin-off from the University of Basel, has developed the world’s first fully personalized neurostimulator for home use. The Miamind® Neurostimulator is a breakthrough in personalized neurostimulation, offering custom 3D-printed neurostimulator caps with up to 34 precisely placed electrodes based on individual MRI scans.
This innovative, non-invasive therapy allows for the stimulation of specific brain regions that may be affected in cases of Alzheimer’s disease. The personalized neurostimulation takes into account the unique anatomical differences of each patient and can be used as a complementary treatment for Alzheimer’s alongside traditional therapies.
FAQ: Neurostimulation in Alzheimer’s
Frequently Asked Questions
When do we talk about dementia and when about Alzheimer’s?
Dementia is the umbrella term for about 50 different diseases that lead to progressive loss of cognitive abilities. Alzheimer’s is the most common form of dementia and accounts for 60-80% of all dementia cases. Every Alzheimer’s patient has dementia, but not every dementia patient has Alzheimer’s.
What is meant by neurostimulation in Alzheimer's?
Neurostimulation in Alzheimer’s dementia refers to methods that use electrical impulses to enhance brain function in Alzheimer’s patients and alleviate cognitive deficits.
What neurostimulation methods are available for Alzheimer's?
The most important procedures for brain stimulation in Alzheimer’s are transcranial alternating current stimulation (tACS) and direct current stimulation (tDCS), which are considered innovative therapies for Alzheimer’s.
Is neurostimulation safe for Alzheimer’s?
Yes. Both procedures are non-invasive, well-tolerated, and have few side effects. Particularly in early stages, complementary treatment is advised for Alzheimer’s.
Can neurostimulation cure Alzheimer's?
Neurostimulation for Alzheimer’s disease cannot cure the condition, but it offers an alternative treatment method that may slow symptoms and support cognitive function.
What makes the Swiss innovation Miamind® Neurostimulator for Alzheimer’s stand out?
The personalized neurostimulation provided by the Miamind® neurostimulator enables fully individualized brain stimulation for Alzheimer’s based on patient-specific MRI scans and 3D-printed treatment caps.
References
Potential Clinical Applications
- Gauthier, S., Rosa-Neto, P., Morais, J. & Webster, C. World Alzheimer Report 2021: Journey through the diagnosis of dementia. World Alzheimers Dis. Int. 1–314 (2021).
- Verret, L. et al. Inhibitory Interneuron Deficit Links Altered Network Activity and Cognitive Dysfunction in Alzheimer Model. Cell 149, 708–721 (2012).
- Kuchibhotla, K. V. et al. Abeta plaques lead to aberrant regulation of calcium homeostasis in vivo resulting in structural and functional disruption of neuronal networks. Neuron 59, 214–225 (2008).
- Shaftel, S. S., Griffin, W. S. T. & O’Banion, M. K. The role of interleukin-1 in neuroinflammation and Alzheimer disease: an evolving perspective. J. Neuroinflammation 5, 7 (2008).
- Sprugnoli, G. et al. Impact of multisession 40Hz tACS on hippocampal perfusion in patients with Alzheimer’s disease. Alzheimers Res. Ther. 13, 203 (2021). 13, 203 (2021).
- Mateo, C., Knutsen, P. M., Tsai, P. S., Shih, A. Y. & Kleinfeld, D. Entrainment of Arteriole Vasomotor Fluctuations by Neural Activity Is a Basis of Blood-Oxygenation-Level-Dependent ‘Resting-State’ Connectivity. Neuron 96, 936-948.e3 (2017).
- Smeralda, C. L. et al. The role of parvalbumin interneuron dysfunction across neurodegenerative dementias. Ageing Res. Rev. 101, 102509 (2024).
- De Paolis, M. L. et al. Transcranial alternating current stimulation (tACS) at gamma frequency: an up-and-coming tool to modify the progression of Alzheimer’s Disease. Transl. Neurodegener. 13, 33 (2024). 13, 33 (2024).
- Cappon, D. et al. Tele-supervised home-based transcranial alternating current stimulation (tACS) for Alzheimer’s disease: a pilot study. Front. Hum. Neurosci. 17, (2023).
- Dhaynaut, M. et al. Impact of 40 Hz Transcranial Alternating Current Stimulation on Cerebral Tau Burden in Patients with Alzheimer’s Disease: A Case Series. J. Alzheimers Dis. JAD 85, 1667–1676 (2022).
- Bréchet, L. et al. Patient-Tailored, Home-Based Non-invasive Brain Stimulation for Memory Deficits in Dementia Due to Alzheimer’s Disease. Front. Neurol. 12, (2021).
- Palop, J. J. & Mucke, L. Network abnormalities and interneuron dysfunction in Alzheimer disease. Nat. Rev. Neurosci. 17, 777–792 (2016).
- Seoane, S., Van Den Heuvel, M., Acebes, Á. & Janssen, N. The subcortical default mode network and Alzheimer’s disease: a systematic review and meta-analysis. Brain Commun. 6, fcae128 (2024).
- Benussi, A. et al. Exposure to gamma tACS in Alzheimer’s disease: A randomized, double-blind, sham-controlled, crossover, pilot study. Brain Stimulat. (2021) doi:10.1016/j.brs.2021.03.007.
- Benussi et al. Increasing Brain Gamma Activity Improves Episodic Memory and Restores Cholinergic Dysfunction in Alzheimer’s Disease. (2022).
- Rezakhani, S., Amiri, M., Hassani, A., Esmaeilpour, K. & Sheibani, V. Anodal HD-tDCS on the dominant anterior temporal lobe and dorsolateral prefrontal cortex: clinical results in patients with mild cognitive impairment. Alzheimers Res. Ther. 16, 27 (2024).
- Boggio, P. S. et al. Prolonged visual memory enhancement after direct current stimulation in Alzheimer’s disease. Brain Stimulat. 5, 223–230 (2012).
- McKendrick, R., Falcone, B., Scheldrup, M. & Ayaz, H. Effects of Transcranial Direct Current Stimulation on Baseline and Slope of Prefrontal Cortex Hemodynamics During a Spatial Working Memory Task. Front. Hum. Neurosci. 14, 64 (2020).
- Im, J. J. et al. Effects of 6-month at-home transcranial direct current stimulation on cognition and cerebral glucose metabolism in Alzheimer’s disease. Brain Stimul. Basic Transl. Clin. Res. Neuromodulation 12, 1222–1228 (2019).
- Gangemi, A., Colombo, B. & Fabio, R. A. Effects of short- and long-term neurostimulation (tDCS) on Alzheimer’s disease patients: two randomized studies. Aging Clin. Exp. Res. 33, 383–390 (2021).